WorldWideScience

Sample records for patient survival f1-5spla2

  1. Novel genetic approach to investigate the role of plasma secretory phospholipase A2 (sPLA2)-V isoenzyme in coronary heart disease: modified Mendelian randomization analysis using PLA2G5 expression levels.

    Science.gov (United States)

    Holmes, Michael V; Exeter, Holly J; Folkersen, Lasse; Nelson, Christopher P; Guardiola, Montse; Cooper, Jackie A; Sofat, Reecha; Boekholdt, S Matthijs; Khaw, Kay-Tee; Li, Ka-Wah; Smith, Andrew J P; Van't Hooft, Ferdinand; Eriksson, Per; Franco-Cereceda, Anders; Asselbergs, Folkert W; Boer, Jolanda M A; Onland-Moret, N Charlotte; Hofker, Marten; Erdmann, Jeanette; Kivimaki, Mika; Kumari, Meena; Reiner, Alex P; Keating, Brendan J; Humphries, Steve E; Hingorani, Aroon D; Mallat, Ziad; Samani, Nilesh J; Talmud, Philippa J

    2014-04-01

    Secretory phospholipase A2 (sPLA2) enzymes are considered to play a role in atherosclerosis. sPLA2 activity encompasses several sPLA2 isoenzymes, including sPLA2-V. Although observational studies show a strong association between elevated sPLA2 activity and CHD, no assay to measure sPLA2-V levels exists, and the only evidence linking the sPLA2-V isoform to atherosclerosis progression comes from animal studies. In the absence of an assay that directly quantifies sPLA2-V levels, we used PLA2G5 mRNA levels in a novel, modified Mendelian randomization approach to investigate the hypothesized causal role of sPLA2-V in coronary heart disease (CHD) pathogenesis. Using data from the Advanced Study of Aortic Pathology, we identified the single-nucleotide polymorphism in PLA2G5 showing the strongest association with PLA2G5 mRNA expression levels as a proxy for sPLA2-V levels. We tested the association of this SNP with sPLA2 activity and CHD events in 4 prospective and 14 case-control studies with 27 230 events and 70 500 controls. rs525380C>A showed the strongest association with PLA2G5 mRNA expression (P=5.1×10(-6)). There was no association of rs525380C>A with plasma sPLA2 activity (difference in geometric mean of sPLA2 activity per rs525380 A-allele 0.4% (95% confidence intervals [-0.9%, 1.6%]; P=0.56). In meta-analyses, the odds ratio for CHD per A-allele was 1.02 (95% confidence intervals [0.99, 1.04]; P=0.20). This novel approach for single-nucleotide polymorphism selection for this modified Mendelian randomization analysis showed no association between rs525380 (the lead single-nucleotide polymorphism for PLA2G5 expression, a surrogate for sPLA2-V levels) and CHD events. The evidence does not support a causal role for sPLA2-V in CHD.

  2. sPLA2-IIA

    Indian Academy of Sciences (India)

    67

    Recent research showed that maslinic acid interacts with sPLA2-IIA ... Further analysis revealed that sPLA2-IIA only induced modest LDL ..... MDA/mg protein) compared to native LDL (2.043 nmol MDA/mg protein) while .... to modify extracellular non-cellular lipid components such as lipoproteins, ... The main pathway for.

  3. Hydrolysis of lipoproteins by sPLA2's enhances mitogenesis and eicosanoid release from vascular smooth muscle cells: Diverse activity of sPLA2's IIA, V and X.

    Science.gov (United States)

    Pruzanski, Waldemar; Kopilov, Julia; Kuksis, Arnis

    2016-01-01

    Mitogenesis of Vascular Smooth Muscle Cells (VSMC) plays an important role in atherogenesis. Until recently, the effect of lipid subfractions has not been clarified. Secretory phospholipases A2 (sPLA2's) hydrolyse glycerophospholipids and release pro-inflammatory lyso-lipids, oxidized and non-oxidized fatty acids and isoprostanes. They localize in the vascular wall. We hypothesized that structurally similar sPLA2's may exert different impact on VSMC. The influence of sPLA2's, IIA, V, X, HDL, LDL, and hydrolysis products was tested on mitogenesis of VSMC, i.e., the early effect on the cell membrane phospholipids, and on PGE2 and LTB4 release, i.e., late effect of Cyclooxygenase and 5-lipooxygenase activity in VSMC. Mitogenesis was significantly enhanced by HDL and LDL, and by products of sPLA2 hydrolysis. Hydrolysis of HDL or LDL enhanced mitogenic activity in order V>X>IIA. The release of PGE2 was enhanced by group X sPLA2 and by HDL hydrolyzed by groups V and X. LDL and its hydrolysis products enhanced the release of PGE2 in order X>V>IIA. The release of LTB4 was markedly increased by LDL and HDL, and by hydrolytic products of group V and X, but not group IIA sPLA2. Our study demonstrates a diverse interaction of pro-inflammatory sPLA2's with HDL and LDL affecting both mitogenesis and eicosanoid release from VSMC, therefore potentially enhancing their pro-atherogenic activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. A dangerous liaison: Leptin and sPLA2-IIA join forces to induce proliferation and migration of astrocytoma cells.

    Directory of Open Access Journals (Sweden)

    Rubén Martín

    Full Text Available Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA. Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions. sPLA2-IIA induced up-regulation of leptin receptors in 1321N1 human astrocytoma cells. Leptin, as well as sPLA2-IIA, increased growth and migration in these cells, through activation/phosphorylation of key proteins of survival cascades. Leptin, at concentrations with minimal or no activating effects on astrocytoma cells, enhanced growth and migration promoted by low doses of sPLA2-IIA. sPLA2-IIA alone induced a transient phosphorylation pattern in the Src/ERK/Akt/mTOR/p70S6K/rS6 pathway through EGFR transactivation, and co-addition of leptin resulted in a sustained phosphorylation of these signaling regulators. Mechanistically, EGFR transactivation and tyrosine- and serine/threonine-protein phosphatases revealed a key role in this leptin-sPLA2-IIA cross-talk. This cooperative partnership between both proteins was also found in primary astrocytes. These findings thus indicate that the adipokine leptin, by increasing the susceptibility of cells to inflammatory mediators, could contribute to worsen the prognosis of tumoral and neurodegenerative processes, being a potential mediator of some obesity-related medical complications.

  5. Interactions of pharmacologically active snake venom sPLA2 with different cell lines

    Science.gov (United States)

    Doumanov, Jordan; Mladenova, Kirilka; Aleksandrov, Radoslav; Danovski, Georgi; Petrova, Svetla

    2014-01-01

    Secreted Phospholipases A2 (sPLA2s) represent a large family of structurally related enzymes, which target different tissues and organs and induce numerous pharmacological effects based on their catalytic specificity – hydrolysis of the sn-2 ester bond of glycerophospholipids. The neurotoxin vipoxin, isolated from the venom of Vipera ammodytes meriodionalis, is a heterodimeric postsynaptic ionic complex composed of two protein subunits – a basic and toxic His48 sPLA2 enzyme and an acidic, enzymatically inactive and non-toxic component. In this paper, for the first time, we demonstrate that vipoxin sPLA2 enzyme affects cell integrity and viability of four cell types and causes different cell responses. The most dramatic local tissue effects were observed with RPE-1 (retinal pigment epithelial) cells followed by A549 (adenocarcinomic human alveolar epithelial) cells and MDCK (Madin-Darby Canine Kidney epithelial) cells. Products of the enzymatic reaction, lysophospholipids and unsaturated free fatty acids, act as lipid mediators that can induce membrane damaging or can stimulate cell proliferation. Our preliminary results on the cytotoxic effect of vipoxin sPLA2 on A549 cells are promising in searching of its eventual anticancer potential. PMID:26019578

  6. Bim and Mcl-1 exert key roles in regulating JAK2V617F cell survival

    International Nuclear Information System (INIS)

    Rubert, Joëlle; Qian, Zhiyan; Andraos, Rita; Guthy, Daniel A; Radimerski, Thomas

    2011-01-01

    The JAK2 V617F mutation plays a major role in the pathogenesis of myeloproliferative neoplasms and is found in the vast majority of patients suffering from polycythemia vera and in roughly every second patient suffering from essential thrombocythemia or from primary myelofibrosis. The V617F mutation is thought to provide hematopoietic stem cells and myeloid progenitors with a survival and proliferation advantage. It has previously been shown that activated JAK2 promotes cell survival by upregulating the anti-apoptotic STAT5 target gene Bcl-xL. In this study, we have investigated the role of additional apoptotic players, the pro-apoptotic protein Bim as well as the anti-apoptotic protein Mcl-1. Pharmacological inhibition of JAK2/STAT5 signaling in JAK2 V617F mutant SET-2 and MB-02 cells was used to study effects on signaling, cell proliferation and apoptosis by Western blot analysis, WST-1 proliferation assays and flow cytometry. Cells were transfected with siRNA oligos to deplete candidate pro- and anti-apoptotic proteins. Co-immunoprecipitation assays were performed to assess the impact of JAK2 inhibition on complexes of pro- and anti-apoptotic proteins. Treatment of JAK2 V617F mutant cell lines with a JAK2 inhibitor was found to trigger Bim activation. Furthermore, Bim depletion by RNAi suppressed JAK2 inhibitor-induced cell death. Bim activation following JAK2 inhibition led to enhanced sequestration of Mcl-1, besides Bcl-xL. Importantly, Mcl-1 depletion by RNAi was sufficient to compromise JAK2 V617F mutant cell viability and sensitized the cells to JAK2 inhibition. We conclude that Bim and Mcl-1 have key opposing roles in regulating JAK2 V617F cell survival and propose that inactivation of aberrant JAK2 signaling leads to changes in Bim complexes that trigger cell death. Thus, further preclinical evaluation of combinations of JAK2 inhibitors with Bcl-2 family antagonists that also tackle Mcl-1, besides Bcl-xL, is warranted to assess the therapeutic potential

  7. Revisiting the use of sPLA2-sensitive liposomes in cancer therapy

    DEFF Research Database (Denmark)

    Pourhassan, Houman; Clergeaud Veiga, Gael; Hansen, Anders Elias

    2017-01-01

    The first developed secretory phospholipase A2 (sPLA2) sensitive liposomal cisplatin formulation (LiPlaCis®) is currently undergoing clinical evaluation. In the present study we revisit and evaluate critical preclinical parameters important for the therapeutic potential and safety of platinum drugs......, here oxaliplatin (L-OHP), formulated in sPLA2 sensitive liposomes. We show the mole percentage of negatively charged phospholipid needed to obtain enzyme-sensitivity for saturated systems is ≥ 25% for 16-carbon chain lipid membranes, and > 40% for 18-chain lipid membranes, which was surprising as 25......% is used clinically in LiPlaCis®. Efficient sPLA2-dependent growth inhibition of colorectal cancer cells was demonstrated in vitro, where cell membrane degradation and cytolysis depends on the sensitivity of the formulation towards the enzyme and is governed by the amount of lysolipids generated...

  8. Mechanistic Study of the sPLA2 Mediated Hydrolysis of a Thio-ester Pro Anticancer Ether Lipid

    DEFF Research Database (Denmark)

    Linderoth, Lars; Fristrup, Peter; Hansen, Martin

    2009-01-01

    Secretory phospholipase A2 (sPLA2) is an interesting enzyme for triggered liposomal drug delivery to tumor tissue due the overexpression of sPLA2 in cancerous tissue. A drug delivery system based on the triggered release of therapeutics from sPLA2-sensitive liposomes constituted of pro anticancer...... ether lipids, which become cytotoxic upon sPLA2-catalyzed hydrolysis has previously been established. To optimize the hydrolysis rate of the lipids and thereby optimizing the release profile of the drugs from the liposomes, we have synthesized a thio-ester pro anticancer ether lipid. Liposomes...... constituted of this lipid showed an altered rate of hydrolysis by sPLA2. We have tested the cytotoxicity of the thio-ester pro anticancer ether lipids toward cancer cells, and the results showed that the cytotoxicity is indeed maintained upon sPLA2 exposure. To further understand the origin for the observed...

  9. The anti-inflammatory activity of standard aqueous stem bark extract of Mangifera indica L. as evident in inhibition of Group IA sPLA2.

    Science.gov (United States)

    Dhananjaya, Bhadrapura Lakkappa; Shivalingaiah, Sudharshan

    2016-03-01

    The standard aqueous stem bark extract is consumed as herbal drink and used in the pharmaceutical formulations to treat patients suffering from various disease conditions in Cuba. This study was carried out to evaluate the modulatory effect of standard aqueous bark extract of M. indica on Group IA sPLA2. M. indica extract, dose dependently inhibited the GIA sPLA2 (NN-XIa-PLA2) activity with an IC50 value 8.1 µg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ~40 µg/ml concentration and at various concentrations (0-50 µg/ml), it dose dependently inhibited the edema formation. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect on the GIA sPLA2. Furthermore, the inhibition was irreversible as evidenced from binding studies. It is observed that the aqueous extract ofM. indica effectively inhibits sPLA2 and it is associated inflammatory activities, which substantiate their anti-inflammatory properties. The mode of inhibition could be due to direct interaction of components present in the extract, with sPLA2 enzyme. Further studies on understanding the principal constituents, responsible for the anti-inflammatory activity would be interesting to develop this into potent anti-inflammatory agent.

  10. Clinical Significance of POU5F1P1 rs10505477 Polymorphism in Chinese Gastric Cancer Patients Receving Cisplatin-Based Chemotherapy after Surgical Resection

    Directory of Open Access Journals (Sweden)

    Lili Shen

    2014-07-01

    Full Text Available This study aimed to investigate the association between POU class5 homeobox 1 pseudogene 1 gene (POU5F1P1 rs10505477 polymorphism and the prognosis of Chinese gastric cancer patients, who received cisplatin-based chemotherapy after surgical resection. POU5F1P1 rs10505477 was genotyped using the SNaPshot method in 944 gastric cancer patients who received gastrectomy. The association of rs10505477 G > A polymorphism with the progression and prognosis in gastric cancer patients was statistically analyzed using the SPSS version 18.0 for Windows. The results reveal that rs10505477 polymorphism has a negatively effect on the overall survival of gastric cancer patients in cisplatin-based chemotherapy subgroup (HR = 1.764, 95% CI = 1.069–2.911, p = 0.023. Our preliminary study indicates for the first time that POU5F1P1 rs10505477 is correlated with survival of gastric cancer patients who receving cisplatin-based chemotherapy after gastrectomy. Further studies are warranted to investigate the mechanism and to verify our results in different populations.

  11. Maslinic acid modulates secreted phospholipase A2-IIA (sPLA2-IIA ...

    Indian Academy of Sciences (India)

    Wei Hsum Yap

    2018-03-29

    Mar 29, 2018 ... Further analysis revealed that sPLA2-IIA only induced modest LDL oxidation and that inhibitory .... COX-2, was also reduced in primary human chondrocyte, primary rat .... oxidation (4.34 nmol MDA/mg protein) compared to native ..... rheumatoid fibroblast-like synoviocyte arachidonic acid meta- bolism.

  12. Efficiency, safety, and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog

    Directory of Open Access Journals (Sweden)

    Shimizu Y

    2015-03-01

    Full Text Available Yoshie Shimizu,1 Shunsuke Nakakura,1 Makiko Nishiyama,1 Hitoshi Tabuchi,1 Yoshiaki Kiuchi2 1Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, 2Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Background: We investigated the efficiency, safety and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog.Methods: We initially enrolled 44 eyes from 44 primary open angle glaucoma patients, and a total of 42 patients completed the study. All patients were under treatment with various prostaglandin F2α analogs and dorzolamide 1%/timolol 0.5%. While maintaining the prostaglandin F2α analog, dorzolamide 1%/timolol 0.5% was switched to brinzolamide 1%/timolol 0.5%. Conjunctival hyperemia, superficial punctate keratopathy, and intraocular pressure (IOP were evaluated at baseline and at 4, 12, and 24 weeks. Adverse events and patient preferences, measured using a questionnaire at study initiation and at 24 weeks, were also noted.Results: The IOP was 17.7±1.7, 16.8±2.6, 16.7±2.2, and 16.7±2.4 mmHg at baseline and at 4, 12, and 24 weeks, respectively, with no significant differences in IOP values at any time point (P=0.117, one-way analysis of variance. In addition, no significant differences were found in the incidence of conjunctival hyperemia or SPK score at any time point (all P>0.5, by Kruskal–Wallis test. Based on the evaluation of side effects using the questionnaire, stinging/burning was less common (P=0.042, while blurred vision was more common (P=0.003, after switching to brinzolamide 1%/timolol 0.5%. Regarding patient preferences, 13 patients (31% preferred dorzolamide 1%/timolol 0.5%, 12 patients (29% preferred brinzolamide 1%/timolol 0.5%, and 17 patients (40% preferred neither.Conclusion: When switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1

  13. Efficiency, safety, and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog.

    Science.gov (United States)

    Shimizu, Yoshie; Nakakura, Shunsuke; Nishiyama, Makiko; Tabuchi, Hitoshi; Kiuchi, Yoshiaki

    2015-01-01

    We investigated the efficiency, safety and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog. We initially enrolled 44 eyes from 44 primary open angle glaucoma patients, and a total of 42 patients completed the study. All patients were under treatment with various prostaglandin F2α analogs and dorzolamide 1%/timolol 0.5%. While maintaining the prostaglandin F2α analog, dorzolamide 1%/timolol 0.5% was switched to brinzolamide 1%/timolol 0.5%. Conjunctival hyperemia, superficial punctate keratopathy, and intraocular pressure (IOP) were evaluated at baseline and at 4, 12, and 24 weeks. Adverse events and patient preferences, measured using a questionnaire at study initiation and at 24 weeks, were also noted. The IOP was 17.7±1.7, 16.8±2.6, 16.7±2.2, and 16.7±2.4 mmHg at baseline and at 4, 12, and 24 weeks, respectively, with no significant differences in IOP values at any time point (P=0.117, one-way analysis of variance). In addition, no significant differences were found in the incidence of conjunctival hyperemia or SPK score at any time point (all P>0.5, by Kruskal-Wallis test). Based on the evaluation of side effects using the questionnaire, stinging/burning was less common (P=0.042), while blurred vision was more common (P=0.003), after switching to brinzolamide 1%/timolol 0.5%. Regarding patient preferences, 13 patients (31%) preferred dorzolamide 1%/timolol 0.5%, 12 patients (29%) preferred brinzolamide 1%/timolol 0.5%, and 17 patients (40%) preferred neither. When switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5%, the IOP values and incidence of superficial punctate keratopathy and conjunctival hyperemia were sustained throughout the 24-week observation period, and the patient preferences were similar for the two regimens. However, differences were observed in the ocular sensations of stinging/burning with dorzolamide 1%/timolol 0.5

  14. Long-term survival of 42 patients with resected N2 non-small-cell lung cancer: the impact of 2-(18)F-fluoro-2-deoxy-D-glucose positron emission tomogram mediastinal staging.

    Science.gov (United States)

    Barnett, Stephen; Baste, Jean-Marc; Murugappan, Kowsi; Tog, Check; Berlangieri, Salvatore; Scott, Andrew; Seevanayagam, Siven; Knight, Simon

    2011-01-01

    Prognostic information known preoperatively allows stratification of patients to surgery; induction therapy and surgery; or definitive chemoradiotherapy and may prevent a futile thoracotomy. Attention has focussed on the standard uptake value (SUV) of the primary tumour but less has been described regarding the 18F-fluoro-2-deoxy-D-glucose (18F-FDG) avidity of mediastinal nodes. We aimed, in a group of surgically resected cN0-1 but pN2 tumours, to compare the survival of patients with and without 18F-FDG avid mediastinal nodes. Retrospective review of a surgical database identified cN0-1 non-small-cell lung cancer (NSCLC) patients with pN2 disease after resection. Survival of non-FDG avid N2 versus FDG avid N2 groups was compared after stratification according to variables found on univariate analysis to affect survival. From January 1993 to December 2006, 42 patients were identified; 27 (64%) had non-FDG avid N2 disease. Five-year and median survival were better in the non-FDG avid N2 disease group, 25% versus 0% and 30 (16-44) versus 13 (10-16) months, respectively (p=0.02). After 1998, the difference in survival was 41% versus 0% and 35 (14-56) versus 12 (16-18) months, respectively (p=0.02). After resection, patients with non-FDG avid N2 disease have better survival than patients with FDG avid N2 disease. Exploratory thoracotomy alone (after frozen section analysis) cannot be advocated in patients with non-FDG avid N2 disease as survival after resection appears at least equivalent to alternate therapeutic approaches in this group. This assertion may be tempered if right pneumonectomy is required or R0 resection is unachievable. Mediastinal nodal avidity may improve stratification in future studies of long-term survival in NSCLC. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  15. Efficiency, safety, and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog

    OpenAIRE

    Shimizu, Yoshie; Nakakura,Shunsuke; Nishiyama,Makiko; Tabuchi,Hitoshi; Kiuchi,Yoshiaki

    2015-01-01

    Yoshie Shimizu,1 Shunsuke Nakakura,1 Makiko Nishiyama,1 Hitoshi Tabuchi,1 Yoshiaki Kiuchi2 1Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, 2Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan Background: We investigated the efficiency, safety and patient preference of switching from dorzolamide 1%/timolol 0.5% to brinzolamide 1%/timolol 0.5% while maintaining the prostaglandin F2α analog...

  16. Initial results of hypoxia imaging using 1-α-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA)

    International Nuclear Information System (INIS)

    Postema, Ernst J.; McEwan, Alexander J.B.; Riauka, Terence A.; Kumar, Piyush; Richmond, Dacia A.; Abrams, Douglas N.; Wiebe, Leonard I.

    2009-01-01

    Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-α-d-(5-deoxy-5-[ 18 F]-fluoroarabinofuranosyl)-2-nitroimidazole ( 18 F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of 18 F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal 18 F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of 18 F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of 18 F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased 18 F-FAZA uptake in the primary lung tumour. No side effects of the administration of 18 F-FAZA were observed. This study suggests that 18 F-FAZA may be a very useful radiopharmaceutical

  17. Efficient automated synthesis of 2-(5-["1"8F]fluoropentyl)-2-methylmalonic acid (["1"8F]ML-10) on a commercial available ["1"8F]FDG synthesis module

    International Nuclear Information System (INIS)

    Liu, Shaoyu; Nie, Dahong; Jiang, Shende; Tang, Ganghua

    2017-01-01

    ["1"8F]ML-10 (2-(5-["1"8F]fluoro-pentyl)-2-methylmalonic acid) is a small molecule positron emission tomography (PET) probe for apoptosis imaging. Automated synthesis of ["1"8F]ML-10 was developed by using two different purification methods through a direct saponification procedure on a modified commercial ["1"8F]Fluoro-2-Deoxyglucose (["1"8F]FDG) synthesizer. C18 purification method 1: The final ["1"8F]ML-10 solution containing ethanol was obtained with radiochemical yields of 60±5% (n=5) at the end of bombardment (EOB) and radiochemical purity of 98% in 35 min. Al_2O_3 and SCX purification method 2: To avoid possible side effects of a conventional ethanol-containing formulation, an new ethanol-free solution of ["1"8F]ML-10 was also developed, the radiochemical yields was 50±5% (n=5, EOB) within 45 min and the radiochemical purity was 98%. - Highlights: • The production of ["1"8F]ML-10 was optimized by using a straightforward saponification procedure. • Automated synthesis was performed on a commonly FDG synthesis module. • An ethanol-containing ["1"8F]ML-10 formulation was obtained with high radiochemical yield in a shorter time. • An ethanol-free formulation method of ["1"8F]ML-10 was also developed.

  18. Initial results of hypoxia imaging using 1-{alpha}-d-(5-deoxy-5-[{sup 18}F]-fluoroarabinofuranosyl)-2-nitroimidazole ({sup 18}F-FAZA)

    Energy Technology Data Exchange (ETDEWEB)

    Postema, Ernst J.; McEwan, Alexander J.B.; Riauka, Terence A.; Kumar, Piyush; Richmond, Dacia A.; Abrams, Douglas N. [University of Alberta, Department of Oncology, Edmonton, Alberta (Canada); Wiebe, Leonard I. [University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, Alberta (Canada)

    2009-10-15

    Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-{alpha}-d-(5-deoxy-5-[{sup 18}F]-fluoroarabinofuranosyl)-2-nitroimidazole ({sup 18}F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of {sup 18}F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal {sup 18}F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of {sup 18}F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of {sup 18}F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased {sup 18}F-FAZA uptake in the primary lung tumour. No side effects of the administration of {sup 18}F-FAZA were observed. This study suggests

  19. WHO-defined 'myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations.

    Science.gov (United States)

    Patnaik, M M; Lasho, T L; Finke, C M; Gangat, N; Caramazza, D; Holtan, S G; Pardanani, A; Knudson, R A; Ketterling, R P; Chen, D; Hoyer, J D; Hanson, C A; Tefferi, A

    2010-07-01

    The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with 'myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age >or=70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or >or=2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations.

  20. Prognostic significance of ASXL1, JAK2V617F mutations and JAK2V617F allele burden in Philadelphia-negative myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Yonal-Hindilerden I

    2015-06-01

    Full Text Available Ipek Yonal-Hindilerden, Aynur Daglar-Aday, Basak Akadam-Teker, Ceylan Yilmaz, Meliha Nalcaci, Akif Selim Yavuz, Deniz SarginDivision of Hematology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Fatih-Istanbul, Turkey Background: Despite insights into the genetic basis of Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs, a significant proportion of essential thrombocythemia (ET and primary myelofibrosis (PMF patients present with no known MPN disease alleles. There were no previous studies investigating the impact of ASXL1 mutations in Ph-negative MPNs in Turkey. In the current study, we investigated the prognostic significance of ASXL1 mutations in Turkish MPN patients. We also aimed to determine the prognostic significance of JAK2V617F allele burden and the relationship of JAK2V617F mutation with ASXL1 mutations in Ph-negative MPNs. Methods: About 184 patients from a single center diagnosed with Ph-negative MPNs were screened for ASXL1, JAK2V617F mutations, and JAK2V617F allele burden: 107 ET and 77 PMF. Results: A total of 29 ASXL1 mutations were detected in 24.7% of PMF and 8.4% of ET patients. ASXL1-mutated ET patients showed a trend toward an increase in the incidence of cerebrovascular events and higher total leukocyte counts. ASXL1-mutation in PMF was associated with older age and a higher prevalence of bleeding complications. In univariate analysis, overall survival (OS was significantly reduced in ASXL1-mutated PMF patients. In multivariate analysis, Dynamic International Prognostic Scoring System-plus high-risk category and ASXL1 mutation status were independently associated with shorter survival in PMF. In PMF, mutational status and allele burden of JAK2V617F showed no difference in terms of OS and leukemia-free survival. Conclusion: We conclude that ASXL1 mutations are molecular predictors of short OS in PMF. Keywords: Philadelphia-negative myeloproliferative neoplasms (Ph

  1. Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.

    Directory of Open Access Journals (Sweden)

    Tatjana I Djukic

    Full Text Available OBJECTIVE: To examine the association of six glutathione transferase (GST gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357 with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy. PATIENTS AND METHODS: A total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival. RESULTS: GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006. CONCLUSION: GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer.

  2. Prognostic value of tumour blood flow, [18F]EF5 and [18F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy

    International Nuclear Information System (INIS)

    Komar, Gaber; Eskola, Olli; Sipilae, Hannu; Solin, Olof; Lehtioe, Kaisa; Levola, Helena; Lindholm, Paula; Seppaelae, Jan; Seppaenen, Marko; Grenman, Reidar; Minn, Heikki

    2014-01-01

    In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour's biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [ 18 F]FDG, a new hypoxia tracer [ 18 F]EF5 and the perfusion tracer [ 15 O]H 2 O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy. The study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [ 15 O]H 2 O PET images using a one-tissue compartment model. [ 18 F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [ 18 F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival. Tumour stage and T-classification did not show any significant differences in comparison to the patients' metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [ 18 F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [ 18 F]EF5 maximum T/M ratio was the closest (p = 0.109). By contrast

  3. WHO-defined ‘myelodysplastic syndrome with isolated del(5q)' in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations

    Science.gov (United States)

    Patnaik, M M; Lasho, T L; Finke, C M; Gangat, N; Caramazza, D; Holtan, S G; Pardanani, A; Knudson, R A; Ketterling, R P; Chen, D; Hoyer, J D; Hanson, C A; Tefferi, A

    2010-01-01

    The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with ‘myelodysplastic syndrome with isolated del(5q)' (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age ⩾70 years (P=0.01), transfusion need at diagnosis (P=0.04) and dysgranulopoiesis (P=0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or ⩾2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations. PMID:20485371

  4. Improved synthesis of 2'-deoxy-2'-[18F]-fluoro-1-β-D-arabinofuranosyl-5-iodouracil ([18F]-FIAU)

    International Nuclear Information System (INIS)

    Anderson, Harry; Pillarsetty, NagaVaraKishore; Cantorias, Melchor; Lewis, Jason S.

    2010-01-01

    An improved synthesis of 2'-[ 18 F]-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil ([ 18 F]-FIAU) has been developed. The method utilizes trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed coupling of 2-deoxy-2-[ 18 F]-fluoro-1,3,5-tri-O-benzoyl-D-arabinofuranose with 2,4-bis(trimethylsilyloxy)-5-iodouracil to yield the protected dibenzoyl-[ 18 F]-FIAU. Dibenzoyl-[ 18 F]-FIAU was deprotected with sodium methoxide to yield a mixture of α- and β-anomers in a ratio of 1:1, which were purified by HPLC. The procedure described in this article eliminates the need for HBr activation of the sugar prior to coupling with silylated iodouracil and is suitable for automation. The total reaction time was about 110 min, starting from [ 18 F]-fluoride. The average isolated yield of the required β-anomer was 10±6% (decay corrected) with average specific activity of 125 mCi/μmol.

  5. Prospective study of serial 18F-FDG PET and 18F-fluoride (18F-NaF) PET to predict time to skeletal related events, time-to-progression, and survival in patients with bone-dominant metastatic breast cancer.

    Science.gov (United States)

    Peterson, Lanell M; O'Sullivan, Janet; Wu, Qian Vicky; Novakova-Jiresova, Alena; Jenkins, Isaac; Lee, Jean H; Shields, Andrew; Montgomery, Susan; Linden, Hannah M; Gralow, Julie R; Gadi, Vijayakrishna K; Muzi, Mark; Kinahan, Paul E; Mankoff, David A; Specht, Jennifer M

    2018-05-10

    Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial 18 F-FDG PET was predictive of time to skeletal related events (tSRE) and time-to-progression (TTP). 18 F-NaF PET improves bone metastasis detection compared to bone scans. We prospectively tested 18 F-FDG PET and 18 F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (BD MBC). Methods: Patients with BD MBC were imaged with 18 F-FDG PET and 18 F-NaF PET prior to starting new therapy (scan1) and again at a range of times centered around approximately 4 months later (scan2). SUV max and SULpeak were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and 18 F-FDG PET and 18 F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) criteria were also applied. Survival curves for mPERCIST compared response categories of Complete Response+Partial Response+Stable Disease versus Progressive Disease (CR+PR+SD vs PD) for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher FDG SULpeak at scan2 predicted shorter time to tSRE ( P = PET mPERCIST, tSRE and TTP were longer in responders (CR, PR, or stable) compared to non-responders (PD) ( P = 0.007, 0.028 respectively), with a trend toward improved survival ( P = 0.1). An increase in the uptake between scans of up to 5 lesions by 18 F-NaF PET was associated with longer OS ( P = 0.027). Conclusion: Changes in 18 F-FDG PET parameters during therapy are predictive of tSRE and TTP, but not OS. mPERCIST evaluation in bone lesions may be useful in assessing response to therapy and is worthy of evaluation in multicenter, prospective trials. Serial 18 F-NaF PET was associated with OS, but was not useful for predicting TTP or tSRE in BD MBC

  6. Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab'2 in mice

    Directory of Open Access Journals (Sweden)

    Li Yanbin

    2006-03-01

    Full Text Available Abstract Background Avian influenza virus H5N1 has demonstrated considerable pandemic potential. Currently, no effective vaccines for H5N1 infection are available, so passive immunotherapy may be an alternative strategy. To investigate the possible therapeutic effect of antibody against highly pathogenic H5N1 virus on a mammal host, we prepared specific equine anti-H5N1 IgGs from horses vaccinated with inactivated H5N1 virus, and then obtained the F(ab'2 fragments by pepsin digestion of IgGs. Methods The horses were vaccinated with inactivated H5N1 vaccine to prepare anti-H5N1 IgGs. The F(ab'2 fragments were purified from anti-H5N1 hyperimmune sera by a protocol for 'enhanced pepsin digestion'. The protective effect of the F(ab'2 fragments against H5N1 virus infection was determined in cultured MDCK cells by cytopathic effect (CPE assay and in a BALB/c mouse model by survival rate assay. Results By the protocol for 'enhanced pepsin digestion', total 16 g F(ab'2 fragments were finally obtained from one liter equine antisera with the purity of over 90%. The H5N1-specific F(ab'2 fragments had a HI titer of 1:1024, and the neutralization titre of F(ab'2 reached 1: 2048. The in vivo assay showed that 100 μg of the F(ab'2 fragments could protect BALB/c mice infected with a lethal dose of influenza H5N1 virus. Conclusion The availability of highly purified H5N1-specific F(ab'2 fragments may be promising for treatment of influenza H5N1 infection. Our work has provided experimental support for the application of the therapeutic equine immunoglobulin in future large primate or human trials.

  7. Endogenous secreted phospholipase A2 group X regulates cysteinyl leukotrienes synthesis by human eosinophils.

    Science.gov (United States)

    Hallstrand, Teal S; Lai, Ying; Hooper, Kathryn A; Oslund, Rob C; Altemeier, William A; Matute-Bello, Gustavo; Gelb, Michael H

    2016-01-01

    Phospholipase A2s mediate the rate-limiting step in the formation of eicosanoids such as cysteinyl leukotrienes (CysLTs). Group IVA cytosolic PLA2α (cPLA2α) is thought to be the dominant PLA2 in eosinophils; however, eosinophils also have secreted PLA2 (sPLA2) activity that has not been fully defined. To examine the expression of sPLA2 group X (sPLA2-X) in eosinophils, the participation of sPLA2-X in the formation of CysLTs, and the mechanism by which sPLA2-X initiates the synthesis of CysLTs in eosinophils. Peripheral blood eosinophils were obtained from volunteers with asthma and/or allergy. A rabbit polyclonal anti-sPLA2-X antibody identified sPLA2-X by Western blot. We used confocal microscopy to colocalize the sPLA2-X to intracellular structures. An inhibitor of sPLA2-X (ROC-0929) that does not inhibit other mammalian sPLA2s, as well as inhibitors of the mitogen-activated kinase cascade (MAPK) and cPLA2α, was used to examine the mechanism of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-mediated formation of CysLT. Eosinophils express the mammalian sPLA2-X gene (PLA2G10). The sPLA2-X protein is located in the endoplasmic reticulum, golgi, and granules of eosinophils and moves to the granules and lipid bodies during fMLP-mediated activation. Selective sPLA2-X inhibition attenuated the fMLP-mediated release of arachidonic acid and CysLT formation by eosinophils. Inhibitors of p38, extracellular-signal-regulated kinases 1/2 (p44/42 MAPK), c-Jun N-terminal kinase, and cPLA2α also attenuated the fMLP-mediated formation of CysLT. The sPLA2-X inhibitor reduced the phosphorylation of p38 and extracellular-signal-regulated kinases 1/2 (p44/42 MAPK) as well as cPLA2α during cellular activation, indicating that sPLA2-X is involved in activating the MAPK cascade leading to the formation of CysLT via cPLA2α. We further demonstrate that sPLA2-X is activated before secretion from the cell during activation. Short-term priming with IL-13 and TNF/IL-1β increased the

  8. Cooption of secretory phospholipase (SPLA2) for different aspects of gravity receptor-associated mineralization in vertebrate phylogeny

    Science.gov (United States)

    Thalmann, R.; Lu, W.

    2009-04-01

    not induce formation of aragonite, but of calcite as default option, analogous to other aragonitic matrix proteins, e.g. AP8 alpha and beta of the avalone nacre. It has been shown that aragonitic proteins are able to express aragonite only in association with the appropriate insoluble matrix. The effects of the protein upon calcite modification are qualitatively identical to the effects of OC90 (nucleation density, crystal size and morphologic change), but are quantitatively much less. The most unexpected SPLA2 domain-related aspect is the recent discovery of an OC90 ortholog (Otoc1) in otoliths even though OMP, a derivative of melanotransferin is the principal soluble matrix protein of otoliths. We, heretofore, assumed that OC22, as a single SPLAL domain, constituted the earliest manifestation of this cooption in vertebrate phylogeny. Significantly, the presence of Otoc1 is not incidental. Knock-down of the gene results in agenesis or malformation of otolith with a change from aragonite to calcite. In summary, this presentation serves to illustrate the wide distribution and varied function of a coopted lipolytic enzyme in a wide range of mineralization-related contexts.

  9. [JAK2 V617F and exon 12 genetic variations in Korean patients with BCR/ABL1-negative myeloproliferative neoplasms].

    Science.gov (United States)

    Kim, Jeong Tae; Cho, Yong Gon; Choi, Sam Im; Lee, Young Jin; Kim, Hye Ran; Jang, Sook Jin; Moon, Dae Soo; Park, Young Jin; Park, Geon

    2010-12-01

    JAK2 genetic variations have been described in a high proportion of patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN). This study was designed to analyze the frequencies of JAK2 V617F and exon 12 variations, and their correlations with clinical characteristics of Korean patients with BCR/ABL1-negative MPN. We examined a total of 154 patients with BCR/ABL1-negative MPN that included 24, 26, 89, and 15 patients with polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), and unclassified myeloproliferative neoplasms (MPNU), respectively. We performed allele-specific PCR to detect V617F in all BCR/ABL1-negative patients, and performed direct sequencing to detect exon 12 variations in 47 V617F-negative MPN patients. JAK2 c.1641+179_183del5 variation was detected by restriction fragment length polymorphism assay in 176 healthy subjects. JAK2 V617F was detected in 91 patients (59.1%): PV (91.6%), PMF (46.2%), ET (52.8%), and MPNU (66.7%). In V617F-negative MPN patients, no mutations were found in exon 12. The c.1641+179_183del5 was detected in 68.1% of V617F-negative MPN patients and 45.4% of healthy subjects (P=0.008). JAK2 V617F was closely correlated with age and leukocytosis in BCR/ABL1-negative MPN patients (P<0.05). However, c.1641+179_183del5 was not related to age, sex, or complete blood cell count parameters in V617F-negative MPN patients and healthy subjects. The c.1641+179_183del5 was associated with an increased odds ratio for MPN (odds ratio, 2.6; 95% confidences interval, 1.3-5.1; P=0.007). Frequencies of V617F are similar to reported results. JAK2 exon 12 mutations may be rare and c.1641+179_183del5 may influence the occurrence of MPN in Korean patients with V6 17F-negative MPN.

  10. Adducts of UF5 with SbF5 and structure of UF5 . 2SbF5

    International Nuclear Information System (INIS)

    Sawodny, W.; Rediess, K.

    1980-01-01

    Both α-UF 5 and β-UF 5 form only a 1:2 compound UF 5 . 2SbF 5 reacting directly with SbF 5 , from which UF 5 . SbF 5 can be obtained by thermal decomposition. UF 5 . 2SbF 5 crystallizes in the monoclinic space group P2 1 /c with the following lattice constants a = 8.110(4), b = 14.129(6), c = 10.032(6) A and β = 96.97(5) 0 ; Z = 4. An X-ray study shows centrosymmetric four-membered rings of alternating UF 8 and SbF 6 polyhedra connected by other SbF 6 entities. This structure is similar to that of UOF 5 . 2SbF 5 , but the distorted pentagonal-bipyramidal coordination of the U atom found there is increased to a dodecahedral coordination by an additional U-F-Sb bridge, though with a somewaht larger UF distance. (author)

  11. Prognostic value of tumour blood flow, [{sup 18}F]EF5 and [{sup 18}F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Komar, Gaber; Eskola, Olli; Sipilae, Hannu; Solin, Olof [Turku PET Centre, Turku (Finland); Lehtioe, Kaisa; Levola, Helena; Lindholm, Paula; Seppaelae, Jan [Turku University Hospital and University of Turku, Department of Oncology and Radiotherapy, Turku (Finland); Seppaenen, Marko [Turku PET Centre, Turku (Finland); Turku University Hospital and University of Turku, Department of Nuclear Medicine, Turku (Finland); Grenman, Reidar [Turku University Hospital and University of Turku, Department of Otorhinolaryngology, Head and Neck Surgery, Turku (Finland); Minn, Heikki [Turku PET Centre, Turku (Finland); Turku University Hospital and University of Turku, Department of Oncology and Radiotherapy, Turku (Finland)

    2014-11-15

    In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour's biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [{sup 18}F]FDG, a new hypoxia tracer [{sup 18}F]EF5 and the perfusion tracer [{sup 15}O]H{sub 2}O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy. The study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [{sup 15}O]H{sub 2}O PET images using a one-tissue compartment model. [{sup 18}F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [{sup 18}F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival. Tumour stage and T-classification did not show any significant differences in comparison to the patients' metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [{sup 18}F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [{sup 18}F]EF5 maximum T

  12. E2F1-Mediated Induction of NFYB Attenuates Apoptosis via Joint Regulation of a Pro-Survival Transcriptional Program.

    Directory of Open Access Journals (Sweden)

    Xiaolei Jiang

    Full Text Available The E2F1 transcription factor regulates cell proliferation and apoptosis through the control of a considerable variety of target genes. Previous work has detailed the role of other transcription factors in mediating the specificity of E2F function. Here we identify the NF-YB transcription factor as a novel direct E2F1 target. Genome-wide expression analysis of the effects of NFYB knockdown on E2F1-mediated transcription identified a large group of genes that are co-regulated by E2F1 and NFYB. We also provide evidence that knockdown of NFYB enhances E2F1-induced apoptosis, suggesting a pro-survival function of the NFYB/E2F1 joint transcriptional program. Bioinformatic analysis suggests that deregulation of these NFY-dependent E2F1 target genes might play a role in sarcomagenesis as well as drug resistance.

  13. Intratumoral heterogeneity of 18F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Hyun, Seung Hyup; Kim, Ho Seong; Lee, Kyung-Han; Kim, Byung-Tae; Choi, Joon Young; Choi, Seong Ho; Choi, Dong Wook; Lee, Jong Kyun; Lee, Kwang Hyuck; Park, Joon Oh

    2016-01-01

    To assess whether intratumoral heterogeneity measured by 18 F-FDG PET texture analysis has potential as a prognostic imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). We evaluated a cohort of 137 patients with newly diagnosed PDAC who underwent pretreatment 18 F-FDG PET/CT from January 2008 to December 2010. First-order (histogram indices) and higher-order (grey-level run length, difference, size zone matrices) textural features of primary tumours were extracted by PET texture analysis. Conventional PET parameters including metabolic tumour volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) were also measured. To assess and compare the predictive performance of imaging biomarkers, time-dependent receiver operating characteristic (ROC) curves for censored survival data and areas under the ROC curve (AUC) at 2 years after diagnosis were used. Associations between imaging biomarkers and overall survival were assessed using Cox proportional hazards regression models. The best imaging biomarker for overall survival prediction was first-order entropy (AUC = 0.720), followed by TLG (AUC = 0.697), MTV (AUC = 0.692), and maximum SUV (AUC = 0.625). After adjusting for age, sex, clinical stage, tumour size and serum CA19-9 level, multivariable Cox analysis demonstrated that higher entropy (hazard ratio, HR, 5.59; P = 0.028) was independently associated with worse survival, whereas TLG (HR 0.98; P = 0.875) was not an independent prognostic factor. Intratumoral heterogeneity of 18 F-FDG uptake measured by PET texture analysis is an independent predictor of survival along with tumour stage and serum CA19-9 level in patients with PDAC. In addition, first-order entropy as a measure of intratumoral metabolic heterogeneity is a better quantitative imaging biomarker of prognosis than conventional PET parameters. (orig.)

  14. RAD50 germline mutations are associated with poor survival in BRCA1/2-negative breast cancer patients.

    Science.gov (United States)

    Fan, Cong; Zhang, Juan; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2018-05-04

    RAD50 is a highly conserved DNA double-strand break (DSB) repair gene. However, the associations between RAD50 germline mutations and the survival and risk of breast cancer have not been fully elucidated. Here, we aimed to investigate the clinical impact of RAD50 germline mutations in a large cohort of unselected breast cancer patients. In this study, RAD50 germline mutations were determined using next-generation sequencing in 7657 consecutive unselected breast cancer patients without BRCA1/2 mutations. We also screened for RAD50 recurrent mutations (L719fs, K994fs, and H1269fs) in 5000 healthy controls using Sanger sequencing. We found that 26 out of 7657 (0.34%) patients had RAD50 pathogenic mutations, and 16 patients carried one of the three recurrent mutations (L719fs, n=6 cases; K994fs, n=5 cases; and H1269fs, n=5 cases); the recurrent mutation rate was 0.21%. The frequency of the three recurrent mutations in the 5000 healthy controls was 0.18% (9/5000). These mutations did not confer an increased risk of breast cancer in the studied patients [odds ratios (OR), 1.16; 95% confidence interval (CI), 0.51-2.63; P = 0.72]. Nevertheless, multivariate analysis revealed that RAD50 pathogenic mutations were an independent unfavourable predictor of recurrence-free survival (RFS) [adjusted hazard ratio (HR) 2.66; 95% CI, 1.18-5.98; P=0.018] and disease-specific survival (DSS) (adjusted HR 4.36; 95% CI, 1.58-12.03; P=0.004) in the entire study cohort. Our study suggested that RAD50 germline mutations are not associated with an increased risk of breast cancer, but patients with RAD50 germline mutations have unfavourable survival compared with patients without these mutations. This article is protected by copyright. All rights reserved. © 2018 UICC.

  15. Using positron emission tomography (PET) response criteria in solid tumours (PERCIST) 1.0 for evaluation of 2'-deoxy-2'-[18F] fluoro-D-glucose-PET/CT scans to predict survival early during treatment of locally advanced non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Fledelius, Joan; Khalil, Azza Ahmed; Hjorthaug, Karin; Frøkiaer, Jørgen

    2016-04-01

    The demand for early-response evaluation with 2'-deoxy-2'-[18F] fluoro-D-glucose (F-18-FDG) positron emission tomography combined with whole body CT (PET/CT) is rapidly growing. This study was initiated to evaluate the applicability of the PET response criteria in solid tumours (PERCIST 1.0) for response evaluation. We performed a retrospective study of 21 patients with locally advanced non-small cell lung cancer (NSCLC), who had undergone both a baseline and a follow-up F-18-FDG-PET/CT scan during their treatments. The scans were performed at our institution in the period September 2009 and March 2011 and were analysed visually and according to PERCIST 1.0 by one board-certified nuclear medicine physician. The response was compared with overall survival (OS) and progression-free survival (PFS). The variation in key parameters affecting the F-18-FDG uptake was assessed. A kappa of 0.94 corresponding to an almost perfect agreement was found for the comparison of the visual evaluation with PERCIST. Patients with partial metabolic response and stable metabolic disease (as evaluated by PERCIST 1.0) had statistically significant longer median time to progression: 8.4 months (confidence interval (CI) 5.1-11.8 months) as compared with 2.7 months (CI 0-5.6 months) in patients classified with progression. The variation in uptake time between baseline and follow-up scans was more than the recommended 15 min in 48% of patients. PERCIST 1.0 is readily implementable and highly comparable with visual evaluation of response using early F-18-FDG-PET/CT scanning for locally advanced NSCLC patients. In spite of variations in parameters affecting F-18-FDG uptake, evaluation of F-18-FDG-PET/CT during treatment with PERCIST 1.0 is shown to separate non-responders from responders, each with statistically significant differences in both OS and PFS. © 2015 The Royal Australian and New Zealand College of Radiologists.

  16. Immunohistochemical detection of cdc2 is useful in predicting survival in patients with mantle cell lymphoma.

    Science.gov (United States)

    Hui, David; Reiman, Tony; Hanson, John; Linford, Rick; Wong, Winson; Belch, Andrew; Lai, Raymond

    2005-09-01

    Recent cDNA microarray studies have reported the prognostic value of several genes in mantle cell lymphoma patients. We aimed to validate the prognostic significance of three of these genes: alpha-tubulin, cdc2, and CENP-F. The protein expression of alpha-tubulin, cdc2, and CENP-F was assessed using immunohistochemistry. Their immunoreactivity in 48 formalin-fixed/paraffin-embedded mantle cell lymphoma tumors was determined by estimating the percentage of positive cells. These results were correlated with the expression of proliferation marker Ki67 and survival. Of these 48 mantle cell lymphoma patients, 41 were men and seven were women. The median age at time of diagnosis was 64.5 years, and the overall median survival was 40 months. In benign lymph nodes, the expression of cdc2 and alpha-tubulin was restricted to the germinal centers; mantle zones were negative. Expression of CENP-F was more uniformly distributed. In mantle cell lymphoma, Ki67 significantly correlated with all three markers (P50%) and cdc2 (>25%) significantly correlated with shorter survival (Por=2 correlated with worse clinical outcome, and high clinical stage (ie 4 vs survival. The prognostic significance of cdc2 and Ki67 was independent of international prognostic index and clinical stage. We have validated the prognostic value of cdc2, and confirmed that of Ki67, in a cohort of mantle cell lymphoma patients. Immunohistochemical detection of cdc2 and Ki67 may be a useful and simple method in evaluating the prognosis of mantle cell lymphoma patients.

  17. [{sup 18}F]FPRGD{sub 2} PET/CT imaging of integrin α{sub v}β{sub 3} levels in patients with locally advanced rectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Withofs, Nadia; Hustinx, Roland [Division of Nuclear Medicine and Oncological Imaging, Department of Medical Physics, Liege (Belgium); Martinive, Philippe; Vanderick, Jean; Coucke, Philippe [CHU Liege, Division of Radiation Oncology, Department of Medical Physics, Liege (Belgium); Bletard, Noella; Scagnol, Irene; Delvenne, Philippe [CHU Liege, Department of Pathology, Liege (Belgium); Mievis, Frederic; Giacomelli, Fabrice [University of Liege, CYCLOTRON Research Centre, Liege (Belgium); Cataldo, Didier [University of Liege, Laboratory of Tumour and Developmental Biology, GIGA-Research, Liege (Belgium); Gambhir, Sanjiv S. [Stanford University, Molecular Imaging Program at Stanford (MIPS), Radiology Department, Stanford, CA (United States)

    2016-04-15

    Our primary objective was to determine if [{sup 18}F]FPRGD{sub 2} PET/CT performed at baseline and/or after chemoradiotherapy (CRT) could predict tumour regression grade (TRG) in locally advanced rectal cancer (LARC). Secondary objectives were to compare baseline [{sup 18}F]FPRGD{sub 2} and [{sup 18}F]FDG uptake, to evaluate the correlation between posttreatment [{sup 18}F]FPRGD{sub 2} uptake and tumour microvessel density (MVD) and to determine if [{sup 18}F]FPRGD{sub 2} and FDG PET/CT could predict disease-free survival. Baseline [{sup 18}F]FPRGD{sub 2} and FDG PET/CT were performed in 32 consecutive patients (23 men, 9 women; mean age 63 ± 8 years) with LARC before starting any therapy. A posttreatment [{sup 18}F]FPRGD{sub 2} PET/CT scan was performed in 24 patients after the end of CRT (median interval 7 weeks, range 3 - 15 weeks) and before surgery (median interval 4 days, range 1 - 15 days). All LARC showed uptake of both [{sup 18}F]FPRGD{sub 2} (SUV{sub max} 5.4 ± 1.5, range 2.7 - 9) and FDG (SUV{sub max} 16.5 ± 8, range 7.1 - 36.5). There was a moderate positive correlation between [{sup 18}F]FPRGD{sub 2} and FDG SUV{sub max} (Pearson's r = 0.49, p = 0.0026). There was a moderate negative correlation between baseline [{sup 18}F]FPRGD{sub 2} SUV{sub max} and the TRG (Spearman's r = -0.37, p = 0.037), and a [{sup 18}F]FPRGD{sub 2} SUV{sub max} of >5.6 identified all patients with a complete response (TRG 0; AUC 0.84, 95 % CI 0.68 - 1, p = 0.029). In the 24 patients who underwent a posttreatment [{sup 18}F]FPRGD{sub 2} PET/CT scan the response index, calculated as [(SUV{sub max}1 - SUV{sub max}2)/SUV{sub max}1] x 100 %, was not associated with TRG. Post-treatment [{sup 18}F]FPRGD{sub 2} uptake was not correlated with tumour MVD. Neither [{sup 18}F]FPRGD{sub 2} nor FDG uptake predicted disease-free survival. Baseline [{sup 18}F]FPRGD{sub 2} uptake was correlated with the pathological response in patients with LARC treated with CRT. However, the

  18. Atmospheric chemistry of C2F5CHO: mechanism of the C2F5C(O)O-2+HO2 reaction

    DEFF Research Database (Denmark)

    Andersen, Mads Peter Sulbæk; Hurley, MD; Wallington, TJ

    2003-01-01

    in a yield of 76 +/- 4 The gas phase reaction of CnF2n+1C(O)O-2 with HO2 radicals offers a potential explanation for at least part of the observed environmental burden of fluorinated carboxylic acids, CnF2n+1C(O)OH. As part of this work an upper limit for the rate constant of reaction of Cl atorns with C2F5C......(O)OH at 296 K was determined; k(Cl + C2F5C(O)OH) 1 x 10(-11) cm(3) molecule(-1) s(-1). (C) 2003 Published by Elsevier B.V....

  19. Postmastectomy radiotherapy improves disease-free survival of high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

    Directory of Open Access Journals (Sweden)

    Zhen-Yu He

    Full Text Available The indications for post-mastectomy radiotherapy (PMRT with T1-2 breast cancer and 1-3 positive axillary lymph nodes is still controversial. The purpose of this study was to investigate the role of PMRT in T1-2 breast cancer with 1-3 positive axillary lymph node.We retrospectively reviewed the file records of 79 patients receiving PMRT and not receiving PMRT (618 patients.The median follow-up was 65 months. Multivariate analysis showed that PMRT was an independent prognostic factor of locoregional recurrence-free survival (LRFS (P = 0.010. Subgroup analysis of patients who did not undergo PMRT showed that pT stage, number of positive axillary lymph nodes, and molecular subtype were independent prognostic factors of LRFS. PMRT improved LRFS in the entire group (P = 0.005, but did not affect distant metastasis-free survival (DMFS (P = 0.494, disease-free survival (DFS (P = 0.215, and overall survival (OS (P = 0.645. For patients without PMRT, the 5-year LRFS of low-risk patients (0-1 risk factor for locoregional recurrence of 94.5% was significantly higher than that of high-risk patients (2-3 risk factors for locoregional recurrence (80.9%, P < 0.001. PMRT improved LRFS (P = 0.001 and DFS (P = 0.027 in high-risk patients, but did not improve LRFS, DMFS, DFS, and OS in low-risk patients.PMRT is beneficial in patients with high risk of locoregional recurrence breast cancer patients with T1-2 and 1 to 3 positive nodes.

  20. Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus GM-CSF: Impact of body weight, immunogenicity and anti-GD2 response on pharmacokinetics and survival.

    Science.gov (United States)

    Cheung, Irene Y; Kushner, Brian H; Modak, Shakeel; Basu, Ellen M; Roberts, Stephen S; Cheung, Nai-Kong V

    2017-01-01

    Fifty-seven stage 4 patients with refractory/relapsed neuroblastoma were enrolled in a phase I trial (Clinicaltrials.gov NCT01757626) using humanized anti-GD2 monoclonal antibody hu3F8 in combination with granulocyte-macrophage colony-stimulating factor. The influence of body weight and human anti-human antibody (HAHA) on the pharmacokinetics (PK) of hu3F8, and the effect of de novo anti-GD2 response on patient outcome were explored. Serum samples before hu3F8 infusion, and serially up to day 12 during treatment cycle #1, and at 5 min after each hu3F8 infusion for all subsequent cycles were collected. PK was analyzed using non-compartmental modeling. Immunogenicity was assayed by HAHA response, and vaccination effect by induced host anti-GD2 response measured periodically until disease progression or last followup. Progression-free and overall survival was estimated by the Kaplan-Meier method. Despite dosing being based on body weight, smaller patients had consistently lower area-under-the-curve and faster clearance over the 15 dose levels (0.9 to 9.6 mg/kg per treatment cycle) in this trial. Positive HAHA, defined by the upper limit of normal, when measured within 10 days from the last hu3F8 dose received, was associated with significantly lower serum hu3F8. Despite prior sensitization to other anti-GD2 antibody, e.g. mouse 3F8 or ch14.18, 75% of the patients never developed HAHA response even after getting more treatment cycles. Hu3F8 induced a de novo anti-GD2 response in patients, which was prognostic of progression-free survival. We conclude that hu3F8 had low immunogenicity. During treatment, positive HAHA and low body weight affected PK adversely, whereas induced anti-GD2 response was an outcome predictor.

  1. Molecular CsF 5 and CsF 2 +

    KAUST Repository

    Rogachev, Andrey Yu.; Miao, Mao-sheng; Merino, Gabriel; Hoffmann, Roald

    2015-01-01

    D5h star-like CsF5, formally isoelectronic with known XeF5− ion, is computed to be a local minimum on the potential energy surface of CsF5, surrounded by reasonably large activation energies for its exothermic decomposition to CsF+2F2, or to CsF3 (three isomeric forms)+F2, or for rearrangement to a significantly more stable isomer, a classical Cs+ complex of F5−. Similarly the CsF2+ ion is computed to be metastable in two isomeric forms. In the more symmetrical structures of these molecules there is definite involvement in bonding of the formally core 5p levels of Cs.

  2. Molecular CsF 5 and CsF 2 +

    KAUST Repository

    Rogachev, Andrey Yu.

    2015-06-03

    D5h star-like CsF5, formally isoelectronic with known XeF5− ion, is computed to be a local minimum on the potential energy surface of CsF5, surrounded by reasonably large activation energies for its exothermic decomposition to CsF+2F2, or to CsF3 (three isomeric forms)+F2, or for rearrangement to a significantly more stable isomer, a classical Cs+ complex of F5−. Similarly the CsF2+ ion is computed to be metastable in two isomeric forms. In the more symmetrical structures of these molecules there is definite involvement in bonding of the formally core 5p levels of Cs.

  3. AMPK Signaling Involvement for the Repression of the IL-1β-Induced Group IIA Secretory Phospholipase A2 Expression in VSMCs.

    Directory of Open Access Journals (Sweden)

    Khadija El Hadri

    Full Text Available Secretory Phospholipase A2 of type IIA (sPLA2 IIA plays a crucial role in the production of lipid mediators by amplifying the neointimal inflammatory context of the vascular smooth muscle cells (VSMCs, especially during atherogenesis. Phenformin, a biguanide family member, by its anti-inflammatory properties presents potential for promoting beneficial effects upon vascular cells, however its impact upon the IL-1β-induced sPLA2 gene expression has not been deeply investigated so far. The present study was designed to determine the relationship between phenformin coupling AMP-activated protein kinase (AMPK function and the molecular mechanism by which the sPLA2 IIA expression was modulated in VSMCs. Here we find that 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleotide (AICAR treatment strongly repressed IL-1β-induced sPLA2 expression at least at the transcriptional level. Our study reveals that phenformin elicited a dose-dependent inhibition of the sPLA2 IIA expression and transient overexpression experiments of constitutively active AMPK demonstrate clearly that AMPK signaling is involved in the transcriptional inhibition of sPLA2-IIA gene expression. Furthermore, although the expression of the transcriptional repressor B-cell lymphoma-6 protein (BCL-6 was markedly enhanced by phenformin and AICAR, the repression of sPLA2 gene occurs through a mechanism independent of BCL-6 DNA binding site. In addition we show that activation of AMPK limits IL-1β-induced NF-κB pathway activation. Our results indicate that BCL-6, once activated by AMPK, functions as a competitor of the IL-1β induced NF-κB transcription complex. Our findings provide insights on a new anti-inflammatory pathway linking phenformin, AMPK and molecular control of sPLA2 IIA gene expression in VSMCs.

  4. S-phase checkpoint elements of the E2F-1 family increase radiosensitivity in fibrosarcoma cells lacking p53

    International Nuclear Information System (INIS)

    Bodis, Stephan; Pruschy, Martin; Wirbelauer, Christiane; Glanzmann, Christoph; Krek, Wilhelm

    1997-01-01

    Purpose: Correct advance of cells through the S-phase of the mammalian cell cycle depends on the timely controlled activity of the E2F-1 transcription factor by cyclin A-cdk2. We are studying the reproductive integrity and radiosensitation of isogenic mouse fibrosarcoma cells, differing only in their p53 status, after expression of E2F-1 wildtype (wt) and specific E2F-1 mutants (mt) lacking the cyclin-A-binding domain. In this tumor model system only p53 wild-type expressing tumor cells are sensitive to ionizing radiation in vitro and in vivo. Material and Methods: Either wild-type p53 or genetically engineered p53 'null' mouse embryo fibroblasts were transfected with the oncogenes E1A and ras. These otherwise isogenic fibrosarcoma cells, with a malignant phenotype and tumorigenic in nude mice, were transfected with retroviruses containing either E2F-1 wild-type or specific E2F-1 mutants lacking the cyclin-A binding domain. Reproductive integrity after E2F-1 transfection with or without ionizing radiation (RT) was tested using the clonogenic assay. Tumor cell morphology of treated cells is analyzed for cell death mechanism. Results: E2F-1 wild-type expression in fibrosarcoma cells induced a clear p53 dependent cell death. While clonogenic survival of p53 'null' tumor cells was only slightly reduced with the expression of E2F-1 wild type (survival fraction of 0.5), the clonogenic survival of p53 wild-type fibrosarcoma tumor cells was reduced by at least one logarithm (survival fraction of 0.05). However, expression of the specific E2F-1 mutant lacking the cyclin-A binding domain reduced clonogenic survival in both the p53 'null' and the p53 wild-type fibrosarcoma cells by at least 2 logarithms (survival fraction 0.01 for p53 'null' and 0.002 for p53 wild-type). The mean values of the survival fractions after 2 and 5 Gy radiation alone in p53 'null' fibrosarcoma cells (SF 2 and SF 5) were SF 2 0.7, SF 5 = 0.15, respectively. The combination of ionizing RT in the p53

  5. Reactions UF4 - ClO2F and UF5 - ClO2F

    International Nuclear Information System (INIS)

    Benoit, Raymond; Besnard, Ginette; Hartmanshenn, Olivier; Luce, Michel; Mougin, Jacques; Pelissie, Jean

    1970-02-01

    The study of the reaction UF 4 - ClO 2 F between 0 deg. and 100 deg. C, by various techniques (micro-sublimation, isopiestic method, IR and UV spectrography, thermogravimetry and X-ray diffraction) shows that intermediate steps are possible before the production of UF 5 . The whole reaction may be schematised by two equations: (1) n UF 4 + ClO 2 F → n UF x + ClO 2 (4 4 + ClO 2 F → UF x + 1/2 Cl 2 + O 2 . The more the temperature rises, the more the second equation becomes experimentally verified. The reaction at 0 deg. C between UF 5 and ClO 2 F may be represented by: UF 5 + ClO 2 F → UF 6 ClO 2 . The reactions: UF 5 + ClO 2 F → UF 6 + ClO 2 , UF 5 + ClO 2 F → UF 6 + 1/2 Cl 2 + O 2 are verified, the first and the second at 25 deg. C., the second from 50 deg. to 150 deg. C. From the results of AGRON it is possible to predict the residual solids before complete volatilization as UF 6 . The IR spectra of ClO 2 F adsorbed on UF 4 and UF x at 60 deg. C have been compared with those of gaseous ClO 2 F and UF 6 adsorbed on UF 4 . (authors) [fr

  6. The role of 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography in the management of patients with carcinoma of unknown primary.

    Science.gov (United States)

    Deonarine, P; Han, S; Poon, F W; de Wet, C

    2013-08-01

    Carcinoma of unknown primary is one of the ten most frequent cancers worldwide. Its median survival time is less than 10 months. Detecting primary tumour locations and/or occult metastatic lesions may inform definitive treatment and improve patients' prognosis. We aimed to determine: (1) the sensitivity, specificity and accuracy of (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography; (2) its detection rate of primary tumour locations and occult metastases and (3) factors associated with improved survival times. We retrospectively reviewed all cases in the West of Scotland for the period 1 December 2007 to 31 May 2011 that met all our selection criteria: (1) diagnosis of carcinoma of unknown primary; (2) a thorough but negative 'work-up' and (3) (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography report. Statistical methods included frequencies, Kaplan-Meier graphs and log-rank tests to compare survival times. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected primary tumour sites in 19/51 (37.3%) and occult metastases in 28/51 (54.9%) of eligible patients. Its sensitivity, specificity and accuracy were 79.2%, 70.4% and 74.5%, respectively; 20/51 (39.2%) patients died during the study period with a median survival of 8.4 months (range 21.4, SD ± 6.2). The number of metastatic locations was strongly associated with survival (p = 0.002), but detection of a primary tumour site (p = 0.174) or histopathology (p = 0.301) was not. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected occult metastatic sites in the majority and a primary cancer location in a substantial minority of patients. Our results were comparable with international literature and may indicate that (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography have an early role to improve the accuracy of cancer staging and to optimise carcinoma of unknown

  7. Survival and breast relapse in 3834 patients with T1-T2 breast cancer after conserving surgery and adjuvant treatment

    International Nuclear Information System (INIS)

    Livi, Lorenzo; Paiar, Fabiola; Saieva, Calogero; Scoccianti, Silvia; Dicosmo, Dora; Borghesi, Simona; Agresti, Benedetta; Nosi, Fabiano; Orzalesi, Lorenzo; Santini, Roberto; Barca, Raffaella; Biti, Giampaolo P.

    2007-01-01

    Purpose: The aim of the present analysis is to determine the long-term results in terms of breast relapse and specific survival in patients treated with conserving surgery and adjuvant treatment for early breast cancer. Methods: From January 1980 to December 2001, 3834 patients with pT1-T2 breast cancer were treated consecutively at the University of Florence. The median age of the patient population was 55 years (range 30-80). All patients were followed for a median of 7.4 years (range 0.6 year to 22.5 years). The crude probability of survival (or local recurrence) was estimated by using Kaplan-Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. Results: The Cox regression model by stepwise selection showed some parameters, such as chemotherapy (HR 1.53; CI 1.19-1.95), pT status (HR 1.62, CI 1.31-2.01), positive axillary lymph nodes (HR 1.92, CI 1.66-2.22), and local recurrence (HR 4.58; CI 3.66-5.73), as independent prognostic factors for breast cancer death. Moreover, we found lower rate survival among patients treated before 1991 in comparison to women treated after 1991 (p = 0.0001) probably due to inadequate treatment. For local disease free survival, age at presentation (HR 0.47; CI 0.35-0.63), use of tamoxifen (HR 0.42; CI 0.25-0.71), surgical margins (HR 2.00; CI 1.21-3.30), and chemotherapy (HR 0.53; CI 0.31-0.91) emerged by multivariate analyses as significant breast relapse predictors. Conclusion: In our experience breast conserving surgery followed by adjuvant radiotherapy treatment gives high rates of local control in women with early breast cancer. The use of routinely adjuvant chemotherapy and hormone therapy lowered the local recurrence and probably the modification of therapeutic approach in the last decades also improved the specific survival

  8. Hydrazinium(1+) hexafluorotitanate(IV), 2N2H5+.TiF62-

    International Nuclear Information System (INIS)

    Leban, I.

    1994-01-01

    The crystals exhibit racemic twinning. The structure consists of hydrazinium(1+), N 2 H 5 + , cations and usual octahedral hexafluorotitanate(IV) anions. They are linked together via hydrogen bonds of the types N-H..F and N-H..N. (orig.)

  9. Syntheses, Raman spectra, and X-ray crystal structures of [XeF(5)][mu-F(OsO(3)F(2))(2)] and [M][OsO(3)F(3)] (M = XeF(5)(+), Xe(2)F(11)(+)).

    Science.gov (United States)

    Hughes, Michael J; Mercier, Hélène P A; Schrobilgen, Gary J

    2010-04-05

    Stoichiometric amounts of XeF(6) and (OsO(3)F(2))(infinity) react at 25-50 degrees C to form salts of the known XeF(5)(+) and Xe(2)F(11)(+) cations, namely, [XeF(5)][mu-F(OsO(3)F(2))(2)], [XeF(5)][OsO(3)F(3)], and [Xe(2)F(11)][OsO(3)F(3)]. Although XeF(6) is oxophilic toward a number of transition metal and main-group oxides and oxide fluorides, fluoride/oxide metathesis was not observed. The series provides the first examples of noble-gas cations that are stabilized by metal oxide fluoride anions and the first example of a mu-F(OsO(3)F(2))(2)(-) salt. Both [XeF(5)][mu-F(OsO(3)F(2))(2)] and [Xe(2)F(11)][OsO(3)F(3)] are orange solids at room temperature. The [XeF(5)][OsO(3)F(3)] salt is an orange liquid at room temperature that solidifies at 5-0 degrees C. When the salts are heated at 50 degrees C under 1 atm of N(2) for more than 2 h, significant XeF(6) loss occurs. The X-ray crystal structures (-173 degrees C) show that the salts exist as discrete ion pairs and that the osmium coordination spheres in OsO(3)F(3)(-) and mu-F(OsO(3)F(2))(2)(-) are pseudo-octahedral OsO(3)F(3)-units having facial arrangements of oxygen and fluorine atoms. The mu-F(OsO(3)F(2))(2)(-) anion is comprised of two symmetry-related OsO(3)F(2)-groups that are fluorine-bridged to one another. Ion pairing results from secondary bonding interactions between the fluorine/oxygen atoms of the anions and the xenon atom of the cation, with the Xe...F/O contacts occurring opposite the axial fluorine and from beneath the equatorial XeF(4)-planes of the XeF(5)(+) and Xe(2)F(11)(+) cations so as to avoid the free valence electron lone pairs of the xenon atoms. The xenon atoms of [XeF(5)][mu-F(OsO(3)F(2))(2)] and [Xe(2)F(11)][OsO(3)F(3)] are nine-coordinate and the xenon atom of [XeF(5)][OsO(3)F(3)] is eight-coordinate. Quantum-chemical calculations at SVWN and B3LYP levels of theory were used to obtain the gas-phase geometries, vibrational frequencies, and NBO bond orders, valencies, and NPA charges of

  10. Expression of EIF5A2 associates with poor survival of nasopharyngeal carcinoma patients treated with induction chemotherapy

    International Nuclear Information System (INIS)

    Huang, Pei-Yu; Zeng, Ting-Ting; Ban, Xiaojiao; Li, Meng-Qing; Zhang, Bao-Zhu; Zhu, Ying-Hui; Hua, Wen-Feng; Mai, Hai-Qiang; Zhang, Li; Guan, Xin-Yuan; Li, Yan

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a type of head-neck cancer with a distinguishable geographic and racial distribution worldwide. Increasing evidence supports that the accumulation of additional genetic and epigenetic abnormalities is important in driving the NPC tumorigenic process. In this study, we aim to investigate the association between EIF5A2 (Eukaryotic translation initiation factor 5A2) expression status and NPC clinical outcomes. The expression status of EIF5A2 was investigated in the NPC tissue microarray. Tissues were from 166 NPC patients staging II-IV, collected between 1999 and 2005. All patients were administered 2–3 cycles of DDP (cisplatin) + 5-Fu (5-fluorouracil) induction therapy and then treated with a uniform conventional two-dimensional radiotherapy. Cell motility assay, tumor growth assay and cytotoxicity assay were performed on the EIF5A2 overexpressed cells and control cells. siRNA was also used in the in vitro studies. Positive staining of EIF5A2 was observed in 85.4 % (105/123) informative tumor cases. Multivariate analyses demonstrated that EIF5A2 was an independent prognostic marker of poor overall survival (OS) (P = 0.041), failure-free survival (FFS) (P = 0.029), and distant failure-free survival (D-FFS) (P = 0.043) in patients with locoregionally advanced NPC patients treated with cisplatin + 5-Fu chemoradiotherapy. The forced expression of EIF5A2 in NPC cells enhanced the cells’ motility and growth ability. Knock-down of EIF5A2 in NPC cells decreased the cell’s motility and growth ability. Our results also demonstrated that EIF5A2 overexpression induced chemoresistance of NPC cells to 5-Fu. Our findings suggested that EIF5A2 expression, as examined by immunohistochemistry, could function as an independent prognostic factor of outcomes in NPC patients with cisplatin + 5-Fu chemoradiotherapy. EIF5A2 might be a novel therapeutic target for the inhibition of NPC progress. The online version of this article (doi:10.1186/s12885-016-2714-2

  11. Larval development of Spodoptera eridania and Spodoptera frugiperda fed on fresh ear of field corn expressing the Bt proteins (Cry1F and Cry1F + Cry1A.105 + Cry2Ab2

    Directory of Open Access Journals (Sweden)

    Orcial Ceolin Bortolotto

    Full Text Available ABSTRACT: The objective of this study was to evaluate extent of larval period, larval survival (%, food consumption, and pupal biomass of Spodoptera eridania and Spodoptera frugiperda (Lepidoptera: Noctuidae fed on fresh ears of field corn expressing Bt proteins (Cry1F and Cry1F+Cry1A.105+Cry2Ab2. Larvae of Spodoptera spp. survived less than two days when they consumed Bt corncobs and showed 100% mortality. Spodoptera eridania reared on non-Bt corn cobs showed higher larval development (21.6 days than S. frugiperda (18.4 days and lower viability (56.4% and 80.2% for S. eridania and S. frugiperda , respectively. A higher amount of corn grains was consumed by S. eridania (5.4g than by S. frugiperda (3.9g. In summary, this study demonstrated that the toxins Cry1F and Cry1F + Cry1A.105 + Cry2Ab2 expressed in fresh corn cobs contributed to protect ears of corn against S. frugiperda and the non-target pest S. eridania . However, itis important to monitor non-Bt cornfields because of the potential of both species to cause damage to ear sof corn.

  12. Expression and location of mRNAs encoding multiple forms of secretory phospholipase A2 in the rat retina

    DEFF Research Database (Denmark)

    Kolko, Miriam; Christoffersen, Nanna R; Barreiro, Sebastian G

    2004-01-01

    of sPLA(2)s in neuronal signaling and survival [Kolko et al. (1996) J. Biol. Chem. 271: 32722-32728]. To date, no retinal sPLA(2)s have been cloned or characterized. We evaluated the existence and abundance of sPLA(2) subtypes in rat retina and explored their possible involvement in light...

  13. Diagnosis of pseudoprogression in patients with glioblastoma using O-(2-[{sup 18}F]fluoroethyl)-l-tyrosine PET

    Energy Technology Data Exchange (ETDEWEB)

    Galldiks, Norbert [University of Cologne, Department of Neurology, Cologne (Germany); Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); University of Cologne, Center of Integrated Oncology (CIO), Cologne (Germany); Dunkl, Veronika; Fink, Gereon R. [University of Cologne, Department of Neurology, Cologne (Germany); Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); Stoffels, Gabriele [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); Hutterer, Markus; Hau, Peter [University of Regensburg, Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg (Germany); Rapp, Marion; Sabel, Michael [Heinrich Heine University Duesseldorf, Department of Neurosurgery, Duesseldorf (Germany); Reifenberger, Guido [Heinrich Heine University Duesseldorf, Department of Neuropathology, Duesseldorf (Germany); Kebir, Sied [University of Bonn, Department of Neurology, Bonn (Germany); Dorn, Franziska [University of Cologne, Department of Neuroradiology, Cologne (Germany); Blau, Tobias [University of Cologne, Department of Neuropathology, Cologne (Germany); Herrlinger, Ulrich [University of Cologne, Center of Integrated Oncology (CIO), Cologne (Germany); University of Bonn, Department of Neurology, Bonn (Germany); Ruge, Maximilian I. [University of Cologne, Center of Integrated Oncology (CIO), Cologne (Germany); University of Cologne, Department of Stereotaxy and Functional Neurosurgery, Cologne (Germany); Kocher, Martin [University of Cologne, Center of Integrated Oncology (CIO), Cologne (Germany); University of Cologne, Department of Radiation Oncology, Cologne (Germany); Goldbrunner, Roland [University of Cologne, Center of Integrated Oncology (CIO), Cologne (Germany); University of Cologne, Department of Neurosurgery, Cologne (Germany); Drzezga, Alexander; Schmidt, Matthias [University of Cologne, Department of Nuclear Medicine, Cologne (Germany); Langen, Karl-Josef [Forschungszentrum Juelich, Institute of Neuroscience and Medicine, Juelich (Germany); University of Aachen, Department of Nuclear Medicine, Aachen (Germany)

    2015-04-01

    The follow-up of glioblastoma patients after radiochemotherapy with conventional MRI can be difficult since reactive alterations to the blood-brain barrier with contrast enhancement may mimic tumour progression (i.e. pseudoprogression, PsP). The aim of this study was to assess the clinical value of O-(2-{sup 18}F-fluoroethyl)-l-tyrosine ({sup 18}F-FET) PET in the differentiation of PsP and early tumour progression (EP) after radiochemotherapy of glioblastoma. A group of 22 glioblastoma patients with new contrast-enhancing lesions or lesions showing increased enhancement (>25 %) on standard MRI within the first 12 weeks after completion of radiochemotherapy with concomitant temozolomide (median 7 weeks) were additionally examined using amino acid PET with {sup 18}F-FET. Maximum and mean tumour-to-brain ratios (TBR{sub max}, TBR{sub mean}) were determined. {sup 18}F-FET uptake kinetic parameters (i.e. patterns of time-activity curves, TAC) were also evaluated. Classification as PsP or EP was based on the clinical course (no treatment change at least for 6 months), follow-up MR imaging and/or histopathological findings. Imaging results were also related to overall survival (OS). PsP was confirmed in 11 of the 22 patients. In patients with PsP, {sup 18}F-FET uptake was significantly lower than in patients with EP (TBR{sub max} 1.9 ± 0.4 vs. 2.8 ± 0.5, TBR{sub mean} 1.8 ± 0.2 vs. 2.3 ± 0.3; both P < 0.001) and presence of MGMT promoter methylation was significantly more frequent (P = 0.05). Furthermore, a TAC type II or III was more frequently present in patients with EP (P = 0.04). Receiver operating characteristic analysis showed that the optimal {sup 18}F-FET TBR{sub max} cut-off value for identifying PsP was 2.3 (sensitivity 100 %, specificity 91 %, accuracy 96 %, AUC 0.94 ± 0.06; P < 0.001). Univariate survival analysis showed that a TBR{sub max} <2.3 predicted a significantly longer OS (median OS 23 vs. 12 months; P = 0.046). {sup 18}F-FET PET may facilitate

  14. Identification and functional analysis of the S-layer protein SplA of Paenibacillus larvae, the causative agent of American Foulbrood of honey bees.

    Directory of Open Access Journals (Sweden)

    Lena Poppinga

    Full Text Available The gram-positive, spore-forming bacterium Paenibacillus larvae is the etiological agent of American Foulbrood (AFB, a globally occurring, deathly epizootic of honey bee brood. AFB outbreaks are predominantly caused by two genotypes of P. larvae, ERIC I and ERIC II, with P. larvae ERIC II being the more virulent genotype on larval level. Recently, comparative proteome analyses have revealed that P. larvae ERIC II but not ERIC I might harbour a functional S-layer protein, named SplA. We here determine the genomic sequence of splA in both genotypes and demonstrate by in vitro self-assembly studies of recombinant and purified SplA protein in combination with electron-microscopy that SplA is a true S-layer protein self-assembling into a square 2D lattice. The existence of a functional S-layer protein is novel for this bacterial species. For elucidating the biological function of P. larvae SplA, a genetic system for disruption of gene expression in this important honey bee pathogen was developed. Subsequent analyses of in vivo biological functions of SplA were based on comparing a wild-type strain of P. larvae ERIC II with the newly constructed splA-knockout mutant of this strain. Differences in cell and colony morphology suggest that SplA is a shape-determining factor. Marked differences between P. larvae ERIC II wild-type and mutant cells with regard to (i adhesion to primary pupal midgut cells and (ii larval mortality as measured in exposure bioassays corroborate the assumption that the S-layer of P. larvae ERIC II is an important virulence factor. Since SplA is the first functionally proven virulence factor for this species, our data extend the knowledge of the molecular differences between these two genotypes of P. larvae and contribute to explaining the observed differences in virulence. These results present an immense advancement in our understanding of P. larvae pathogenesis.

  15. Growth, straightness and survival at age 32 in a Pinus strobus x P. wallichiana F1 hybrid population (Experiment 1

    Directory of Open Access Journals (Sweden)

    Ioan Blada

    2013-11-01

    . The narrow-sensefamily heritability estimates were 0.657 for diameter, 0.586 for height, 0.505 for volume, 0.705 for stem straightness and 0.734 for tree survival. The individual-tree narrow-sense heritability estimates were 0.336 for diameter, 0.253 for height, 0.205 for volume and 0.121 for stem straightness. Assuming selection of 5, 10, or 15 familiesout of the 28 tested ones and sexual propagation, a genetic gain of 9.5%, 6.8% and 4.8% in diameter, and 11.2%, 8.1% and 5.7% in volume and 16.4%, 11.8% and 8.4% in tree survival, respectively, might be achieved. Selecting the most outstanding 5%, 10%, or 15% individual F1 hybrids would yield a genetic progress of 9.7%, 8.3% and 7,4% in diameter and 10.2%, 8.8% and 7.8% in volume growth rate. The hybrid population mean surpassed in tree survival the open pollinated eastern white pine mean by 70.7% while the eastern white pine, surpassed the hybrid in all growth traits. The F1 hybrid and P. strobus open pollinated parent species averaged 0.993 and 1.069 m3 volume per tree, respectively. By extrapolation the yield results from the hybrid trial area to 1 ha results in a yield of 559.9 m3 per hectare for hybrids and 602.5 m3 for P. strobus female parent species. In conclusion, hybrids should be taken into consideration and used in plantation programs in high-blister-rust-hazard areas.

  16. ANTIBODIES TO BENZO[A]PYRENE AND POLYMORPHISMS OF CYP1A1*2A, CYP1A2*1F, GSTT1, AND GSTM1 GENES IN HEALTHY MEN AND LUNG CANCER PATIENTS

    Directory of Open Access Journals (Sweden)

    A. N. Glushkov

    2016-01-01

    Full Text Available Some genetic polymorphisms of CYP and GST enzymes metabolizing low-molecular weight xenobiotics may represent endogenous risk factors for carcinogenesis. However, possible relationships between the enzyme activities, amounts of carcinogen adducts and synthesis of anticarcinogen antibodies in humans (including cancer patients are still poorly studied. The purpose of this study was to identify possible associations between occurrence of antibodies against benzo[a]pyrene, and frequency of genetic polymorphisms of CYP1A1*2A, CYP1A2*1F, GSTT1, GSTM1 in healthy men and in lung cancer patients. Materials and methods. We have examined 203 men with non-small cell lung cancer and 267 apparently healthy donors without respiratory diseases. A non-competitive solid phase immunoassay of antibodies to benzo[a]pyrene was performed. Analysis of polymorphic loci within CYP1A1 (rs4646903, CYP1A2 (rs762551, GSTP1 (rs1695, rs1138272 was performed by means of real-time PCR using TaqMan technology. Null-alleles of GSTM1 (del, GSTT1 (del genes were detected by multiplex PCR with real-time fluorescent assay. Results. Among the lung cancer patients, the proportion of cases with a high level of IgG antibodies to benzo[a]pyrene in carriers of GSTT1+ and GSTM1+ in conjunction with the CYP1A2*1F C allele was significantly greater than in AA homozygotes CYP1A2*1F. The risk of lung cancer was increased to 5.5 in carriers of CYP1A2*1F C allele combined with GSTT1+ and GSTM1+ at high levels of IgG antibodies to benzo [a] pyrene. In healthy male donors, we have not found differences between the incidence of low and high levels of IgG anti-benzo[a]pyrene antibodies in the carriers of certain CYP1A1*2A, CYP1A2*1F, GSTT1 and GSTM1 genotypes. Conclusions. We have first reported a relationship between CYP1 and GST gene polymorphisms and specific immune response to chemical carcinogens in lung cancer patients. Immunoassays of IgG antibodies to benzo[a]pyrene combined with molecular

  17. Survival rates and predictors of survival among colorectal cancer patients in a Malaysian tertiary hospital.

    Science.gov (United States)

    Magaji, Bello Arkilla; Moy, Foong Ming; Roslani, April Camilla; Law, Chee Wei

    2017-05-18

    patients with data on their Duke's staging, independent predictors of poor colorectal cancer (5-year) survival were male sex (Hazard Ratio [HR]: 1.41; 95% CI: 1.12, 1.76), Chinese ethnicity (HR: 1.41; 95% CI: 1.07,1.85), elevated (≥ 5.1 ng/ml) pre-operative carcino-embryonic antigen (CEA) level (HR: 2.13; 95% CI: 1.60, 2.83), Duke's stage C (HR: 1.68; 95% CI: 1.28, 2.21), Duke's stage D (HR: 4.61; 95% CI: 3.39, 6.28) and emergency surgery (HR: 1.52; 95% CI: 1.07, 2.15). The survival rates of colorectal cancer among our patients were comparable with those of some Asian countries but lower than those found in more developed countries. Males and patients from the Chinese ethnic group had lower survival rates compared to their counterparts. More advanced staging and late presentation were important predictors of colorectal cancer survival. Health education programs targeting high risk groups and emphasizing the importance of screening and early diagnosis, as well as the recognition of symptoms and risk factors should be implemented. A nationwide colorectal cancer screening program should be designed and implemented to increase early detection and improve survival outcomes.

  18. 18F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

    International Nuclear Information System (INIS)

    Salaun, Pierre-Yves; Robin, Philippe; Campion, Loic; Ansquer, Catherine; Mathieu, Cedric; Frampas, Eric; Bournaud, Claire; Vuillez, Jean-Philippe; Taieb, David; Rousseau, Caroline; Drui, Delphine; Mirallie, Eric; Borson-Chazot, Francoise; Goldenberg, David M.; Chatal, Jean-Francois; Barbet, Jacques; Kraeber-Bodere, Francoise

    2014-01-01

    PET is a powerful tool for assessing targeted therapy. Since 18 F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated 18 F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV max , location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUV max (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the analysis of OS from MTC

  19. Survival benefit of post-mastectomy radiotherapy in breast carcinoma patients with T1-2 tumor and 1-3 axillary lymph node(s) metastasis

    International Nuclear Information System (INIS)

    Duraker, N.; Demir, D.; Bati, B.; Yilmaz, B.D.; Bati, Y.; Sobutay, E.; Caynak, Z.C.

    2012-01-01

    The objective of this study was to investigate the role of post-mastectomy radiotherapy in breast carcinoma patients with a tumor size of 5 cm or smaller (T1-2) and 1-3 axillary lymph node(s) metastasis (N1). We retrospectively reviewed the file records of 575 patients receiving radiotherapy (452 patients) and not receiving radiotherapy (123 patients). In the whole series, locoregional recurrence-free survival was significantly better in patients receiving radiotherapy compared with patients not receiving radiotherapy (P 0.25 and in T2N1 breast carcinoma patients with a lymph node ratio of >0.08. In patients with a lymph node ratio equal to or less than these ratios, post-mastectomy radiotherapy could be omitted to avoid radiotherapy-related risks. (author)

  20. Dimethyl ester of bilirubin exhibits anti-inflammatory activity through inhibition of secretory phospholipase A2, lipoxygenase and cyclooxygenase.

    Science.gov (United States)

    Joshi, Vikram; Umashankara, M; Ramakrishnan, Chandrasekaran; Nanjaraj Urs, Ankanahalli N; Suvilesh, Kanve Nagaraj; Velmurugan, Devadasan; Rangappa, Kanchugarakoppal S; Vishwanath, Bannikuppe Sannanaik

    2016-05-15

    Overproduction of arachidonic acid (AA) mediated by secretory phospholipase A2 group IIA (sPLA2IIA) is a hallmark of many inflammatory disorders. AA is subsequently converted into pro-inflammatory eicosanoids through 5-lipoxygenase (5-LOX) and cyclooxygenase-1/2 (COX-1/2) activities. Hence, inhibition of sPLA2IIA, 5-LOX and COX-1/2 activities is critical in regulating inflammation. We have previously reported unconjugated bilirubin (UCB), an endogenous antioxidant, as sPLA2IIA inhibitor. However, lipophilic UCB gets conjugated in liver with glucuronic acid into hydrophilic conjugated bilirubin (CB). Since hydrophobicity is pre-requisite for sPLA2IIA inhibition, conjugation reduces the efficacy of UCB. In this regard, UCB was chemically modified and derivatives were evaluated for sPLA2IIA, 5-LOX and COX-1/2 inhibition. Among the derivatives, BD1 (dimethyl ester of bilirubin) exhibited ∼ 3 fold greater inhibitory potency towards sPLA2IIA compared to UCB. Both UCB and BD1 inhibited human 5-LOX and COX-2 activities; however only BD1 inhibited AA induced platelet aggregation. Molecular docking studies demonstrated BD1 as better inhibitor of aforesaid enzymes than UCB and other endogenous antioxidants. These data suggest that BD1 exhibits strong anti-inflammatory activity through inhibition of AA cascade enzymes which is of great therapeutic importance. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. A study of analysis PB1-F2 protein of Influenza Viruses A/H1N1pdm09, A/ H3N2, and A/H5N1

    Directory of Open Access Journals (Sweden)

    Hana Apsari Pawestri

    2016-07-01

    Full Text Available Abstrak Tujuan. Protein PB1-F2 (polymerase basic 1-frame 2 adalah protein terbaru yang ditemukan pada virus Influenza dan telah terbukti berperan dalam induksi kematian sel dan patogenitas. Tujuan dari tulisan ini adalah untuk menganalisis protein PB1-F2 pada virus Influenza A/H5N1 dan A/H1N1pdm09. Metode. Kami melakukan pencarian data yang relevan yaitu sekuens gen virus Influenza A/H5N1 dan A/H1N1pdm09 dari Gen Bank National Center for Biotechnology Information (NCBI selama tahun 1997-2015. Data yang digunakan adalah data sekuens nukleotida gen PB1 (polymerase basic1 virus influenza A/H5N1 dan A/H1N1pdm09. Kemudian dilakukan analisis alignment untuk mengetahui variasi protein dan mutasi yang berhubungan dengan patogenitas dan virulensi. Hasil. Kami melakukan penelitian terhadap sekuens PB1-F2 sebanyak 3262 influenza A/H5N1 dan 2472 Influenza A/H1N1pdm09. Hasil analisis menunjukkan bahwa semua sekuens A/H5N1 memiliki panjang yang penuh sebanyak 90 asam amino, kecuali influenza pandemi 2009 hanya memiliki panjang 87 asam amino. Kemudian, ditemukan mutasi yang berhubungan dengan virulensi yang ditunjukan dengan perubahan asam amino Asparagin (N menjadi Serin (S. Mutasi tersebut terjadi pada Influenza A/H5N1 sebanyak 8.5% dan Influenza A/H1N1pdm09 sebanyak 0.5%. Kesimpulan. Ditemukan beberapa variasi panjang asam amino dan mutasi penting pada sekuens PB1-F2 dari subtipe yang berbeda yaitu influenza A/H5N1 dan A/H1N1pdm09  yang mengindikasikan seleksi spesifik karena introduksi dan adaptasi terhadap inang yang berbeda. Diperlukan penelitian lanjutan untuk lebih memahami variasi dan kontribusi protein PB1-F2 tersebut terhadap virulensi dan patogenitas virus Influenza. Kata kunci : Patogenesis, Virus Influenza, Protein  PB1-F2 Abstract Aim. Influenza virus PB1-F2 (polymerase basic 1-frame 2 protein is a novel protein previously shown to be involved in cell death induction and pathogenesis. Here we analysis the PB1-F2 protein of Influenza virus A

  2. A study of analysis PB1-F2 protein of Influenza Viruses A/H1N1pdm09, A/ H3N2, and A/H5N1

    Directory of Open Access Journals (Sweden)

    Hana Apsari Pawestri

    2016-07-01

    Full Text Available Abstrak Tujuan. Protein PB1-F2 (polymerase basic 1-frame 2 adalah protein terbaru yang ditemukan pada virus Influenza dan telah terbukti berperan dalam induksi kematian sel dan patogenitas. Tujuan dari tulisan ini adalah untuk menganalisis protein PB1-F2 pada virus Influenza A/H5N1 dan A/H1N1pdm09. Metode. Kami melakukan pencarian data yang relevan yaitu sekuens gen virus Influenza A/H5N1 dan A/H1N1pdm09 dari Gen Bank National Center for Biotechnology Information (NCBI selama tahun 1997-2015. Data yang digunakan adalah data sekuens nukleotida gen PB1 (polymerase basic1 virus influenza A/H5N1 dan A/H1N1pdm09. Kemudian dilakukan analisis alignment untuk mengetahui variasi protein dan mutasi yang berhubungan dengan patogenitas dan virulensi. Hasil. Kami melakukan penelitian terhadap sekuens PB1-F2 sebanyak 3262 influenza A/H5N1 dan 2472 Influenza A/H1N1pdm09. Hasil analisis menunjukkan bahwa semua sekuens A/H5N1 memiliki panjang yang penuh sebanyak 90 asam amino, kecuali influenza pandemi 2009 hanya memiliki panjang 87 asam amino. Kemudian, ditemukan mutasi yang berhubungan dengan virulensi yang ditunjukan dengan perubahan asam amino Asparagin (N menjadi Serin (S. Mutasi tersebut terjadi pada Influenza A/H5N1 sebanyak 8.5% dan Influenza A/H1N1pdm09 sebanyak 0.5%. Kesimpulan. Ditemukan beberapa variasi panjang asam amino dan mutasi penting pada sekuens PB1-F2 dari subtipe yang berbeda yaitu influenza A/H5N1 dan A/H1N1pdm09  yang mengindikasikan seleksi spesifik karena introduksi dan adaptasi terhadap inang yang berbeda. Diperlukan penelitian lanjutan untuk lebih memahami variasi dan kontribusi protein PB1-F2 tersebut terhadap virulensi dan patogenitas virus Influenza. Kata kunci : Patogenesis, Virus Influenza, Protein  PB1-F2 Abstract Aim. Influenza virus PB1-F2 (polymerase basic 1-frame 2 protein is a novel protein previously shown to be involved in cell death induction and pathogenesis. Here we analysis the PB1-F2 protein of Influenza virus A

  3. Constitutive STAT5 Activation Correlates With Better Survival in Cervical Cancer Patients Treated With Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Helen H.W. [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan (China); Chou, Cheng-Yang [Department of Obstetrics and Gynecology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Wu, Yuan-Hua; Hsueh, Wei-Ting; Hsu, Chiung-Hui [Department of Radiation Oncology, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Guo, How-Ran [Department of Environmental and Occupational Health, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China); Lee, Wen-Ying, E-mail: 7707@so-net.net.tw [Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan (China) and Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Su, Wu-Chou, E-mail: sunnysu@mail.ncku.edu.tw [Department of Internal Medicine, National Cheng Kung University, Medical College and Hospital, Tainan, Taiwan (China)

    2012-02-01

    Purpose: Constitutively activated signal transducers and activators of transcription (STAT) factors, in particular STAT1, STAT3, and STAT5, have been detected in a wide variety of human primary tumors and have been demonstrated to directly contribute to oncogenesis. However, the expression pattern of these STATs in cervical carcinoma is still unknown, as is whether or not they have prognostic significance. This study investigated the expression patterns of STAT1, STAT3, and STAT5 in cervical cancer and their associations with clinical outcomes in patients treated with radical radiation therapy. Methods and Materials: A total of 165 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) Stages IB to IVA cervical cancer underwent radical radiation therapy, including external beam and/or high-dose-rate brachytherapy between 1989 and 2002. Immunohistochemical studies of their formalin-fixed, paraffin-embedded tissues were performed. Univariate and multivariate analyses were performed to identify and to evaluate the effects of these factors affecting patient survival. Results: Constitutive activations of STAT1, STAT3, and STAT5 were observed in 11%, 22%, and 61% of the participants, respectively. While STAT5 activation was associated with significantly better metastasis-free survival (p < 0.01) and overall survival (p = 0.04), STAT1 and STAT3 activation were not. Multivariate analyses showed that STAT5 activation, bulky tumor ({>=}4 cm), advanced stage (FIGO Stages III and IV), and brachytherapy (yes vs. no) were independent prognostic factors for cause-specific overall survival. None of the STATs was associated with local relapse. STAT5 activation (odds ratio = 0.29, 95% confidence interval = 0.13-0.63) and advanced stage (odds ratio = 2.54; 95% confidence interval = 1.03-6.26) were independent predictors of distant metastasis. Conclusions: This is the first report to provide the overall expression patterns and prognostic significance of

  4. β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma.

    Science.gov (United States)

    Xu, Chuan; Xie, Dan; Yu, Shi-Cang; Yang, Xiao-Jun; He, Li-Ru; Yang, Jing; Ping, Yi-Fang; Wang, Bin; Yang, Lang; Xu, Sen-Lin; Cui, Wei; Wang, Qing-Liang; Fu, Wen-Juan; Liu, Qing; Qian, Cheng; Cui, You-Hong; Rich, Jeremy N; Kung, Hsiang-Fu; Zhang, Xia; Bian, Xiu-Wu

    2013-05-15

    Cancer stem-like cells (CSLC) are crucial in tumor initiation and progression; however, the underlying mechanism for the self-renewal of cancer cells remains undefined. In the study, immunohistochemical analysis of specimens freshly excised from patients with lung adenocarcinoma showed that high expression of insulin-like growth factor I receptor (IGF-IR) in lung adenocarcinoma cells was positively correlated with the expressions of cancer stem cell markers CD133 and aldehyde dehydrogenase 1 family member A1 (ALDH1A1). IGF-IR activation enhanced POU class 5 homeobox 1 (POU5F1) expression on human lung adenocarcinoma stem-like cells (LACSLC) through PI3K/AKT/GSK3β/β-catenin cascade. POU5F1 could form a novel complex with β-catenin and SOX2 to bind Nanog promoter for transcription to maintain self-renewal of LACSLCs, which was dependent on the functional IGF-IR. Genetic and pharmacologic inhibition of IGF-IR abrogated LACSLC capabilities for self-renewal and tumorigenicity in vitro. In an in vivo xenograft tumor model, knockdown of either IGF-IR or POU5F1 impeded tumorigenic potentials of LACSLCs. By analyzing pathologic specimens excised from 200 patients with lung adenocarcinoma, we found that colocalization of highly expressed IGF-IR with β-catenin and POU5F1 predicted poor prognosis. Taken together, we show that IGF-IR-mediated POU5F1 expression to form a complex with β-catenin and SOX2 is crucial for the self-renewal and oncogenic potentials of LACSLCs, and the integrative clinical detection of the expressions of IGF-IR, β-catenin, and POU5F1 is indicatory for predicting prognosis in the patients of lung adenocarcinoma. ©2013 AACR.

  5. 18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer.

    Science.gov (United States)

    Brito, Ana E; Santos, Allan; Sasse, André Deeke; Cabello, Cesar; Oliveira, Paulo; Mosci, Camila; Souza, Tiago; Amorim, Barbara; Lima, Mariana; Ramos, Celso D; Etchebehere, Elba

    2017-05-30

    In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease. Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months. 18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients.

  6. Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer.

    Science.gov (United States)

    Cheng, Nai-Ming; Fang, Yu-Hua Dean; Lee, Li-yu; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Liao, Chun-Ta; Yang, Lan-Yan; Hsu, Ching-Han; Yen, Tzu-Chen

    2015-03-01

    The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.

  7. JAK2 46/1 haplotype is associated with JAK2 V617F--positive myeloproliferative neoplasms in Brazilian patients.

    Science.gov (United States)

    Macedo, L C; Santos, B C; Pagliarini-e-Silva, S; Pagnano, K B B; Rodrigues, C; Quintero, F C; Ferreira, M E; Baraldi, E C; Ambrosio-Albuquerque, E P; Sell, A M; Visentainer, J E L

    2015-10-01

    This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR-ABL-negative chronic myeloproliferative neoplasms (cMPNs) in our population. The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR-RFLP assay. The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F positive, than in the control population. We also compared the 46/1 haplotype status in each MPN disease entity, polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and MPNu with controls. The G allele frequency relative to controls was significantly enriched in patients with PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all of whom had the JAK2 V617F mutation, showed significant excess of the G allele. The frequency of JAK2 V617F mutation was associated with elevated hematological parameters, but when we analyze the occurrence of the mutation and the presence of the G allele, just the high hemoglobin was significantly. In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients. © 2015 John Wiley & Sons Ltd.

  8. Growth, straightness and survival at age 32 in a Pinus strobus x P. wallichiana F1 hybrid population (Experiment 1

    Directory of Open Access Journals (Sweden)

    Ioan Blada

    2013-12-01

    in a breeding program. The narrow-sense family heritability estimates were 0.657 for diameter, 0.586 for height, 0.505 for volume, 0.705 for stem straightness and 0.734 for tree survival. The individual-tree narrow-sense heritability estimates were 0.336 for diameter, 0.253 for height, 0.205 for volume and 0.121 for stem straightness. Assuming selection of 5, 10, or 15 families out of the 28 tested ones and sexual propagation, a genetic gain of 9.5%, 6.8% and 4.8% in diameter, and 11.2%, 8.1% and 5.7% in volume and 16.4%, 11.8% and 8.4% in tree survival, respectively, might be achieved. Selecting the most outstanding 5%, 10%, or 15% individual F1 hybrids would yield a genetic progress of 9.7%, 8.3% and 7,4% in diameter and 10.2%, 8.8% and 7.8% in volume growth rate. The hybrid population mean surpassed in tree survival the open pollinated eastern white pine mean by 70.7% while the eastern white pine, surpassed the hybrid in all growth traits. The F1 hybrid and P. strobus open pollinated parent species averaged 0.993 and 1.069 m3 volume per tree, respectively. By extrapolation the yield results from the hybrid trial area to 1 ha results in a yield of 559.9 m3 per hectare for hybrids and 602.5 m3 for P. strobus female parent species. In conclusion, hybrids should be taken into consideration and used in plantation programs in high-blister-rust-hazard areas.

  9. {sup 18}F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Salaun, Pierre-Yves; Robin, Philippe [University Hospital, Nuclear Medicine Department, Brest (France); Campion, Loic [ICO-Gauducheau Cancer Institute, Statistical Department, Nantes (France); Ansquer, Catherine; Mathieu, Cedric [University Hospital, Nuclear Medicine Department, Nantes (France); Frampas, Eric [University Hospital, Radiology Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); Bournaud, Claire [University Hospital, Nuclear Medicine Department, Lyon (France); Vuillez, Jean-Philippe [University Hospital, Nuclear Medicine Department, Grenoble (France); Taieb, David [University Hospital, Nuclear Medicine Department, Marseille (France); Rousseau, Caroline [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Drui, Delphine [University Hospital, Endocrinology Department, Nantes (France); Mirallie, Eric [University Hospital, Surgery Department, Nantes (France); Borson-Chazot, Francoise [University Hospital, Endocrinology Department, Lyon (France); Goldenberg, David M. [IBC Pharmaceuticals, Inc., and Immunomedics, Inc., Morris Plains, NJ (United States); Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, NJ (United States); Chatal, Jean-Francois [GIP ARRONAX, Saint-Herblain (France); Barbet, Jacques [Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); GIP ARRONAX, Saint-Herblain (France); Kraeber-Bodere, Francoise [University Hospital, Nuclear Medicine Department, Nantes (France); Universite de Nantes, Nantes-Angers Cancer Research Center, Inserm, U 892, CNRS, UMR 6299, Nantes (France); ICO-Rene Gauducheau, Nuclear Medicine Department, Nantes (France); Hotel Dieu University Hospital, Nuclear Medicine Department, Nantes (France)

    2014-08-15

    PET is a powerful tool for assessing targeted therapy. Since {sup 18}F-FDG shows a potential prognostic value in medullary thyroid carcinoma (MTC), this study evaluated {sup 18}F-FDG PET alone and combined with morphological and biomarker evaluations as a surrogate marker of overall survival (OS) in patients with progressive metastatic MTC treated with pretargeted anti-CEA radioimmunotherapy (pRAIT) in a phase II clinical trial. Patients underwent PET associated with morphological imaging (CT and MRI) and biomarker evaluations, before and 3 and 6 months, and then every 6 months, after pRAIT for 36 months. A combined evaluation was performed using anatomic, metabolic and biomarker methods. The prognostic value of the PET response was compared with demographic parameters at inclusion including age, sex, RET mutation, time from initial diagnosis, calcitonin and CEA concentrations and doubling times (DT), SUV{sub max}, location of disease and bone marrow involvement, and with response using RECIST, biomarker concentration variation, impact on DT, and combined methods. Enrolled in the study were 25 men and 17 women with disease progression. The median OS from pRAIT was 3.7 years (0.2 to 6.5 years) and from MTC diagnosis 10.9 years (1.7 to 31.5 years). After pRAIT, PET/CT showed 1 patient with a complete response, 4 with a partial response and 24 with disease stabilization. The combined evaluation showed 20 responses. For OS from pRAIT, univariate analysis showed the prognostic value of biomarker DT (P = 0.011) and SUV{sub max} (P = 0.038) calculated before pRAIT and impact on DT (P = 0.034), RECIST (P = 0.009), PET (P = 0.009), and combined response (P = 0.004) measured after pRAIT. PET had the highest predictive value with the lowest Akaike information criterion (AIC 74.26) as compared to RECIST (AIC 78.06), biomarker variation (AIC 81.94) and impact on DT (AIC 79.22). No benefit was obtained by combining the methods (AIC 78.75). This result was confirmed by the

  10. Hydrazinium(1+) hexafluorotitanate(IV), 2N[sub 2]H[sub 5][sup +]. TiF[sub 6][sup 2-]. [N[sub 2]H[sub 5]TiF[sub 6

    Energy Technology Data Exchange (ETDEWEB)

    Leban, I. (Dept. of Chemistry and Chemical Technology, Univ. Ljubljana (Slovenia))

    1994-06-15

    The crystals exhibit racemic twinning. The structure consists of hydrazinium(1+), N[sub 2]H[sub 5][sup +], cations and usual octahedral hexafluorotitanate(IV) anions. They are linked together via hydrogen bonds of the types N-H..F and N-H..N. (orig.).

  11. Fine structure of the 1s5f and 1s5g levels of He I

    International Nuclear Information System (INIS)

    Kriescher, Y.; Hilt, O.; Oppen, G. v.

    1994-01-01

    The fine structure of the 1s 5f and 1s 5g levels of He I was measured using microwave spectroscopy. The helium atoms were excited by ion impact, and the eleven allowed 1s 5f 2S+1 F J -1s 5g 2S'+1 G J , transitions near ν∼15 GHz were induced and detected by measuring the 1s 4d-1s 2p or 1s 3d-1s 2p spectral-line intensities of the impact radiation as a function of the microwave frequency. The measured transition frequencies are in accord with theoretical values and, except for one transition frequency, with earlier experimental data. The existing discrepancy between these earlier data and theory could be solved. (orig.)

  12. Prognostic value of negative interim 2-["1"8F]-fluoro-2-deoxy-D-glucose PET/CT in diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Kwon, S.H.; Kang, D.R.; Kim, J.; Yoon, J.-K.; Lee, S.J.; Jeong, S.H.; Lee, H.W.; An, Y.-S.

    2016-01-01

    Aim: To assess the prognostic value of negative interim combined 2-["1"8F]-fluoro-2-deoxy-D-glucose ("1"8F-FDG) positron-emission tomography/computed tomography (PET/CT) in patients with diffuse large B-cell lymphoma (DLBCL). Materials and methods: Ninety-two patients with histologically proven DLBCL were enrolled. All of the patients underwent "1"8F-FDG PET/CT at diagnosis, and interim PET/CT after the second cycle of chemotherapy with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (R-CHOP). Negative interim PET/CT was defined as the disappearance of all abnormal "1"8F-FDG uptake compared to the pretreatment PET/CT image, as determined by visual assessment. The clinical outcome of patients was estimated as progression-free survival (PFS), and the prognostic significance of clinicopathological and imaging parameters were assessed using the Cox proportional hazards model. Results: Thirty-six patients (39.1%) showed lymphoma progression within a median follow-up of 30.8 months. According to univariate analysis, Ann Arbor stage, serum lactate dehydrogenase level, Eastern Cooperative Oncology Group scale, International Prognostic Index (IPI) score, and maximum standardised uptake values on initial PET/CT were significant prognostic factors for PFS (all p<0.05). Among these parameters, only the IPI score was an independent predictor for PFS (p=0.044). Survival of patients with a high IPI score (≥3) was poorer than those with a low IPI score (0–2; p<0.001). Conclusion: Despite a negative interim "1"8F-FDG PET/CT, approximately 39% of DLBCL patients showed progression during follow-up. Although the negative PET/CT was obtained during chemotherapy, it is important to closely follow-up patients, especially those with a high IPI score. - Highlights: • About 39% of patients showed progression after negative interim PET/CT. • The IPI score was an independent predictor for PFS. • It is important to closely follow-up with high IPI score

  13. Molecular CsF{sub 5} and CsF{sub 2}{sup +}

    Energy Technology Data Exchange (ETDEWEB)

    Rogachev, Andrey Yu. [Illinois Institute of Technology, IL (United States). Dept. of Biological and Chemical Sciences; Miao, Mao-sheng [California State Univ., Northridge, CA (United States). Dept. of Chemistry and Biochemistry; Beijing Computational Science Research Center (China); Merino, Gabriel [Centro de Investigacion y de Estudios Avanzados, Unidad Merida (Mexico). Dept. de Fisica Aplicada; Hoffmann, Roald [Cornell Univ., Ithaca, NY (United States). Dept. of Chemistry and Chemical Biology

    2015-07-06

    D{sub 5h} star-like CsF{sub 5}, formally isoelectronic with known XeF{sub 5}{sup -} ion, is computed to be a local minimum on the potential energy surface of CsF{sub 5}, surrounded by reasonably large activation energies for its exothermic decomposition to CsF + 2F{sub 2}, or to CsF{sub 3} (three isomeric forms) + F{sub 2}, or for rearrangement to a significantly more stable isomer, a classical Cs{sup +} complex of F{sub 5}{sup -}. Similarly the CsF{sub 2}{sup +} ion is computed to be metastable in two isomeric forms. In the more symmetrical structures of these molecules there is definite involvement in bonding of the formally core 5p levels of Cs.

  14. {sup 18}F-FDG PET/CT predicts survival after {sup 90}Y transarterial radioembolization in unresectable hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jreige, Mario; Mitsakis, Periklis; Gucht, Axel van der; Pomoni, Anastasia; Silva-Monteiro, Marina; Boubaker, Ariane; Nicod-Lalonde, Marie; Prior, John O.; Schaefer, Niklaus [Lausanne University Hospital, Department of Nuclear Medicine and Molecular Imaging, Lausanne (Switzerland); Gnesin, Silvano [Lausanne University Hospital, Institute of Radiation Physics, Lausanne (Switzerland); Duran, Rafael; Denys, Alban [Lausanne University Hospital, Department of Radiodiagnostic and Interventional Radiology, Lausanne (Switzerland)

    2017-07-15

    SUV{sub max}; HR 2.6, 95% CI 1.1-5.9, P = 0.02, for median SUV{sub max}:) and OS (HR 3.2, 95% CI 1-10.9, P = 0.04 for Q1 SUV{sub max}; HR 3.7, 95% CI 1.1-12.2, P = 0.03, for Q1 T/L uptake ratio), respectively, when testing with either the BCLC staging system or serum AFP level. Lesion SUV{sub max} and T/L uptake ratio as assessed by {sup 18}F-FDG PET/CT, but not morphological imaging, were predictive markers of survival in patients undergoing {sup 90}Y-TARE for uHCC. (orig.)

  15. Zone-size nonuniformity of {sup 18}F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Nai-Ming [Chang Gung Memorial Hospital and Chang Gung University, Departments of Nuclear Medicine, Taiyuan (China); Chang Gung Memorial Hospital, Department of Nuclear Medicine, Keelung (China); National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Fang, Yu-Hua Dean [Chang Gung University, Department of Electrical Engineering, Taiyuan (China); Lee, Li-yu [Chang Gung University College of Medicine, Department of Pathology, Chang Gung Memorial Hospital, Taoyuan (China); Chang, Joseph Tung-Chieh; Tsan, Din-Li [Chang Gung University College of Medicine, Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan (China); Ng, Shu-Hang [Chang Gung University College of Medicine, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Taoyuan (China); Wang, Hung-Ming [Chang Gung University College of Medicine, Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan (China); Liao, Chun-Ta [Chang Gung University College of Medicine, Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan (China); Yang, Lan-Yan [Chang Gung Memorial Hospital, Biostatistics Unit, Clinical Trial Center, Taoyuan (China); Hsu, Ching-Han [National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Yen, Tzu-Chen [Chang Gung Memorial Hospital and Chang Gung University, Departments of Nuclear Medicine, Taiyuan (China); Chang Gung University College of Medicine, Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taipei (China)

    2014-10-23

    The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUV{sub max} 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment {sup 18}F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUV{sub max} 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification. (orig.)

  16. Larval development of Spodoptera eridania and Spodoptera frugiperda fed on fresh ear of field corn expressing the Bt proteins (Cry1F and Cry1F + Cry1A.105 + Cry2Ab2)

    OpenAIRE

    Bortolotto,Orcial Ceolin; Bueno,Adeney de Freitas; Queiroz,Ana Paula de; Silva,Gabriela Vieira

    2016-01-01

    ABSTRACT: The objective of this study was to evaluate extent of larval period, larval survival (%), food consumption, and pupal biomass of Spodoptera eridania and Spodoptera frugiperda (Lepidoptera: Noctuidae ) fed on fresh ears of field corn expressing Bt proteins (Cry1F and Cry1F+Cry1A.105+Cry2Ab2). Larvae of Spodoptera spp. survived less than two days when they consumed Bt corncobs and showed 100% mortality. Spodoptera eridania reared on non-Bt corn cobs showed higher larval development (...

  17. Synthesis and Spectral Analysis of 3,4,5-trichloro-6-(dibenzo[d,f][1,3]diazepin-5-yl-[1,2]-benzoquinones

    Directory of Open Access Journals (Sweden)

    Mohsen A. M. Gomaa

    2011-01-01

    Full Text Available Reaction of N1,N2-di-(4-methoxyphenyl- or N1,N2-di-(4-hydroxyphenyl -amidines (1a-d with 3,4,5,6-tetrachloro-1,2-benzoquinone (2 in ethyl acetate at room temperature led to formation of new 3,4,5-trichloro-6-(2-hydroxy-6-methyldibenzo[d,f][1,3]diazepin-5-yl[1,2]-benzoquinones (3a-d in addition to N-aryl-N'-(6,7,8,9-tetrachloro-4-hydroxydibenzo-[1,4]dioxin-2-ylacetamidines (4a,b. The rational of formation of products 3a-d and 4a,b was discussed and structures were confirmed on the basis of elemental analysis and spectral data.

  18. Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients

    Directory of Open Access Journals (Sweden)

    See-Hyoung Park

    2015-08-01

    Full Text Available BACKGROUND: Poly(ADP-ribose polymerase 1 (PARP1, γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS, and relapse-free survival (RFS by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph was an additional independent prognostic predictor for OS (P < .001 and RFS (P < .001. The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1 subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4 subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

  19. Pilot Study on Genetic Polymorphisms CYP1A2*1F on Asthma Patients and Nonasthma in Indonesia

    Directory of Open Access Journals (Sweden)

    Doddy de Queljoe

    2015-03-01

    Full Text Available Genetic polymorphisms of CYP1A2 is related to the theophylline metabolism that may affect drug levels in the blood, which can also affect incidence of adverse drug reaction (ADR and clinical outcomes of asthma therapy. The frequency of CYP1A2 polymorphism is known to vary among ethnic. Allegedly the Indonesian population has high frequency of gene variants of CYP1A2*1F. This study aims to determine the profile of CYP1A2*1F gene polymorphism in a sample of nonasthma and asthma in Indonesia with other populations based on the literature. Data were taken on January–June 2014. Blood samples were obtained from 29 nonasthma samples and 16 patients with asthma. After extraction of genomic DNA, CYP1A2*1F gene polymorphisms determined by PCR-RFLP. The results of this study indicate that the CYP1A2*1F gene polymorphism in nonasthma samples was 10.35% (3/29 for C/C, 37.93% (11/29 for the C/A, and 51.72% (15/29 for A/A. The asthmatics genotype have a frequency distribution of C/A genotype of 81.25% (13/16 and A/A of 18.75% (3/16. There was no significant difference (p=0.276 allele frequencies between samples of nonasthma and asthma patients. The frequency of CYP1A2*1F gene in Indonesian population is higher than the population of Egypt, Japan, and UK, but lower compared to Malaysia. It can be concluded that there is no difference in frequency.

  20. Biodistribution of the 18F-FPPRGD2 PET radiopharmaceutical in cancer patients: an atlas of SUV measurements

    International Nuclear Information System (INIS)

    Minamimoto, Ryogo; Jamali, Mehran; Gambhir, Sanjiv Sam; Barkhodari, Amir; Mosci, Camila; Mittra, Erik; Iagaru, Andrei; Shen, Bin; Chin, Frederick

    2015-01-01

    The aim of this study was to investigate the biodistribution of 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) ( 18 F-FPPRGD 2 ) in cancer patients and to compare its uptake in malignant lesions with 18 F-FDG uptake. A total of 35 patients (11 men, 24 women, mean age 52.1 ± 10.8 years) were enrolled prospectively and had 18 F-FPPRGD 2 PET/CT prior to treatment. Maximum standardized uptake values (SUV max ) and mean SUV (SUV mean ) were measured in 23 normal tissues in each patient, as well as in known or suspected cancer lesions. Differences between 18 F-FPPRGD 2 uptake and 18 F-FDG uptake were also evaluated in 28 of the 35 patients. Areas of high 18 F-FPPRGD 2 accumulation (SUV max range 8.9 - 94.4, SUV mean range 7.1 - 64.4) included the bladder and kidneys. Moderate uptake (SUV max range 2.1 - 6.3, SUV mean range 1.1 - 4.5) was found in the choroid plexus, salivary glands, thyroid, liver, spleen, pancreas, small bowel and skeleton. Compared with 18 F-FDG, 18 F-FPPRGD 2 showed higher tumor-to-background ratio in brain lesions (13.4 ± 8.5 vs. 1.1 ± 0.5, P < 0.001), but no significant difference in body lesions (3.2 ± 1.9 vs. 4.4 ± 4.2, P = 0.10). There was no significant correlation between the uptake values (SUV max and SUV mean ) for 18 F FPPRGD 2 and those for 18 F-FDG. The biodistribution of 18 F-FPPRGD 2 in cancer patients is similar to that of other RGD dimer peptides and it is suitable for clinical use. The lack of significant correlation between 18 F-FPPRGD 2 and 18 F-FDG uptake confirms that the information provided by each PET tracer is different. (orig.)

  1. Monitoring of Radiochemotherapy in Patients with Glioblastoma Using O-(2-[18F]Fluoroethyl-L-Tyrosine Positron Emission Tomography: Is Dynamic Imaging Helpful?

    Directory of Open Access Journals (Sweden)

    Marc D. Piroth

    2013-09-01

    Full Text Available Monitoring of radiochemotherapy (RCX in patients with glioblastoma is difficult because unspecific alterations in magnetic resonance imaging with contrast enhancement can mimic tumor progression. Changes in tumor to brain ratios (TBRs in positron emission tomography (PET using O-(2-[18F]fluoroethyl-L-tyrosine (18F-FET after RCX with temozolomide of patients with glioblastoma have been shown to be valuable parameters to predict survival. The kinetic behavior of 18F-FET in the tumors is another promising parameter to analyze tumor metabolism. In this study, we investigated the predictive value of dynamic 18F-FET PET during RCX of glioblastoma. Time-activity curves (TACs of 18F-FET uptake of 25 patients with glioblastoma were evaluated after surgery (FET-1, early (7–10 days after completion of RCX (FET-2, and 6 to 8 weeks later (FET-3. Changes in the time to peak (TTP and the slope of the TAC (10–50 minutes postinjection were analyzed and related to survival. Changes in kinetic parameters of 18F-FET uptake after RCX showed no relationship with survival time. In contrast, the high predictive value of changes of TBR to predict survival was confirmed. We conclude that dynamic 18F-FET PET does not provide additional prognostic information during RCX. Static 18F-FET PET imaging (20–40 minutes postinjection appears to be sufficient for this purpose and reduces costs.

  2. Pretreatment F-18 FDG PET/CT Parameters to Evaluate Progression-Free Survival in Gastric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeonghun; Lim, Seok Tae; Na, Chang Ju; Han, Yeonhee; Kim, Chanyoung; Jeong, Hwanjeong; Sohn, Myunghee [Chonbuk National Univ., Jeonju (Korea, Republic of)

    2014-03-15

    We performed this study to evaluate the predictive value of pretreatment F-18 FDG PET/CT for progression-free survival (PFS) in patients with gastric cancer. Of 321 patients with a diagnosis of gastric cancer, we retrospectively enrolled 97 patients (men:women = 61:36, age 59.8±13.2 years), who underwent pretreatment F-18 fluoro-2-deoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) from January 2009 to December 2009. Maximum standardized uptake value (SUVmax) was measured for each case with detectable primary lesions. In the remaining non-detectable cases, SUVmax was measured from the corresponding site seen on gastroduodenoscopy for analysis. In subgroup analysis, metabolic tumor volume (MTV) was measured in 50 patients with clearly distinguishable primary lesions. SUVmax, stage, depth of tumor invasion and presence of lymph node metastasis were analyzed in terms of PFS. Receiver operating characteristic (ROC) curves were used to find optimal cutoff values of SUVmax and MTV for disease progression. The relationship between SUVmax, MTV and PFS was analyzed using the Kaplan-Meier with log-rank test and Cox's proportional hazard regression methods. Of 97 patients, 15 (15.5 %) had disease progression. The mean follow-up duration was 29.6±10.2 months. The mean PFS of low SUVmax group (≤5.74) was significantly longer than that of the high SUVmax group (>5.74) (30.9±8.0 vs 24.3±13.6 months, p =0.008). In univariate analysis, stage (I vs II, III, IV), depth of tumor invasion (T1 vs T2, T3, T4), presence of lymph node metastasis and SUVmax (>5.74 vs ≤5.74) were significantly associated with recurrence. In multivariate analysis, high SUVmax (>5.74) was the only poor prognostic factor for PFS (p =0.002, HR 11.03, 95% CI 2.48.49.05). Subgroup multivariate analysis revealed that high MTV (>16.42) was the only poor prognostic factor for PFS (p =0.034, HR 3.59, 95 % CI 1.10.11.71). In gastric cancer, SUVmax measured by pretreatment F-18

  3. Plasma Levels of Soluble HLA-E and HLA-F at Diagnosis May Predict Overall Survival of Neuroblastoma Patients

    Directory of Open Access Journals (Sweden)

    Fabio Morandi

    2013-01-01

    Full Text Available The purpose of this study was to identify the plasma/serum biomarkers that are able to predict overall survival (OS of neuroblastoma (NB patients. Concentration of soluble (s biomarkers was evaluated in plasma (sHLA-E, sHLA-F, chromogranin, and B7H3 or serum (calprotectin samples from NB patients or healthy children. The levels of biomarkers that were significantly higher in NB patients were then analyzed considering localized or metastatic subsets. Finally, biomarkers that were significantly different in these two subsets were correlated with patient’s outcome. With the exception of B7H3, levels of all molecules were significantly higher in NB patients than those in controls. However, only chromogranin, sHLA-E, and sHLA-F levels were different between patients with metastatic and localized tumors. sHLA-E and -F levels correlated with each other but not chromogranin. Chromogranin levels correlated with different event-free survival (EFS, whereas sHLA-E and -F levels also correlated with different OS. Association with OS was also detected considering only patients with metastatic disease. In conclusion, low levels of sHLA-E and -F significantly associated with worse EFS/OS in the whole cohort of NB patients and in patients with metastatic NB. Thus, these molecules deserve to be tested in prospective studies to evaluate their predictive power for high-risk NB patients.

  4. Jak2 46/1 Haplotype Is Associated With Jak2 V617f--positive Myeloproliferative Neoplasms In Brazilian Patients.

    OpenAIRE

    Macedo, L C; Santos, B C; Pagliarini-e-Silva, S; Pagnano, K B B; Rodrigues, C; Quintero, F C; Ferreira, M E; Baraldi, E C; Ambrosio-Albuquerque, E P; Sell, A M; Visentainer, J E L

    2016-01-01

    This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR-ABL-negative chronic myeloproliferative neoplasms (cMPNs) in our population. The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR-RFLP assay. The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially t...

  5. Life prolongation and 5-year survival by intensive irradiation of inoperable lung cancer

    International Nuclear Information System (INIS)

    Eichhorn, H.-J.

    1982-01-01

    The effect of intensive radiotherapy on 1-5 year survival rates of patients with inoperable lung cancer is investigated. Some 123 cases were treated with 200 kV X-rays (> 3500 cGy tumour dose) and 1046 with cobalt-60 ν-rays (> 5000 cGy tumour dose). All patients had inoperable, histologically confirmed tumours, limited to one side of the thorax. Survival rates for 1 year were 22% and 37% respectively; for 3 years 1% and 5%; and for 5 years 0 and 2.5%. In all highly differentiated tumours the authors obtained a 5-year survival with telecobalt therapy of 6.5%, and for all oat-cell cases, 2.5%. By comparing the total result with their own control group of 'untreated', but prognostically more favourable patients (122 thoracotomized cases without resection) the increase of survival rates achieved by Cobalt-60 therapy is convincing (2.5 times for 1 year, 5 times for 2 years). Nevertheless, the very unfavourable prognosis for more than half of the cases justifies trials with systemic therapy. To date chemotherapy does not appear to influence survival times (except for small-cell tumours). Therefore randomized trials with two half-body irradiations (800 cGy each, 'Toronto method') are recommended. (Auth.)

  6. Predicting Outcome in Patients with Rhabdomyosarcoma: Role of [18F]Fluorodeoxyglucose Positron Emission Tomography

    International Nuclear Information System (INIS)

    Casey, Dana L.; Wexler, Leonard H.; Fox, Josef J.; Dharmarajan, Kavita V.; Schoder, Heiko; Price, Alison N.; Wolden, Suzanne L.

    2014-01-01

    Purpose: To evaluate whether [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) response of the primary tumor after induction chemotherapy predicts outcomes in rhabdomyosarcoma (RMS). Methods and Materials: After excluding those with initial tumor resection, 107 patients who underwent FDG-PET after induction chemotherapy at Memorial Sloan Kettering Cancer Center from 2002 to 2013 were reviewed. Local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated according to FDG-PET response and maximum standardized uptake value (SUV) at baseline (PET1/SUV1), after induction chemotherapy (PET2/SUV2), and after local therapy (PET3/SUV3). Receiver operator characteristic curves were used to determine the optimal cutoff for dichotomization of SUV1 and SUV2 values. Results: The SUV1 (<9.5 vs ≥9.5) was predictive of PFS (P=.02) and OS (P=.02), but not LC. After 12 weeks (median) of induction chemotherapy, 45 patients had negative PET2 scans and 62 had positive scans: 3-year PFS was 72% versus 44%, respectively (P=.01). The SUV2 (<1.5 vs ≥1.5) was similarly predictive of PFS (P=.005) and was associated with LC (P=.02) and OS (P=.03). A positive PET3 scan was predictive of worse PFS (P=.0009), LC (P=.05), and OS (P=.03). Conclusions: [ 18 F]fluorodeoxyglucose positron emission tomography is an early indicator of outcomes in patients with RMS. Future prospective trials may incorporate FDG-PET response data for risk-adapted therapy and early assessment of new treatment regimens

  7. The association of {sup 18}F-FDG PET/CT parameters with survival in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Klabatsa, Astero; Lang-Lazdunski, Loic [Guys and St Thomas' NHS Foundation Trust, Department of Thoracic Oncology, London (United Kingdom); Chicklore, Sugama; Barrington, Sally F.; Goh, Vicky [Kings College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Cook, Gary J.R. [Kings College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Kings College London, Clinical PET Centre, Division of Imaging Sciences and Biomedical Engineering, St Thomas' Hospital, London (United Kingdom)

    2014-02-15

    Malignant pleural mesothelioma (MPM) is a disease with poor prognosis despite multimodal therapy but there is variation in survival between patients. Prognostic information is therefore potentially valuable in managing patients, particularly in the context of clinical trials where patients could be stratified according to risk. Therefore we have evaluated the prognostic ability of parameters derived from baseline 2-[{sup 18}F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT). In order to determine the relationships between metabolic activity and prognosis we reviewed all {sup 18}F-FDG PET/CT scans used for pretreatment staging of MPM patients in our institution between January 2005 and December 2011 (n = 60) and measured standardised uptake values (SUV) including mean, maximum and peak values, metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Overall survival (OS) or time to last censor was recorded, as well as histological subtypes. Median follow-up was 12.7 months (1.9-60.9) and median OS was 14.1 months (1.9-54.9). By univariable analysis histological subtype (p = 0.013), TLG (p = 0.024) and MTV (p = 0.038) were significantly associated with OS and SUV{sub max} was borderline (p = 0.051). On multivariable analysis histological subtype and TLG were associated with OS but at borderline statistical significance (p = 0.060 and 0.058, respectively). No statistically significant differences in any PET parameters were found between the epithelioid and non-epithelioid histological subtypes. {sup 18}F-FDG PET/CT parameters that take into account functional volume (MTV, TLG) show significant associations with survival in patients with MPM before adjusting for histological subtype and are worthy of further evaluation to determine their ability to stratify patients in clinical trials. (orig.)

  8. Investigation into the MgF2-NiF2, CaF2-NiF2, SrF2-NiF2 systems

    International Nuclear Information System (INIS)

    Ikrami, D.D.; Petrov, S.V.; Fedorov, P.P.; Ol'khovaya, L.A.; Luginina, A.A.; AN SSSR, Moscow. Inst. Fizicheskikh Problem; AN SSSR, Moscow. Inst. Kristallografii)

    1984-01-01

    Using the methods of differential thermal and X-ray phase analyses the systems MgF 2 -NiF 2 , CaF 2 -NiF 2 , SrF 2 -NiF 2 have been studied. In the system SrF 2 -NiF 2 the only orthorhombic compounds SrNiF 4 (a=14.43; b=3.93; c=5.66 (+-0.01 A)) is formed. SrNiF 4 density constitutes: dsub(X-ray)=4.60+-0.01 g/cm 3 , dsub(exp.)=4.60+-0.03 g/cm 3 . Refraction indices are as follows SrNiF 4 :Ng=1.500; Nsub(m)=1.497; Nsub(p)=1.479. SrNiF 4 magnetic ordering temperature Tsub(N) approximately 100 K

  9. Radioimmunotherapy of human colon cancer xenografts by using 131I labeled-CAb1 F(ab')2

    International Nuclear Information System (INIS)

    Li Ling; Xu Huiyun; Mi Li; Bian Huijie; Qin Jun; Xiong Hua; Feng Qiang; Wen Ning; Tian Rong; Xu Liqing; Shen Xiaomei; Tang Hao; Chen Zhinan

    2006-01-01

    Purpose: Therapeutic efficacy, suitable dose, and administration times of 131 I-CAb 1 F(ab') 2 , a new monoclonal antibody therapeutics specifically directed against a cell surface-associated glycoprotein of colon cancer, were investigated in this article. Methods and Materials: In human colon cancer xenografts, 131 I-CAb 1 F(ab') 2 at the dose of 125 μCi, 375 μCi, and 1125 μCi were administrated intraperitoneally on Days 6 and 18 after implantation of HR8348 cells with CAb 1 high reactivity. Survival time and tumor growth inhibition rate were used to evaluate the efficacy and safety of 131 I-CAb 1 F(ab') 2 in treatment of colon cancer xenografts. Results: Treatment of 125, 375, and 1125 μCi 131 I-CAb1 F(ab') 2 did not significantly decrease the mean survival time of nude mice when compared with nontreated groups (p = 0.276, 0.865, 0.582, respectively). Moreover, the mean survival times of nude mice receiving 375 μCi and 1125 μCi 131 I-CAb1 F(ab') 2 were significantly longer than that of 5-FU-treated groups (p 0.018 and 0.042). Tumor growth inhibition rates of the first therapy were 35.67% and 41.37%, with corresponding 131 I-labeled antibody dosage of 375 μCi and 1125 μCi. After single attack dosage, second reinforcement therapy may rise efficacy significantly. Tumor growth inhibition rates of 125 μCi, 375 μCi, and 1125 μCi 131 I-labeled antibody on Day 20 posttherapy were 42.65%, 56.56%, and 84.41%, respectively. Histopathology examination revealed that tissue necrosis of various degrees was found in 131 I-CAb1 F(ab') 2 -treated groups. Conclusion: 131 I-CAb 1 F(ab') 2 is safe and effective for colon cancer. It may be a novel and potentially adjuvant therapeutics for colon cancer

  10. 1g(9/2), 1f(5/2), and 1f(7/2) neutron inner hole responses in Sn-115 and Sn-119 via the ((d)over-right-arrow,t) reaction at E-d=200 MeV

    NARCIS (Netherlands)

    Langevin-Joliot, H; Van de Wiele, J; Guillot, J; Gerlic, E; Rosier, LH; Willis, A; Djalali, C; Morlet, M; Tomasi-Gustafsson, E; Blasi, N; Micheletti, S; van der Werf, SY

    Neutron inner hole responses in Sn-115 and Sn-119 nuclei have been studied via the ((d) over right arrow ,t) reaction at E-d=200 MeV using a polarized beam with both vector and tensor components. One-step pickup observables corresponding to the overlapping 1g(9/2), 1f(5/2), and 1f(7/2) responses

  11. Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoid arthritis

    Science.gov (United States)

    Liu, Nathan J.; Chapman, Robert; Lin, Yiyang; Mmesi, Jonas; Bentham, Andrew; Tyreman, Matthew; Abraham, Sonya; Stevens, Molly M.

    2016-02-01

    Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08423g

  12. Microwave-assisted one-pot radiosynthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil ([18F]-FMAU)

    International Nuclear Information System (INIS)

    Chen, Kai; Li Zibo; Conti, Peter S.

    2012-01-01

    Objectives: [ 18 F]-FMAU is a PET tracer being evaluated for imaging cell proliferation. Current multi-step procedures of [ 18 F]-FMAU synthesis are time-consuming, resulting in low radiochemical yield and inconvenient applications for the clinic. We have previously reported the use of Friedel-Crafts catalysts for an improved synthesis of [ 18 F]-FMAU. In this study, we investigated the efficiency of microwave-assisted radiosynthesis of [ 18 F]-FMAU in comparison with conventional thermal conditions. Methods: A simplified one-pot synthesis of [ 18 F]-FMAU was developed under microwave conditions. Various reaction times, temperatures, and microwave powers were systematically explored to optimize the coupling reaction of 2-deoxy-2-[ 18 F]fluoro-1,3,5-tri-O-benzoyl-D-arabinofuranose ([ 18 F]-sugar) and bis-2,4-(trimethylsilyloxy)-5-methyluracil (silylated uracil) in the presence of a Friedel-Crafts catalyst, trimethylsilyl trifluoromethanesulfonate (TMSOTf). Results: Microwave significantly enhanced the coupling efficiency of [ 18 F]-sugar and silylated uracil by reducing the reaction time to 10 min (6-fold reduction as compared to conventional heating) at 95 °C. Base hydrolysis followed by high-performance liquid chromatography purification produced the desired [ 18 F]-FMAU. The overall radiochemical yield was 20 ± 4% (decay corrected, n = 3). Radiochemical purity was > 99% and specific activity was > 400 mCi/μmol. The α/β anomer ratio was 1:2. The radiosynthesis time was about 90 min from the end of bombardment. Conclusions: A reliable microwave-assisted approach has been developed for routine synthesis of [ 18 F]-FMAU. The new approach affords a simplified process with shorter synthesis time and higher radiochemical yield as compared to conventional heating. A fully automated microwave-assisted synthesis of [ 18 F]-FMAU can be readily achieved under new reaction conditions.

  13. Magnetic anisotropy of cobalt nanoparticle 2D arrays grown on corrugated MnF{sub 2}(1 1 0) and CaF{sub 2}(1 1 0) surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Baranov, D.A., E-mail: dbaranov@mail.ioffe.ru [Ioffe Physical-Technical Institute, Russian Academy of Sciences, 26 Polytechnicheskaya str., St. Petersburg 194021 (Russian Federation); Krichevtsov, B.B.; Gastev, S.V.; Banschikov, A.G.; Fedorov, V.V. [Ioffe Physical-Technical Institute, Russian Academy of Sciences, 26 Polytechnicheskaya str., St. Petersburg 194021 (Russian Federation); Koshmak, K.V. [Ioffe Physical-Technical Institute, Russian Academy of Sciences, 26 Polytechnicheskaya str., St. Petersburg 194021 (Russian Federation); Dipartimento di Ingegneria dei Materiali e dell’Ambiente, Università di Modena e Reggio Emilia, Via Vignolese 905, 41100 Modena (Italy); Suturin, S.M.; Sokolov, N.S. [Ioffe Physical-Technical Institute, Russian Academy of Sciences, 26 Polytechnicheskaya str., St. Petersburg 194021 (Russian Federation)

    2013-02-15

    Cobalt nanoparticle 2D arrays with different effective thicknesses of cobalt layer (2 nm < d{sub eff} < 10 nm) were grown by molecular beam epitaxy on CaF{sub 2}(1 1 0)/Si(0 0 1) and MnF{sub 2}(1 1 0)/CaF{sub 2}(1 1 0)/Si(0 0 1) substrates with corrugated morphology of the surface. Surface morphology analysis showed that for effective thickness of cobalt layer d{sub eff} = 5 nm the lateral dimensions of cobalt islands are about 5–10 nm and the distances between the islands differs in a half along and across the grooves. In both types of the heterostructures the shape of hysteresis loops measured by LMOKE depend on orientation of in-plane magnetic field relative to the direction of the grooves. The azimuthal dependence of coercive field H{sub c} in Co/CaF{sub 2}(1 1 0)/Si(0 0 1) structures corresponds to Stoner–Wohlfarth model's predictions, which takes into account the anisotropy of individual particles. In contrast to that, in Co/MnF{sub 2}(1 1 0)/CaF{sub 2}(1 1 0)/Si(0 0 1) structures these dependences are analogous to those predicted by the model based on account of magnetic–dipole interaction between particles which are placed in chains (chain-of-spheres-model). Possible explanations of the difference in magnetic anisotropy are suggested.

  14. H5N1 Influenza A Virus PB1-F2 Relieves HAX-1-Mediated Restriction of Avian Virus Polymerase PA in Human Lung Cells.

    Science.gov (United States)

    Mazel-Sanchez, B; Boal-Carvalho, I; Silva, F; Dijkman, R; Schmolke, M

    2018-06-01

    Highly pathogenic influenza A viruses (IAV) from avian hosts were first reported to directly infect humans 20 years ago. However, such infections are rare events, and our understanding of factors promoting or restricting zoonotic transmission is still limited. One accessory protein of IAV, PB1-F2, was associated with pathogenicity of pandemic and zoonotic IAV. This short (90-amino-acid) peptide does not harbor an enzymatic function. We thus identified host factors interacting with H5N1 PB1-F2, which could explain its importance for virulence. PB1-F2 binds to HCLS1-associated protein X1 (HAX-1), a recently identified host restriction factor of the PA subunit of IAV polymerase complexes. We demonstrate that the PA of a mammal-adapted H1N1 IAV is resistant to HAX-1 imposed restriction, while the PA of an avian-origin H5N1 IAV remains sensitive. We also showed HAX-1 sensitivity for PAs of A/Brevig Mission/1/1918 (H1N1) and A/Shanghai/1/2013 (H7N9), two avian-origin zoonotic IAV. Inhibition of H5N1 polymerase by HAX-1 can be alleviated by its PB1-F2 through direct competition. Accordingly, replication of PB1-F2-deficient H5N1 IAV is attenuated in the presence of large amounts of HAX-1. Mammal-adapted H1N1 and H3N2 viruses do not display this dependence on PB1-F2 for efficient replication in the presence of HAX-1. We propose that PB1-F2 plays a key role in zoonotic transmission of avian H5N1 IAV into humans. IMPORTANCE Aquatic and shore birds are the natural reservoir of influenza A viruses from which the virus can jump into a variety of bird and mammal host species, including humans. H5N1 influenza viruses are a good model for this process. They pose an ongoing threat to human and animal health due to their high mortality rates. However, it is currently unclear what restricts these interspecies jumps on the host side or what promotes them on the virus side. Here we show that a short viral peptide, PB1-F2, helps H5N1 bird influenza viruses to overcome a human restriction

  15. Increased frequency of co-existing JAK2 exon-12 or MPL exon-10 mutations in patients with low JAK2(V617F) allelic burden.

    Science.gov (United States)

    Nussenzveig, Roberto H; Pham, Ha T; Perkins, Sherrie L; Prchal, Josef T; Agarwal, Archana M; Salama, Mohamed E

    2016-01-01

    The frequency of co-existing JAK2(V617F)/MPL and JAK2(V617F)/JAK2 exon-12 mutations has not been previously investigated in MPNs. Poor survival was reported in primary myelofibrosis with low JAK2(V617F) allelic burden. However, mutational status of JAK2 exon-12 or MPL were not reported in these patients. This study developed a cost-effective multiplex high resolution melt assay that screens for mutations in JAK2 gene exons-12 and -14 ((V617F)) and MPL gene exon-10. Co-existing mutations with JAK2(V617F) were detected in 2.9% (6/208; two JAK2 exon-12 and four MPL exon-10) patient specimens with known JAK2(V617F) (allelic-burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with MPL exon-10 mutation should be pursued.

  16. Increased expression and activity of group IIA and X secretory phospholipase A2 in peritumoral versus central colon carcinoma tissue

    DEFF Research Database (Denmark)

    Tribler, Line; Jensen, Lotte T.; Jørgensen, Kent

    2007-01-01

    Secretory phospholipase A2 (sPLA2) type IIA and X was analyzed in tumors from 22 patients with colon adenocarcinomas in order to determine the involvement and activity of sPLA2 in colon cancer. Evaluation of immunoreactive sPLA2 IIA by Western blotting showed a significantly higher level...... in the periphery of the tumors, compared to central tumor regions. Increased levels of sPLA2 IIA protein correlated with a two-fold increase in sPLA2 enzymatic activity in the peripheral regions compared to central regions. Nineteen out of 22 tumors showed high levels of sPLA2 IIA, whereas 7 out of the 22 tumors...... showed sPLA2 type X. These data demonstrate that both sPLA2 type IIA and X are present in human colon cancer and suggest a role for sPLA2 in colon cancer tumor immunology and tumorigenesis....

  17. Radiosynthesis of F-18 labeled cytidine analog 2'-fluoro-5-iodo-l-β-D-arabinofuranosylcytosine ([18F]FIAC)

    International Nuclear Information System (INIS)

    Wu, C.-Y.; Chan, P.-C.; Chang, W.-T.; Liu, R.-S.; Alauddin, Mian M.; Wang, H-E.

    2009-01-01

    We reported the synthesis of 2'-deoxy-2'-[ 18 F]fluoro-5-iodo-1-β-D-arabinofuranosyl-5-iodo-cytosine ([ 18 F]FIAC) with 15-20% radiochemical yield (decay corrected) in 3.5 h. 2-deoxy-2-[ 18 F]fluoro-1,3,5-tri-O-benzoyl-α-D-arabinofuranose was prepared following literature procedures with some modifications (yield>70%). The 18 F-fluorosugar was converted to 1-bromo- 18 F-fluorosugar, and then coupled with 5-iodocytocine silyl ether. A mixture of acetonitrile (ACN) and 1,2-dichloroethane (DCE) were employed to achieve optimum radiochemical yield and acceptable β-anomer selectivity (α/β=1/3). After hydrolyzed with sodium methoxide, the crude product was purified using HPLC to afford the β-[ 18 F]FIAC with high radiochemical purity (≥98%).

  18. New organic superconductors beta-(BDA-TTP)2X [BDA-TTP + 2,5-bis(1,3-dithian-2ylidene)-1,3,4,6-tetrathiapentalene; X(-) = SbF6(-), AsF6(-), and PF6(-)].

    Science.gov (United States)

    Yamada, J; Watanabe, M; Akutsu, H; Nakatsuji, S; Nishikawa, H; Ikemoto, I; Kikuchi, K

    2001-05-09

    The synthesis, electrochemical properties, and molecular structure of a new pi-electron donor, 2,5-bis(1,3-dithian-2-ylidene)-1,3,4,6-tetrathiapentalene (BDA-TTP), is described. In contrast to the hitherto-known tetrachalcogenafulvalene pi-donors providing organic superconductors, this donor contains only the bis-fused 1,3-dithiole-2-ylidene unit as a pi-electron system, yet produces a series of ambient-pressure superconductors beta-(BDA-TTP)2X [X = SbF6 (magnetic T(c) = 6.9 K, resistive T(c) = 7.5 K), AsF6 (magnetic T(c) = 5.9 K, resistive T(c) = 5.8 K), and PF6 (magnetic T(c) = 5.9 K)], which are isostructural. The values of the intermolecular overlap integrals calculated on the donor layers of these superconductors suggest a two-dimensional (2D) electronic structure with loose donor packing. Tight-binding band calculations also indicate that these superconductors have the 2D band dispersion relations and closed Fermi surfaces.

  19. Lipid droplets induced by secreted phospholipase A2 and unsaturated fatty acids protect breast cancer cells from nutrient and lipotoxic stress.

    Science.gov (United States)

    Jarc, Eva; Kump, Ana; Malavašič, Petra; Eichmann, Thomas O; Zimmermann, Robert; Petan, Toni

    2018-03-01

    Cancer cells driven by the Ras oncogene scavenge unsaturated fatty acids (FAs) from their environment to counter nutrient stress. The human group X secreted phospholipase A 2 (hGX sPLA 2 ) releases FAs from membrane phospholipids, stimulates lipid droplet (LD) biogenesis in Ras-driven triple-negative breast cancer (TNBC) cells and enables their survival during starvation. Here we examined the role of LDs, induced by hGX sPLA 2 and unsaturated FAs, in protection of TNBC cells against nutrient stress. We found that hGX sPLA 2 releases a mixture of unsaturated FAs, including ω-3 and ω-6 polyunsaturated FAs (PUFAs), from TNBC cells. Starvation-induced breakdown of LDs induced by low micromolar concentrations of unsaturated FAs, including PUFAs, was associated with protection from cell death. Interestingly, adipose triglyceride lipase (ATGL) contributed to LD breakdown during starvation, but it was not required for the pro-survival effects of hGX sPLA 2 and unsaturated FAs. High micromolar concentrations of PUFAs, but not OA, induced oxidative stress-dependent cell death in TNBC cells. Inhibition of triacylglycerol (TAG) synthesis suppressed LD biogenesis and potentiated PUFA-induced cell damage. On the contrary, stimulation of LD biogenesis by hGX sPLA 2 and suppression of LD breakdown by ATGL depletion reduced PUFA-induced oxidative stress and cell death. Finally, lipidomic analyses revealed that sequestration of PUFAs in LDs by sPLA 2 -induced TAG remodelling and retention of PUFAs in LDs by inhibition of ATGL-mediated TAG lipolysis protect from PUFA lipotoxicity. LDs are thus antioxidant and pro-survival organelles that guard TNBC cells against nutrient and lipotoxic stress and emerge as attractive targets for novel therapeutic interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Lower Bmi-1 Expression May Predict Longer Survival of Colon Cancer Patients

    Directory of Open Access Journals (Sweden)

    Xiaodong Li

    2016-11-01

    Full Text Available Background: This study aimed to investigate the Bmi-1 expression and the clinical significance in colon cancer (CC. Patients and Methods: Bmi-1 expression in tumor tissue and the corresponding normal tissue was detected using immunohistological staining. The correlations between Bmi-1 expression and clinicopathological characteristics and the overall survival (OS time were analyzed. Results: The median H-scores of Bmi-1 in CC tissues and the corresponding tissues were 80.0 (0-270 and 5.0 (0-90, with no statistically significant difference (Z=-13.7, PP = 0.123. The survival rates of patients with low Bmi-1 expression were higher than those of patients with high Bmi-1 expression but the differences were not statistically significant. Conclusion: Bmi-1 expression in CC tissue is significantly higher than that in corresponding normal tissue. While there may be a trend towards improved survival, this is not statistically significant.

  1. Serum Mac-2 binding protein glycosylation isomer predicts grade F4 liver fibrosis in patients with biliary atresia.

    Science.gov (United States)

    Yamada, Naoya; Sanada, Yukihiro; Tashiro, Masahisa; Hirata, Yuta; Okada, Noriki; Ihara, Yoshiyuki; Urahashi, Taizen; Mizuta, Koichi

    2017-02-01

    Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) is a novel fibrosis marker. We examined the ability of M2BPGi to predict liver fibrosis in patients with biliary atresia. Sixty-four patients who underwent living donor liver transplantation (LDLT) were included [median age, 1.1 years (range 0.4-16.0), male 16 patients (25.0 %)]. We examined M2BPGi levels in serum obtained the day before LDLT, and we compared the value of the preoperative M2BPGi levels with the histological evaluation of fibrosis using the METAVIR fibrosis score. Subsequently, we assessed the ability of M2BPGi levels to predict fibrosis. The median M2BPGi level in patients with BA was 6.02 (range, 0.36-20.0), and 0, 1, 1, 11, and 51 patients had METAVIR fibrosis scores of F0, F1, F2, F3, and F4, respectively. In patients with F4 fibrosis, the median M2BPGi level was 6.88 (quartile; 5.235, 12.10), significantly higher than that in patients with F3 fibrosis who had a median level of 2.42 (quartile; 1.93, 2.895, p F4 fibrosis. M2BPGi is a novel fibrosis marker for evaluating the status of the liver in patients with BA, especially when predicting grade F4 fibrosis.

  2. Synthesis of sn-1 functionalized phospholipids as substrates for secretory phospholipase A2

    DEFF Research Database (Denmark)

    Linderoth, Lars; Peters, Günther H.J.; Jørgensen, K.

    2007-01-01

    Secretory phospholipase A2 (sPLA2) represents a family of small water-soluble enzymes that catalyze the hydrolysis of phospholipids in the sn-2 position liberating free fatty acids and lysophospholipids. Herein we report the synthesis of two new phospholipids (1 and 2) with bulky allyl-substituen......Secretory phospholipase A2 (sPLA2) represents a family of small water-soluble enzymes that catalyze the hydrolysis of phospholipids in the sn-2 position liberating free fatty acids and lysophospholipids. Herein we report the synthesis of two new phospholipids (1 and 2) with bulky allyl...... of the allyl-substituents by a zinc mediated allylation. Small unilamellar liposomes composed of phospholipids 1 and 2 were subjected to sPLA2 activity measurements. Our results show that only phospholipid 1 is hydrolyzed by the enzyme. Molecular dynamics simulations revealed that the lack of hydrolysis...

  3. Concurrent Chemoradiotherapy Improves Survival in Patients With Hypopharyngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Paximadis, Peter, E-mail: ppaximad@med.wayne.edu [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States); Yoo, George; Lin, Ho-Sheng; Jacobs, John [Department of Otolaryngology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Sukari, Ammar [Department of Medical Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Dyson, Greg [Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI (United States); Christensen, Michael; Kim, Harold [Department of Radiation Oncology, Wayne State University, Detroit, MI (United States)

    2012-03-15

    Purpose: To retrospectively review our institutional experience with hypopharyngeal carcinoma with respect to treatment modality. Methods and Materials: A total of 70 patients with hypopharyngeal cancer treated between 1999 and 2009 were analyzed for functional and survival outcomes. The treatments included surgery alone (n = 5), surgery followed by radiotherapy (RT) (n = 3), surgery followed by chemoradiotherapy (CRT) (n = 13), RT alone (n = 2), CRT alone (n = 22), induction chemotherapy followed by RT (n = 3), and induction chemotherapy followed by CRT (n = 22). Results: The median follow-up was 18 months. The median overall survival and disease-free survival for all patients was 28.3 and 17.6 months, respectively. The 1- and 2-year local control rate for all patients was 87.1% and 80%. CRT, given either as primary therapy or in the adjuvant setting, improved overall survival and disease-free survival compared with patients not receiving CRT. The median overall survival and disease-free survival for patients treated with CRT was 36.7 and 17.6 months vs. 14.0 and 8.0 months, respectively (p < .01). Of the patients initially treated with an organ-preserving approach, 4 (8.2%) required salvage laryngectomy for local recurrence or persistent disease; 8 (16.3%) and 12 (24.5%) patients were dependent on a percutaneous gastrostomy and tracheostomy tube, respectively. The 2-year laryngoesophageal dysfunction-free survival rate for patients treated with an organ-preserving approach was estimated at 31.7%. Conclusions: Concurrent CRT improves survival in patients with hypopharyngeal cancer. CRT given with conventional radiation techniques yields poor functional outcomes, and future efforts should be directed at determining the feasibility of pharyngeal-sparing intensity-modulated radiotherapy in patients with hypopharyngeal tumors.

  4. The prognostic value of metabolic tumor volume in FDG PET/CT evaluation of post-operative survival in patients with esophageal squamous cell cancer

    International Nuclear Information System (INIS)

    Zhu Wanqi; Yu Jinming; Sun Xiaorong; Xing Ligang; Xie Peng; Sun Xindong; Guo Hongbo; Yang Guoren; Kong Li

    2011-01-01

    Objective: To evaluate the prognostic value of MTV on 18 F-FDG PET/CT in patients with esophageal cancer. Methods: Forty-nine patients with esophageal cancer underwent 18 F-FDG PET/CT scan before surgery. The median follow-up time for the patients was 29 months (range, 8-57 months). The prognostic significance of MTV, age, sex, histologic grade, SUV max of the primary tumor, tumor size measured on PET/CT, T stage, N stage, M stage, American Joint Committee on Cancer (AJCC) stage, number and location of lymph nodes metastases were assessed by Kaplan-Meier analysis and multivariate Cox model. Results: In the univariate analysis, AJCC stage (χ 2 =16.206, hazard ratio (HR)=1.177, P<0.001), N stage (χ 2 =9.536, HR=10.833, P=0.002), T stage (χ 2 =5.810, HR=2.397, P=0.016), number of lymph nodes metastases (χ 2 =11.423, HR=1.567, P=0.001), and MTV (χ 2 =3.872, HR=2.433, P=0.049) were significant predictors of survival.Multivariate analysis showed that MTV and AJCC stage were independent predictors of survival2 =4.525, HR 1.170, P=0.033; χ 2 =4.875, HR=3.071, P=0.027). Kaplan-Meier survival curves revealed longer survival time of low-MTV group as compared to high-MTV group (Log-rank, χ 2 =4.186, P=0.041). Conclusion: MTV on 18 F-FDG PET/CT may be an independent prognostic factor in patients with esophageal cancer. (authors)

  5. Herpes simplex virus thymidine kinase imaging in mice with (1-(2'-deoxy-2'-[{sup 18}F]fluoro-1-{beta}-D-arabinofuranosyl)-5-iodouracil) and metabolite (1-(2'-deoxy-2'-[{sup 18}F]fluoro-1-{beta}-D-arabinofuranosyl)-5-uracil)

    Energy Technology Data Exchange (ETDEWEB)

    Nimmagadda, Sridhar; Lawhorn-Crews, Jawana M.; Shields, Anthony F. [Wayne State University, Karmanos Cancer Institute, Detroit, MI (United States); Wayne State University, Department of Medicine, Detroit, MI (United States); Mangner, Thomas J. [Wayne State University, Karmanos Cancer Institute, Detroit, MI (United States); Wayne State University, Department of Radiology, Detroit, MI (United States); Haberkorn, Uwe [University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany)

    2009-12-15

    FIAU, (1-(2{sup '}-deoxy-2{sup '}-fluoro-1-{beta}-D-arabinofuranosyl)-5-iodouracil) has been used as a substrate for herpes simplex virus thymidine kinases (HSV-TK and HSV-tk, for protein and gene expression, respectively) and other bacterial and viral thymidine kinases for noninvasive imaging applications. Previous studies have reported the formation of a de-iodinated metabolite of {sup 18}F-FIAU. This study reports the dynamic tumor uptake, biodistribution, and metabolite contribution to the activity of {sup 18}F-FIAU seen in HSV-tk gene expressing tumors and compares the distribution properties with its de-iodinated metabolite {sup 18}F-FAU. CD-1 nu/nu mice with subcutaneous MH3924A and MH3924A-stb-tk+ xenografts on opposite flanks were used for the biodistribution and imaging studies. Mice were injected IV with either {sup 18}F-FIAU or {sup 18}F-FAU. Mice underwent dynamic imaging with each tracer for 65 min followed by additional static imaging up to 150 min post-injection for some animals. Animals were sacrificed at 60 or 150 min post-injection. Samples of blood and tissue were collected for biodistribution and metabolite analysis. Regions of interest were drawn over the images obtained from both tumors to calculate the time-activity curves. Biodistribution and imaging studies showed the highest uptake of {sup 18}F-FIAU in the MH3924A-stb-tk+ tumors. Dynamic imaging studies revealed a continuous accumulation of {sup 18}F-FIAU in HSV-TK expressing tumors over 60 min. The mean biodistribution values (SUV {+-} SE) for MH3924A-stb-tk+ were 2.07 {+-} 0.40 and 6.15 {+-} 1.58 and that of MH3924A tumors were 0.19 {+-} 0.07 and 0.47 {+-} 0.06 at 60 and 150 min, respectively. In {sup 18}F-FIAU injected mice, at 60 min nearly 63% of blood activity was present as its metabolite {sup 18}F-FAU. Imaging and biodistribution studies with {sup 18}F-FAU demonstrated no specific accumulation in MH3924A-stb-tk+ tumors and SUVs for both the tumors were similar to those

  6. Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by dynamic 18F-FDG PET/CT.

    Science.gov (United States)

    Epelbaum, Ron; Frenkel, Alex; Haddad, Riad; Sikorski, Natalia; Strauss, Ludwig G; Israel, Ora; Dimitrakopoulou-Strauss, Antonia

    2013-01-01

    This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG influx). The single significant variable for overall survival (OS) in patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in nonresectable and resected tumors, respectively (P measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The (18)F-FDG INF was the single most significant variable for OS in patients with localized disease, whether resectable or not.

  7. The novel superacid systems HSO3F-Nb(SO3F)5 and HSO3F-Ta(SO3F)5

    International Nuclear Information System (INIS)

    Cicha, W.V.; Aubke, F.

    1989-01-01

    The in situ oxidation of niobium and tantalum in HSO 3 F by bis(fluorosulfuryl) peroxide, S 2 O 6 F 2 , results in the formation of solvated Lewis acids M(SO 3 F) 5 , M = Nb or Ta. Both solutes behave as moderately strong, monoprotonic acids, based on electrical conductivity measurements over the concentration range 0-0.05 m and on conductometric titrations against KSO 3 F. These measurements suggest a general order of acidity, Au(SO 3 F) 3 > Ta(SO 3 F) 5 ≥ SbF 5 > Nb(SO 3 F) 5 > NbF 5 , all giving rise to monoprotonic acids. Supporting evidence comes from 1 H, 19 F, and 93 Nb NMR spectroscopy and the successful isolation and characterization of complexes of the type Cs n [M(SO 3 F) 5+n ], with M = Nb or Ta and n = 1 or 2, from these solutions

  8. Analysis list: E2f1 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available E2f1 Blood,Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/E2f1.5.tsv http://dbarchive.biosciencedbc.jp/kyus...hu-u/mm9/target/E2f1.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/E2f1.Blood.tsv,http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/E2f1.Liver.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/colo/Blood.gml,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  9. Three-component synthesis of C2F5-substituted pyrazoles from C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes

    Directory of Open Access Journals (Sweden)

    Pavel K. Mykhailiuk

    2015-01-01

    Full Text Available A one-pot reaction between C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes gives C2F5-substituted pyrazoles in excellent yields. The transformation smoothly proceeds in dichloromethane/water, tolerates the presence of air, and requires no purification of products by column chromatography. Mechanistically, C2F5CH2NH2·HCl and NaNO2 react first in water to generate C2F5CHN2, that participates in a [3 + 2] cycloaddition with electron-deficient alkynes in dichloromethane.

  10. Immunomodulatory effects of intravenous bis-1 f(ab')(2) administration in renal-cell cancer-patients

    NARCIS (Netherlands)

    Janssen, R. A. J.; Kroesen, B. J.; Mesander, G.; Sleijfer, D. T.; The, T. Hauw; Mulder, N. H.; de Leij, L

    We report the immunomodulatory effects of an intravenous treatment with F(ab')(2) fragments of the bispecific monoclonal antibody BIS-1 during subcutaneous recombinant interleukin 2 (rIL-2) therapy of renal cell cancer (RCC) patients. BIS-1 is directed against both the CD3 antigen on T cells and the

  11. Expression of eicosanoid biosynthetic and catabolic enzymes in peritoneal endometriosis.

    Science.gov (United States)

    Lousse, J-C; Defrère, S; Colette, S; Van Langendonckt, A; Donnez, J

    2010-03-01

    Increased peritoneal eicosanoid concentrations have been reported in endometriosis patients and might be important in disease-associated pain and inflammation. Here, we evaluated the expression of key biosynthetic and catabolic enzymes involved in this abnormal eicosanoid production in peritoneal macrophages and endometriotic lesions. Peritoneal macrophages, endometriotic lesions and matched eutopic endometrium were collected from endometriosis patients (n = 40). Peritoneal macrophages and eutopic endometrium samples were also collected from disease-free women (n = 25). Expression of type IIA secretory phospholipase A(2) (sPLA(2)-IIA), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 5-lipoxygenase (5-LO) was quantified by real-time PCR, and these five key enzymes were localized by immunohistochemistry. sPLA(2)-IIA, COX-2 and mPGES-1 mRNA was significantly increased in peritoneal macrophages of endometriosis patients compared with controls (P = 0.006, P = 0.016 and P = 0.025, respectively). In endometriosis patients, sPLA(2)-IIA, mPGES-1 and 15-PGDH mRNA was significantly enhanced in peritoneal lesions compared with matched eutopic endometrium (P endometriosis group compared with controls (P = 0.023). Finally, sPLA(2)-IIA, COX-2, mPGES-1 and 15-PGDH immunostaining was found mainly in endometrial glands, whereas 5-LO was distributed throughout the glands and stroma. Our study highlights an imbalance between eicosanoid biosynthesis and degradation in endometriosis patients. Both peritoneal macrophages and endometriotic lesions may be involved. Research into new molecules inhibiting biosynthetic enzymes (such as sPLA(2)-IIA and mPGES-1) and/or activating catabolic enzymes (such as 15-PGDH) may prove to be a major field of investigation in the development of targeted medical therapies.

  12. Primary myelofibrosis with or without mutant MPL: comparison of survival and clinical features involving 603 patients.

    Science.gov (United States)

    Pardanani, A; Guglielmelli, P; Lasho, T L; Pancrazzi, A; Finke, C M; Vannucchi, A M; Tefferi, A

    2011-12-01

    MPL and JAK2V617F mutation analysis was performed in 603 patients with primary myelofibrosis (PMF) seen at the Mayo Clinic, USA (n=329) or University of Florence, Italy (n=274). Mutant MPL was detected in 49 (8.1%) patients and JAK2V617F in 350 (58%); 4 patients showed both mutations. MPLW515L/K was the commonest mutation; 2 patients showed novel mutations (L513ins and Q516-P518insAAAA). The US and Italy patient cohorts were separately analyzed for comparison of survival and clinical features between MPL-mutated, JAK2-mutated and JAK2/MPL-unmutated cases. JAK2/MPL-unmutated patients were significantly younger than their JAK2-mutated counterparts, in both patient cohorts (PMPL was associated with older age (PMPL has narrow and inconsistent phenotypic effect in PMF and does not influence overall or leukemia-free survival.

  13. Biodistribution of the {sup 18}F-FPPRGD{sub 2} PET radiopharmaceutical in cancer patients: an atlas of SUV measurements

    Energy Technology Data Exchange (ETDEWEB)

    Minamimoto, Ryogo; Jamali, Mehran; Gambhir, Sanjiv Sam [Stanford University, Stanford, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford, CA (United States); Barkhodari, Amir; Mosci, Camila; Mittra, Erik; Iagaru, Andrei [Stanford University, Stanford, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States); Shen, Bin; Chin, Frederick [Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford, CA (United States)

    2015-11-15

    The aim of this study was to investigate the biodistribution of 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) ({sup 18}F-FPPRGD{sub 2}) in cancer patients and to compare its uptake in malignant lesions with {sup 18}F-FDG uptake. A total of 35 patients (11 men, 24 women, mean age 52.1 ± 10.8 years) were enrolled prospectively and had {sup 18}F-FPPRGD{sub 2} PET/CT prior to treatment. Maximum standardized uptake values (SUV{sub max}) and mean SUV (SUV{sub mean}) were measured in 23 normal tissues in each patient, as well as in known or suspected cancer lesions. Differences between {sup 18}F-FPPRGD{sub 2} uptake and {sup 18}F-FDG uptake were also evaluated in 28 of the 35 patients. Areas of high {sup 18}F-FPPRGD{sub 2} accumulation (SUV{sub max} range 8.9 - 94.4, SUV{sub mean} range 7.1 - 64.4) included the bladder and kidneys. Moderate uptake (SUV{sub max} range 2.1 - 6.3, SUV{sub mean} range 1.1 - 4.5) was found in the choroid plexus, salivary glands, thyroid, liver, spleen, pancreas, small bowel and skeleton. Compared with {sup 18}F-FDG, {sup 18}F-FPPRGD{sub 2} showed higher tumor-to-background ratio in brain lesions (13.4 ± 8.5 vs. 1.1 ± 0.5, P < 0.001), but no significant difference in body lesions (3.2 ± 1.9 vs. 4.4 ± 4.2, P = 0.10). There was no significant correlation between the uptake values (SUV{sub max} and SUV{sub mean}) for {sup 18}F FPPRGD{sub 2} and those for {sup 18}F-FDG. The biodistribution of {sup 18}F-FPPRGD{sub 2} in cancer patients is similar to that of other RGD dimer peptides and it is suitable for clinical use. The lack of significant correlation between {sup 18}F-FPPRGD{sub 2} and {sup 18}F-FDG uptake confirms that the information provided by each PET tracer is different. (orig.)

  14. Outcomes of Patients With Revised Stage I Clear Cell Sarcoma of Kidney Treated in National Wilms Tumor Studies 1-5

    International Nuclear Information System (INIS)

    Kalapurakal, John A.; Perlman, Elizabeth J.; Seibel, Nita L.; Ritchey, Michael; Dome, Jeffrey S.; Grundy, Paul E.

    2013-01-01

    Purpose: To report the clinical outcomes of children with revised stage I clear cell sarcoma of the kidney (CCSK) using the National Wilms Tumor Study Group (NWTS)-5 staging criteria after multimodality treatment on NWTS 1-5 protocols. Methods and Materials: All CCSK patients enrolled in the National Wilms Tumor Study Group protocols had their pathology slides reviewed, and only those determined to have revised stage I tumors according to the NWTS-5 staging criteria were included in the present analysis. All patients were treated with multimodality therapy according to the NWTS 1-5 protocols. Results: A total of 53 children were identified as having stage I CCSK. All patients underwent primary surgery with radical nephrectomy. The chemotherapy regimens used were as follows: regimen A, C, F, or EE in 4 children (8%); regimen DD or DD4A in 33 children (62%); regimen J in 4 children (8%); and regimen I in 12 children (22%). Forty-six patients (87%) received flank radiation therapy (RT). Seven children (13%) did not receive flank RT. The median delay between surgery and the initiation of RT was 9 days (range, 3-61). The median RT dose was 10.8 Gy (range, 10-36). The flank RT doses were as follows: 10.5 or 10.8 Gy in 25 patients (47%), 11-19.9 Gy in 2 patients (4%), 20-29.9 Gy in 9 patients (17%), and 30-40 Gy in 10 patients (19%). The median follow-up for the entire group was 17 years (range, 2-36). The relapse-free and cancer-specific survival rate was 100% at the last follow-up examination. Conclusions: The present results have demonstrated that children with revised stage I CCSK using the NWTS-5 staging criteria have excellent survival rates despite the use of varying RT doses and chemotherapy regimens in the NWTS 1-5 protocols.

  15. Schedules of Controlled Substances: Temporary Placement of Six Synthetic Cannabinoids (5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-

    Science.gov (United States)

    2016-12-21

    The Administrator of the Drug Enforcement Administration is issuing this notice of intent to temporarily schedule six synthetic cannabinoids: methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [5F-ADB; 5F-MDMB-PINACA]; methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3-methylbutanoate [5F-AMB]; N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide [5F-APINACA, 5F-AKB48]; N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide [ADB-FUBINACA]; methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-CHMICA, MMB-CHMINACA] and methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-FUBINACA], into schedule I pursuant to the temporary scheduling provisions of the Controlled Substances Act (CSA). This action is based on a finding by the Administrator that the placement of these synthetic cannabinoids into schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. Any final order will impose the administrative, civil, and criminal sanctions and regulatory controls applicable to schedule I substances under the Controlled Substances Act on the manufacture, distribution, possession, importation, exportation of, and research and conduct with, instructional activities of these synthetic cannabinoids.

  16. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation.

    LENUS (Irish Health Repository)

    Rishi, Loveena

    2014-04-10

    The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein α (C\\/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop for E2F1, C\\/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C\\/EBPα-p42, and in normal granulocyte\\/macrophage progenitor cells, we detect C\\/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle or Trib2 knockdown resulted in a block in AML cell proliferation. Our work proposes a novel paradigm whereby E2F1 plays a key role in the regulation of Trib2 expression important for AML cell proliferation control. Importantly, we identify the contribution of dysregulated C\\/EBPα and E2F1 to elevated Trib2 expression and leukemic cell survival, which likely contributes to the initiation and maintenance of AML and may have significant implications for normal and malignant hematopoiesis.

  17. The feasibility of single-port laparoscopic appendectomy using a solo approach: a comparative study.

    Science.gov (United States)

    Kim, Say-June; Choi, Byung-Jo; Jeong, Wonjun; Lee, Sang Chul

    2016-03-01

    To investigate the feasibility and safety of solo surgery with single-port laparoscopic appendectomy, which is termed herein solo-SPLA (solo-single-port laparoscopic appendectomy). This study prospectively collected and retrospectively analyzed data from patients who had undergone either non-solo-SPLA (n = 150) or solo-SPLA (n = 150). Several devices were utilized for complete, skin-to-skin solo-SPSA, including a Lone Star Retractor System and an adjustable mechanical camera holder. Operating times were not significantly different between solo- and non-solo-SPLA (45.0 ± 21.0 minutes vs. 46.7 ± 26.1 minutes, P = 0.646). Most postoperative variables were also comparable between groups, including the necessity for intravenous analgesics (0.7 ± 1.2 ampules [solo-SPLA] vs. 0.9 ± 1.5 ampules [non-solo-SPLA], P = 0.092), time interval to gas passing (1.3 ± 1.0 days vs. 1.4 ± 1.0 days, P = 0.182), and the incidence of postoperative complications (4.0% vs. 8.7%, P = 0.153). Moreover, solo-SPLA effectively lowered the operating cost by reducing surgical personnel expenses. Solo-SPLA economized staff numbers and thus lowered hospital costs without lengthening of operating time. Therefore, solo-SPLA could be considered a safe and feasible alternative to non-solo-SPLA.

  18. Bridging Binding Modes of Phosphine-Stabilized Nitrous Oxide to Zn(C6F5)2

    NARCIS (Netherlands)

    Neu, Rebecca C.; Otten, Edwin; Stephan, Douglas W.

    2009-01-01

    Reaction of [tBu3PN2O(B(C6H4F)3)] with 1, 1.5, or 2 equivalents of Zn(C6F5)2 affords the species [{tBu3PN2OZn(C6F5)2}2], [{tBu3PN2OZn(C6F5)2}2Zn(C6F5)2], and [tBu3PN2O{Zn(C6F5)2}2] displaying unique binding modes of Zn to the phosphine-stabilized N2O fragment.

  19. Atomic structure of CaF2/MnF2-Si(1 1 1) superlattices from X-ray diffraction

    International Nuclear Information System (INIS)

    Alcock, Simon G.; Nicklin, C.L.; Howes, P.B.; Norris, C.A.; Kyutt, R.N.; Sokolov, N.S.; Yakovlev, N.L.

    2007-01-01

    X-ray reflectivity and non-specular crystal truncation rod scans have been used to determine the three-dimensional atomic structure of the buried CaF 2 -Si(1 1 1) interface and ultrathin films of MnF 2 and CaF 2 within a superlattice. We show that ultrathin films of MnF 2 , below a critical thickness of approximately four monolayers, are crystalline, pseudomorphic, and adopt the fluorite structure of CaF 2 . High temperature deposition of the CaF 2 buffer layer produces a fully reacted, CaF 2 -Si(1 1 1) type-B interface. The mature, 'long' interface is shown to consist of a partially occupied layer of CaF bonded to the Si substrate, followed by a distorted CaF layer. Our atomistic, semi-kinematical scattering method extends the slab reflectivity method by providing in-plane structural information

  20. Polarization dependence of double-resonance optical pumping and electromagnetically induced transparency in the 5S1/2-5P3/2-5D5/2 transition of 87Rb atoms

    International Nuclear Information System (INIS)

    Moon, Han Seb; Noh, Heung-Ryoul

    2011-01-01

    The polarization dependence of double-resonance optical pumping (DROP) in the ladder-type electromagnetically induced transparency (EIT) of the 5S 1/2 -5P 3/2 -5D 5/2 transition of 87 Rb atoms is studied. The transmittance spectra in the 5S 1/2 (F=2)-5P 3/2 (F'=3)-5D 5/2 (F''=2,3,4) transition were observed as caused by EIT, DROP, and saturation effects in the various polarization combinations between the probe and coupling lasers. The features of the double-structure transmittance spectra in the 5S 1/2 (F=2)-5P 3/2 (F'=3)-5D 5/2 (F''=4) cycling transition were attributed to the difference in saturation effect according to the transition routes between the Zeeman sublevels and the EIT according to the two-photon transition probability.

  1. High endothelin-converting enzyme-1 expression independently predicts poor survival of patients with esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wu, Ching-Fang; Lee, Ching-Tai; Kuo, Yao-Hung; Chen, Tzu-Haw; Chang, Chi-Yang; Chang, I-Wei; Wang, Wen-Lun

    2017-09-01

    Patients with esophageal squamous cell carcinoma have poor survival and high recurrence rate, thus an effective prognostic biomarker is needed. Endothelin-converting enzyme-1 is responsible for biosynthesis of endothelin-1, which promotes growth and invasion of human cancers. The role of endothelin-converting enzyme-1 in esophageal squamous cell carcinoma is still unknown. Therefore, this study investigated the significance of endothelin-converting enzyme-1 expression in esophageal squamous cell carcinoma clinically. We enrolled patients with esophageal squamous cell carcinoma who provided pretreated tumor tissues. Tumor endothelin-converting enzyme-1 expression was evaluated by immunohistochemistry and was defined as either low or high expression. Then we evaluated whether tumor endothelin-converting enzyme-1 expression had any association with clinicopathological findings or predicted survival of patients with esophageal squamous cell carcinoma. Overall, 54 of 99 patients with esophageal squamous cell carcinoma had high tumor endothelin-converting enzyme-1 expression, which was significantly associated with lymph node metastasis ( p = 0.04). In addition, tumor endothelin-converting enzyme-1 expression independently predicted survival of patients with esophageal squamous cell carcinoma, and the 5-year survival was poorer in patients with high tumor endothelin-converting enzyme-1 expression ( p = 0.016). Among patients with locally advanced and potentially resectable esophageal squamous cell carcinoma (stage II and III), 5-year survival was poorer with high tumor endothelin-converting enzyme-1 expression ( p = 0.003). High tumor endothelin-converting enzyme-1 expression also significantly predicted poorer survival of patients in this population. In patients with esophageal squamous cell carcinoma, high tumor endothelin-converting enzyme-1 expression might indicate high tumor invasive property. Therefore, tumor endothelin-converting enzyme-1 expression

  2. Radiosynthesis of F-18 labeled cytidine analog 2'-fluoro-5-iodo-l-{beta}-D-arabinofuranosylcytosine ([{sup 18}F]FIAC)

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C.-Y.; Chan, P.-C.; Chang, W.-T. [Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 155, Li-Nong Street, Sector 2, Bei-tou, Taipei 112, Taiwan (China); Liu, R.-S. [Department of Nuclear Medicine, Faculty of Medicine, National Yang-Ming University, Taiwan (China); Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taiwan (China); Alauddin, Mian M. [Department of Experimental Diagnostic Imagiing, MD Anderson Cancer Center, University of Texas (United States); Wang, H-E. [Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 155, Li-Nong Street, Sector 2, Bei-tou, Taipei 112, Taiwan (China)], E-mail: hewang@ym.edu.tw

    2009-07-15

    We reported the synthesis of 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyl-5-iodo-cytosine ([{sup 18}F]FIAC) with 15-20% radiochemical yield (decay corrected) in 3.5 h. 2-deoxy-2-[{sup 18}F]fluoro-1,3,5-tri-O-benzoyl-{alpha}-D-arabinofuranose was prepared following literature procedures with some modifications (yield>70%). The {sup 18}F-fluorosugar was converted to 1-bromo-{sup 18}F-fluorosugar, and then coupled with 5-iodocytocine silyl ether. A mixture of acetonitrile (ACN) and 1,2-dichloroethane (DCE) were employed to achieve optimum radiochemical yield and acceptable {beta}-anomer selectivity ({alpha}/{beta}=1/3). After hydrolyzed with sodium methoxide, the crude product was purified using HPLC to afford the {beta}-[{sup 18}F]FIAC with high radiochemical purity ({>=}98%)

  3. Associations between advanced cancer patients' survival and family caregiver presence and burden.

    Science.gov (United States)

    Dionne-Odom, J Nicholas; Hull, Jay G; Martin, Michelle Y; Lyons, Kathleen Doyle; Prescott, Anna T; Tosteson, Tor; Li, Zhongze; Akyar, Imatullah; Raju, Dheeraj; Bakitas, Marie A

    2016-05-01

    We conducted a randomized controlled trial (RCT) of an early palliative care intervention (ENABLE: Educate, Nurture, Advise, Before Life Ends) for persons with advanced cancer and their family caregivers. Not all patient participants had a caregiver coparticipant; hence, we explored whether there were relationships between patient survival, having an enrolled caregiver, and caregiver outcomes prior to death. One hundred and twenty-three patient-caregiver dyads and 84 patients without a caregiver coparticipant participated in the ENABLE early versus delayed (12 weeks later) RCT. We collected caregiver quality-of-life (QOL), depression, and burden (objective, stress, and demand) measures every 6 weeks for 24 weeks and every 3 months thereafter until the patient's death or study completion. We conducted survival analyses using log-rank and Cox proportional hazards models. Patients with a caregiver coparticipant had significantly shorter survival (Wald = 4.31, HR = 1.52, CI: 1.02-2.25, P = 0.04). After including caregiver status, marital status (married/unmarried), their interaction, and relevant covariates, caregiver status (Wald = 6.25, HR = 2.62, CI: 1.23-5.59, P = 0.01), being married (Wald = 8.79, HR = 2.92, CI: 1.44-5.91, P = 0.003), and their interaction (Wald = 5.18, HR = 0.35, CI: 0.14-0.87, P = 0.02) were significant predictors of lower patient survival. Lower survival in patients with a caregiver was significantly related to higher caregiver demand burden (Wald = 4.87, CI: 1.01-1.20, P = 0.03) but not caregiver QOL, depression, and objective and stress burden. Advanced cancer patients with caregivers enrolled in a clinical trial had lower survival than patients without caregivers; however, this mortality risk was mostly attributable to higher survival by unmarried patients without caregivers. Higher caregiver demand burden was also associated with decreased patient survival. © 2016 The Authors. Cancer Medicine published by

  4. Overall survival and disease-free survival in endometrial cancer: prognostic factors in 276 patients

    Directory of Open Access Journals (Sweden)

    Tejerizo-García A

    2013-09-01

    Full Text Available Álvaro Tejerizo-García,1 Jesús S Jiménez-López,1 José L Muñoz-González,1 Sara Bartolomé-Sotillos,1 Laura Marqueta-Marqués,1 Gregorio López-González,1 José F Pérez-Regadera Gómez21Service of Obstetrics and Gynecology, 2Radiation Oncology Service, Hospital Universitario 12 de Octubre, Madrid, SpainObjective: The aim of the study reported here was to assess the disease-free survival and overall survival of patients with endometrial cancer and to determine independent factors affecting the prognosis.Materials and methods: This was a retrospective study of a single-center clinical series of 276 patients (mean age 64 years with histologically confirmed cancer of the corpus uteri. The standard treatments were extrafascial total hysterectomy and bilateral salpingo-oophorectomy with selective pelvic/para-aortic node dissection, according to risk for recurrence. Actuarial overall survival and disease-free survival were estimated according to the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards analyses were used to assess the prognostic significance of the different variables.Results: The estimated median follow-up, determined using the inverse Kaplan–Meier method, was 45 months (95% confidence interval [CI] 41.2–48.8 for disease-free survival and 46 months (95% CI 43.0–49.0 for overall survival. The statistically significant variables affecting disease-free survival and overall survival were age, serous-papillary and clear-cell histological types, outer-half myometrial invasion, advanced International Federation of Gynecology and Obstetrics (FIGO stage, tumor grades G2 and G3, incomplete surgical resection, positive lymph nodes, lymphovascular space invasion, tumor remnants of >1 cm after surgery, and high-risk group. In the multivariate Cox regression model, predictors of tumor recurrence included advanced FIGO stage (hazard ratio [HR] 4.90, 95% CI 2.57–9.36, P < 0.001 and tumor grades G2 (HR 4.79, 95

  5. In vivo evaluation of 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]FIAU) and 2'-deoxy-2'-[{sup 18}F]fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]FEAU) as markers for suicide gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Alauddin, Mian M. [University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. T8.3895, P.O. Box 059, Houston, TX (United States); Shahinian, Antranic; Park, Ryan; Fissekis, John D.; Conti, Peter S. [University of Southern California, PET Imaging Science Center, Keck School of Medicine, Los Angeles, CA (United States); Tohme, Michel [University of Southern California, PET Imaging Science Center, Keck School of Medicine, Los Angeles, CA (United States); Department of Biomedical Engineering, UC Davis, Davis, CA (United States)

    2007-06-15

    FIAU and FEAU were evaluated in vitro and in vivo as markers for HSV1-tk gene expression. In vitro and biodistribution studies were performed in wild type and transduced HT-29 cells using [{sup 14}C]FIAU and [{sup 3}H]FEAU. PET imaging was performed using [{sup 18}F]FIAU and [{sup 18}F]FEAU. In vitro uptake of [{sup 14}C]FIAU in tk-positive cells was 39-fold, 49-fold, and 43-fold higher (p < 0.001) than in wild type cells at 30, 60, and 120 min, respectively. Uptake of [{sup 3}H]FEAU in transduced cells was 46-fold, 62-fold, and 121-fold higher (p < 0.001) than in wild type cells at the same time points. In vivo uptake of [{sup 14}C]FIAU at 2 h in HSV1-tk positive tumors was 15.48 {+-} 3.94, 6.7-fold higher (p < 0.001) than in wild type tumors. Uptake of [{sup 3}H]FEAU in transduced tumors was 9.98 {+-} 1.99, 5.0-fold higher (p < 0.001) than in wild type tumors. Micro-PET images using [{sup 18}F]FIAU and [{sup 18}F]FEAU also showed very high uptake in HSV-tk tumors. [{sup 18}F]FIAU and [{sup 18}F]FEAU appear to be potential PET imaging agents for gene expression. (orig.)

  6. Low ERCC1 mRNA and protein expression are associated with worse survival in cervical cancer patients treated with radiation alone

    International Nuclear Information System (INIS)

    Doll, Corinne M.; Prystajecky, Michael; Eliasziw, Misha; Klimowicz, Alexander C.; Petrillo, Stephanie K.; Craighead, Peter S.; Hao, Desiree; Diaz, Roman; Lees-Miller, Susan P.; Magliocco, Anthony M.

    2010-01-01

    Purpose: To evaluate the association of excision repair cross-complementation group 1 (ERCC1) expression, using both mRNA and protein expression analysis, with clinical outcome in cervical cancer patients treated with radical radiation therapy (RT). Experimental design: Patients (n = 186) with locally advanced cervical cancer, treated with radical RT alone from a single institution were evaluated. Pre-treatment FFPE biopsy specimens were retrieved from 112 patients. ERCC1 mRNA level was determined by real-time PCR, and ERCC1 protein expression (FL297, 8F1) was measured using quantitative immunohistochemistry (AQUA (registered) ). The association of ERCC1 status with local response, 10-year disease-free (DFS) and overall survival (OS) was analyzed. Results: ERCC1 protein expression levels using both FL297 and 8F1 antibodies were determined for 112 patients; mRNA analysis was additionally performed in 32 patients. Clinical and outcome factors were comparable between the training and validation sets. Low ERCC1 mRNA expression status was associated with worse OS (17.9% vs 50.1%, p = 0.046). ERCC1 protein expression using the FL297 antibody, but not the 8F1 antibody, was significantly associated with both OS (p = 0.002) and DFS (p = 0.010). After adjusting for pre-treatment hemoglobin in a multivariate analysis, ERCC1 FL297 expression status remained statistically significant for OS [HR 1.9 (1.1-3.3), p = 0.031]. Conclusions: Pre-treatment tumoral ERCC1 mRNA and protein expression, using the FL297 antibody, are predictive factors for survival in cervical cancer patients treated with RT, with ERCC1 FL297 expression independently associated with survival. These results identify a subset of patients who may derive the greatest benefit from the addition of cisplatin chemotherapy.

  7. MABGEL 1: first phase 1 trial of the anti-HIV-1 monoclonal antibodies 2F5, 4E10 and 2G12 as a vaginal microbicide.

    Directory of Open Access Journals (Sweden)

    Georgina C Morris

    Full Text Available BACKGROUND: Monoclonal antibodies (mAbs which potently neutralize a broad range of HIV isolates are potential microbicide candidates. To date, topical application of mAbs in humans and their stability in vaginal secretions has not been studied. OBJECTIVES: To assess the pharmacokinetics and safety of the mAbs 2F5, 4E10 and 2G12 when applied vaginally in women. DESIGN: A randomized, double-blind, placebo-controlled phase 1 trial. METHODS: Twenty-eight healthy, sexually abstinent women administered 2.5 g of gel daily for 12 days containing either 10 or 20 mg/g of each mAb (MABGEL or placebo. Main clinical evaluations and sampling occurred at baseline, 1, 8, and 24 hours post-1st dose and 12 and 36 hours post-12th dose. RESULTS: After adjustment for dilution factors, median levels of 2F5, 4E10 and 2G12 in vaginal secretions at 1 hour post high-dose MABGEL were 7.74, 5.28 and 7.48 mg/ml respectively. Levels of 2F5 and 4E10 declined exponentially thereafter with similar estimated half-lives (4.6 and 4.3 hours. In contrast, 2G12 levels declined more rapidly in the first 8 hours, with an estimated half-life of 1.4 hours during this period. There was no evidence of systemic absorption. There were no significant differences in local or systemic adverse event rates or vaginal flora changes (by qPCR between active and placebo gel arms. Whilst at least 1 adverse event was recorded in 96% of participants, 95% were mild and none were serious. CONCLUSIONS: Vaginal application of 50 mg of each mAb daily was safe over a 12 day period. Median mAb concentrations detected at 8 hours post dose were potentially sufficient to block HIV transmission.2G12 exhibited more rapid elimination from the human vagina than 4E10 and 2F5, likely due to poor stability of 2G12 in acidic human vaginal secretions. Further research is needed to develop mAb-based vaginal microbicides and delivery systems. TRIAL REGISTRATION: ISRCTN 64808733 UK CRN Portfolio 6470.

  8. Isotope Shifts and Hyperfine Structure in the[Xe]4f(7)5d 6s(2) D-2(J)->[Xe]4f(7)5d 6s 6p F-9(J+1) Transitions of Gadolinium

    International Nuclear Information System (INIS)

    Blaum, K.; Bushaw, Bruce A.; Diel, S; Geppert, Ch; Kuschnick, A; Muller, P.; Nortershauser, W.; Schmitt, A.; Wendt, K.

    1999-01-01

    High-resolution resonance ionization mass spectrometry has been used to measure isotope shifts and hyperfine structure in all[Xe] 4f 7 5d 6s2 9DJ ---[Xe] 4f 7 5d 6s 6p 9FJ+1 (J= 2-6) and the[Xe] 4f 7 5d 6s2 9D6---[Xe] 4f 7 5d 6s 6p 9D5 transitions of gadolinium (Gd I). Gadolinium atoms in an atomic beam were excited with a tunable single-frequency laser in the wavelength range of 422 - 429 nm. Resonant excitation was followed by photoionization with the 363.8 nm line of an argon ion laser and resulting ions were mass separated and detected with a quadrupole mass spectrometer. Isotope shifts for all stable gadolinium isotopes in these transitions have been measured for the first time. Additionally, the hyperfine structure constants of the upper states have been derived for the isotopes 155, 157Gd and are compared with previous work. Using prior experimental values for the mean nuclear charge radii, derived from the combination of muonic atoms and electron scattering data, field shift a nd specific mass shift coefficients for the investigated transitions have been determined and nuclear charge parameters l for the minor isotopes 152, 154Gd have been calculated

  9. catena-Poly[[bis(μ3-5-hydroxyisophthalatobis(pyrazino[2,3-f][1,10]phenanthrolinedicadmium] dihydrate

    Directory of Open Access Journals (Sweden)

    Peng-Cheng Zhao

    2012-04-01

    Full Text Available The title coordination polymer, {[Cd2(C8H4O52(C14H8N42]·2H2O}n, has a layered structure. The asymmetric unit contains two CdII ions, two pyrazino[2,3-f][1,10]phenanthroline, two 5-hydroxyisophthalate (hip ligands and two lattice water molecules. Each CdII ion is coordinated by two N atoms from a chelating pyrazino[2,3-f][1,10]phenanthroline and four O atoms from three different hip ligands, resulting in a distorted CdN2O4 octahedral coordination environment. The hip ligand connects adjacent CdII ions, forming forming layers parallel to (010. Intralayer O—H...O hydrogen bonds involving the hydroxy groups and solvent water molecules consolidate the crystal packing.

  10. Clinical Predictors of Survival for Patients with Stage IV Cancer Referred to Radiation Oncology.

    Directory of Open Access Journals (Sweden)

    Johnny Kao

    Full Text Available There is an urgent need for a robust, clinically useful predictive model for survival in a heterogeneous group of patients with metastatic cancer referred to radiation oncology.From May 2012 to August 2013, 143 consecutive patients with stage IV cancer were prospectively evaluated by a single radiation oncologist. We retrospectively analyzed the effect of 29 patient, laboratory and tumor-related prognostic factors on overall survival using univariate analysis. Variables that were statistically significant on univariate analysis were entered into a multivariable Cox regression to identify independent predictors of overall survival.The median overall survival was 5.5 months. Four prognostic factors significantly predicted survival on multivariable analysis including ECOG performance status (0-1 vs. 2 vs. 3-4, number of active tumors (1 to 5 vs. ≥ 6, albumin levels (≥ 3.4 vs. 2.4 to 3.3 vs. 31.4 months for very low risk patients compared to 14.5 months for low risk, 4.1 months for intermediate risk and 1.2 months for high risk (p < 0.001.These data suggest that a model that considers performance status, extent of disease, primary tumor site and serum albumin represents a simple model to accurately predict survival for patients with stage IV cancer who are potential candidates for radiation therapy.

  11. Comparative effectiveness and survival of infliximab, adalimumab, and etanercept for rheumatoid arthritis patients in the Hellenic Registry of Biologics: Low rates of remission and 5-year drug survival.

    Science.gov (United States)

    Flouri, Irini; Markatseli, Theodora E; Voulgari, Paraskevi V; Boki, Kyriaki A; Papadopoulos, Ioannis; Settas, Loukas; Zisopoulos, Dimitrios; Skopouli, Fotini N; Iliopoulos, Alexios; Bertsias, George K; Geborek, Pierre; Drosos, Alexandros A; Boumpas, Dimitrios T; Sidiropoulos, Prodromos

    2014-02-01

    To compare effectiveness, drug survival, and safety between infliximab, adalimumab, and etanercept, in a nationwide cohort of rheumatoid arthritis (RA) patients. This study is a prospective cohort study of 1208 active RA patients. Effectiveness, drug survival, and serious adverse events during entire follow-up (median 2.9 years) were monitored. EULAR and CDAI responses were comparable between the three agents (EULAR good/moderate responses at 12 months ranged 76-79%). At 12 months, 15-23% achieved remission. For adalimumab and etanercept, adjusted hazard rate (HR) for EULAR/ACR remission (reference: infliximab) was 2.7 and 2.1 (95% confidence interval was 1.7-4.1 and 1.3-3.4, respectively); males (HR 1.6; 1.1-2.4), use of glucocorticoids (HR 2.0; 1.3-3.0), and swollen joint count >7 (HR 0.36; 0.24-0.55) were independent predictors. Five-year drug survival was 31%, 43%, and 49% for infliximab, adalimumab, and etanercept, respectively (p = 0.010). Infliximab was associated with significantly more withdrawals due to adverse events. Disease activity, CRP, and use of glucocorticoids predicted efficacy-related drug survival; age, use of methotrexate, and prior DMARDs failures predicted safety-related survival. Risk for serious infections was lower with adalimumab (odds ratio [OR] 0.62; 0.38-1.00) or etanercept (OR 0.39; 0.21-0.72) than infliximab, independent of the effects of age (OR 1.65; 1.37-2.00 per 10 years), tender joint count >10 (OR 1.86; 1.21-2.86), and glucocorticoids >35mg/week (OR 1.83; 1.12-2.99). Response rates were comparable among anti-TNF agents. Overall, 5-year drug survival was below 50%, with infliximab demonstrating increased safety-related discontinuations. Remission rates are low in clinical practice. Strategies to increase effectiveness and long-term survival of anti-TNF agents in RA are needed. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Radionuclide fistulogram (RnF) in hemodialysis patients

    Energy Technology Data Exchange (ETDEWEB)

    Seo, I.S.; Sy, W.M.; Heneghan, W.; Manoli, A.; Gozum, M.

    1984-01-01

    Prosthetic graft A-V fistulae (AVf) (10 adults) and internal AVf (14 adults) as avenues of hemodialysis were created surgically in the limbs of 24 renal failure patients. AVf can malfunction or become obstructed and to date only contrast fistulography (CnF) is used to document such problems. Thirty-three RnF's were performed in 24 patients and CnF's in seven patients. Eleven had clinical features of AVf malfunction and 13 were asymptomatic. 99mTc compounds, TcO/sup -//sub 4/ or MDP (20 mCi) were injected into the AVf through a 19-gauge butterfly. 2 sec. dynamic images (qualitative data) and simultaneous computer acquisition in 64 x 64 byte mode with 0.5 sec/frame for 120 frames (quantitative data) were obtained. Normal qualitative and quantitative criteria were established. 10/11 symptomatic and 2/13 asymptomatic patients showed abnormal scintigraphic features and time activity curves indicating AVf malfunction. All 12 patients demonstrated abnormal collateral formation; 8/12 had stenosis, 3/12 showed equivocal stenosis and in 1/12 no stenosis was shown. In these 12 patients the S/sub 2/ (second circulation)/S/sub 1/ (initial circulation) ratio was below 10%. In 5/12 whose S/sub 2//S/sub 1/ ratio was less than 1%, the CnF and surgical repair confirmed the presence of stenosis. RnF appears to be a simple, benign, and accurate imaging procedure in the evaluation of AVf malfunction.

  13. Luminescent properties of Sr{sub 2.5-3x/2}Ba{sub 0.5}Sm{sub x}AlO{sub 4}F oxyfluorides

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sangmoon, E-mail: spark@silla.ac.kr [Department of Engineering in Energy and Applied Chemistry, Silla University, Busan 617-736 (Korea, Republic of)

    2012-04-15

    Effective orange Sm{sup 3+}-doped Sr{sub 2.5}Ba{sub 0.5}AlO{sub 4}F phosphors excited at 254 and 408 nm excitation were prepared by the solid-state method. The excitation and emission spectra of Sr{sub 2.5-3x/2}Ba{sub 0.5}Sm{sub x}AlO{sub 4}F and Sr{sub 2.5-3x/2}Ba{sub 0.5}Sm{sub x}AlO{sub 4-{alpha}}F{sub 1-{delta}} (x=0.001{approx}0.1) based on photoluminescence spectroscopy are investigated. The defects in anion-deficient Sr{sub 2.5-3x/2}Ba{sub 0.5}Sm{sub x}AlO{sub 4-{alpha}}F{sub 1-{delta}} (x=0.001, 0.01) are monitored by broad-band photoluminescence emission centered near 480 nm along with the orange emission transitions of Sm{sup 3+}. CIE values and relative luminescent intensities of Sr{sub 2.5-3x/2}Ba{sub 0.5}Sm{sub x}AlO{sub 4}F and Sr{sub 2.5-3x/2}Ba{sub 0.5}Sm{sub x}AlO{sub 4-{alpha}}F{sub 1-{delta}} by changing the Sm{sup 3+} content (x=0.001{approx}0.1) are discussed. - Highlights: Black-Right-Pointing-Pointer Under the excitation of 408 nm competent orange emitting Sr{sub 2.5-3x/2}Ba{sub 0.5}Sm{sub x}AlO{sub 4}F phosphor is initiated. Black-Right-Pointing-Pointer Sm{sup 3+}-activated oxyfluoride phosphor is quite effective to prepare white-emitting light for near-UV LED applications. Black-Right-Pointing-Pointer Defects could be visibly created in the Sr{sub 2.5-3x/2}Ba{sub 0.5}Sm{sub x}Al O{sub 4}F host lattices when Sm{sup 3+} ions are doped less than 5 mol %. Black-Right-Pointing-Pointer The gradual substitution of Sm{sup 3+} contents in oxyfluoride hosts is amenable to change CIE values and desired emitting intensity.

  14. 18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start

    Energy Technology Data Exchange (ETDEWEB)

    Seith, Ferdinand; Schmidt, Holger; Pfannenberg, Christina; Gueckel, Brigitte; Schwenzer, Nina [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); Forschner, Andrea; Garbe, Claus [Eberhard Karls University, Department of Dermatology, Tuebingen (Germany); Nikolaou, Konstantin [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); German Cancer Consortium (DKTK), Heidelberg (Germany); La Fougere, Christian [German Cancer Consortium (DKTK), Heidelberg (Germany); Eberhard Karls University, Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Tuebingen (Germany)

    2018-01-15

    The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation. Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t{sub 0}, base-line), two weeks (t{sub 1}, study examination) and three months after treatment initiation (t{sub 2}, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients. Three patients with partial metabolic response in PET at t{sub 1} turned out to have complete response at t{sub 2}. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t{sub 2}, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t{sub 1}. OS in patients with PMD at t{sub 2} varied between 148 and 814 days. SMD at both t{sub 1} and t{sub 2} was seen in one patient, tumor progress was observed after 308 days. Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future. (orig.)

  15. MiR-205-5p and miR-342-3p cooperate in the repression of the E2F1 transcription factor in the context of anticancer chemotherapy resistance

    Science.gov (United States)

    Lai, Xin; Gupta, Shailendra K; Schmitz, Ulf; Marquardt, Stephan; Knoll, Susanne; Spitschak, Alf; Wolkenhauer, Olaf; Pützer, Brigitte M; Vera, Julio

    2018-01-01

    High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance. Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the expression of E2F1 could be a promising approach for treating patients showing chemoresistance. Methods: We integrated bioinformatics, structural and kinetic modelling, and experiments to study cooperative regulation of E2F1 by microRNA (miRNA) pairs in the context of anticancer chemotherapy resistance. Results: We showed that an enhanced E2F1 repression efficiency can be achieved in chemoresistant tumour cells through two cooperating miRNAs. Sequence and structural information were used to identify potential miRNA pairs that can form tertiary structures with E2F1 mRNA. We then employed molecular dynamics simulations to show that among the identified triplexes, miR-205-5p and miR-342-3p can form the most stable triplex with E2F1 mRNA. A mathematical model simulating the E2F1 regulation by the cooperative miRNAs predicted enhanced E2F1 repression, a feature that was verified by in vitro experiments. Finally, we integrated this cooperative miRNA regulation into a more comprehensive network to account for E2F1-related chemoresistance in tumour cells. The network model simulations and experimental data indicate the ability of enhanced expression of both miR-205-5p and miR-342-3p to decrease tumour chemoresistance by cooperatively repressing E2F1. Conclusions: Our results suggest that pairs of cooperating miRNAs could be used as potential RNA therapeutics to reduce E2F1-related chemoresistance. PMID:29464002

  16. Synthesis of fused 1,2,4-dithiazines and 1,2,3,5-trithiazepines.

    Science.gov (United States)

    Koyioni, Maria; Manoli, Maria; Koutentis, Panayiotis A

    2014-10-17

    Reacting (Z)-N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)-1H-pyrazol-5-amines 5 with Et2NH and then with concd H2SO4 gives 5H-pyrazolo[3,4-e][1,2,4]dithiazine-3-carbonitriles 7 in good yields (74-85%) and 6H-pyrazolo[3,4-f][1,2,3,5]trithiazepine-4-carbonitriles 9 as minor products (0-6%). Furthermore, the 1,3-dimethylpyrazole analogue 5a was transformed into the dithiazine 7a in two discrete steps, allowing the isolation of a disulfide intermediate (Z)-2-[(diethylamino)disulfan-yl]-2-[(1H-pyrazol-5-yl)imino]acetonitrile (8a). The one-pot, two-step reaction also worked with electron-rich hydroxy- and methoxy-substituted anilines. Thermolysis of the pyrazolo[3,4-e][1,2,4]dithiazines 7 gave the ring-contracted 1H-pyrazolo[3,4-d]thiazole-5-carbonitriles 6 (94-100%). With active sulfur, 1,3-dimethyl-5H-pyrazolo[3,4-e][1,2,4]dithiazine-3-carbonitrile (7a) gave 1,3-dimethyl-6H-pyrazolo[3,4-f][1,2,3,5]trithiazepine-4-carbonitrile (9a), but on prolonged reaction times, it gave 5,7-dimethyl-5H-[1,2,3]dithiazolo[4,5-b]pyrazolo[3,4-e][1,4]thiazine (13). Finally, in the absence of acid, heating a solution of (Z)-2-[(diethylamino)disulfanyl]-2-[(1,3-dimethyl-1H-pyrazol-5-yl)imino]acetonitrile (8a) gave 4,6,10,12-tetramethyl-6H-pyrazolo[3,4-f]pyrazolo[3',4':4,5]pyrimido[6,1-d][1,2,3,5]trithiazepine-8,12b(10H)-dicarbonitrile (19) (67%).

  17. Clinical outcomes and survival in AA amyloidosis patients

    Directory of Open Access Journals (Sweden)

    Yavuz Ayar

    Full Text Available Abstract Aim Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. Methods: A total of 81 patients (51 males, 30 females with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. Results: Most of the patients (55.6% had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2% and rheumatoid arthritis (10.6% in the good outcome group and malignancy (20% in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively. Median duration of renal survival was 65 ± 3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p = 0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p = 0.006 and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p = 0.027 were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3 ± 16 months. Conclusion Our study indicated that familial Mediterranean fever constituted

  18. Ex vivo effect of varespladib on secretory phospholipase A2 alveolar activity in infants with ARDS.

    Directory of Open Access Journals (Sweden)

    Daniele De Luca

    Full Text Available Secretory phospholipase A2 (sPLA2 plays a pivotal role in acute respiratory distress syndrome (ARDS. This enzyme seems an interesting target to reduce surfactant catabolism and lung tissue inflammation. Varespladib is a specifically designed indolic sPLA2 inhibitor, which has shown promising results in animals and adults. No specific data in pediatric ARDS patients are yet available.We studied varespladib in broncho-alveolar lavage (BAL fluids obtained ex vivo from pediatric ARDS patients. Clinical data and worst gas exchange values during the ARDS course were recorded. Samples were treated with saline or 10-40-100 µM varespladib and incubated at 37°C. Total sPLA2 activity was measured by non-radioactive method. BAL samples were subjected to western blotting to identify the main sPLA isotypes with different sensitivity to varespladib. Results was corrected for lavage dilution using the serum-to-BAL urea ratio and for varespladib absorbance.Varespladib reduces sPLA2 activity (p<0.0001 at 10,40 and 100 µM; both sPLA2 activity reduction and its ratio to total proteins significantly raise with increasing varespladib concentrations (p<0.001. IC(50 was 80 µM. Western blotting revealed the presence of sPLA2-IIA and -IB isotypes in BAL samples. Significant correlations exist between the sPLA2 activity reduction/proteins ratio and PaO(2 (rho = 0.63;p<0.001, PaO(2/FiO(2 (rho = 0.7; p<0.001, oxygenation (rho = -0.6; p<0.001 and ventilation (rho = -0.4;p = 0.038 indexes.Varespladib significantly inhibits sPLA2 in BAL of infants affected by post-neonatal ARDS. Inhibition seems to be inversely related to the severity of gas exchange impairment.

  19. Conditional survival is greater than overall survival at diagnosis in patients with osteosarcoma and Ewing's sarcoma.

    Science.gov (United States)

    Miller, Benjamin J; Lynch, Charles F; Buckwalter, Joseph A

    2013-11-01

    Conditional survival is a measure of the risk of mortality given that a patient has survived a defined period of time. These estimates are clinically helpful, but have not been reported previously for osteosarcoma or Ewing's sarcoma. We determined the conditional survival of patients with osteosarcoma and Ewing's sarcoma given survival of 1 or more years. We used the Surveillance, Epidemiology, and End Results (SEER) Program database to investigate cases of osteosarcoma and Ewing's sarcoma in patients younger than 40 years from 1973 to 2009. The SEER Program is managed by the National Cancer Institute and provides survival data gathered from population-based cancer registries. We used an actuarial life table analysis to determine any cancer cause-specific 5-year survival estimates conditional on 1 to 5 years of survival after diagnosis. We performed a similar analysis to determine 20-year survival from the time of diagnosis. The estimated 5-year survival improved each year after diagnosis. For local/regional osteosarcoma, the 5-year survival improved from 74.8% at baseline to 91.4% at 5 years-meaning that if a patient with localized osteosarcoma lives for 5 years, the chance of living for another 5 years is 91.4%. Similarly, the 5-year survivals for local/regional Ewing's sarcoma improved from 72.9% at baseline to 92.5% at 5 years, for metastatic osteosarcoma 35.5% at baseline to 85.4% at 5 years, and for metastatic Ewing's sarcoma 31.7% at baseline to 83.6% at 5 years. The likelihood of 20-year cause-specific survival from the time of diagnosis in osteosarcoma and Ewing's sarcoma was almost 90% or greater after 10 years of survival, suggesting that while most patients will remain disease-free indefinitely, some experience cancer-related complications years after presumed eradication. The 5-year survival estimates of osteosarcoma and Ewing's sarcoma improve with each additional year of patient survival. Knowledge of a changing risk profile is useful in counseling

  20. Long-term graft and patient survival following renal transplantation in diabetic patients

    DEFF Research Database (Denmark)

    Rømming Sørensen, Vibeke; Schwartz Sørensen, Søren; Feldt-Rasmussen, Bo

    2006-01-01

    . The groups were similar with respect to age and sex. RESULTS: The patient survival rates (diabetic versus non-diabetic patients) were 88% vs 91% (p=NS) at 1 year, 68% vs 73% (p=NS) at 5 years and 31% vs 52% (pnon-diabetic patients) were 72% vs 72...... patients, 55% were smokers. Among the diabetic patients, graft and patient survival were independent of smoking habits, blood pressure, HbA1c and total cholesterol. CONCLUSIONS: Graft survival was similar in diabetic and non-diabetic patients. For the first 5 years following renal transplantation......OBJECTIVE: To study long-term graft and patient survival following renal transplantation in diabetic and non-diabetic patients. MATERIAL AND METHODS: Over the time period 1985-99, 498 transplantations in 399 non-diabetic patients and 68 transplantations in 62 diabetic patients were performed...

  1. Impact of JAK2V617F Mutation Burden on Disease Phenotype in Chinese Patients with JAK2V617F-positive Polycythemia Vera (PV) and Essential thrombocythemia (ET).

    Science.gov (United States)

    Zhao, Shixiang; Zhang, Xiang; Xu, Yang; Feng, Yufeng; Sheng, Wenhong; Cen, Jiannong; Wu, Depei; Han, Yue

    2016-01-01

    Most patients with polycythemia vera (PV) and half of essential thrombocythemia (ET) possess an activating JAK2V617F mutation. The objective of this study was to better define the effect of JAK2V617F mutant allele burden on clinical phenotypes in Chinese patients, especially thrombosis. By real-time polymerase chain reaction (RT-PCR), the JAK2V617F mutation burden was detected in 170 JAK2V617F-positive patients, including 54 PV and 116 ET. The results showed that JAK2V617F allele burden was higher in PV than in ET (PET (68.5% VS 26.7%) (PET patients showed increased JAK2V617F allele burden in the group with higher hemoglobin (HGB above 150 g/L) (PET. In PV patients, JAK2V617F mutation burden had influence on WBC counts. And the clinical characteristics of ET patients, such as WBC counts, hemoglobin level, splenomegaly and thrombosis, were influenced by JAK2V617F mutation burden. Male, high hemoglobin (HGB above 150 g/L), and increased JAK2V617F mutation burden (JAK2V617F allele burden ≥ 16.5%) were risks of thrombosis (PET patients by Logistic Regression.

  2. Super-No-Scale F-SU(5): A dynamic determination of M{sub 1/2} and tan{beta}

    Energy Technology Data Exchange (ETDEWEB)

    Li Tianjun, E-mail: junlt@physics.tamu.edu [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, TX 77843 (United States); Key Laboratory of Frontiers in Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190 (China); Maxin, James A., E-mail: jmaxin@physics.tamu.edu [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, TX 77843 (United States); Nanopoulos, Dimitri V., E-mail: dimitri@physics.tamu.edu [George P. and Cynthia W. Mitchell Institute for Fundamental Physics, Texas A and M University, College Station, TX 77843 (United States); Astroparticle Physics Group, Houston Advanced Research Center (HARC), Mitchell Campus, Woodlands, TX 77381 (United States); Academy of Athens, Division of Natural Sciences, 28 Panepistimiou Avenue, Athens 10679 (Greece); Walker, Joel W., E-mail: jwalker@shsu.edu [Department of Physics, Sam Houston State University, Huntsville, TX 77341 (United States)

    2011-09-20

    We study the Higgs potential in No-Scale F-SU(5), a model built on the tripodal foundations of the F-lipped SU(5)xU(1){sub X} Grand Unified Theory, extra F-theory derived TeV scale vector-like particle multiplets, and the high scale boundary conditions of no-scale supergravity. V{sub min}, the minimum of the potential following radiative electroweak symmetry breaking, is a function at fixed Z-boson mass of the universal gaugino boundary mass M{sub 1/2} and tan{beta}, the ratio of Higgs vacuum expectation values. The so-scale nullification of the bilinear Higgs soft term B{sub {mu}} at the boundary reduces V{sub min}(M{sub 1/2}) to a one-dimensional dependency, which may be secondarily minimized. This 'Super-No-Scale' condition dynamically fixes tan{beta} and M{sub 1/2} at the local minimum minimorum of V{sub min}. Fantastically, the walls of this theoretically established secondary potential coalesce in descent to a striking concurrency with the previously phenomenologically favored 'Golden Point' and 'Golden Strip'.

  3. Key role of group v secreted phospholipase A2 in Th2 cytokine and dendritic cell-driven airway hyperresponsiveness and remodeling.

    Directory of Open Access Journals (Sweden)

    William R Henderson

    Full Text Available Previous work has shown that disruption of the gene for group X secreted phospholipase A2 (sPLA2-X markedly diminishes airway hyperresponsiveness and remodeling in a mouse asthma model. With the large number of additional sPLA2s in the mammalian genome, the involvement of other sPLA2s in the asthma model is possible - in particular, the group V sPLA2 (sPLA2-V that like sPLA2-X is highly active at hydrolyzing membranes of mammalian cells.The allergen-driven asthma phenotype was significantly reduced in sPLA2-V-deficient mice but to a lesser extent than observed previously in sPLA2-X-deficient mice. The most striking difference observed between the sPLA2-V and sPLA2-X knockouts was the significant impairment of the primary immune response to the allergen ovalbumin (OVA in the sPLA2-V(-/- mice. The impairment in eicosanoid generation and dendritic cell activation in sPLA2-V(-/- mice diminishes Th2 cytokine responses in the airways.This paper illustrates the diverse roles of sPLA2s in the immunopathogenesis of the asthma phenotype and directs attention to developing specific inhibitors of sPLA2-V as a potential new therapy to treat asthma and other allergic disorders.

  4. Neodymium-doped Sr5(PO4)3F and Sr5(VO4)3F

    International Nuclear Information System (INIS)

    Corker, D.L.; Nicholls, J.; Loutts, G.B.

    1995-01-01

    Neodymium-doped Sr 5 (PO 4 ) 3 F [neodymium strontium fluoride phosphate, (Nd,Sr) 5 (PO 4 ) 3 F] and neodymium-doped Sr 5 (VO 4 ) 3 F [neodymium strontium fluoride vanadate, (Nd,Sr) 5 (VO 4 ) 3 F] crystallize in space group P6 3 /m and are isostructural with calcium fluorophosphate, Ca 5 (PO 4 ) 3 F. There are two different Sr sites in Sr 5 (XO 4 ) 3 F, denoted Sr(1) and Sr(2). Using single-crystal X-ray diffraction the two structures were refined to R factors of 2.3 and 2.2%, respectively, showing that Nd is present at both Sr sites in (Sr,Nd) 5 (VO 4 ) 3 F but only at the Sr(2) site in (Sr,Nd) 5 (PO 4 ) 3 F. (orig.)

  5. Die Interhalogenkationen [Br2F5]+ und [Br3F8].

    Science.gov (United States)

    Ivlev, Sergei; Karttunen, Antti; Buchner, Magnus; Conrad, Matthias; Kraus, Florian

    2018-05-02

    Wir berichten über die Synthese und Charakterisierung der bislang einzigen Polyhalogenkationen, in denen verbrückende Fluoratome vorliegen. Das [Br2F5]+-Kation enthält eine symmetrische [F2Br-µ-F-BrF2]-Brücke, das [Br3F8]+-Kation enthält unsymmetrische µ-F-Brücken. Die Fluoronium-Ionen wurden in Form ihrer [SbF6]--Salze erhalten und Raman-, und 19F-NMR-spektroskopisch, sowie durch Röntgenbeugung am Einkristall untersucht. Quantenchemische Rechnungen, sowohl für die isolierten Kationen in der Gasphase, als auch für die Festkörper selbst, wurden durchgeführt. Populationsanalysen zeigen, dass die µ-F-Atome die am stärksten negativ partialgeladenen Atome der Kationen sind. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Antiferromagnetic CsCrF{sub 5} and canted antiferromagnetism in RbCrF{sub 5} and KCrF{sub 5}

    Energy Technology Data Exchange (ETDEWEB)

    Jagličić, Zvonko, E-mail: zvonko.jaglicic@imfm.si [University of Ljubljana, Faculty of Civil and Geodetic Engineering, and Institute of Mathematics, Physics and Mechanics, Jadranska 19, 1000 Ljubljana (Slovenia); Mazej, Zoran, E-mail: zoran.mazej@ijs.si [Department of Inorganic Chemistry and Technology, Jožef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia)

    2017-07-15

    Highlights: • Cr(IV) ions are antiferromagnetically coupled within chains in ACrF{sub 5} (A = Cs, Rb, K). • Small structural difference causes huge difference in magnetic properties below 10 K. • Canted antiferromagnetism has been observed in RbCrF{sub 5} and KCrF{sub 5} at low temperature. - Abstract: In ACrF{sub 5} (A = Cs, Rb, K), Cr(IV) ions are coordinated by six fluoride ligands where the resulting CrF{sub 6} octahedra share cis vertexes to form infinite chains of ([Cr{sup IV}F{sub 5}]{sup −}){sub n}. The geometry of the latter in Cs compound differs from that in K and Rb compounds. The results of investigations of the magnetic behaviour of these compounds have shown that an antiferromagnetic superexchange interaction is present within the chains with J{sub Cs} = −10.2 cm{sup −1}, J{sub Rb} = −13.3 cm{sup −1}, and J{sub K} = −13.1 cm{sup −1}. Additional ferromagnetic-like long-range ordering has been observed in KCrF{sub 5} and RbCrF{sub 5} below 6 K which can be explained, in a correlation with their crystal structures, as canted antiferromagnetism.

  7. Prognostic value of {sup 18}F-FDG PET/CT in patients with soft tissue sarcoma: comparisons between metabolic parameters

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Sun-pyo [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Lee, Seung Eun; Choi, Yoon-La [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of); Seo, Sung Wook; Sung, Ki-Sun [Sungkyunkwan University School of Medicine, Department of Orthopedic Surgery, Samsung Medical Center, Seoul (Korea, Republic of); Koo, Hong Hoe [Sungkyunkwan University School of Medicine, Department of Pediatrics, Samsung Medical Center, Seoul (Korea, Republic of); Choi, Joon Young [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of)

    2014-05-15

    To investigate the relationship between volume-based PET parameters and prognosis in patients with soft tissue sarcoma (STS). We retrospectively reviewed 55 patients with pathologically proven STS who underwent pretreatment with {sup 18} F-Fluorodeoxyglucose ({sup 18}F-FDG) PET/CT. The maximum standardized uptake value (SUV{sub max}), average SUV (SUV{sub avg}), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors were measured using a threshold SUV as liver activity for determining the boundary of tumors. Univariate and multivariate survival analyses for overall survival were performed according to the metabolic parameters and other clinical variables. Cancer-related death occurred in 19 of 55 patients (35 %) during the follow-up period (29 ± 23 months). On univariate analysis, AJCC stage (stage IV vs. I-III, hazard ratio (HR) = 2.837, p = 0.028), necrosis (G2 vs. G0-G1, HR = 3.890, p = 0.004), SUV{sub max} (1 unit - increase, HR = 1.146, p = 0.008), SUV{sub avg} (1 unit - increase, HR = 1.469, p = 0.032) and treatment modality (non-surgical therapy vs. surgery, HR = 4.467, p = 0.002) were significant predictors for overall survival. On multivariate analyses, SUV{sub max} (HR = 1.274, p = 0.015), treatment modality (HR = 3.353, p = 0.019) and necrosis (HR = 5.985, p = 0.006) were identified as significant independent prognostic factors associated with decreased overall survival. The SUV{sub max} of the primary tumor is a significant independent metabolic prognostic factor for overall survival in patients with STS. Volume-based PET parameters may not add prognostic information outside of the SUV{sub max}. (orig.)

  8. Association Between a Germline OCA2 Polymorphism at Chromosome 15q13.1 and Estrogen Receptor-Negative Breast Cancer Survival

    DEFF Research Database (Denmark)

    Azzato, E.M.; Tyrer, J.; Fasching, P.A.

    2010-01-01

    -sided. In the hypothesis-generating dataset, SNP rs4778137 (C > G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried.......92, P = 5 x 10(-4)). The rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer...

  9. Effects of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) metabolites on cricket (Acheta domesticus) survival and reproductive success

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Baohong [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States); Freitag, Christina M. [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States); Canas, Jaclyn E. [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States); Cheng Qiuqiong [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States); Anderson, Todd A. [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States)]. E-mail: todd.anderson@tiehh.ttu.edu

    2006-11-15

    The effect of two major hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) metabolites, hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX), on cricket (Acheta domesticus) survival and reproduction was studied. RDX metabolites did not have adverse effects on cricket survival, growth, and egg production. However, MNX and TNX did affect egg hatching. MNX and TNX were more toxic in spiked-sand than in topical tests. TNX was more toxic to egg than MNX. Developmental stage and exposure time affected hatching. After 30 days exposure to MNX or TNX, the EC{sub 2}, EC{sub 5}, and EC{sub 95} were 47, 128, and 247 {mu}g/g for TNX, and 65, 140, and 253 {mu}g/g for MNX in topical tests. The ECs for 20, 50, and 95 were 21, 52, and 99 {mu}g/g for MNX, and 12, 48, and 97 {mu}g/g for TNX in sand. No gross abnormalities in cricket nypmhs were observed in all experiments indicating that neither TNX or MNX is teratogenic in this assay. - RDX metabolites did not have adverse effects on cricket survival, growth, and egg production, but adversely affected egg hatching.

  10. Effects of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) metabolites on cricket (Acheta domesticus) survival and reproductive success

    International Nuclear Information System (INIS)

    Zhang Baohong; Freitag, Christina M.; Canas, Jaclyn E.; Cheng Qiuqiong; Anderson, Todd A.

    2006-01-01

    The effect of two major hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) metabolites, hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX), on cricket (Acheta domesticus) survival and reproduction was studied. RDX metabolites did not have adverse effects on cricket survival, growth, and egg production. However, MNX and TNX did affect egg hatching. MNX and TNX were more toxic in spiked-sand than in topical tests. TNX was more toxic to egg than MNX. Developmental stage and exposure time affected hatching. After 30 days exposure to MNX or TNX, the EC 2 , EC 5 , and EC 95 were 47, 128, and 247 μg/g for TNX, and 65, 140, and 253 μg/g for MNX in topical tests. The ECs for 20, 50, and 95 were 21, 52, and 99 μg/g for MNX, and 12, 48, and 97 μg/g for TNX in sand. No gross abnormalities in cricket nypmhs were observed in all experiments indicating that neither TNX or MNX is teratogenic in this assay. - RDX metabolites did not have adverse effects on cricket survival, growth, and egg production, but adversely affected egg hatching

  11. The Osmium(VIII) Oxofluoro Cations OsO(2)F(3)(+) and F(cis-OsO(2)F(3))(2)(+): Syntheses, Characterization by (19)F NMR Spectroscopy and Raman Spectroscopy, X-ray Crystal Structure of F(cis-OsO(2)F(3))(2)(+)Sb(2)F(11)(-), and Density Functional Theory Calculations of OsO(2)F(3)(+), ReO(2)F(3), and F(cis-OsO(2)F(3))(2)(+).

    Science.gov (United States)

    Casteel, William J.; Dixon, David A.; Mercier, Hélène P. A.; Schrobilgen, Gary J.

    1996-07-17

    Osmium dioxide tetrafluoride, cis-OsO(2)F(4), reacts with the strong fluoride ion acceptors AsF(5) and SbF(5) in anhydrous HF and SbF(5) solutions to form orange salts. Raman spectra are consistent with the formation of the fluorine-bridged diosmium cation F(cis-OsO(2)F(3))(2)(+), as the AsF(6)(-) and Sb(2)F(11)(-) salts, respectively. The (19)F NMR spectra of the salts in HF solution are exchange-averaged singlets occurring at higher frequency than those of the fluorine environments of cis-OsO(2)F(4). The F(cis-OsO(2)F(3))(2)(+)Sb(2)F(11)(-) salt crystallizes in the orthorhombic space group Imma. At -107 degrees C, a = 12.838(3) Å, b = 10.667(2) Å, c = 11.323(2) Å, V = 1550.7(8) Å(3), and Z = 4. Refinement converged with R = 0.0469 [R(w) = 0.0500]. The crystal structure consists of discrete fluorine-bridged F(cis-OsO(2)F(3))(2)(+) and Sb(2)F(11)(-) ions in which the fluorine bridge of the F(cis-OsO(2)F(3))(2)(+) cation is trans to an oxygen atom (Os-O 1.676 Å) of each OsO(2)F(3) group. The angle at the bridge is 155.2(8) degrees with a bridging Os---F(b) distance of 2.086(3) Å. Two terminal fluorine atoms (Os-F 1.821 Å) are cis to the two oxygen atoms (Os-O 1.750 Å), and two terminal fluorine atoms of the OsO(2)F(3) group are trans to one another (1.813 Å). The OsO(2)F(3)(+) cation was characterized by (19)F NMR and by Raman spectroscopy in neat SbF(5) solution but was not isolable in the solid state. The NMR and Raman spectroscopic findings are consistent with a trigonal bipyramidal cation in which the oxygen atoms and a fluorine atom occupy the equatorial plane and two fluorine atoms are in axial positions. Density functional theory calculations show that the crystallographic structure of F(cis-OsO(2)F(3))(2)(+) is the energy-minimized structure and the energy-minimized structures of the OsO(2)F(3)(+) cation and ReO(2)F(3) are trigonal bipyramidal having C(2)(v)() point symmetry. Attempts to prepare the OsOF(5)(+) cation by oxidative fluorination of cis

  12. E2F1 and E2F2 induction in response to DNA damage preserves genomic stability in neuronal cells.

    Science.gov (United States)

    Castillo, Daniela S; Campalans, Anna; Belluscio, Laura M; Carcagno, Abel L; Radicella, J Pablo; Cánepa, Eduardo T; Pregi, Nicolás

    2015-01-01

    E2F transcription factors regulate a wide range of biological processes, including the cellular response to DNA damage. In the present study, we examined whether E2F family members are transcriptionally induced following treatment with several genotoxic agents, and have a role on the cell DNA damage response. We show a novel mechanism, conserved among diverse species, in which E2F1 and E2F2, the latter specifically in neuronal cells, are transcriptionally induced after DNA damage. This upregulation leads to increased E2F1 and E2F2 protein levels as a consequence of de novo protein synthesis. Ectopic expression of these E2Fs in neuronal cells reduces the level of DNA damage following genotoxic treatment, while ablation of E2F1 and E2F2 leads to the accumulation of DNA lesions and increased apoptotic response. Cell viability and DNA repair capability in response to DNA damage induction are also reduced by the E2F1 and E2F2 deficiencies. Finally, E2F1 and E2F2 accumulate at sites of oxidative and UV-induced DNA damage, and interact with γH2AX DNA repair factor. As previously reported for E2F1, E2F2 promotes Rad51 foci formation, interacts with GCN5 acetyltransferase and induces histone acetylation following genotoxic insult. The results presented here unveil a new mechanism involving E2F1 and E2F2 in the maintenance of genomic stability in response to DNA damage in neuronal cells.

  13. Prehospital helicopter transport and survival of patients with traumatic brain injury.

    Science.gov (United States)

    Bekelis, Kimon; Missios, Symeon; Mackenzie, Todd A

    2015-03-01

    To investigate the association of helicopter transport with survival of patients with traumatic brain injury (TBI), in comparison with ground emergency medical services (EMS). Helicopter utilization and its effect on the outcomes of TBI remain controversial. We performed a retrospective cohort study involving patients with TBI who were registered in the National Trauma Data Bank between 2009 and 2011. Regression techniques with propensity score matching were used to investigate the association of helicopter transport with survival of patients with TBI, in comparison with ground EMS. During the study period, there were 209,529 patients with TBI who were registered in the National Trauma Data Bank and met the inclusion criteria. Of these patients, 35,334 were transported via helicopters and 174,195 via ground EMS. For patients transported to level I trauma centers, 2797 deaths (12%) were recorded after helicopter transport and 8161 (7.8%) after ground EMS. Multivariable logistic regression analysis demonstrated an association of helicopter transport with increased survival [OR (odds ratio), 1.95; 95% confidence interval (CI), 1.81-2.10; absolute risk reduction (ARR), 6.37%]. This persisted after propensity score matching (OR, 1.88; 95% CI, 1.74-2.03; ARR, 5.93%). For patients transported to level II trauma centers, 1282 deaths (10.6%) were recorded after helicopter transport and 5097 (7.3%) after ground EMS. Multivariable logistic regression analysis demonstrated an association of helicopter transport with increased survival (OR, 1.81; 95% CI, 1.64-2.00; ARR 5.17%). This again persisted after propensity score matching (OR, 1.73; 95% CI, 1.55-1.94; ARR, 4.69). Helicopter transport of patients with TBI to level I and II trauma centers was associated with improved survival, in comparison with ground EMS.

  14. Clinical outcomes for T1-2N0-1 oral tongue cancer patients underwent surgery with and without postoperative radiotherapy

    International Nuclear Information System (INIS)

    Shim, Su Jung; Cha, Jihye; Koom, Woong Sub; Kim, Gwi Eon; Lee, Chang Geol; Choi, Eun Chang; Keum, Ki Chang

    2010-01-01

    The aim of this study was to assess the results of curative surgery with and without radiotherapy in patients with T 1-2 N 0-1 oral tongue squamous cell carcinoma (OSCC) and to evaluate survival and prognostic factors. Retrospective analysis of 86 patients with T 1-2 N 0-1 OSCC who received surgery between January 2000 and December 2006. Fourteen patients (16.3%) received postoperative radiotherapy (PORT). Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were analyzed. The median follow-up was 45 months. The five-year overall survival (OS) and disease-free survival (DFS) rates were 80.8% and 80.2%, respectively. Higher tumor grade and invasion depth ≥ 0.5 cm were the significant prognostic factors affecting five-year OS and DFS (OS rate; 65% vs. 91%, p = 0.001 for grade; 66% vs. 92%, p = 0.01 for invasion depth: DFS rate; 69% vs. 88%, p = 0.005 for grade; 66% vs. 92%, p = 0.013 for invasion depth). In the risk group, there was no local failure in patients with postoperative radiotherapy. In T 1-2 N 0-1 OSCC, factors that affected prognosis after primary surgery were higher tumor grade and deep invasion depth over 0.5 cm. Postoperative radiotherapy should be considered in early oral tongue cancer patients with these high-risk pathologic features

  15. Novel compounds TAD-1822-7-F2 and F5 inhibited HeLa cells growth through the JAK/Stat signaling pathway.

    Science.gov (United States)

    Yang, Tianfeng; Shi, Xianpeng; Kang, Yuan; Zhu, Man; Fan, Mengying; Zhang, Dongdong; Zhang, Yanmin

    2018-07-01

    Cervical carcinoma remains the second most common malignancy with a high mortality rate among women worldwide. TAD-1822-7-F2 (F2) and TAD-1822-7-F5 (F5) are novel compounds synthesized on the chemical structure of taspine derivatives, and show an effective suppression for HeLa cells. Our study aims to confirm the potential targets of F2 and F5, and investigate the underlying mechanism of the inhibitory effect on HeLa cells. In this study, Real Time Cell Analysis and crystal violet staining assay were conducted to investigate the effect of F2 and F5 on HeLa cells proliferation. And the analytical methods of surface plasmon resonance and quartz crystal microbalance were established and employed to study the interaction between F2 and F5 and potential target protein JAK2, suggesting that both compounds have strong interaction with the JAK2 protein. Western blot analysis, immunofluorescence staining study and PCR was conducted to investigate the molecules of JAK/Stat signaling pathway. Interestingly, F2 and F5 showed diverse regulation for signaling molecules because of their different chemical structure. F2 increased the expression of JAK2 and downregulated the level of P-JAK1 and P-JAK2, and decreased P-Stat3 (Ser727). While F5 could increase the expression of JAK2 and naturally decrease the phosphorylation of JAK1 and Tyk2, and decreased the expression of P-Stat6. Moreover, F2 and F5 showed the same downregulation on the P-Stat3 (Tyr705). Therefore, F2 and F5 could target the JAK2 protein and prevent the phosphorylation of JAKs to suppress the phosphorylation of the downstream effector Stats, which suggested that F2 and F5 have great potential to be the inhibitors of the JAK/Stat signaling pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  16. Basal 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

    International Nuclear Information System (INIS)

    Garcia Vicente, Ana Maria; Soriano Castrejon, Angel; Lopez-Fidalgo, Jesus Fernando; Amo-Salas, Mariano; Mar Munoz Sanchez, Maria del; Alvarez Cabellos, Ruth; Espinosa Aunion, Ruth

    2015-01-01

    To explore the relationship between basal 18 F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent 18 F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with 18 F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

  17. Role of BRCA2 mutation status on overall survival among breast cancer patients from Sardinia

    International Nuclear Information System (INIS)

    Budroni, Mario; Palmieri, Giuseppe; Cesaraccio, Rosaria; Coviello, Vincenzo; Sechi, Ornelia; Pirino, Daniela; Cossu, Antonio; Tanda, Francesco; Pisano, Marina; Palomba, Grazia

    2009-01-01

    Germline mutations in BRCA1 or BRCA2 genes have been demonstrated to increase the risk of developing breast cancer. Conversely, the impact of BRCA mutations on prognosis and survival of breast cancer patients is still debated. In this study, we investigated the role of such mutations on breast cancer-specific survival among patients from North Sardinia. Among incident cases during the period 1997–2002, a total of 512 breast cancer patients gave their consent to undergo BRCA mutation screening by DHPLC analysis and automated DNA sequencing. The Hakulinen, Kaplan-Meier, and Cox regression methods were used for both relative survival assessment and statistical analysis. In our series, patients carrying a germline mutation in coding regions and splice boundaries of BRCA1 and BRCA2 genes were 48/512 (9%). Effect on overall survival was evaluated taking into consideration BRCA2 carriers, who represented the vast majority (44/48; 92%) of mutation-positive patients. A lower breast cancer-specific overall survival rate was observed in BRCA2 mutation carriers after the first two years from diagnosis. However, survival rates were similar in both groups after five years from diagnosis. No significant difference was found for age of onset, disease stage, and primary tumour histopathology between the two subsets. In Sardinian breast cancer population, BRCA2 was the most affected gene and the effects of BRCA2 germline mutations on patients' survival were demonstrated to vary within the first two years from diagnosis. After a longer follow-up observation, breast cancer-specific rates of death were instead similar for BRCA2 mutation carriers and non-carriers

  18. BSG and MCT1 Genetic Variants Influence Survival in Multiple Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Piotr Łacina

    2018-04-01

    Full Text Available Multiple myeloma (MM is a haematologic malignancy characterized by the presence of atypical plasma cells. Basigin (BSG, CD147 controls lactate export through the monocarboxylic acid transporter 1 (MCT1, SLC16A1 and supports MM survival and proliferation. Additionally, BSG is implicated in response to treatment with immunomodulatory drugs (thalidomide and its derivatives. We investigated the role of single nucleotide polymorphisms (SNPs in the gene coding for BSG and SLC16A1 in MM. Following an in silico analysis, eight SNPs (four in BSG and four in SLC16A1 predicted to have a functional effect were selected and analyzed in 135 MM patients and 135 healthy individuals. Alleles rs4919859 C, rs8637 G, and haplotype CG were associated with worse progression-free survival (p = 0.006, p = 0.017, p = 0.002, respectively, while rs7556664 A, rs7169 T and rs1049434 A (all in linkage disequilibrium (LD, r2 > 0.98 were associated with better overall survival (p = 0.021. Similar relationships were observed in thalidomide-treated patients. Moreover, rs4919859 C, rs8637 G, rs8259 A and the CG haplotype were more common in patients in stages II–III of the International Staging System (p < 0.05, while rs8259 A correlated with higher levels of β-2-microglobulin and creatinine (p < 0.05. Taken together, our results show that BSG and SLC16A1 variants affect survival, and may play an important role in MM.

  19. MiR-371-5p facilitates pancreatic cancer cell proliferation and decreases patient survival.

    Directory of Open Access Journals (Sweden)

    De He

    Full Text Available microRNAs (miRNAs play a critical role in tumorigenesis, either as a tumor suppressor or as an oncogenic miRNA, depending on different tumor types. To date, scientists have obtained a substantial amount of knowledge with regard to miRNAs in pancreatic cancer. However, the expression and function of miR-371-5p in pancreatic cancer has not been clearly elucidated. The aim of this study was to investigate the roles of miR-371-5p in pancreatic cancer and its association with the survival of patients with pancreatic cancer.The expression of miR-371-5p was examined in pancreatic duct adenocarcinoma (PDAC and their adjacent normal pancreatic tissues (ANPT or in pancreatic cancer cell lines by qRT-PCR. The association of miR-371-5p expression with overall survival was determined. The proliferation and apoptosis of SW-1990 and Panc-1 cells, transfected with miR-371-5p mimics or inhibitor, were assessed using MTT assay and flow cytometry, respectively. The tumorigenicity was evaluated via mice xenograft experiments. miR-371-5p promoter interactions were analyzed by chromatin immunoprecipitation assays (ChIP. Protein expression was analyzed by Western blot.The expression level of miR-371-5p was dramatically upregulated in clinical PDAC tissues compared with ANPT. Patients with high miR-371-5p expression had a significantly shorter survival than those with low miR-371-5p expression. The in vitro and in vivo assays showed that overexpression of miR-371-5p resulted in cell proliferation and increased tumor growth, which was associated with inhibitor of growth 1 (ING1 downregulation. Interestingly, we also found that ING1, in turn, inhibited expression of miR-371-5p in the promoter region.our study demonstrates a novel ING1-miR-371-5p regulatory feedback loop, which may have a critical role in PDAC. Thus miR-371-5p can prove to be a novel prognostic factor and therapeutic target for pancreatic cancer treatment.

  20. Evaluation of outcome prediction and disease extension by quantitative 2-deoxy-2-[18F] fluoro-D-glucose with positron emission tomography in patients with small cell lung cancer

    International Nuclear Information System (INIS)

    Arslan, N.; Tuncel, M.; Kuzhan, O.; Alagoz, E.; Budakoglu, B.; Ozet, A.; Ozguven, M.A.

    2011-01-01

    The objective of this study is to determine whether 2-deoxy-2-[18F] fluoro-D-glucose with positron emission tomography (FDG-PET) imaging and quantitative PET parameters can predict outcome and differentiate patients with limited disease (LD) from extensive disease (ED) in patients with small cell lung cancer (SCLC). We retrospectively evaluated data from 25 patients who underwent either initial staging (Group A, n 12) or restaging (Group B, n 13) by conventional imaging methods and FDG-PET according to the simplified staging scheme developed by the Veterans Administration Lung Cancer Study Group-2. FDG-PET images were both visually and quantitatively evaluated with standardized uptake value (SUV) max , SUV ave , total metabolic tumor volume (with SUV max >%50 and SUV max >2.5), total lesion glycolysis (TLG) (with SUV max >%50 and SUV max >2.5). The correlation between quantitative PET parameters, disease stages and survival were analyzed. By conventional methods 14 of 25 (56%) patients were reported to have LD and 11 of 25 (44%) had ED. FDG-PET scan upstaged 9 out of 25 (36%) and downstaged 2 out of 25 (%8) patients. Among the quantitative PET parameters, TLGs were the only PET parameters that differentiated between Group A and Group B patients. FDG-PET staging (p=0.019) could predict significant survival difference between stages on contrary to conventional staging (p=0.055). Moreover, TLG [SUV max >%50] was the only quantitative PET parameter that could predict survival (p=0.027). FDG-PET imaging is a valuable tool in the management of patients with SCLC for a more accurate staging. The use of quantitative PET parameters may have a role in prediction of stage and survival. (author)

  1. A calibration-free ammonia breath sensor using a quantum cascade laser with WMS 2f/1f

    KAUST Repository

    Owen, Kyle

    2013-12-22

    The amount of ammonia in exhaled breath has been linked to a variety of adverse medical conditions, including chronic kidney disease (CKD). The development of accurate, reliable breath sensors has the potential to improve medical care. Wavelength modulation spectroscopy with second harmonic normalized by the first harmonic (WMS 2f/1f) is a sensitive technique used in the development of calibration-free sensors. An ammonia gas sensor is designed and developed that uses a quantum cascade laser operating near 1,103.44 cm -1 and a multi-pass cell with an effective path length of 76.45 m. The sensor has a 7 ppbv detection limit and 5 % total uncertainty for breath measurements. The sensor was successfully used to detect ammonia in exhaled breath and compare healthy patients to patients diagnosed with CKD. © 2013 Springer-Verlag Berlin Heidelberg.

  2. Expression of Transketolase like gene 1 (TKTL1 predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Hofmann Wolf-Karsten

    2011-08-01

    Full Text Available Abstract Background For patients with locally advanced rectal cancer (LARC neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an important role in tumour progression and metastasis. Enhanced expression of Vascular-endothelial-growth-factor-receptor (VEGF-R and Transketolase-like-1 (TKTL1 are related to hypoxic conditions in tumours. In search for potential prognostic molecular markers we investigated the expression of VEGFR-1, VEGFR-2 and TKTL1 in patients with LARC treated with neoadjuvant chemoradiotherapy and cetuximab. Methods Tumour and corresponding normal tissue from pre-therapeutic biopsies of 33 patients (m: 23, f: 10; median age: 61 years with LARC treated in phase-I and II trials with neoadjuvant chemoradiotherapy (cetuximab, irinotecan, capecitabine in combination with radiotherapy were analysed by quantitative PCR. Results Significantly higher expression of VEGFR-1/2 was found in tumour tissue in pre-treatment biopsies as well as in resected specimen after neoadjuvant chemoradiotherapy compared to corresponding normal tissue. High TKTL1 expression significantly correlated with disease free survival. None of the markers had influence on early response parameters such as tumour regression grading. There was no correlation of gene expression between the investigated markers. Conclusion High TKTL-1 expression correlates with poor prognosis in terms of 3 year disease-free survival in patients with LARC treated with intensified neoadjuvant chemoradiotherapy and may therefore serve as a molecular prognostic marker which should be further evaluated in randomised clinical trials.

  3. Comparison of a 4.5 F semi-rigid ureteroscope with a 7.5 F rigid ureteroscope in the treatment of ureteral stones in preschool-age children.

    Science.gov (United States)

    Atar, Murat; Sancaktutar, Ahmet Ali; Penbegul, Necmettin; Soylemez, Haluk; Bodakci, Mehmet Nuri; Hatipoglu, Namik Kemal; Bozkurt, Yasar; Cakmakci, Suleyman

    2012-12-01

    The aim of this study was to compare the success and complication rates of a 4.5 F ureteroscope with a 7.5 F ureteroscope in the treatment of urolithiasis in preschool-age children. We retrospectively reviewed 69 ureteroscopy (URS) procedures in a pediatric population (40 boys, 29 girls). We divided the patients into two groups according to the type of ureteroscope used: group 1 (n = 42, Storz 7.5 F) and group 2 (n = 27, Wolf 4.5 F). We statistically compared all the procedures performed in both groups regarding patient age, complication rates, whether the procedure was therapeutic, and whether we used a guidewire. Additionally, in cases with ureteral stones, we also compared the stone clearance rate and the necessity of X-ray imaging between the two groups. The mean patient age was 56.04 months in group 1 and 47.48 months in group 2 (p = 0.057). The stone-free rate was 78.6 % in group 1 and 92.6 % in group 2 (p > 0.05). However, when we compared the stone-free rates for patients younger than 3 years, the rate was 66.7 % in group 1 and 93.8 % in group 2 (p < 0.05). The difference was not statistically significant for patients between the ages of 4 and 7 years. The success and failure rates revealed better outcomes for treatment of ureteral stones with a 4.5 F ureteroscope. We recommend the use of the mini-ureteroscope, especially in infants and preschool-age children.

  4. E2F transcription factors and digestive system malignancies: how much do we know?

    Science.gov (United States)

    Xanthoulis, Athanasios; Tiniakos, Dina G

    2013-06-07

    E2F family of transcription factors regulates various cellular functions related to cell cycle and apoptosis. Its individual members have traditionally been classified into activators and repressors, based on in vitro studies. However their contribution in human cancer is more complicated and difficult to predict. We review current knowledge on the expression of E2Fs in digestive system malignancies and its clinical implications for patient prognosis and treatment. E2F1, the most extensively studied member and the only one with prognostic value, exhibits a tumor-suppressing activity in esophageal, gastric and colorectal adenocarcinoma, and in hepatocellular carcinoma (HCC), whereas in pancreatic ductal adenocarcinoma and esophageal squamous cell carcinoma may function as a tumor-promoter. In the latter malignancies, E2F1 immunohistochemical expression has been correlated with higher tumor grade and worse patient survival, whereas in esophageal, gastric and colorectal adenocarcinomas is a marker of increased patient survival. E2F2 has only been studied in colorectal cancer, where its role is not considered significant. E2F4's role in colorectal, gastric and hepatic carcinogenesis is tumor-promoting. E2F8 is strongly upregulated in human HCC, thus possibly contributing to hepatocarcinogenesis. Adenoviral transfer of E2F as gene therapy to sensitize pancreatic cancer cells for chemotherapeutic agents has been used in experimental studies. Other therapeutic strategies are yet to be developed, but it appears that targeted approaches using E2F-agonists or antagonists should take into account the tissue-dependent function of each E2F member. Further understanding of E2Fs' contribution in cellular functions in vivo would help clarify their role in carcinogenesis.

  5. Hypoxia imaging of uterine cervix carcinoma with (18)F-FETNIM PET/CT.

    Science.gov (United States)

    Vercellino, Laetitia; Groheux, David; Thoury, Anne; Delord, Marc; Schlageter, Marie-Hélène; Delpech, Yann; Barré, Emmanuelle; Baruch-Hennequin, Valérie; Tylski, Perrine; Homyrda, Laurence; Walker, Francine; Barranger, Emmanuel; Hindié, Elif

    2012-11-01

    Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG. We included 16 patients with cervical carcinoma. After imaging with FDG, (18)F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients' outcomes. All tumors were detected by (18)F-FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake (T/M > 3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 μg/L (median, 102.5 μg/L). Patients with OPN greater than 144 μg/L had reduced progression-free survival compared with those with OPN less than 144 μg/L (log-rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and OPN blood levels. Our preliminary results showed that a high uptake of (18)F-FETNIM was associated with a worse progression-free and overall survival.

  6. The 1:1 co-crystal of triphenyl(2,3,5,6-tetrafluorobenzylphosphonium bromide and 1,1,2,2-tetrafluoro-1,2-diiodoethane

    Directory of Open Access Journals (Sweden)

    Gabriella Cavallo

    2014-01-01

    Full Text Available The title compound, C25H18F4P+·Br−·C2F4I2, is a 1:1 co-crystal of triphenyl(2,3,5,6-tetrafluorobenzylphosphonium (TTPB bromide and 1,1,2,2-tetrafluoro-1,2-diiodoethane (TFDIE. The crystal structure consists of a framework of TTPB cations held together by C—H...Br interactions. In this framework, infinite channels along [100] are filled by TFDIE molecules held together in infinite ribbons by short F...F [2.863 (22.901 (2Å] interactions. The structure contains halogen bonds (XB and hydrogen bonds (HB in the bromide coordination sphere. TFDIE functions as a monodentate XB donor as only one I atom is linked to the Br− anion and forms a short and directional interaction [I...Br− 3.1798 (7 Å and C—I...Br− 177.76 (5°]. The coordination sphere of the bromide anion is completed by two short HBs of about 2.8 Å (for H...Br with the acidic methylene H atoms and two longer HBs of about 3.0 Å with H atoms of the phenyl rings. Surprisingly neither the second iodine atom of TFDIE nor the H atom on the tetrafluorophenyl group make any short contacts.

  7. Improved long-term survival after intra-operative single high-dose ATG-Fresenius induction in renal transplantation: a single centre experience.

    Science.gov (United States)

    Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

    2009-01-01

    In organ grafts donor-specific sensitization is initiated immediately after revascularization. Therefore, in 1990 we introduced the intra-operative single high-dose ATG-Fresenius (ATG-F) induction in addition to standard triple drug therapy (TDT) consisting of steroids, azathioprine and cyclosporin. A total of 778 first renal transplantations from deceased donors, performed between 1987 and 1998, were included in this evaluation. This retrospective analysis of clinic records and electronic databases presents data of all recipients of first kidney grafts who received two different ATG-F inductions (1(st) group: 9 mg/kg body weight as single high-dose intra-operatively, n=484; 2(nd) group: 3 mg/kg body weight on 7 or 8 consecutive days as multiple-dose starting also intra-operatively, n=78) and standard TDT alone (3(rd) group: TDT alone, n=216). The 10-year patient survival rates were 72.6+/-2.6% (TDT + ATG-F single high-dose), 79.5+/-5.1% (TDT + ATG-F multiple-dose) and 67.2+/-3.7%% (TDT alone; Kaplan-Meier estimates with standard errors; ATG-F vs TDT alone, p=0.001). The 10-year graft survival rates with censoring of patients that died with a functioning graft were 73.8+/-2.4%, 57.7+/-5.8% and 58.4+/-3.6% (Kaplan-Meier estimates with standard errors; 1(st) vs 2(nd )and 3(rd) group, respectively, p<0.001) and the 10-year graft survival rates with patient death counted as graft failure were 58.3+/-2.7%, 55.7+/-5.8% and 48.2+/-3.5% (Kaplan-Meier estimates with standard errors; ATG-F single high-dose vs TDT, p=0.023). In pre-sensitized recipients there were also significant differences in favour of ATG-F, more notably in the single high-dose ATG-F induction. A total of 69% of the patients in the two cohorts receiving ATG-F did not experience any transplant rejections compared to 56% in patients undergoing TDT alone (p=0.018). The incidence of infectious complications was comparable across all groups. According to evidence obtained from the routine documentation of 778

  8. Clinical outcomes for T1-2N0-1 oral tongue cancer patients underwent surgery with and without postoperative radiotherapy

    Directory of Open Access Journals (Sweden)

    Choi Eun

    2010-05-01

    Full Text Available Abstract Background The aim of this study was to assess the results of curative surgery with and without radiotherapy in patients with T1-2N0-1 oral tongue squamous cell carcinoma (OSCC and to evaluate survival and prognostic factors. Methods Retrospective analysis of 86 patients with T1-2N0-1 OSCC who received surgery between January 2000 and December 2006. Fourteen patients (16.3% received postoperative radiotherapy (PORT. Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were analyzed. Results The median follow-up was 45 months. The five-year overall survival (OS and disease-free survival (DFS rates were 80.8% and 80.2%, respectively. Higher tumor grade and invasion depth ≥ 0.5 cm were the significant prognostic factors affecting five-year OS and DFS (OS rate; 65% vs. 91%, p = 0.001 for grade; 66% vs. 92%, p = 0.01 for invasion depth: DFS rate; 69% vs. 88%, p = 0.005 for grade; 66% vs. 92%, p = 0.013 for invasion depth. In the risk group, there was no local failure in patients with postoperative radiotherapy. Conclusions In T1-2N0-1 OSCC, factors that affected prognosis after primary surgery were higher tumor grade and deep invasion depth over 0.5 cm. Postoperative radiotherapy should be considered in early oral tongue cancer patients with these high-risk pathologic features.

  9. The Aryl Hydrocarbon Receptor Binds to E2F1 and Inhibits E2F1-induced Apoptosis

    Science.gov (United States)

    Marlowe, Jennifer L.; Fan, Yunxia; Chang, Xiaoqing; Peng, Li; Knudsen, Erik S.; Xia, Ying

    2008-01-01

    Cellular stress by DNA damage induces checkpoint kinase-2 (CHK2)-mediated phosphorylation and stabilization of the E2F1 transcription factor, leading to induction of apoptosis by activation of a subset of proapoptotic E2F1 target genes, including Apaf1 and p73. This report characterizes an interaction between the aryl hydrocarbon (Ah) receptor (AHR), a ligand-activated transcription factor, and E2F1 that results in the attenuation of E2F1-mediated apoptosis. In Ahr−/− fibroblasts stably transfected with a doxycycline-regulated AHR expression vector, inhibition of AHR expression causes a significant elevation of oxidative stress, γH2A.X histone phosphorylation, and E2F1-dependent apoptosis, which can be blocked by small interfering RNA-mediated knockdown of E2F1 expression. In contrast, ligand-dependent AHR activation protects these cells from etoposide-induced cell death. In cells expressing both proteins, AHR and E2F1 interact independently of the retinoblastoma protein (RB), because AHR and E2F1 coimmunoprecipitate from extracts of RB-negative cells. Additionally, chromatin immunoprecipitation assays indicate that AHR and E2F1 bind to the Apaf1 promoter at a region containing a consensus E2F1 binding site but no AHR binding sites. AHR activation represses Apaf1 and TAp73 mRNA induction by a constitutively active CHK2 expression vector. Furthermore, AHR overexpression blocks the transcriptional induction of Apaf1 and p73 and the accumulation of sub-G0/G1 cells resulting from ectopic overexpression of E2F1. These results point to a proproliferative, antiapoptotic function of the Ah receptor that likely plays a role in tumor progression. PMID:18524851

  10. Basal {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Vicente, Ana Maria; Soriano Castrejon, Angel [University General Hospital, Nuclear Medicine Department, Ciudad Real (Spain); Lopez-Fidalgo, Jesus Fernando; Amo-Salas, Mariano [University of Castilla-La Mancha, Department of Mathematics, Ciudad Real (Spain); Mar Munoz Sanchez, Maria del [Virgen de la Luz Hospital, Oncology Department, Cuenca (Spain); Alvarez Cabellos, Ruth [Virgen de la Salud Hospital, Oncology Department, Toledo (Spain); Espinosa Aunion, Ruth [La Mancha Centro Hospital, Oncology Department, Ciudad Real (Spain)

    2015-11-15

    To explore the relationship between basal {sup 18}F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent {sup 18}F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with {sup 18}F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

  11. Post-relapse survival in patients with Ewing sarcoma.

    Science.gov (United States)

    Ferrari, Stefano; Luksch, Roberto; Hall, Kirsten Sundby; Fagioli, Franca; Prete, Arcangelo; Tamburini, Angela; Tienghi, Amelia; DiGirolamo, Stefania; Paioli, Anna; Abate, Massimo Eraldo; Podda, Marta; Cammelli, Silvia; Eriksson, Mikael; Brach del Prever, Adalberto

    2015-06-01

    Post-relapse survival (PRS) was evaluated in patients with Ewing sarcoma (EWS) enrolled in chemotherapy protocols based on the use of high-dose chemotherapy with busulfan and melfalan (HDT) as a first-line consolidation treatment in high-risk patients. EWS patients enrolled in ISG/SSG III and IV trials who relapsed after complete remission were included in the analysis. At recurrence, chemotherapy based on high-dose ifosfamide was foreseen, and patients who responded but had not received HDT underwent consolidation therapy with HDT. Data from 107 EWS patients were included in the analysis. Median time to recurrence (RFI) was 18 months, and 45 (42%) patients had multiple sites of recurrence. Patients who had previously been treated with HDT had a significantly (P = 0.02) shorter RFI and were less likely to achieve a second complete remission (CR2). CR2 status was achieved by 42 (39%) patients. Fifty patients received high-dose IFO (20 went to consolidation HDT). The 5-year PRS was 19% (95% CI 11 to 27%). With CR2, the 5-year PRS was 48% (95% CI 31 to 64%). Without CR2, median time to death was six months (range 1-45 months). According to the multivariate analysis, patients younger than 15 years, recurrence to the lung only, and RFI longer than 24 months significantly influenced the probability of PRS. Age, pattern of recurrence, RFI, and response to second-line chemotherapy influence post-relapse survival in patients with recurrent Ewing sarcoma. No survival advantage was observed from chemotherapy consolidation with HDT. © 2015 Wiley Periodicals, Inc.

  12. Prolonged Delayed Graft Function Is Associated with Inferior Patient and Kidney Allograft Survivals.

    Directory of Open Access Journals (Sweden)

    Tainá Veras de Sandes-Freitas

    Full Text Available It is unclear if there is an association between the duration of delayed graft function (DGF and kidney transplant (KT outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412. Patients were grouped in quartiles according to duration of DGF (1-5, 6-10, 11-15, and >15 days, designated as prolonged DGF. The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064-4.184,p = 0.033 and more than 3 HLA mismatches (OR 1.819, CI95% 1.117-2.962,p = 0.016. The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001. Compared to patients without DGF, DGF(1-5, DGF(6-10, and DGF(11-15, patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003, graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001, death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001, and creatinine clearance (58.0±24.6 vs. 55.8±22.2 vs. 53.8±24.1 vs. 53.0±27.2 vs. 36.8±27.0 mL/min, p<0.001, respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270-6.618, p<0.001, death censored graft loss (OR 4.103, CI95% 2.055-8.193, p<0.001, and death (OR 3.065, CI95% 1.536-6.117, p = 0.001. Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year.

  13. [18F]F15599, a novel 5-HT1A receptor agonist, as a radioligand for PET neuroimaging

    International Nuclear Information System (INIS)

    Lemoine, Laetitia; Verdurand, Mathieu; Vacher, Bernard; Blanc, Elodie; Newman-Tancredi, Adrian; Le Bars, Didier; Zimmer, Luc

    2010-01-01

    The serotonin-1A (5-HT 1A ) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT 1A receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT 1A receptors. Since all clinical PET 5-HT 1A radiopharmaceuticals are antagonists, it is of great interest to develop a 18 F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{ [(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT 1A receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT 1A receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [ 18 F]MPPF, a validated 5-HT 1A antagonist radiopharmaceutical. The chemical and radiochemical purities of [ 18 F]F15599 were >98%. In vitro [ 18 F ]F15599 binding was consistent with the known 5-HT 1A receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [ 18 F ]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [ 18 F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT 1A antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer readily entered the rat and the cat brain and generated few brain radioactive

  14. [18F]F15599, a novel 5-HT1A receptor agonist, as a radioligand for PET neuroimaging.

    Science.gov (United States)

    Lemoine, Laëtitia; Verdurand, Mathieu; Vacher, Bernard; Blanc, Elodie; Le Bars, Didier; Newman-Tancredi, Adrian; Zimmer, Luc

    2010-03-01

    The serotonin-1A (5-HT(1A)) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT(1A) receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT(1A) receptors. Since all clinical PET 5-HT(1A) radiopharmaceuticals are antagonists, it is of great interest to develop a( 18)F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT(1A) receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT(1A) receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [(18)F]MPPF, a validated 5-HT(1A) antagonist radiopharmaceutical. The chemical and radiochemical purities of [(18)F]F15599 were >98%. In vitro [(18)F]F15599 binding was consistent with the known 5-HT(1A) receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [(18)F]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [(18)F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT(1A) antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer readily entered the rat and the cat brain and generated few brain

  15. Properties and Crystallization Phenomena in Li2Si2O5–Ca5(PO4)3F and Li2Si2O5–Sr5(PO4)3F Glass–Ceramics Via Twofold Internal Crystallization

    Science.gov (United States)

    Rampf, Markus; Dittmer, Marc; Ritzberger, Christian; Schweiger, Marcel; Höland, Wolfram

    2015-01-01

    The combination of specific mechanical, esthetic, and chemical properties is decisive for the application of materials in prosthodontics. Controlled twofold crystallization provides a powerful tool to produce special property combinations for glass–ceramic materials. The present study outlines the potential of precipitating Ca5(PO4)3F as well as Sr5(PO4)3F as minor crystal phases in Li2Si2O5 glass–ceramics. Base glasses with different contents of CaO/SrO, P2O5, and F− were prepared within the glasses of the SiO2–Li2O–K2O–CaO/SrO–Al2O3–P2O5F system. Preliminary studies of nucleation by means of XRD and scanning electron microscopy (SEM) of the nucleated base glasses revealed X-ray amorphous phase separation phenomena. Qualitative and quantitative crystal phase analyses after crystallization were conducted using XRD in combination with Rietveld refinement. As a main result, a direct proportional relationship between the content of apatite-forming components in the base glasses and the content of apatite in the glass–ceramics was established. The microstructures of the glass–ceramics were investigated using SEM. Microstructural and mechanical properties were found to be dominated by Li2Si2O5 crystals and quite independent of the content of the apatite present in the glass–ceramics. Biaxial strengths of up to 540 MPa were detected. Ca5(PO4)3F and Sr5(PO4)3F influence the translucency of the glass–ceramics and, hence, help to precisely tailor the properties of Li2Si2O5 glass–ceramics. The authors conclude that the twofold crystallization of Li2Si2O5–Ca5(PO4)3F or Li2Si2O5–Sr5(PO4)3F glass–ceramics involves independent solid-state reactions, which can be controlled via the chemical composition of the base glasses. The influence of the minor apatite phase on the optical properties helps to achieve new combinations of features of the glass–ceramics and, hence, displays new potential for dental applications. PMID:26389112

  16. O-(2-[18F]fluoroethyl)-L-tyrosine uptake is an independent prognostic determinant in patients with glioma referred for radiation therapy

    International Nuclear Information System (INIS)

    Sweeney, Reinhart; Polat, Bülent; Flentje, Michael; Samnick, Samuel; Reiners, Christoph; Verburg, Frederik A.

    2014-01-01

    To evaluate the prognostic value of O-(2-[ 18 F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organization (WHO) tumor grade II-IV gliomas. We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40% of the SUVmax. Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40% SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality (p=0.005) and progression-free survival (p=0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade (p=0.001) and SUVmax ≥ 2.6 (p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 (p=0.007) and being treated for a recurrence rather than for a primary tumor manifestation (p=0.014) were predictors for progression-free survival, but not TBRmax or TBRmean. In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval. (author)

  17. The improved syntheses of 5-substituted 2'-[18F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU) using a multistep one-pot strategy

    International Nuclear Information System (INIS)

    Cai Hancheng; Li Zibo; Conti, Peter S.

    2011-01-01

    Introduction: We and others have previously reported a four-step radiosynthesis of a series of 2'-deoxy-2'-[ 18 F]fluoro-5-substituted-1-β-D-arabinofuranosyluracil derivatives including [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU as thymidine derivatives for tumor proliferation and/or reporter gene expression imaging with positron emission tomography (PET). Although the radiosynthesis has been proven to be reproducible and efficient, this complicated multistep reaction is difficult to incorporate into an automated cGMP-compliant radiosynthesis module for routine production. Recently, we have developed a simple and efficient one-pot method for routine production of [ 18 F]FMAU. In this study, we studied the feasibility of radiosynthesizing [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU using this newly developed method. Methods: Similar to the radiosynthesis of [ 18 F]FMAU, 5-substituted 2'-[ 18 F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU) were synthesized in one-pot radiosynthesis module in the presence of Friedel-Crafts catalyst TMSOTf and HMDS. Results: This one-pot radiosynthesis method could be used to produce [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU. The overall radiochemical yields of these tracers varied from 4.1%±0.8% to 10.11.9% (decay-corrected, n=4). The overall reaction time was reduced from 210 min to 150 min from the end of bombardment, and the radiochemical purity was >99%. Conclusions: The improved radiosyntheses of [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU have been achieved with reasonable yields and high purity using a multistep one-pot method. The synthetic time has been reduced, and the reaction procedures have been significantly simplified. The success of this approach may make PET tracers [ 18 F]FAU, [ 18 F

  18. Prognostic value of 18F-FDG-PET/CT in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Lin, Jie; Xie, Guozhu; Liao, Guixiang; Wang, Baiyao; Yan, Miaohong; Li, Hui; Yuan, Yawei

    2017-05-16

    The prognostic role of 18F-fluorodeoxyglucose positron emission tomography CT (18F-FDG PET/CT) parameters is still controversial in nasopharyngeal carcinoma patients. We sought to perform a systematic review and meta-analysis to explore the prognostic value of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on event-free survival (EFS) and overall survival (OS) in nasopharyngeal carcinoma patients. Fifteen studies comprising 1,938 patients were included in this study. The combined hazard ratios (HRs) for EFS were 2.63 (95%CI 1.71-4.05) for SUVmax, 2.55 (95%CI 1.49-4.35) for MTV, and 3.32 (95%CI 1.23-8.95) for TLG. The pooled HRs for OS were 2.07 (95%CI 1.54-2.79) for SUVmax, 3.86 (95%CI 1.85-8.06) for MTV, and 2.60 (95%CI 1.55-4.34) for TLG. The prognostic role of SUVmax, MTV and TLG remained similar in the sub-group analyses. A systematic literature search was performed to identify studies which associated 18F-FDG PET/CT to clinical survival outcomes of nasopharyngeal carcinoma patients. The summarized HRs for EFS and OS were estimated by using fixed- or random-effect models according to heterogeneity between trials. The present meta-analysis confirms that high values of SUVmax, MTV and TLG predicted a higher risk of adverse events or death in patients with nasopharyngeal carcinoma, despite clinically heterogeneous nasopharyngeal carcinoma patients and the various methods adopted between these studies.

  19. Long-Term Survival of Dental Implants with Different Prosthetic Loading Times in Healthy Patients: A 5-Year Retrospective Clinical Study.

    Science.gov (United States)

    Muelas-Jiménez, M Isabel; Olmedo-Gaya, Maria Victoria; Manzano-Moreno, Francisco J; Reyes-Botella, Candela; Vallecillo-Capilla, Manuel

    2017-02-01

    To compare survival rates among dental implants restored with immediate, early, and conventional loading protocols, also comparing between maxillary and mandibular implants, and to evaluate the influence of implant length and diameter and the type of prosthesis on treatment outcomes. This retrospective cohort study initially included all 52 patients receiving dental implants between July 2006 and February 2008 at a private oral surgery clinic in Granada (Southern Spain). Clinical and radiographic examinations were performed, including periapical or panoramic radiographs, and incidences during completion of the restoration were recorded at 1 week, 3 months, 6 months, and at 1, 2, 3, 4, and 5 years. After a 5-year follow-up, 1 patient had died, 3 were lost to follow-up, and 6 required grafting before implant placement; therefore, the final study sample comprised 42 patients with 164 implants. Variables associated with the survival/failure of the restoration were: number of implants (higher failure rate with fewer implants), bone type (higher failure rate in type III or IV bone), and type of prosthesis (higher failure rate with single crowns). No significant association was found in univariate or multivariate analyses between survival rate and the loading protocol, implant length or diameter, or maxillary/mandibular location. Immediate occlusal loading, immediate provisionalization without occlusal loading, and early loading are viable treatment options with similar survival rates to those obtained with conventional loading. Bone quality and number of implants per patient were the most influential factors. © 2015 by the American College of Prosthodontists.

  20. Analysis of ({sup 7}F{sub 0}){gamma}{sub 1g}{yields}({sup 5}D{sub 2}){gamma}{sub 5g}, {gamma}{sub 3g} and ({sup 7}F{sub 0}){gamma}{sub 1g}{yields}({sup 5}L{sub 6}){gamma}{sub 1g}, a{gamma}{sub 5g} two-photon absorption spectra of Cs{sub 2}NaYF{sub 6}:Eu{sup 3+}

    Energy Technology Data Exchange (ETDEWEB)

    Ning Lixin; Wang Dianyuan; Xia Shangda [Structure Research Laboratory, Academica Sinica, Department of Physics, University of Science and Technology of China, Heifei, Anhui (China); Thorne, Jonathan R.G. [Inorganic Chemistry Laboratory, Department of Chemistry, University of Oxford (United Kingdom); Tanner, Peter A. [Department of Biology and Chemistry, City University of Hong Kong, Kowloon (China)

    2002-04-15

    The direct calculation of transition line strengths and relative intensities is presented for two intraconfigurational two-photon absorption (TPA) transitions of Eu{sup 3+} in the cubic Cs{sub 2}NaYF{sub 6} host. Crystal field wavefunctions were utilized for the initial and final f{sup N}-electron states and various approaches were used in constructing all the 4f{sup N-1} 5d{sup 1} intermediate-state wavefunctions. The calculated relative intensities of the ({sup 7}F{sub 0}) {gamma}{sub 1g}{yields}({sup 5}D{sub 2}){gamma}{sub 5g}, {gamma}{sub 3g} TPA transitions are in reasonable agreement with experiment. The neglect of J-mixing in the initial state has only a small effect upon the calculation, whereas the neglect of spin-orbit couplings within the initial and terminal states drastically reduces the calculated transition linestrengths, but does not markedly change the intensity ratios. In the case of the ({sup 7}F{sub 0}){gamma}{sub 1g}{yields}({sup 5}L{sub 6}){gamma}{sub 1g}, a{gamma}{sub 5g} transitions, serious discrepancies between experiment and theory are found if the intermediate states are constructed from a 4f{sup 5} core comprising free ion states and the 5d{sup 1} crystal field states. Satisfactory agreement is, however, found when the 4f{sup 5} crystal field states are utilized in constructing the intermediate states. The contributions to the transition moment have been evaluated for various Hamiltonian terms and the results are discussed. (author)

  1. Radiosynthesis of a novel potential adenosine A3 receptor ligand, 5-ethyl 2,4-diethyl-3-((2-[18F]fluoroethyl)sulfanylcarbonyl) -6-phenylpyridine-5-carbox ylate ([18F]FE rate at SUPPY:2)

    International Nuclear Information System (INIS)

    Haeusler, D.; Mitterhauser, M.; Mien, L.K.; Shanab, K.; Spreitzer, H.; Lanzenberger, R.R; Schirmer, E.; Ungersboeck, J.; Wadsak, W.; Nics, L.; Viernstein, H.; Dudezak, R.; Kletter, K.

    2009-01-01

    Since, to date very limited information on the distribution and function of the adenosine A 3 receptor is available, the development of suitable radioligands is needed. Recently, we introduced [ 18 F]FE rate at SUPPY (5-(2-[ 18 F]fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate) as the first PET-ligand for the A3R. Regarding the metabolic profile - this class of dialkylpyridines comprises two ester functions within one molecule, one carboxylic and one thiocarboxylic - one could expect carboxylesterases significantly contributing to cleavage and degradation. Therefore, our aim was the development of [ 18 F]FE rate at SUPPY:2 (5-ethyl 2,4-diethyl-3-((2-[ 18 F]fluoroethyl)sulfanylcarbonyl)-6-phenylpyridine -5-carbox ylate), the functional isomer containing the label at the thiocarboxylic moiety. For satisfactory yields in high scale radiosyntheses, a reaction temperature of 75 C has to be applied for at least 20 min using 20 mg/mL of precursor. So far, 6 complete high-scale radiosyntheses were performed. Starting from an average of 51.2 ± 21.8 GBq (mean±SD) [ 18 F]fluoride, 5.8 ± 4.1 GBq of formulated [ 18 F]FE rate at SUPPY:2 (12.0±5.4%, based on [ 18 F]fluoride, not corrected for decay) were prepared in 75 ± 8 min. (orig.)

  2. Elevated urinary levels of 8-oxo-2'-deoxyguanosine, (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines, and 8-iso-prostaglandin F2α as potential biomarkers of oxidative stress in patients with prediabetes.

    Science.gov (United States)

    Kant, Melis; Akış, Merve; Çalan, Mehmet; Arkan, Tuğba; Bayraktar, Fırat; Dizdaroglu, Miral; İşlekel, Hüray

    2016-12-01

    Prediabetes is the preclinical stage of type 2 diabetes mellitus (T2DM) with intermediate state of hyperglycemia. Hyperglycemia results in a state of oxidative stress, which may contribute to the production of insulin resistance, β-cell dysfunction and long-term complications of diabetes. Novel approaches are required for prevention and treatment of diabetes. New biomarkers that can be used in risk stratification and therapy control as supplementary to current parameters are needed. These biomarkers may facilitate a more individualized and sufficient treatment of diabetes. Therefore, the aim of this study was to investigate the levels of oxidatively induced DNA damage products, 8-oxo-2'-deoxyguanosine (8-oxo-dG) (also known as 8-OH-dG), (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA), and the lipid peroxidation product 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) as reliable oxidative stress markers in patients with prediabetes or T2DM in comparison with healthy volunteers. Urine samples were collected from these subjects. Absolute quantification of 8-oxo-dG, R-cdA, S-cdA and 8-iso-PGF 2α was achieved by liquid chromatography-isotope dilution tandem mass spectrometry. The levels of 8-oxo-dG, S-cdA and 8-iso-PGF 2α were significantly greater in prediabetes patients than those in healthy volunteers. T2DM patients also had higher levels of 8-oxo-dG than healthy volunteers. No statistically significant difference was observed for R-cdA levels. 8-Oxo-dG levels positively correlated with R-cdA and S-cdA levels for prediabetes and newly diagnosed T2DM. S-cdA levels and HbA1c were found negatively correlated in prediabetes patients. Also 8-iso-PGF 2α levels and HbA1c were found negatively correlated in prediabetes patients. These results indicate that oxidatively induced macromolecular damage appears before the establishment of T2DM. Thus, our data suggest that oxidatively induced DNA damage and lipid peroxidation products that were found to be elevated

  3. Gender, Race, and Survival: A Study in Non-Small-Cell Lung Cancer Brain Metastases Patients Utilizing the Radiation Therapy Oncology Group Recursive Partitioning Analysis Classification

    International Nuclear Information System (INIS)

    Videtic, Gregory M.M.; Reddy, Chandana A.; Chao, Samuel T.; Rice, Thomas W.; Adelstein, David J.; Barnett, Gene H.; Mekhail, Tarek M.; Vogelbaum, Michael A.; Suh, John H.

    2009-01-01

    Purpose: To explore whether gender and race influence survival in non-small-cell lung cancer (NSCLC) in patients with brain metastases, using our large single-institution brain tumor database and the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) brain metastases classification. Methods and materials: A retrospective review of a single-institution brain metastasis database for the interval January 1982 to September 2004 yielded 835 NSCLC patients with brain metastases for analysis. Patient subsets based on combinations of gender, race, and RPA class were then analyzed for survival differences. Results: Median follow-up was 5.4 months (range, 0-122.9 months). There were 485 male patients (M) (58.4%) and 346 female patients (F) (41.6%). Of the 828 evaluable patients (99%), 143 (17%) were black/African American (B) and 685 (83%) were white/Caucasian (W). Median survival time (MST) from time of brain metastasis diagnosis for all patients was 5.8 months. Median survival time by gender (F vs. M) and race (W vs. B) was 6.3 months vs. 5.5 months (p = 0.013) and 6.0 months vs. 5.2 months (p = 0.08), respectively. For patients stratified by RPA class, gender, and race, MST significantly favored BFs over BMs in Class II: 11.2 months vs. 4.6 months (p = 0.021). On multivariable analysis, significant variables were gender (p = 0.041, relative risk [RR] 0.83) and RPA class (p < 0.0001, RR 0.28 for I vs. III; p < 0.0001, RR 0.51 for II vs. III) but not race. Conclusions: Gender significantly influences NSCLC brain metastasis survival. Race trended to significance in overall survival but was not significant on multivariable analysis. Multivariable analysis identified gender and RPA classification as significant variables with respect to survival.

  4. Reduced 5-HT2A receptor binding in patients with mild cognitive impairment

    DEFF Research Database (Denmark)

    Hasselbalch, S G; Madsen, K; Svarer, C

    2008-01-01

    cerebral 5-HT(2A) receptor binding in patients with mild cognitive impairment (MCI) and related 5-HT(2A) receptor binding to clinical symptoms. Sixteen patients with MCI of the amnestic type (mean age 73, mean MMSE 26.1) and 17 age and sex matched control subjects were studied with MRI and [(18)F......Previous studies of patients with Alzheimer's disease (AD) have described reduced brain serotonin 2A (5-HT(2A)) receptor density. It is unclear whether this abnormality sets in early in the course of the disease and whether it is related to early cognitive and neuropsychiatric symptoms. We assessed...

  5. Elevated electrochemical performance of (NH4)3AlF6-coated 0.5Li2MnO3·0.5LiNi1/3Co1/3Mn1/3O2 cathode material via a novel wet coating method

    International Nuclear Information System (INIS)

    Xu, Guofeng; Li, Jianling; Xue, Qingrui; Dai, Yu; Zhou, Hongwei; Wang, Xindong; Kang, Feiyu

    2014-01-01

    A novel wet method of (NH 4 ) 3 AlF 6 coating was explored to enhance the electrochemical performance of Mn-based solid-solution cathode material 0.5Li 2 MnO 3 ·0.5LiNi 1/3 Co 1/3 Mn 1/3 O 2 . The X-ray powder diffraction patterns show that the coating material is pure-phase (NH 4 ) 3 AlF 6 and both pristine and coated samples can be indexed to hexagonal α-NaFeO 2 layered structure with space group of R-3 m. The field-emission scanning electron microscope images and the energy dispersive X-ray spectroscopy show that (NH 4 ) 3 AlF 6 is successfully coated on the surface of active particle. The (NH 4 ) 3 AlF 6 coated electrodes exhibit improved electrochemical performance, for instance, the initial charge-discharge efficiency was promoted by 5% (NH 4 ) 3 AlF 6 coating, the 1 wt.% and 3 wt.% coated electrodes deliver elevated cycling ability which is ascribed to the lower resistance between electrode and electrolyte as indicated by AC impedance measurement at different cycles. In addition, the coated-electrodes also give enhanced rate capability particularly for 1 wt.% NAF-coated electrode performing surprising capacity of 143.4 mAh g −1 at 5 C higher than that of 109.4 mAh g −1 for pristine electrode. Furthermore, the 1 wt.% NAF-coated electrode also shows improved cycle and rate performance at 55°C

  6. Lack of retroperitoneal lymphadenopathy predicts survival of patients with metastatic renal cell carcinoma.

    Science.gov (United States)

    Vasselli, J R; Yang, J C; Linehan, W M; White, D E; Rosenberg, S A; Walther, M M

    2001-07-01

    Patients with metastatic renal cell carcinoma have a reported 5-year survival of 0% to 20%. The ability to predict which patients would benefit from nephrectomy and interleukin-2 (IL-2) therapy before any treatment is initiated would be useful for maximizing the advantage of therapy and improving the quality of life. A retrospective analysis of the x-rays and charts of patients treated at the National Institutes of Health Surgery Branch between 1985 and 1996, who presented with metastatic renal cancer beyond the locoregional area and the primary tumor in place, was performed. Preoperative computerized tomography or magnetic resonance imaging, or radiological reports if no scans were available, were used to obtain an estimate of the volume of retroperitoneal lymphadenopathy. Operative notes were used to evaluate whether all lymphadenopathy was resected or disease left in situ, or if any extrarenal resection, including venacavotomy, was performed. Mean survival rate was calculated from the time of nephrectomy to the time of death or last clinical followup. If patients received IL-2 therapy, the response to treatment was recorded. Mean survival and response rate for IL-2 were compared among patients in 3 separate analyses. Patients without preoperatively detected lymphadenopathy were compared with those with at least 1 cm.3 retroperitoneal lymphadenopathy. Also, the patients who had detectable lymphadenopathy were divided into subgroups consisting of all resected, incompletely resected, unresectable and unknown if all disease was resected. Each subgroup was compared with patients without detectable preoperative lymphadenopathy. Patients with less than were compared to those with greater than 50 cm.3 retroperitoneal lymphadenopathy. Patients undergoing extrarenal resection at nephrectomy (complex surgery) due to direct invasion of the tumor into another intra-abdominal organ were compared with those undergoing radical nephrectomy alone, regardless of lymph node status

  7. Case of a cardiac arrest patient who survived after extracorporeal cardiopulmonary resuscitation and 1.5 hours of resuscitation: A case report.

    Science.gov (United States)

    Moon, Seong Ho; Kim, Jong Woo; Byun, Joung Hun; Kim, Sung Hwan; Kim, Ki Nyun; Choi, Jun Young; Jang, In Seok; Lee, Chung Eun; Yang, Jun Ho; Kang, Dong Hun; Park, Hyun Oh

    2017-11-01

    Per the American Heart Association guidelines, extracorporeal cardiopulmonary resuscitation should be considered for in-hospital patients with easily reversible cardiac arrest. However, there are currently no consensus recommendations regarding resuscitation for prolonged cardiac arrest cases. We encountered a 48-year-old man who survived a cardiac arrest that lasted approximately 1.5 hours. He visited a local hospital's emergency department complaining of chest pain and dyspnea that had started 3 days earlier. Immediately after arriving in the emergency department, a cardiac arrest occurred; he was transferred to our hospital for extracorporeal membrane oxygenation (ECMO). Resuscitation was performed with strict adherence to the American Heart Association/American College of Cardiology advanced cardiac life support guidelines until ECMO could be placed. On hospital day 7, he had a full neurologic recovery. On hospital day 58, additional treatments, including orthotopic heart transplantation, were considered necessary; he was transferred to another hospital. To our knowledge, this is the first case in South Korea of patient survival with good neurologic outcomes after resuscitation that lasted as long as 1.5 hours. Documenting cases of prolonged resuscitation may lead to updated guidelines and improvement of outcomes of similar cases in future. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  8. Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients

    Directory of Open Access Journals (Sweden)

    Snitcovsky Igor

    2010-05-01

    Full Text Available Abstract Background To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC. Patients and Methods We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR to asses the pattern of TGFβ1, TGFβ2, TGFβ3 in oral SCC. Results Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively. In addition, simultaneously Smad2- and Smad6+ oral SCC group of patients did not reach median overall survival (mOS whereas the mOS of Smad2+/Smad6- subgroup was 11.6 months (P = 0.004, univariate analysis. Regarding to TGFβ isoforms, we found that Smad2 mRNA and TGFβ1 mRNA were inversely correlated (p = 0.05, R = -0.33, and that seven of the eight TGFβ1+ patients were Smad2-. In larynx SCC, Smad7- patients did not reach mOS whereas mOS of Smad7+ patients were only 7.0 months (P = 0.04. No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. Conclusion Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFβ signaling should be better clarified in the future.

  9. Revisiting the prognostic value of preoperative 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in early-stage (I and II) non-small cell lung cancers (NSCLC)

    International Nuclear Information System (INIS)

    Agarwal, Mohit; Brahmanday, Govinda; Bajaj, Sunil K.; Wong, Ching-Yee Oliver; Ravikrishnan, K.P.

    2010-01-01

    The aims were to determine if the maximum standardized uptake value (SUV max ) of the primary tumor as determined by preoperative 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) positron emission tomography (PET) is an independent predictor of overall survival and to assess its prognostic value after stratification according to pathological staging. A retrospective clinicopathologic review of 363 patients who had a preoperative 18 F-FDG PET done before undergoing attempted curative resection for early-stage (I and II) non-small cell lung cancer (NSCLC) was performed. Patients who had received any adjuvant or neoadjuvant chemotherapy or radiation therapy were excluded. The primary outcome measure was duration of overall survival. Receiver-operating characteristic (ROC) curves were plotted to find out the optimal cutoff values of SUV max yielding the maximal sensitivity plus specificity for predicting the overall survival. Survival curves stratified by median SUV max and optimal cutoff SUV max were estimated by the Kaplan-Meier method and statistical differences were assessed using the log-rank test. Multivariate proportional hazards (Cox) regression analyses were applied to test the SUV max 's independency of other prognostic factors for the prediction of overall survival. The median duration of follow-up was 981 days (2.7 years). The median SUV max was 5.9 for all subjects, 4.5 for stage IA, 8.4 for stage IB, and 10.9 for stage IIB. The optimal cutoff SUV max was 8.2 for all subjects. No optimal cutoff could be established for specific stages. In univariate analyses, each doubling of SUV max [i.e., each log (base 2) unit increase in SUV max ] was associated with a 1.28-fold [95% confidence interval (CI): 1.03-1.59, p = 0.029] increase in hazard of death. Univariate analyses did not show any significant difference in survival by SUV max when data were stratified according to pathological stage (p = 0.119, p = 0.818, and p = 0.882 for stages IA, IB, and IIB, respectively

  10. Impella 2.5 initiated prior to unprotected left main PCI in acute myocardial infarction complicated by cardiogenic shock improves early survival.

    Science.gov (United States)

    Meraj, Perwaiz M; Doshi, Rajkumar; Schreiber, Theodore; Maini, Brijeshwar; O'Neill, William W

    2017-06-01

    To assess post-procedural outcomes when Impella 2.5 percutaneous left ventricular assist device (pLVAD) support is initiated either prior to or after percutaneous coronary intervention (PCI) on unprotected left main coronary artery (ULMCA) culprit lesion in the context of acute myocardial infarction cardiogenic shock (AMICS). Initiation of Impella 2.5 pLVAD prior to PCI is associated with significant survival benefit in the setting of AMICS. Outcomes of those presenting with a ULMCA culprit lesion in this setting have not been well characterized. Thirty-six consecutive patients in the cVAD Registry supported with Impella 2.5 pLVAD for AMICS who underwent PCI on ULMCA culprit lesion were included in our multicenter study. The average age was 69.8 ± 14.2 years, 77.8% were male, 72.7% were in CS at admission, 44.4% sustained one or multiple cardiac arrests, and 30.6% had anoxic brain injury. Baseline characteristics were comparable between the Pre-PCI group (n = 20) and Post-PCI group (n = 16). Non-ST segment elevation myocardial infarction and greater coronary disease burden were significantly more frequent in the Pre-PCI group but they had significantly better survival to discharge (55.0% vs 18.8%, P = 0.041). Kaplan-Meier 30-day survival analysis showed very poor survival in Post-PCI group (48.1% vs 12.5%, Log-Rank P = 0.004). Initiation of Impella 2.5 pLVAD prior to as compared with after PCI of ULMCA for AMICS culprit lesion is associated with significant early survival. As previously described, patients supported after PCI appear to have very poor survival at 30 days. © 2017, Wiley Periodicals, Inc.

  11. Activated platelets contribute to oxidized low-density lipoproteins and dysfunctional high-density lipoproteins through a phospholipase A2-dependent mechanism

    NARCIS (Netherlands)

    Blache, Denis; Gautier, Thomas; Tietge, Uwe J. F.; Lagrost, Laurent

    Plasma activity of secretory phospholipase A2 (sPLA2) increases in patients with cardiovascular disease. The present study investigated whether platelet-released sPLA2 induces low-density lipoprotein (LDL) and high-density lipoprotein (HDL) modifications that translate into changes in lipoprotein

  12. Regulation of Trib2 by an E2F1-C/EBPα feedback loop in AML cell proliferation

    DEFF Research Database (Denmark)

    Rishi, Loveena; Hannon, Maura; Salomè, Mara

    2014-01-01

    α (C/EBPα)-p42, occurs in acute myeloid leukemia (AML), resulting in the perturbation of cell cycle and apoptosis, emphasizing its importance in the molecular pathogenesis of AML. Here we show that E2F family members directly regulate Trib2 in leukemic cells and identify a feedback regulatory loop......The loss of regulation of cell proliferation is a key event in leukemic transformation, and the oncogene tribbles (Trib)2 is emerging as a pivotal target of transcription factors in acute leukemias. Deregulation of the transcription factor E2F1, normally repressed by CCAAT enhancer-binding protein...... for E2F1, C/EBPα, and Trib2 in AML cell proliferation and survival. Further analyses revealed that E2F1-mediated Trib2 expression was repressed by C/EBPα-p42, and in normal granulocyte/macrophage progenitor cells, we detect C/EBPα bound to the Trib2 promoter. Pharmacological inhibition of the cell cycle...

  13. Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.

    Science.gov (United States)

    De Luca, Maria Antonietta; Castelli, M Paola; Loi, Barbara; Porcu, Alessandra; Martorelli, Mariella; Miliano, Cristina; Kellett, Kathryn; Davidson, Colin; Stair, Jacqueline L; Schifano, Fabrizio; Di Chiara, Gaetano

    2016-06-01

    In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPγS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F-PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 μM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The Value of Serum NR2 Antibody in Prediction of Post-Cardiopulmonary Resuscitation Survival

    Directory of Open Access Journals (Sweden)

    Ali Bidari

    2015-07-01

    Full Text Available Introduction: N-methyl-D-aspartate receptor subunits antibody (NR2-ab is a sensitive marker of ischemic brain damage in clinical circumstances, such as cerebrovascular accidents. We aimed to assess the value of serum NR2-ab in predicting the post-cardiopulmonary resuscitation (CPR survival. Methods: In this cohort study, we examined serum NR2-ab levels 1 hour after the return of spontaneous circulation (ROSC in 49 successfully resuscitated patients. Patients with traumatic or asphyxic arrests, prior neurological insults, or major medical illnesses were excluded. Participants were followed until death or hospital discharge. Demographic data, coronary artery disease risk factors, time before initiation of CPR, and CPR duration were documented.  In addition, Glasgow coma scale (GCS, blood pressure, and survival status of patients were recorded at 1, 6, 24, and 72 hour(s after ROSC. Descriptive analyses were performed, and the Cox proportional hazard model was applied to assess if NR2-ab level is an independent predictive factor of survival. Results: 49 successfully resuscitated patients were evaluated; 27 (55% survived to hospital discharge, 4 (8.1% were in vegetative state, 10 (20.4% were physically disabled, and 13 (26.5% were physically functional. Within 72 hours of ROSC all of the 12 NR2-ab positive patients died. In contrast, 31 (84% of the NR2-ab negative patients survived. Sensitivity, specificity, positive and negative likelihood ratios of NR2-ab in prediction of survival were 54.5% (95%CI=32.7%-74.9%, 100% (95%CI=84.5%-100%, infinite, and 45.5% (95%CI=28.8%-71.8%, respectively. Subsequent analysis showed that both NR2-ab status and GCS were independent risk factors of death. Conclusions: A positive NR2-ab serum test 1 hour after ROSC correlated with lower 72-hour survival. Further studies are required to validate this finding and demonstrate the value of a quantitative NR2-ab assay and its optimal time of measurement.

  15. Purification and biochemical characterization of pancreatic phospholipase A2 from the common stingray Dasyatis pastinaca

    Directory of Open Access Journals (Sweden)

    Gargouri Youssef

    2011-02-01

    Full Text Available Abstract Background Mammalian sPLA2-IB are well characterized. In contrast, much less is known about aquatic ones. The aquatic world contains a wide variety of living species and, hence represents a great potential for discovering new lipolytic enzymes. Results A marine stingray phospholipase A2 (SPLA2 was purified from delipidated pancreas. Purified SPLA2, which is not glycosylated protein, was found to be monomeric protein with a molecular mass of 14 kDa. A specific activity of 750 U/mg for purified SPLA2 was measured at optimal conditions (pH 8.5 and 40 °C in the presence of 4 mM NaTDC and 8 mM CaCl2 using PC as substrate. The sequence of the first twenty first amino-acid residues at the N-terminal extremity of SPLA2 was determined and shows a close similarity with known mammal and bird pancreatic secreted phospholipases A2. SPLA2 stability in the presence of organic solvents, as well as in acidic and alkaline pH and at high temperature makes it a good candidate for its application in food industry. Conclusions SPLA2 has several advantageous features for industrial applications. Stability of SPLA2 in the presence of organic solvents, and its tolerance to high temperatures, basic and acidic pH, makes it a good candidate for application in food industry to treat phospholipid-rich industrial effluents, or to synthesize useful chemical compounds.

  16. [Survival pronostic factors in Mexican patients with multiforme glioblastoma].

    Science.gov (United States)

    Hernández-Reyna, Ricardo; Medellín-Sánchez, Roberto; Cerda-Flores, Ricardo M; Calderón-Garcidueñas, Ana Laura

    2010-01-01

    To study the pre- and transoperative factors that influence patients' survival with GM. Clinical and pathological records of all confirmed cases of GM diagnosed between 2000 and 2006 were included. Postoperative survival was divided in less or more than 8 months. χ2 test was used. One hundred and twenty patients (45 women and 75 men) were studied. Age range was from 7 to 85 years, 3.3% were 16 years old or younger and 12.5% were 70 years old or older. Headache was the most frequent complain, 40 patients developed hemiparesia and 6 had parestesias. Predominance of white matter hemispheric lesions was observed: right hemispheric tumors 65 (54%), left lesions 30 (25%) and bilateral tumors 7%. Histologically, 1.6% of GM had a sarcomatous component; 35% of patients survived less than 8 months. A difference between patients survival was the preoperative Karnofsky Performance Scale Score and the degree of cerebral edema during the surgical procedure. Pre-operative Karnofsky evaluation and edema during the surgical procedure were significant prognostic factors for survival.

  17. Survival and prognostic factors in 321 patients treated with stereotactic body radiotherapy for oligo-metastases

    DEFF Research Database (Denmark)

    Fode, Mette Marie; Høyer, Morten

    2015-01-01

    BACKGROUND AND PURPOSE: To establish a model to predict survival after SBRT for oligo-metastases in patients considered ineligible for surgical resection (SR) and radiofrequency ablation (RFA). MATERIAL AND METHODS: Overall survival (OS) rates were estimated in 321 patients treated for 587...... metastases with SBRT over 13years. Patients were treated for a variety of metastasis types with colorectal cancer (CRC) being the most frequent (n=201). RESULTS: With a median follow-up time of 5.0years, the median OS was 2.4years (95% CI 2.3-2.7) and the survival rates were 80%, 39%, 23% and 12% at 1, 3, 5...... and 7.5years after SBRT, respectively. WHO performance status (PS) (0-1) (HR 0.49; pSBRT chemotherapy (HR 0.59; p

  18. Schedules of Controlled Substances: Temporary Placement of Six Synthetic Cannabinoids (5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA and MDMB-FUBINACA) into Schedule I. Temporary Scheduling Order.

    Science.gov (United States)

    2017-04-10

    The Administrator of the Drug Enforcement Administration is issuing this temporary scheduling order to schedule six synthetic cannabinoids: methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [5F-ADB; 5F-MDMB-PINACA]; methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3-methylbutanoate [5F-AMB]; N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide [5F-APINACA, 5F-AKB48]; N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide [ADB-FUBINACA]; methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-CHMICA, MMB-CHMINACA] and methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate [MDMB-FUBINACA], and their optical, positional, and geometric isomers, salts, and salts of isomers into schedule I pursuant to the temporary scheduling provisions of the Controlled Substances Act. This action is based on a finding by the Administrator that the placement of these synthetic cannabinoids into schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. As a result of this order, the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances will be imposed on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle, 5F-ADB, 5F-AMB, 5F-APINACA, ADB-FUBINACA, MDMB-CHMICA or MDMB-FUBINACA.

  19. E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

    KAUST Repository

    Kothandaraman, Narasimhan

    2010-02-24

    Background: Ovarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.Methods: Using a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.Results: Analysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity

  20. Radiosynthesis of dimethyl-2-[{sup 18}F]-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate for L-type calcium channel imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghpour, H. [Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School (AMIRS), Karaj (Iran); Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran Univ. of Medical Sciences, Tehran (Iran); Jalilian, A.R.; Akhlaghi, M.; Mirzaei, M. [Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School (AMIRS), Karaj (Iran); Shafiee, A. [Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran Univ. of Medical Sciences, Tehran (Iran); Miri, R. [Medicinal and Natural Products Chemistry Research Center, Shiraz Univ. of Medical Sciences, Shiraz (Iran)

    2008-07-01

    Dimethyl 2-(fluoromethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 4a, a fluorinated nifedipine analog, has been shown to elicit significant calcium channel blocker activity using a guinea pig ileal longitudinal smooth muscle model. In order to perform biological studies for detection of L-type calcium channel distribution, we decided to prepare the [{sup 18}F]-labeled compound. The latter compound was prepared in no-carrier-added (n.c.a.) form from dimethyl 2-(bromomethyl)-6-methyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 2 in one step at 80 C in Kryptofix[222]/K[{sup 18}F]F and acetonitrile as a solvent in 15 min. Column chromatography afforded the radiochemically pure compound in 20 min. Radiochemical purity of the {sup 18}F-nifedipine was determined by RTLC and HPLC (> 98%) and specific activity of 21-48 GBq/{mu}mol (EOB). (orig.)

  1. Pilot prospective evaluation of {sup 18}F-FPPRGD{sub 2} PET/CT in patients with cervical and ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Minamimoto, Ryogo; Jamali, Mehran; Gambhir, Sanjiv Sam [Stanford University, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford, CA (United States); Karam, Amer; Dorigo, Oliver [Stanford University, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford, CA (United States); Barkhodari, Amir; Iagaru, Andrei [Stanford University, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States)

    2016-06-15

    We report the effect of antiangiogenic therapy on the biodistribution of {sup 18}F-FPPRGD{sub 2} (a surrogate biomarker of integrin α{sub v}β{sub 3} expression), and the potential of {sup 18}F-FPPRGD{sub 2} to predict the prognosis in patients with cervical cancer and ovarian cancer in this clinical scenario. Data from six women, age range 30 - 59 years (mean ± SD 44.0 ± 12.5 years), who had undergone a {sup 18}F-FPPRGD{sub 2} PET/CT scan and bevacizumab-containing therapy were prospectively collected and analyzed. We compared baseline {sup 18}F-FPPRGD{sub 2} and {sup 18}F-FDG uptake in the lesions and tumor-to-background (T/B) ratios. The maximum and mean {sup 18}F-FPPRGD{sub 2} standardized uptake values (SUV{sub max} and SUV{sub mean}) were recorded for 13 normal organs, as well as in all the identified malignant lesions on the pretreatment scan and the 1-week post-treatment scan. We also measured changes in {sup 18}F-FPPRGD{sub 2} uptake from before to 1 week after treatment{sub ,} and compared them to the changes in {sup 18}F-FDG uptake from before to 6 weeks after treatment. Treatment outcomes were correlated with these changes. The uptake in lesions and T/B ratio of {sup 18}F-FPPRGD{sub 2} were lower than those of {sup 18}F-FDG (SUV{sub max} 3.7 ± 1.3 vs. 6.0 ± 1.8, P < 0.001; SUV{sub mean} 2.6 ± 0.7 vs. 4.2 ± 1.3, P < 0.001; T/B ratio based on SUV{sub max} 2.4 ± 1.0 vs. 2.6 ± 1.0, P < 0.04; T/B ratio based on SUV{sub mean} 1.9 ± 0.6 vs. 2.4 ± 1.0, P < 0.003). One patient did not return for the follow-up scan and in another patient no lesions were identified on the pretreatment scan. {sup 18}F-FPPRGD{sub 2} uptake in lesions in the remaining four patients had significantly changed 1 week after treatment (SUV{sub mean} 3.3 ± 1.0 vs. 2.7 ± 1.0, P < 0.001), while uptake in all normal tissues analyzed was not affected by treatment. One patient with clinical disease progression had a decrease in lesional {sup 18}F-FPPRGD{sub 2} SUV{sub mean} of 1

  2. Association of GSTO1 and GSTO2 Polymorphism with Risk of End-Stage Renal Disease Development and Patient Survival

    Directory of Open Access Journals (Sweden)

    Cimbaljevic Slavica

    2016-09-01

    Full Text Available Background: Oxidative stress in patients with end-stage renal disease (ESRD is associated with long-term cardiovascular complications. The cytosolic family of glutathione S-transferases (GSTs is involved in the detoxication of various toxic compounds and antioxidant protection. GST omega class members, GSTO1 and GSTO2 possess, unlike other GSTs, dehydroascorbate reductase and deglutathionylation activities. The aim of this study was to clarify the role of genetic polymorphisms of GSTO1 (rs4925 and GSTO2 (rs156697 as risk determinants for ESRD development, as well as in the survival of these patients.

  3. JAK2 V617F-dependent upregulation of PU.1 expression in the peripheral blood of myeloproliferative neoplasm patients.

    Directory of Open Access Journals (Sweden)

    Tamotsu Irino

    Full Text Available Myeloproliferative neoplasms (MPN are multiple disease entities characterized by clonal expansion of one or more of the myeloid lineages (i.e. granulocytic, erythroid, megakaryocytic and mast cell. JAK2 mutations, such as the common V617F substitution and the less common exon 12 mutations, are frequently detected in such tumor cells and have been incorporated into the diagnostic criteria published by the World Health Organization since 2008. However, the mechanism by which these mutations contribute to MPN development is poorly understood. We examined gene expression profiles of MPN patients focusing on genes in the JAK-STAT signaling pathway using low-density real-time PCR arrays. We identified the following 2 upregulated genes in MPN patients: a known target of the JAK-STAT axis, SOCS3, and a potentially novel target, SPI1, encoding PU.1. Induction of PU.1 expression by JAK2 V617F in JAK2-wildtype K562 cells and its downregulation by JAK2 siRNA transfection in JAK2 V617F-positive HEL cells supported this possibility. We also found that the ABL1 kinase inhibitor imatinib was very effective in suppressing PU.1 expression in BCR-ABL1-positive K562 cells but not in HEL cells. This suggests that PU.1 expression is regulated by both JAK2 and ABL1. The contribution of the two kinases in driving PU.1 expression was dominant for JAK2 and ABL1 in HEL and K562 cells, respectively. Therefore, PU.1 may be a common transcription factor upregulated in MPN. PU.1 is a transcription factor required for myeloid differentiation and is implicated in erythroid leukemia. Therefore, expression of PU.1 downstream of activated JAK2 may explain why JAK2 mutations are frequently observed in MPN patients.

  4. Marital Status and Survival in Patients with Carcinoid Tumors.

    Science.gov (United States)

    Greenleaf, Erin K; Cooper, Amanda B; Hollenbeak, Christopher S

    2016-01-01

    Marital status is a known prognostic factor in overall and disease-specific survival in several types of cancer. The impact of marital status on survival in patients with carcinoid tumors remains unknown. We hypothesized that married patients have higher rates of survival than similar unmarried patients with carcinoid tumors. Using the Surveillance, Epidemiology, and End Results database, we identified 23,126 people diagnosed with a carcinoid tumor between 2000 and 2011 and stratified them according to marital status. Univariate and multivariable analyses were performed to compare the characteristics and outcomes between patient cohorts. Overall and cancer-related survival were analyzed using the Kaplan-Meier method. Multivariable survival analyses were performed using Cox proportional hazards models (hazards ratio [HR]), controlling for demographics and tumor-related and treatment-related variables. Propensity score analysis was performed to determine surgical intervention distributions among married and unmarried (ie, single, separated, divorced, widowed) patients. Marital status was significantly related to both overall and cancer-related survival in patients with carcinoid tumors. Divorced and widowed patients had worse overall survival (HR, 1.33 [95% confidence interval {CI}, 1.08-1.33] and 1.34 [95% CI, 1.22-1.46], respectively) and cancer-related survival (HR, 1.15 [95% CI, 1.00-1.31] and 1.15 [95% CI, 1.03-1.29], respectively) than married patients over five years. Single and separated patients had worse overall survival (HR, 1.20 [95% CI, 1.08-1.33] and 1.62 [95% CI, 1.25-2.11], respectively) than married patients over five years, but not worse cancer-related survival. Unmarried patients were more likely than matched married patients to undergo definitive surgical intervention (62.67% vs 53.11%, respectively, P married patients have a survival advantage after diagnosis of any carcinoid tumor, potentially reflecting better social support and financial means

  5. A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuzhu Jiang; Seon-Hee Yim; Hai-Dong Xu; Seung-Hyun Jung; So Young Yang; Hae-Jin Hu; Chan-Kwon Jung; Yeun-Jun Chung

    2011-01-01

    AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

  6. Survival of Sami cancer patients

    Directory of Open Access Journals (Sweden)

    Leena Soininen

    2012-07-01

    Full Text Available Objectives. The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. Study design. The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300–500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979–2009 was compared with that of the Finnish patients outside the cohort. Methods. The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan–Meier method and Cox regression modelling. Results. There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85–1.30 and for non-Sami 1.02 (0.86–1.20, indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. Conclusion. Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland.

  7. Patient-prosthesis mismatch after transapical aortic valve implantation: incidence and impact on survival.

    Science.gov (United States)

    Kukucka, Marian; Pasic, Miralem; Dreysse, Stephan; Mladenow, Alexander; Habazettl, Helmut; Hetzer, Roland; Unbehaun, Axel

    2013-02-01

    Transcatheter aortic valve implantation (TAVI) has become an important therapeutic option for high-risk patients with severe aortic valve stenosis. Patient-prosthesis mismatch (P-PM) is an important determinant of morbidity and mortality after open aortic valve replacement. The objective of our study was to evaluate P-PM incidence and its impact on survival in a large cohort of patients treated with TAVI. We retrospectively analyzed transesophageal echocardiographic data of 278 consecutive patients (Society of Thoracic Surgeons score 18.5 ± 15.3, age 80 ± 8 years) who underwent transapical TAVI with Edwards Sapien valves between April 2008 and March 2011. Effective orifice area was calculated using the continuity equation and indexed with body surface area (iEOA). P-PM was stratified as severe (iEOA < 0.65 cm(2)/cm(2)) and moderate (iEOA, 0.65-0.85 cm(2)/m(2)). Midterm survival (up to 30 months) was analyzed by Kaplan-Meier curves and log-rank tests. There was no P-PM in 181 (65.1%) patients; moderate P-PM was found in 76 (27.3%) patients and severe P-PM in 21 (7.6%). Thirty-day survival was 96.0%, 97.3%, and 90.5%. The 3-month survival was 91%, 90%, and 66%, respectively (P = .0013). Combination of severe P-PM with peak pressure gradients greater than 10 mm Hg further reduced the 3-month survival to 48%. Additionally, mean survival time in patients with an ejection fraction less than 50% was significantly shorter than in patients with an ejection fraction greater than 50% (20.8 ± 1.5 vs 24.1 ± 0.8 months; P = .027). P-PM is found in patients undergoing transapical TAVI. Severe mismatch is accompanied by high early mortality, especially when combined with increased pressure gradients. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  8. Preclinical evaluation of [{sup 18}F]2FNQ1P as the first fluorinated serotonin 5-HT{sub 6} radioligand for PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Guillaume [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); Colomb, Julie [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); Sgambato-Faure, Veronique; Tremblay, Leon [Universite Claude Bernard Lyon 1, CNRS, Cognitive Neuroscience Center, Bron (France); Billard, Thierry [Universite Claude Bernard Lyon 1, CNRS, Institute of Chemistry and Biochemistry, Villeurbanne (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France); Zimmer, Luc [Universite Claude Bernard Lyon 1, CNRS INSERM, Lyon Neuroscience Research Center, Lyon (France); Hospices Civils de Lyon, Lyon (France); CERMEP-Imaging Platform, Groupement Hospitalier Est, Lyon (France)

    2014-10-21

    Brain serotonin 6 receptor (5-HT{sub 6}) is one of the most recently identified serotonin receptors. It is a potent therapeutic target for psychiatric and neurological diseases, e.g. schizophrenia and Alzheimer's disease. Since no specific fluorinated radioligand has yet been successfully used to study this receptor by positron emission tomography (PET) neuroimaging, the objective of the present study was to study the first 5-HT{sub 6} {sup 18}F-labelled radiotracer. 2FNQ1P, inspired by the quinolone core of a previous radiotracer candidate, GSK215083, was selected according its 5-HT{sub 6} affinity and selectivity and was radiolabelled by {sup 18}F nucleophilic substitution. The cerebral distribution of [{sup 18}F]2FNQ1P was studied in vivo in rats, cats and macaque monkeys. The chemical and radiochemical purities of [{sup 18}F]2FNQ1P were >98 %. In rats, in vitro competition with the 5-HT{sub 6} antagonist, SB258585, revealed that the radioligand was displaced dose dependently. Rat microPET studies showed low brain uptake of [{sup 18}F]2FNQ1P, reversed by the P-glycoprotein inhibitor, cyclosporin. On the contrary, PET scans in cats showed good brain penetration and specific striatal binding blocked after pretreatment with unlabelled 2FNQ1P. PET scans in macaque monkeys confirmed high specific binding in both cortical and subcortical regions, specifically decreased by pretreatment with the 5-HT{sub 6} receptor antagonist, SB258585. 2FNQ1P was initially selected because of its suitable characteristics for 5-HT{sub 6} receptor probing in vitro in terms of affinity and specificity. Although in vivo imaging in rats cannot be considered as predictive of the clinical characteristics of the radiotracer, [{sup 18}F]2FNQ1P appeared to be a suitable 5-HT{sub 6} PET tracer in feline and primate models. These preclinical results encourage us to pursue the clinical development of this first fluorinated 5-HT{sub 6} PET radiotracer. (orig.)

  9. Hitherto unseen survival in an ALK-positive-patient with advanced stage adult ganglioneuroblastoma treated with personalized medicine

    DEFF Research Database (Denmark)

    Risum, Signe; Knigge, Ulrich; Langer, Seppo W

    2017-01-01

    Survival of stage 4 ganglioneuroblastoma (GNB) patients is poor; no reports exist of patients surviving up to 5 years (1, 2). We report the clinical and therapeutic course of a patient with stage 4 GNB surviving beyond expectations due to a multimodal treatment approach incorporating new technolo...

  10. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl+ K562 and Jak2(V617F)+ HEL Leukemia Cells

    International Nuclear Information System (INIS)

    Weber, Axel; Borghouts, Corina; Brendel, Christian; Moriggl, Richard; Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd

    2015-01-01

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl + K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5

  11. Aryl-1H-imidazole[4,5f][1,10]phenanthroline Cu(II) complexes: Electrochemical and DNA interaction studies.

    Science.gov (United States)

    Rajebhosale, Bharati S; Dongre, Shivali N; Deshpande, Sameer S; Kate, Anup N; Kumbhar, Anupa A

    2017-10-01

    The reaction of aryl imidazo[4,5f] [1,10]phenanthrolines with Cu(NO 3 ) 2 lead to the formation of Cu(II) complexes of the type [Cu(L)(NO 3 ) 2 ] where L=PIP, 2-(phenyl) [4,5f] imidazo phenanthroline; HPIP=2-(2-hydroxyphenyl)imidazo [4,5f] phenanthroline and NIP=2-(naphthyl) [4,5f] imidazo phenanthroline. The interaction of these complexes with calf thymus DNA has been studied using viscosity measurements, UV-visible and fluorescence spectroscopy. Chemical nuclease activity of these complexes has also been investigated. All complexes cleave DNA via oxidative pathway involving singlet oxygen. Molecular docking studies revealed that these complexes bind to DNA through minor groove. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription

    DEFF Research Database (Denmark)

    Cartwright, P; Müller, H; Wagener, C

    1998-01-01

    with E2Fs 1-5, especially within the DNA binding, heterodimerization and marked box domains. Unlike E2Fs 1-5, E2F-6 lacks a transactivation and a pocket protein binding domain, hence, forms a unique third group within the E2F family. E2F-6 is a nuclear protein that can form heterodimers with the DP......The E2F family of transcription factors are essential for the regulation of genes required for appropriate progression through the cell cycle. Five members of the E2F family have been previously reported, namely E2F1-5. All five are key elements in transcriptional regulation of essential genes......, and they can be divided into two functional groups, those that induce S-phase progression when overexpressed in quiescent cells (E2Fs 1-3), and those that do not (E2Fs 4-5). Here, we describe the identification of a novel member of this family, which we refer to as E2F-6. E2F-6 shares significant homology...

  13. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

    Science.gov (United States)

    Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

    2004-05-01

    E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

  14. Extrathyroidal Extension Is Associated with Compromised Survival in Patients with Thyroid Cancer.

    Science.gov (United States)

    Youngwirth, Linda M; Adam, Mohamed A; Scheri, Randall P; Roman, Sanziana A; Sosa, Julie A

    2017-05-01

    Patients with thyroid cancer who have extrathyroidal extension (ETE) are considered to have more advanced tumors. However, data on the impact of ETE on patient outcomes remain limited. The purpose of this study was to evaluate the association between ETE and survival in patients with thyroid cancer. The National Cancer Database (1998-2012) was queried for all adult patients with differentiated thyroid cancer and medullary thyroid cancer. Patients were divided into three groups: no ETE (T1 and T2 tumors), minimal ETE (T3 tumors thyroid cancer met the inclusion criteria; 86.9% had no ETE, 9.1% minimal ETE, and 4.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.4 cm vs. 1.8 cm and 2.0 cm, respectively), lymphovascular invasion (8.6% vs. 28.0% and 35.1%, respectively), positive margins after thyroidectomy (6.1% vs. 35.2% and 45.9%, respectively), and regional lymph node metastases (32.5% vs. 67.0% and 74.6%, respectively; all p thyroid cancer. In total, 3415 patients with medullary thyroid cancer met the inclusion criteria; 87.9% had no ETE, 7.1% minimal ETE, and 5.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.7 cm vs. 2.2 cm and 2.2 cm, respectively), lymphovascular invasion (19.2% vs. 68.9% and 79.3%, respectively), positive margins after thyroidectomy (5.8% vs. 44.1% and 51.9%, respectively), and regional lymph node metastases (39.0% vs. 90.5% and 94.4%, respectively; all p thyroid cancer. In patients with differentiated and medullary thyroid cancers, ETE is associated with compromised survival. Given these findings, ETE should be included in the thyroid cancer treatment guidelines.

  15. Crystal structure of difluorochloronium hexafluoroniobate and hexafluorotantalate, ClF2NbF6 and ClF2TaF6

    International Nuclear Information System (INIS)

    Ehllern, A.M.; Antipin, M.Yu.; Sharabarin, A.V.; Struchkov, Yu.T.

    1991-01-01

    Crystal structure of ClF 2 NbF 6 (1) and ClF 2 TaF 6 (2) were investigated by the method of X-ray diffraction analysis. Salts 1 and 2 are isostructural, crystals are rhombic: a = 9.981(2) and 10.049(2), b = 5.781(1) and 5.775(1), c = 10.552(2) and 10.670(2) A, V = 608.9(3) and 619.2(3) A 3 , Z = 4, d calcd 3.058 and 3.952 g/cm 3 , sp. gr. Pcca. Both salts are characterized by ionic structure. Bond lengths and valent angles, general view of 1 crystal structure are presented

  16. Radiosynthesis of a novel potential adenosine A{sub 3} receptor ligand, 5-ethyl 2,4-diethyl-3-((2-[{sup 18}F]fluoroethyl)sulfanylcarbonyl)-6-phenylpyridine-5-carboxylate ([{sup 18}F]FE rate at SUPPY:2)

    Energy Technology Data Exchange (ETDEWEB)

    Haeusler, D. [Dept. of Nuclear Medicine, Medical Univ. of Vienna (Austria); Dept. of Pharmaceutical Tech. and Biopharmaceutics, Univ. of Vienna (Austria); Mitterhauser, M. [Dept. of Nuclear Medicine, Medical Univ. of Vienna (Austria); Dept. of Pharmaceutical Tech. and Biopharmaceutics, Univ. of Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna (Austria); Mien, L.K. [Dept. of Nuclear Medicine, Medical Univ. of Vienna (Austria); Dept. of Pharmaceutical Tech. and Biopharmaceutics, Univ. of Vienna (Austria); Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna (Austria); Shanab, K.; Spreitzer, H. [Dept. of Drug and Natural Product Synthesis, Univ. of Vienna (Austria); Lanzenberger, R.R [Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna (Austria); Schirmer, E. [Dept. of Nuclear Medicine, Medical Univ. of Vienna (Austria); Dept. of Drug and Natural Product Synthesis, Univ. of Vienna (Austria); Ungersboeck, J.; Wadsak, W. [Dept. of Nuclear Medicine, Medical Univ. of Vienna (Austria); Dept. of Inorganic Chemistry, Univ. of Vienna (Austria); Nics, L. [Dept. of Nuclear Medicine, Medical Univ. of Vienna (Austria); Dept. of Nutritional Sciences, Univ. of Vienna (Austria); Viernstein, H. [Dept. of Pharmaceutical Tech. and Biopharmaceutics, Univ. of Vienna (Austria); Dudezak, R.; Kletter, K. [Dept. of Nuclear Medicine, Medical Univ. of Vienna (Austria)

    2009-07-01

    Since, to date very limited information on the distribution and function of the adenosine A{sub 3} receptor is available, the development of suitable radioligands is needed. Recently, we introduced [{sup 18}F]FE rate at SUPPY (5-(2-[{sup 18}F]fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate) as the first PET-ligand for the A3R. Regarding the metabolic profile - this class of dialkylpyridines comprises two ester functions within one molecule, one carboxylic and one thiocarboxylic - one could expect carboxylesterases significantly contributing to cleavage and degradation. Therefore, our aim was the development of [{sup 18}F]FE rate at SUPPY:2 (5-ethyl 2,4-diethyl-3-((2-[{sup 18}F]fluoroethyl)sulfanylcarbonyl)-6-phenylpyridine-5-carboxylate), the functional isomer containing the label at the thiocarboxylic moiety. For satisfactory yields in high scale radiosyntheses, a reaction temperature of 75 C has to be applied for at least 20 min using 20 mg/mL of precursor. So far, 6 complete high-scale radiosyntheses were performed. Starting from an average of 51.2 {+-} 21.8 GBq (mean{+-}SD) [{sup 18}F]fluoride, 5.8 {+-} 4.1 GBq of formulated [{sup 18}F]FE rate at SUPPY:2 (12.0{+-}5.4%, based on [{sup 18}F]fluoride, not corrected for decay) were prepared in 75 {+-} 8 min. (orig.)

  17. Association Between a Germline OCA2 Polymorphism at Chromosome 15q13.1 and Estrogen Receptor-Negative Breast Cancer Survival

    DEFF Research Database (Denmark)

    Azzato, E.M.; Tyrer, J.; Fasching, P.A.

    2010-01-01

    -sided. In the hypothesis-generating dataset, SNP rs4778137 (C > G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried...... = 0.56, 95% confidence interval [CI] = 0.41 to 0.75, P = 9.2 x 10(-5)). This association was also observed in the validation dataset (HR of death per rare allele carried = 0.88, 95% CI = 0.78 to 0.99, P = .03) and in the combined dataset (HR of death per rare allele carried = 0.82, 95% CI = 0.73 to 0.......92, P = 5 x 10(-4)). The rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer...

  18. A2TiF5.nH2O (A=K, Rb, or Cs; n=0 or 1): Synthesis, structure, characterization, and calculations of three new uni-dimensional titanium fluorides

    International Nuclear Information System (INIS)

    Jo, Vinna; Woo Lee, Dong; Koo, Hyun-Joo; Ok, Kang Min

    2011-01-01

    Three new uni-dimensional alkali metal titanium fluoride materials, A 2 TiF 5 .nH 2 O (A=K, Rb, or Cs; n=0 or 1) have been synthesized by hydrothermal reactions. The structures of A 2 TiF 5 .nH 2 O have been determined by single-crystal X-ray diffraction. The Ti 4+ cations have been reduced to Ti 3+ during the synthesis reactions. All three A 2 TiF 5 .nH 2 O materials contain novel 1-D chain structures that are composed of the slightly distorted Ti 3+ F 6 corner-sharing octahedra attributable to the Jahn-Teller distortion. The coordination environment of the alkali metal cations plays an important role to determine the degree of turning in the chain structures. Complete structural analyses, Infrared and UV-vis diffuse reflectance spectra, and thermal analyses are presented, as are electronic structure calculations. -- Graphical abstract: Ball-and-stick and polyhedral representations for (a) β-K 2 TiF 5 and (b) Rb 2 TiF 5 .H 2 O or Cs 2 TiF 5 .H 2 O with the K + and Rb + (or Cs + ) coordination environment emphasized. Display Omitted Research highlights: → Synthesis, structure, characterization, and calculation of new titanium fluorides. → Study of reduction of starting Ti 4+ cations to Ti 3+ by DMF. → Novel 1-D chain structures with Jahn-Teller distorted TiF 6 octahedra.

  19. Influence of {sup 18}F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Schuele, Susann-Cathrin; Nikolaou, Konstantin; Pfannenberg, Christina [Eberhard-Karls-University Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Eigentler, Thomas Kurt; Garbe, Claus [Eberhard-Karls-University Tuebingen, Skin Cancer Programme, Department of Dermatology, Tuebingen (Germany); Fougere, Christian la [Eberhard-Karls-University Tuebingen, Department of Nuclear Medicine, Tuebingen (Germany)

    2016-03-15

    To evaluate the influence of {sup 18}F-FDG PET/CT in comparison to CT alone on treatment decisions in patients with advanced melanoma and to analyse the 5-year survival data in comparison to literature data. Therapy management in 64 consecutive patients (primary staging n = 52; surveillance n = 12) with stage III/IV melanoma who underwent {sup 18}F-FDG PET/CT between 2004 and 2005 in our department was retrospectively analysed. Treatment decisions were made by two dermatooncologists for each patient twice, first based on the CT results and then based on the PET/CT results. Therapy changes based on the PET/CT results were classified as ''major'' (e.g. change from metastasectomy to systemic therapy) or ''minor'' (e.g. change from first to second line chemotherapy). The 5-year survival data of different patient cohorts were calculated. In the 52 patients in the primary staging group, the results of {sup 18}F-FDG PET/CT led to therapy change in 59 % and a major therapy change in 52 %. {sup 18}F-FDG PET/CT led to the avoidance of futile operations in 13 patients with suspicious lesions on CT that were deemed nontumorous on PET/CT. In the 12 patients in the surveillance group, the results of {sup 18}F-FDG PET/CT led to therapy change in 33 % and a major change in 17 %. The 5-year survival rates were 30 % in the entire cohort, 34 % in the primary staging group, and 17 % in the surveillance group. A significant overall survival benefit was observed in patients in whom {sup 18}F-FDG PET/CT excluded metastases or in whom metastases could be completely removed compared with patients who were not eligible for surgery (41 % vs. 10 %). Primary staging of patients with stage III/IV melanoma should be performed with {sup 18}F-FDG PET/CT, leading to higher diagnostic accuracy and enabling individualized therapeutic management, especially optimal patient selection for metastasectomy. This strategy may extend long-term survival even in patients

  20. A comparison of survival of patients treated for AIDS-related central nervous system lymphoma with and without tissue diagnosis

    International Nuclear Information System (INIS)

    Kaufmann, Thomas; Nisce, Lourdes Z.; Coleman, Morton

    1996-01-01

    Purpose: This is a retrospective review of the treatment outcome of radiation therapy (RT) in acquired immunedeficiency syndrome (AIDS) patients with presumed primary central nervous system (CNS) non-Hodgkin's lymphoma (NHL), with and without tissue verification. Methods and Materials: Twenty-seven patients with AIDS-related CNS NHL were treated between 1986 and 1992. They were divided into two groups. Group 1 consisted of nine patients with a positive histology for NHL. They were treated with dexamethasone (DXM) and whole brain RT. Group 2 consisted of 18 patients who, because of unique circumstances, were treated without histologic confirmation of NHL. Rapid clinical and/or radiologic response to DXM and whole-brain RT was interpreted as NHL. Results: For group 1, the response rate was 87.5%, mean survival 6.1 months, and median survival 4.5 months. For group 2, the response rate was 72.2%, mean survival 5.2 months, and median survival 4.5 months. The overall response rate was 76.9%, mean survival 5.8 months, and median survival 4.5 months. Conclusions: In instances where a tissue diagnosis cannot be established, a positive response to an empiric trial of DXM and RT to 20 Gy may constitute presumptive evidence of NHL

  1. A Novel Regulatory Mechanism of Smooth Muscle α-Actin Expression by NRG-1/circACTA2/miR-548f-5p Axis.

    Science.gov (United States)

    Sun, Yan; Yang, Zhan; Zheng, Bin; Zhang, Xin-Hua; Zhang, Man-Li; Zhao, Xue-Shan; Zhao, Hong-Ye; Suzuki, Toru; Wen, Jin-Kun

    2017-09-01

    Neuregulin-1 (NRG-1) includes an extracellular epidermal growth factor-like domain and an intracellular domain (NRG-1-ICD). In response to transforming growth factor-β1, its cleavage by proteolytic enzymes releases a bioactive fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation by activating ErbB (erythroblastic leukemia viral oncogene homolog) receptor. However, NRG-1-ICD function in VSMCs remains unknown. Here, we characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs. Immunofluorescence staining, Western blotting, and quantitative real-time polymerase chain reaction showed that NRG-1 was expressed in rat, mouse, and human VSMCs and was upregulated and cleaved in response to transforming growth factor-β1. In the cytoplasm of HASMCs (human aortic smooth muscle cells), the NRG-1-ICD participated in filamentous actin formation by interacting with α-SMA (smooth muscle α-actin). In the nucleus, the Nrg-1-ICD induced circular ACTA2 (alpha-actin-2; circACTA2) formation by recruitment of the zinc-finger transcription factor IKZF1 (IKAROS family zinc finger 1) to the first intron of α-SMA gene. We further confirmed that circACTA2, acting as a sponge binding microRNA (miR)-548f-5p, interacted with miR-548f-5p targeting 3' untranslated region of α-SMA mRNA, which in turn relieves miR-548f-5p repression of the α-SMA expression and thus upregulates α-SMA expression, thereby facilitating stress fiber formation and cell contraction in HASMCs. Accordingly, in vivo studies demonstrated that the localization of the interaction of circACTA2 with miR-548f-5p is significantly decreased in human intimal hyperplastic arteries compared with normal arteries, implicating that dysregulation of circACTA2 and miR-548f-5p expression is involved in intimal hyperplasia. These results suggest that circACTA2 mediates NRG-1-ICD regulation of α-SMA expression in HASMCs via the NRG-1-ICD/circACTA2/miR-548f-5p axis. Our data provide a molecular

  2. Reaction of ether and thioether functionalised 1-alkenes with the cationic permethylzirconocene olefin polymerisation catalyst [(eta(5)-C5Me5)(2)ZrMe](+). Molecular structure of the insertion product [(eta(5)-C5Me5)(2)ZrCH2CH(Me)CH2OEt](+)

    NARCIS (Netherlands)

    Bijpost, Erik A; Zuideveld, Martin A.; Meetsma, Auke; Teuben, Jan H

    1998-01-01

    Reaction of [(η5-C5Me5)2ZrMe][MeB(C6F5)3] (1) with (thio)ether functionalised alkenes: 3-ethoxy-1-propene and 3-(methylthio)-1-propene gives stable insertion products [(η5-C5Me5)2ZrCH2CH(Me)CH2XR][MeB(C6F5)3] (2: X = O, R = Et; 3: X = S, R = Me) in which the (thio)ether function is intramolecularly

  3. A preliminary investigation into textural features of intratumoral metabolic heterogeneity in 18F-FDG PET for overall survival prognosis in patients with bulky cervical cancer treated with definitive concurrent chemoradiotherapy

    Science.gov (United States)

    Ho, Kung-Chu; Fang, Yu-Hua Dean; Chung, Hsiao-Wen; Yen, Tzu-Chen; Ho, Tsung-Ying; Chou, Hung-Hsueh; Hong, Ji-Hong; Huang, Yi-Ting; Wang, Chun-Chieh; Lai, Chyong-Huey

    2016-01-01

    We examined the role of intratumoral metabolic heterogeneity on 18F-FDG PET during concurrent chemoradiotherapy (CCRT) in predicting survival outcomes for patients with cervical cancer. This prospective study consisted of 44 patients with bulky (≥ 4 cm) cervical cancer treated with CCRT. All patients underwent serial 18F-FDG PET studies. Primary cervical tumor standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in pretreatment and intra-treatment (2 weeks) PET scans. Regional textural features were analyzed using the grey level run length encoding method (GLRLM) and grey-level size zone matrix. Associations between PET parameters and overall survival (OS) were tested by Kaplan-Meier analysis and Cox regression model. In univariate analysis, pretreatment grey-level nonuniformity (GLNU) > 48 by GLRLM textural analysis and intra-treatment decline of run length nonuniformity 48 and a ∆TLG ≤ 60% as the high-risk group and the other patients as the low-risk. The 5-year OS rate for the high-risk group was significantly worse than that for the low-risk group (42% vs. 81%, respectively, P = 0.001). The heterogeneity of intratumoral FDG distribution and the early temporal change in TLG may be an important predictor for OS in patients with bulky cervical cancer. This gives the opportunity to adjust individualized regimens early in the treatment course. PMID:27508103

  4. A preliminary investigation into textural features of intratumoral metabolic heterogeneity in (18)F-FDG PET for overall survival prognosis in patients with bulky cervical cancer treated with definitive concurrent chemoradiotherapy.

    Science.gov (United States)

    Ho, Kung-Chu; Fang, Yu-Hua Dean; Chung, Hsiao-Wen; Yen, Tzu-Chen; Ho, Tsung-Ying; Chou, Hung-Hsueh; Hong, Ji-Hong; Huang, Yi-Ting; Wang, Chun-Chieh; Lai, Chyong-Huey

    2016-01-01

    We examined the role of intratumoral metabolic heterogeneity on (18)F-FDG PET during concurrent chemoradiotherapy (CCRT) in predicting survival outcomes for patients with cervical cancer. This prospective study consisted of 44 patients with bulky (≥ 4 cm) cervical cancer treated with CCRT. All patients underwent serial (18)F-FDG PET studies. Primary cervical tumor standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in pretreatment and intra-treatment (2 weeks) PET scans. Regional textural features were analyzed using the grey level run length encoding method (GLRLM) and grey-level size zone matrix. Associations between PET parameters and overall survival (OS) were tested by Kaplan-Meier analysis and Cox regression model. In univariate analysis, pretreatment grey-level nonuniformity (GLNU) > 48 by GLRLM textural analysis and intra-treatment decline of run length nonuniformity 48 and a ∆TLG ≤ 60% as the high-risk group and the other patients as the low-risk. The 5-year OS rate for the high-risk group was significantly worse than that for the low-risk group (42% vs. 81%, respectively, P = 0.001). The heterogeneity of intratumoral FDG distribution and the early temporal change in TLG may be an important predictor for OS in patients with bulky cervical cancer. This gives the opportunity to adjust individualized regimens early in the treatment course.

  5. Systematic analysis of spectroscopic characteristics of the lanthanide and actinide ions with the 4f{sup N−1}5d and 5f{sup N−1}6d electronic configurations in a free state

    Energy Technology Data Exchange (ETDEWEB)

    Ma, C.-G. [College of Mathematics and Physics, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China); Brik, M.G., E-mail: brik@fi.tartu.ee [College of Mathematics and Physics, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China); Institute of Physics, University of Tartu, Riia 142, Tartu 51014 (Estonia); Institute of Physics, Jan Dlugosz University, Armii Krajowej 13/15, PL-42200 Czestochowa (Poland); Tian, Y.; Li, Q.-X. [College of Mathematics and Physics, Chongqing University of Posts and Telecommunications, Chongqing 400065 (China)

    2014-08-01

    Highlights: • Calculated spectroscopic parameters of f{sup N−1}d configurations of the 4f and 5f ions. • Relations between the Slater parameters, spin–orbit constant, atomic number were found. • Barycenters of the electronic configuration energies were calculated. • Obtained relations reduce the number of independent terms in a free ion Hamiltonian. - Abstract: Systematic consideration of the spectroscopic properties of the f{sup N−1}d excited electronic configurations of the di-, tri- and tetravalent lanthanide and actinide ions in a free state is presented. Variations of the Hartree–Fock calculated Slater parameters for the f{sup N−1}d electron configurations, spin–orbit (SO) interaction constant ζ for the f and d electrons, and averaged values of the second, fourth and sixth powers of the 4f, 5f, 5d, 6d electrons’ radial coordinate across both series were considered; functional dependencies between the mentioned quantities were obtained. It has been shown that the Coulomb interaction parameters F{sup 2}(ff), F{sup 4}(ff), and F{sup 6}(ff) for the f{sup N−1} core increase linearly with the atomic number Z, whereas the direct and exchange Coulomb parameters F{sup 2}(fd), F{sup 4}(fd), G{sup 1}(fd), G{sup 3}(fd), G{sup 5}(fd) for the f{sup N−1}d configuration decrease linearly with Z. Since the SO interaction constant ζ{sup 1/4} is also proportional to Z, it was possible to find linear relationships between the Coulomb interaction parameters and SO constants for the f and d electrons, which effectively reduce the number of independent parameters in the free ion Hamiltonian. The constraining relations between the free ion Hamiltonian’s parameters obtained in the present paper can be used for simulations of the f–d transition spectra of these ions in various crystals.

  6. Synthesis and evaluation of 18F-labeled 5-HT2A receptor agonists as PET ligands

    International Nuclear Information System (INIS)

    Herth, Matthias M.; Petersen, Ida Nymann; Hansen, Hanne Demant; Hansen, Martin; Ettrup, Anders; Jensen, Anders A.; Lehel, Szabolcs; Dyssegaard, Agnete; Gillings, Nic; Knudsen, Gitte M.

    2016-01-01

    Introduction: The serotonin 2A receptor (5-HT 2A R) is the most abundant excitatory 5-HT receptor in the human brain and implicated in various brain disorders such as schizophrenia, depression, and Alzheimer's disease. Positron emission tomography (PET) can be used to image specific proteins and processes in the human brain and several 5-HT 2A R PET antagonist radioligands are available. In contrast to an antagonist radioligand, an agonist radioligand should be able to image the population of functional receptors, i.e., those capable of inducing neuroreceptor signaling. Recently, we successfully developed and validated the first 5-HT 2A R agonist PET tracer, [ 11 C]Cimbi-36, for neuroimaging in humans and herein disclose some of our efforts to develop an 18 F-labeled 5-HT 2A R agonist PET-ligand. Methods and results: Three fluorine containing derivatives of Cimbi-36 were synthesized and found to be potent 5-HT 2A agonists. 18 F-labeling of the appropriate precursors was performed using [ 18 F]FETos, typically yielding 0.22.0 GBq and specific activities of 40–120 GBq/μmol. PET studies in Danish landrace pigs revealed that [ 18 F]1 displayed brain uptake in 5-HT 2A R rich regions. However, high uptake in bone was also observed. No blocking effect was detected during a competition experiment with a 5-HT 2A R selective antagonist. [ 18 F]2 and [ 18 F]3 showed very low brain uptake. Conclusion: None of the investigated 18 F-labeled Cimbi-36 derivatives [ 18 F]1, [ 18 F]2 and [ 18 F]3 show suitable tracer characteristics for in vivo PET neuroimaging of the 5-HT 2A R. Although for [ 18 F]1 there was reasonable brain uptake, we suggest that a large proportion radioactivity in the brain was due to radiometabolites, which would explain why it could not be displaced by a 5-HT 2A R antagonist.

  7. Survival after Radiofrequency Ablation in 122 Patients with Inoperable Colorectal Lung Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Gillams, Alice, E-mail: alliesorting@gmail.com [The London Clinic, Radiology Department (United Kingdom); Khan, Zahid [Countess of Chester Hospital (United Kingdom); Osborn, Peter [Queen Alexandra Hospital (United Kingdom); Lees, William [University College London Medical School (United Kingdom)

    2013-06-15

    Purpose. To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation. Methods. Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, and factors were compared by log rank test. Results. The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival. Conclusion. Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.

  8. Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FIAU) and micro-PET imaging of suicide gene expression in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

    2004-07-01

    Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FIAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

  9. The Glasgow Prognostic Score. An useful tool to predict survival in patients with advanced esophageal squamous cell carcinoma.

    Science.gov (United States)

    Henry, Maria Aparecida Coelho de Arruda; Lerco, Mauro Masson; de Oliveira, Walmar Kerche; Guerra, Anderson Roberto; Rodrigues, Maria Aparecida Marchesan

    2015-08-01

    To evaluate the usefulness of the Glasgow Prognostic Score (GPS) in patients with esophageal carcinoma (EC). A total of 50 patients with EC were analyzed for GPS, nutritional and clinicopathologic parameters. Patients with CRP ≤ 1.0mg/L and albumin ≥ 3.5mg/L were considered as GPS = 0. Patients with only CRP increased or albumin decreased were classified as GPS = 1 and patients with CRP > 1.0mg/L and albumin L were considered as GPS = 2. GPS of 0, 1 and 2 were observed in seven, 23 and 20 patients, respectively. A significant inverse relationship was observed between GPS scores and the survival rate. The survival rate was greatest in patients with GPS = 0 and significantly higher than those from patients with GPS = 1 and GPS = 2. Minimum 12-month survival was observed in 71% patients with GPS = 0 and in 30% patients with GPS = 1. None of the patients with GPS = 2 survived for 12 months. A significant relationship between CRP or albumin individually and the survival rate was observed. No significant relationship among nutritional, clinic pathological parameters and survival was found. Glasgow Prognostic Score is an useful tool to predict survival in patients with esophageal carcinoma.

  10. Prognostic value of total lesion glycolysis on preoperative {sup 18}F-FDG PET/CT in patients with uterine carcinosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong-Won [Sungkyunkwan University School of Medicine, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of); Sungkyunkwan University School of Medicine, Samsung Advanced Institute for Health Sciences and Technology, Seoul (Korea, Republic of); Heo, Eun Jin [Sungkyunkwan University School of Medicine, Department of Obstetrics and Gynecology, Seoul (Korea, Republic of); Moon, Seung Hwan [Sungkyunkwan University School of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Lee, Hyunjong; Cheon, Gi Jeong [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea, Republic of); Lee, Maria; Kim, Hee Seung; Chung, Hyun Hoon [Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul (Korea, Republic of)

    2016-11-15

    To investigate the relationship between functional tumour parameters measured during preoperative {sup 18}F-FDG PET/CT and clinical outcomes in patients with uterine carcinosarcoma. For patients with pathologically proven uterine carcinosarcoma, we determined the maximal and average standardized uptake values, cumulative total lesion glycolysis (TLG) and sum of all metabolic tumour volumes (MTVs). Their predictive value for recurrence and the effects of pretreatment functional tumour activity on patient survival were compared. Clinicopathological data from 28 eligible patients were reviewed. The median duration of progression-free survival was 18.6 months (range 6.1-84.5 months), and 10 (35.7 %) patients experienced recurrences. Univariate analyses showed significant associations between recurrence and tumour size, lymph node metastasis, high TLG and MTV values, and ovarian invasion. Multivariate analysis identified high TLG value as an independent risk factor for recurrence (p = 0.048, hazard ratio 115.261, 95 % confidence interval 1.041-12,765.483). Kaplan-Meier survival curves showed that progression-free survival significantly differed in groups categorized according to TLG (p = 0.007, log-rank test). Preoperative TLG measured with {sup 18}F-FDG PET/CT was statistically significantly associated with uterine carcinosarcoma recurrence. Metabolic parameters can provide useful quantitative criteria for disease prognostication in patients with uterine carcinosarcoma before treatment. (orig.)

  11. Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Fogh, Isabella; Lin, Kuang; Tiloca, Cinzia; Rooney, James; Gellera, Cinzia; Diekstra, Frank P; Ratti, Antonia; Shatunov, Aleksey; van Es, Michael A; Proitsi, Petroula; Jones, Ashley; Sproviero, William; Chiò, Adriano; McLaughlin, Russell Lewis; Sorarù, Gianni; Corrado, Lucia; Stahl, Daniel; Del Bo, Roberto; Cereda, Cristina; Castellotti, Barbara; Glass, Jonathan D; Newhouse, Steven; Dobson, Richard; Smith, Bradley N; Topp, Simon; van Rheenen, Wouter; Meininger, Vincent; Melki, Judith; Morrison, Karen E; Shaw, Pamela J; Leigh, P Nigel; Andersen, Peter M; Comi, Giacomo P; Ticozzi, Nicola; Mazzini, Letizia; D'Alfonso, Sandra; Traynor, Bryan J; Van Damme, Philip; Robberecht, Wim; Brown, Robert H; Landers, John E; Hardiman, Orla; Lewis, Cathryn M; van den Berg, Leonard H; Shaw, Christopher E; Veldink, Jan H; Silani, Vincenzo; Al-Chalabi, Ammar; Powell, John

    2016-07-01

    Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disorder with a poor prognosis and a median survival of 3 years. However, a significant proportion of patients survive more than 10 years from symptom onset. To identify gene variants influencing survival in ALS. This genome-wide association study (GWAS) analyzed survival in data sets from several European countries and the United States that were collected by the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study population included 4256 patients with ALS (3125 [73.4%] deceased) with genotype data extended to 7 174 392 variants by imputation analysis. Samples of DNA were collected from January 1, 1993, to December 31, 2009, and analyzed from March 1, 2014, to February 28, 2015. Cox proportional hazards regression under an additive model with adjustment for age at onset, sex, and the first 4 principal components of ancestry, followed by meta-analysis, were used to analyze data. Survival distributions for the most associated genetic variants were assessed by Kaplan-Meier analysis. Among the 4256 patients included in the analysis (2589 male [60.8%] and 1667 female [39.2%]; mean [SD] age at onset, 59 [12] years), the following 2 novel loci were significantly associated with ALS survival: at 10q23 (rs139550538; P = 1.87 × 10-9) and in the CAMTA1 gene at 1p36 (rs2412208, P = 3.53 × 10-8). At locus 10q23, the adjusted hazard ratio for patients with the rs139550538 AA or AT genotype was 1.61 (95% CI, 1.38-1.89; P = 1.87 × 10-9), corresponding to an 8-month reduction in survival compared with TT carriers. For rs2412208 CAMTA1, the adjusted hazard ratio for patients with the GG or GT genotype was 1.17 (95% CI, 1.11-1.24; P = 3.53 × 10-8), corresponding to a 4-month reduction in survival compared with TT carriers. This GWAS robustly identified 2 loci at genome-wide levels of

  12. {sup 18}F-fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Pil Soo; Yang, Keungmo; Hwang, Seawon; Song, Myeong Jun; Jang, Jeong Won; Choi, Jong Young; Yoon, Seung Kew; Bae, Si Hyun [The Catholic University of Korea, Division of Hepatology, Department of Internal Medicine, The Catholic University Liver Research Center, College of Medicine, Seoul (Korea, Republic of); Park, Hye Lim; Yoo, Ie Ryung [The Catholic University of Korea, Division of Nuclear Medicine, Department of Radiology, College of Medicine, Seoul (Korea, Republic of)

    2018-03-15

    Sorafenib, an oral multikinase inhibitor, is a recommended treatment option available for patients with Barcelona Clinic Liver Cancer (BCLC)-C stage hepatocellular carcinoma (HCC). This study aimed to evaluate the performance of {sup 18}F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) for predicting tumour progression during sorafenib treatment. We formed a retrospective cohort comprising patients treated with sorafenib for at least 30 days and undergoing {sup 18}F-FDG PET/CT within 1 month before treatment. For statistical analyses, the tumour-to-liver standardised uptake value (SUV) ratio (TLR) of the most hypermetabolic lesion was measured. Among a total of 35 patients, two obtained partial remission, and 11 showed stable disease after the first response evaluation. Patients with a TLR ≥ 2.9 (n = 17) had a median overall survival (OS) of 3.7 months after sorafenib treatment, whereas patients with a TLR < 2.9 (n = 18) had median OS of 12.2 months (P < 0.001), although the disease control rate was not significantly different between the two groups. Pretreatment TLR ≥ 2.9 (hazard ratio [HR] = 6.318, P = 0.002) and Child-Pugh class B (HR = 4.316, P = 0.044) were poor prognostic factors for OS, and a TLR ≥ 2.9 (HR = 2.911, P = 0.024) was the only poor prognostic factor for progression-free survival in a multivariate analysis. Pretreatment tumour metabolic activity assessed by {sup 18}F-FDG PET is an independent prognostic factor for survival in patients with BCLC-C stage HCC receiving sorafenib monotherapy, although it may not predict tumour response to the treatment. (orig.)

  13. Tracheostomy mechanical ventilation in patients with amyotrophic lateral sclerosis: clinical features and survival analysis.

    Science.gov (United States)

    Spataro, Rossella; Bono, Valeria; Marchese, Santino; La Bella, Vincenzo

    2012-12-15

    Tracheostomy mechanical ventilation (TMV) is performed in amyotrophic lateral sclerosis (ALS) patients with a respiratory failure or when the non-invasive ventilation (NIV) is no longer effective. We evaluated the clinical characteristics and survival of a cohort of tracheostomized ALS patients, followed in a single ALS Clinical Center. Between 2001 and 2010, 87 out of 279 ALS patients were submitted to TMV. Onset was spinal in 62 and bulbar in 25. After tracheostomy, most patients were followed up through telephone interviews to caregivers. A complete survival analysis could be performed in fifty-two TMV patients. 31.3% ALS patients underwent tracheostomy, with a male prevalence (M/F=1.69) and a median age of 61 years (interquartile range=47-66). After tracheostomy, nearly all patients were under home care. TMV ALS patients were more likely than non-tracheostomized (NT) patients to be implanted with a PEG device, although the bulbar-/spinal-onset ratio did not differ between the two groups. Kaplan-Meyer analysis showed that tracheostomy increases median survival (TMV, 47 months vs NT, 31 months, p=0.008), with the greatest effect in patients younger than 60 at onset (TMV ≤ 60 years, 57.5 months vs NT ≤ 60 years, 38.5 months, p=0.002). TMV is increasingly performed in ALS patients. Nearly all TMV patients live at home and most of them are fed through a PEG device. Survival after tracheostomy is generally increased, with the stronger effect in patients younger than 60. This survival advantage is apparently lost when TMV is performed in patients older than 60. The results of this study might be useful for the decision-making process of patients and their families about this advanced palliative care. Copyright © 2012. Published by Elsevier B.V.

  14. Positive expression of p53, c-erbB2 and MRP proteins is correlated with survival rates of NSCLC patients.

    Science.gov (United States)

    Xu, Yujin; Wang, Liancong; Zheng, Xiao; Liu, Guan; Wang, Yuezhen; Lai, Xiaojing; Li, Jianqiang

    2013-05-01

    The incidence of lung cancer is one of the leading causes of mortality. This study aimed to investigate the prognostic and predictive importance of p53, c-erbB2 and multidrug resistance proteins (MRP) expression and its correlation with clinicopathological characteristics of patients with non-small cell lung cancer (NSCLC). Expression of p53, c-erbB2 and MRP proteins in 152 tumor samples from resected primary NSCLCs was detected by immunohistochemical staining. The correlation of proteins, survival and clinicopathological characteristics was investigated in 152 patients undergoing potentially curative surgery. The positive rates of p53, c-erbB2 and MRP expression were 53.9 (82/152), 44.1 (67/152) and 43.4% (66/152), respectively. Overall survival rates of patients were markedly correlated with the overexpression of p53, c-erbB2 and MRP proteins. One, 2- and 3-year survival rates of patients exhibiting a positive expression of these proteins were 72.6, 54.8 and 32.2%, respectively. These rates were lower compared with those of patients with a negative expression of these proteins (92.1, 78.5 and 63.4%) (P=0.02, 0.01 or 0.00, respectively). Results of Cox's regression analysis showed that c-erbB2 expression and cell differentiation were independent prognostic factors in patients with NSCLC. These findings suggest that the positive expression of p53, c-erbB2 and MRP proteins is correlated with the survival rates of NSCLC patients. Detection of positive p53, c-erbB2 and MRP expression may be a useful predictive indicator of prognosis. Positive c-erbB2 expression is an independent prognostic factor, with a potential to be used as a predictive indicator of chemotherapy efficacy in NSCLC patients.

  15. Effect of smoking on survival of patients with hepatocellular carcinoma.

    Science.gov (United States)

    Kolly, Philippe; Knöpfli, Marina; Dufour, Jean-François

    2017-11-01

    Lifestyle factors such as smoking, obesity and physical activity have gained interest in the field of hepatocellular carcinoma. These factors play a significant role in the development of hepatocellular carcinoma. Several studies revealed the impact of tobacco consumption on the development of hepatocellular carcinoma and its synergistic effects with viral etiologies (hepatitis B and C). The effects of smoking on survival in patients with a diagnosed hepatocellular carcinoma have not yet been investigated in a Western cohort where hepatitis C infection is a major risk factor. Using data from a prospective cohort of patients with hepatocellular carcinoma who were followed at the University Hospital of Bern, Switzerland, survival was compared by Kaplan-Meier analysis in smokers and nonsmokers, and multivariate Cox regression was applied to control for confounding variables. Of 238 eligible hepatocellular carcinoma patients, 64 were smokers at the time of inclusion and 174 were nonsmokers. Smokers had a significant worse overall survival than nonsmokers (hazard ratio 1.77, 95% confidence interval: 1.22-2.58, P=.003). Analysis of patients according to their underlying liver disease, revealed that smoking, and not nonsmoking, affected survival of hepatitis B virus and C virus-infected patients only. In this subgroup, smoking was an independent predictor for survival (hazard ratio 2.99, 95% confidence interval: 1.7-5.23, Phepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Quadrupole moment and a proton halo structure in 17F (Iπ = 5/2+)

    International Nuclear Information System (INIS)

    Zhou Dongmei; Zheng Yongnan; Yuan Daqing; Xizhen, Zhang; Zuo Yi; Minamisono, T; Matsuta, M; Fukuda, M; Mihara, M; Zhang Chunlei; Zhiqiang, Wang; Du Enpeng; Luo Hailong; Xu Guoji; Zhu Shengyun

    2007-01-01

    The quadrupole moment of light nuclei 17 F in the ground state (I π = 5/2 + ) is measured by the β-NMR method. The effective charge of the last proton in a d 5/2 orbit for 17 F is extracted from the measured quadrupole moment Q( 17 F) divided by the quadrupole moment Q sp calculated with a single particle model. A proton effective charge of e eff p = 1.12 ± 0.07e is obtained, which is in agreement with that given by a particle-vibration coupling model calculation within the experimental error. The present value of the proton effective charge is strong evidence for the existence of a proton skin in 17 F (I π = 5/2 + )

  17. Marital Status and Survival in Patients with Carcinoid Tumors

    Directory of Open Access Journals (Sweden)

    Erin K. Greenleaf

    2016-01-01

    Full Text Available Background Marital status is a known prognostic factor in overall and disease-specific survival in several types of cancer. The impact of marital status on survival in patients with carcinoid tumors remains unknown. We hypothesized that married patients have higher rates of survival than similar unmarried patients with carcinoid tumors. Methods Using the Surveillance, Epidemiology, and End Results database, we identified 23,126 people diagnosed with a carcinoid tumor between 2000 and 2011 and stratified them according to marital status. Univariate and multivariable analyses were performed to compare the characteristics and outcomes between patient cohorts. Overall and cancer-related survival were analyzed using the Kaplan–Meier method. Multivariable survival analyses were performed using Cox proportional hazards models (hazards ratio [HR], controlling for demographics and tumor-related and treatment-related variables. Propensity score analysis was performed to determine surgical intervention distributions among married and unmarried (ie, single, separated, divorced, widowed patients. Results Marital status was significantly related to both overall and cancer-related survival in patients with carcinoid tumors. Divorced and widowed patients had worse overall survival (HR, 1.33 [95% confidence interval {CI}, 1.08–1.33] and 1.34 [95% CI, 1.22–1.46], respectively and cancer-related survival (HR, 1.15 [95% CI, 1.00–1.31] and 1.15 [95% CI, 1.03–1.29], respectively than married patients over five years. Single and separated patients had worse overall survival (HR, 1.20 [95% CI, 1.08–1.33] and 1.62 [95% CI, 1.25–2.11], respectively than married patients over five years, but not worse cancer-related survival. Unmarried patients were more likely than matched married patients to undergo definitive surgical intervention (62.67% vs 53.11%, respectively, P < 0.0001. Conclusions Even after controlling for other prognostic factors, married patients

  18. Impact of different infliximab dose regimens on treatment response and drug survival in 462 patients with psoriatic arthritis

    DEFF Research Database (Denmark)

    Glintborg, Bente; Gudbjornsson, Bjorn; Krogh, Niels Steen

    2014-01-01

    Icelandic patients at baseline [median 3.1 (interquartile range 3.0-3.8) vs 2.3 (2.1-2.9) mg/kg, P drug survival than...... Icelandic patients (1183 vs 483 days). In univariate analyses stratified by country, time until dose escalation, response rates, drug survival and 1-year's disease activity were independent of starting dose. Drug survival was shorter among patients not receiving concomitant MTX. CONCLUSION: In clinical...... practice, > 70% of Icelandic and Danish PsA patients treated with infliximab received sustained doses below the 5 mg/kg every 8 weeks recommended in international guidelines. Lower starting doses did not affect drug survival or response....

  19. Early restaging whole-body 18F-FDG PET during induction chemotherapy predicts clinical outcome in patients with locoregionally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Yen, Ruoh-Fang; Chen, Tony Hsiu-Hsi; Ting, Lai-Lei; Tzen, Kai-Yuan; Pan, Mei-Hsiu; Hong, Ruey-Long

    2005-01-01

    This study was undertaken to evaluate the utility of whole-body 18 F-FDG PET in monitoring therapeutic effect during induction chemotherapy (IC) and in predicting prognosis in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Fifty patients who had histologically proven, locoregionally advanced NPC without distant metastasis and had received IC were recruited in this study. The study cohort consisted of 19 females and 31 males (age 17-72 years, mean 45.9±11.9). Whole-body 18 F-FDG PET was performed in each patient after completion of one (33 patients) or two (17 patients) courses of IC. Each patient was restaged on the basis of the 18 F-FDG PET results. Patients who were downstaged to stage I or II were classified as major responders; the rest were classified as non-major responders. Only 1 of the 23 major responders subsequently developed local recurrence. At the time of data analysis, all major responders were alive; by contrast, of the 27 non-major responders, 15 had locoregional recurrence or distant metastasis and nine had died (seven of NPC and two of treatment-related complications). Kaplan-Meier survival analysis showed significantly longer recurrence-free survival and overall survival in major responders (56.4±9.2 and 58.1±2.2 months) as compared with non-major responders (33.7±23.2 and 44.7±20.0 months), with p 18 F-FDG PET scan after the first or second course of IC is useful for predicting therapeutic response and outcome in patients with locoregionally advanced NPC. (orig.)

  20. Effect of therapy on five- and ten-year survival of malignant melanoma patients

    International Nuclear Information System (INIS)

    Siffnerova; Bustova; Zikmund

    1989-01-01

    The results are reported of five-year and ten-year survival of malignant melanoma patients treated postoperatively by actinotherapy. In patients where lymph flow was not apparent, 2.5 Gy of daily doses of electron irradiation from a 6-8 MeV betatron were used centred on the scar. The total dose was 60 Gy. Where the lymph flow could be identified, cobalt or cesium sources were used to deliver a total dose of 50 Gy in 2.5 Gy daily. Both five-year and ten-year survival was significantly better than in patients treated with surgery only, without irradiation. 55% of the patients on combined management survived for more than 5 years, 86% of them without relapses. 41% patients survived for 10 years, of which 92% without relapse. In contrast, the corresponding figures for the patients treated with surgery only were 42% and 71% respectively for the five-year survival, and 26% and 70% respectively for the ten-year survival. (L.O.). 3 figs., 2 tabs

  1. Hospice Admission and Survival After 18F-Fluoride PET Performed for Evaluation of Osseous Metastatic Disease in the National Oncologic PET Registry.

    Science.gov (United States)

    Gareen, Ilana F; Hillner, Bruce E; Hanna, Lucy; Makineni, Rajesh; Duan, Fenghai; Shields, Anthony F; Subramaniam, Rathan M; Siegel, Barry A

    2018-03-01

    We have previously reported that PET using 18 F-fluoride (NaF PET) for assessment of osseous metastatic disease was associated with substantial changes in intended management in Medicare beneficiaries participating in the National Oncologic PET Registry (NOPR). Here, we use Medicare administrative data to examine the association between NaF PET results and hospice claims within 180 d and 1-y survival. Methods: We classified NOPR NaF PET results linked to Medicare claims by imaging indication (initial staging [IS]; detection of suspected first osseous metastasis [FOM]; suspected progression of osseous metastasis [POM]; or treatment monitoring [TM]) and type of cancer (prostate, lung, breast, or other). Results were classified as definitely positive scan findings versus probably positive scan findings versus negative scan findings for osseous metastasis for IS and FOM; more extensive disease versus no change or less extensive disease for POM; and worse prognosis versus no change or better prognosis for TM, based on the postscan assessment. Our study included 21,167 scans obtained from 2011 to 2014 of consenting NOPR participants aged 65 y or older. Results: The relative risk of hospice claims within 180 d of a NaF PET scan was 2.0-7.5 times higher for patients with evidence of new or progressing osseous metastasis than for those without, depending on indication and cancer type (all P PET scan results are highly associated with subsequent hospice claims and, ultimately, with patient survival. NaF PET provides important information on the presence of osseous metastasis and prognosis to assist patients and their physicians when making decisions on whether to select palliative care and transition to hospice or whether to continue treatment. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  2. Prognostic significance of standardized uptake value on preoperative 18F-FDG PET/CT in patients with ampullary adenocarcinoma

    International Nuclear Information System (INIS)

    Choi, Hye Jin; Kang, Chang Moo; Lee, Woo Jung; Jo, Kwanhyeong; Lee, Jong Doo; Lee, Jae-Hoon; Ryu, Young Hoon

    2015-01-01

    The purpose of this study was to investigate the prognostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with ampullary adenocarcinoma (AAC) after curative surgical resection. Fifty-two patients with AAC who had undergone 18 F-FDG PET/CT and subsequent curative resections were retrospectively enrolled. The maximum standardized uptake value (SUV max ) and tumor to background ratio (TBR) were measured on 18 F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and clinicopathologic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Of the 52 patients, 19 (36.5 %) experienced tumor recurrence during the follow-up period and 18 (35.8 %) died. The 3-year RFS and OS were 62.3 and 61.5 %, respectively. Preoperative CA19-9 level, tumor differentiation, presence of lymph node metastasis, SUV max , and TBR were significant prognostic factors for both RFS and OS (p < 0.05) on univariate analyses, and patient age showed significance only for predicting RFS (p < 0.05). On multivariate analyses, SUV max and TBR were independent prognostic factors for RFS, and tumor differentiation, SUV max , and TBR were independent prognostic factors for OS. SUV max and TBR on preoperative 18 F-FDG PET/CT are independent prognostic factors for predicting RFS and OS in patients with AAC; patients with high SUV max (>4.80) or TBR (>1.75) had poor survival outcomes. The role of and indications for adjuvant therapy after curative resection of AAC are still unclear. 18 F-FDG uptake in the primary tumor could provide additive prognostic information for the decision-making process regarding adjuvant therapy. (orig.)

  3. Association of the CC genotype of the regulatory BCL2 promoter polymorphism (-938C>A) with better 2-year survival in patients with glioblastoma multiforme.

    Science.gov (United States)

    El Hindy, Nicolai; Bachmann, Hagen S; Lambertz, Nicole; Adamzik, Michael; Nückel, Holger; Worm, Karl; Zhu, Yuan; Sure, Ulrich; Siffert, Winfried; Sandalcioglu, I Erol

    2011-06-01

    Bcl-2 plays a key role in the downregulation of apoptosis and proliferation and leads to increased chemoresistance in glioblastoma multiforme (GBM). The authors investigated the role of a common regulatory single-nucleotide polymorphism (-938C>A), which is located in the inhibitory P2 promoter of BCL2. Data from 160 patients suffering from GBM were retrospectively evaluated. Study inclusion criteria consisted of available DNA and, in patients still alive, a follow-up of at least 24 months. Results were analyzed with respect to the basic clinical data, type of surgical intervention (gross-total resection [GTR] versus stereotactic biopsy [SB]), adjuvant therapy, MGMT promoter methylation, and survival at the 2-year follow-up. At the 2-year follow-up, 127 (79.4%) of the 160 patients had died. Kaplan-Meier curves revealed a significantly higher rate of survival for homo- and heterozygous C-allele carriers (p = 0.031). In the GTR group, the survival rate was 47.1% for homozygous C-allele carriers, 32.0% for heterozygous C-allele carriers, and only 21.4% for homozygous A-allele carriers (p = 0.024). The SB group showed no genotype-dependent differences. Multivariable Cox regression revealed that the BCL2 (-938AA) genotype was an independent negative prognostic factor for 2-year survival in the GTR group according to the BCL2 (-938CC) genotype reference group (hazard ratio 2.50, 95% CI 1.14-5.48, p = 0.022). These results suggested that the (-938C>A) polymorphism is a survival prognosticator as well as a marker for a high-risk group among patients with GBM who underwent GTR.

  4. Conventional chemotherapy and long-term survival in multiple myeloma patients

    International Nuclear Information System (INIS)

    Kraj, M; Poglod, R.; Sokolowska, U.; Kruk, B.; Maj, S.

    2010-01-01

    Objectives. The study was especially focused on the estimation of real frequency of long-term survivals in patients with multiple myeloma and finding common clinical and laboratory features present in long-term surviving patients as possible good prognostic factors. Material and methods. The survey was carried out on 600 multiple myeloma patients diagnosed before the year 2000 and treated with conventional chemotherapy in the Institute of Hematology and Transfusion Medicine in Warsaw in the years 1962-2009. All patients who had fulfilled the requirement of more than seven years of survival from the diagnosis and beginning of treatment for myeloma were included into the study group. Results. Out of 600 studied patients with multiple myeloma 88 (14.7%) survived over 7 years including 45 (7.5%) over 10 years, 11 (1.8 %) over 15 years and 7 (1.1%) over 20 years from the disease diagnosis and beginning of antitumor treatment. Patients with long survival were younger (median age 55 years) at the time of diagnosis than the whole studied group and had normal serum creatinine, calcium and beta2-microglobulin levels. Sixty eight percent of these patients had stage I or II clinical progression, 60% presented with IgG monoclonal protein and 58% with osteolysis. Treatment with melphalan only was given to 18 patients, 30 were treated with melphalan, followed by vincristine, cyclophosphamide, BCNU, doxorubicin and prednisone or dexamethasone. Polychemotherapy was given from the time of the diagnosis to 16 patients, 15 received radiotherapy or 60C o irradiation besides chemotherapy and 9 received new agents: thalidomide, bortezomib, lenalidomide. In 66% of the evaluated cases response to treatment was good and in another 34% stabilization of the proliferative process was achieved. The mean duration of treatment till the achievement of partial response was 10 months, range: 2 - 89 months. The mean duration of good therapeutic response was 70 months. Twelve patients are alive and

  5. Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival.

    Science.gov (United States)

    Liu, Yanhong; Shete, Sanjay; Etzel, Carol J; Scheurer, Michael; Alexiou, George; Armstrong, Georgina; Tsavachidis, Spyros; Liang, Fu-Wen; Gilbert, Mark; Aldape, Ken; Armstrong, Terri; Houlston, Richard; Hosking, Fay; Robertson, Lindsay; Xiao, Yuanyuan; Wiencke, John; Wrensch, Margaret; Andersson, Ulrika; Melin, Beatrice S; Bondy, Melissa

    2010-05-10

    Glioblastoma (GBM) is the most common and aggressive type of glioma and has the poorest survival. However, a small percentage of patients with GBM survive well beyond the established median. Therefore, identifying the genetic variants that influence this small number of unusually long-term survivors may provide important insight into tumor biology and treatment. Among 590 patients with primary GBM, we evaluated associations of survival with the 100 top-ranking glioma susceptibility single nucleotide polymorphisms from our previous genome-wide association study using Cox regression models. We also compared differences in genetic variation between short-term survivors (STS; or= 36 months), and explored classification and regression tree analysis for survival data. We tested results using two independent series totaling 543 GBMs. We identified LIG4 rs7325927 and BTBD2 rs11670188 as predictors of STS in GBM and CCDC26 rs10464870 and rs891835, HMGA2 rs1563834, and RTEL1 rs2297440 as predictors of LTS. Further survival tree analysis revealed that patients >or= 50 years old with LIG4 rs7325927 (V) had the worst survival (median survival time, 1.2 years) and exhibited the highest risk of death (hazard ratio, 17.53; 95% CI, 4.27 to 71.97) compared with younger patients with combined RTEL1 rs2297440 (V) and HMGA2 rs1563834 (V) genotypes (median survival time, 7.8 years). Polymorphisms in the LIG4, BTBD2, HMGA2, and RTEL1 genes, which are involved in the double-strand break repair pathway, are associated with GBM survival.

  6. Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the influenza A virus subtypes responsible for the 20th-century pandemics.

    Science.gov (United States)

    Pasricha, Gunisha; Mishra, Akhilesh C; Chakrabarti, Alok K

    2013-07-01

    PB1F2 is the 11th protein of influenza A virus translated from +1 alternate reading frame of PB1 gene. Since the discovery, varying sizes and functions of the PB1F2 protein of influenza A viruses have been reported. Selection of PB1 gene segment in the pandemics, variable size and pleiotropic effect of PB1F2 intrigued us to analyze amino acid sequences of this protein in various influenza A viruses. Amino acid sequences for PB1F2 protein of influenza A H5N1, H1N1, H2N2, and H3N2 subtypes were obtained from Influenza Research Database. Multiple sequence alignments of the PB1F2 protein sequences of the aforementioned subtypes were used to determine the size, variable and conserved domains and to perform mutational analysis. Analysis showed that 96·4% of the H5N1 influenza viruses harbored full-length PB1F2 protein. Except for the 2009 pandemic H1N1 virus, all the subtypes of the 20th-century pandemic influenza viruses contained full-length PB1F2 protein. Through the years, PB1F2 protein of the H1N1 and H3N2 viruses has undergone much variation. PB1F2 protein sequences of H5N1 viruses showed both human- and avian host-specific conserved domains. Global database of PB1F2 protein revealed that N66S mutation was present only in 3·8% of the H5N1 strains. We found a novel mutation, N84S in the PB1F2 protein of 9·35% of the highly pathogenic avian influenza H5N1 influenza viruses. Varying sizes and mutations of the PB1F2 protein in different influenza A virus subtypes with pandemic potential were obtained. There was genetic divergence of the protein in various hosts which highlighted the host-specific evolution of the virus. However, studies are required to correlate this sequence variability with the virulence and pathogenicity. © 2012 John Wiley & Sons Ltd.

  7. Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells.

    Science.gov (United States)

    Li, Q S; Meng, F Y; Zhao, Y H; Jin, C L; Tian, J; Yi, X J

    2017-08-01

    This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing. Blood samples were obtained from patients with hand fracture or intra-articular calcaneal fracture and from healthy controls (HCs). Expression of miR-214-5p was monitored by qRT-PCR at day 7, 14 and 21 post-surgery. Mouse osteoblastic MC3T3-E1 cells were transfected with antisense oligonucleotides (ASO)-miR-214-5p, collagen type IV alpha 1 (COL4A1) vector or their controls; thereafter, cell viability, apoptotic rate, and the expression of collagen type I alpha 1 (COL1A1), type II collagen (COL-II), and type X collagen (COL-X) were determined. Luciferase reporter assay, qRT-PCR, and Western blot were performed to ascertain whether COL4A1 was a target of miR-214-5p. Plasma miR-214-5p was highly expressed in patients with bone fracture compared with HCs after fracture (p extracellular matrix (ECM) formation of osteoblastic MC3T3-E1 cells by targeting COL4A1. Cite this article: Q. S. Li, F. Y. Meng, Y. H. Zhao, C. L. Jin, J. Tian, X. J. Yi. Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells. Bone Joint Res 2017;6:464-471. DOI: 10.1302/2046-3758.68.BJR-2016-0208.R2. © 2017 Yi et al.

  8. Patient survival and surgical re-intervention predictors for intracapsular hip fractures.

    Science.gov (United States)

    González Quevedo, David; Mariño, Iskandar Tamimi; Sánchez Siles, Juan Manuel; Escribano, Esther Romero; Granero Molina, Esther Judith; Enrique, David Bautista; Smoljanović, Tomislav; Pareja, Francisco Villanueva

    2017-08-01

    Choosing between total hip replacement (THR) and partial hip replacement (PHR) for patients with intracapsular hip fractures is often based on subjective factors. Predicting the survival of these patients and risk of surgical re-intervention is essential to select the most adequate implant. We conducted a retrospective cohort study on mortality of patients over 70 years with intracapsular hip fractures who were treated between January 2010 and December 2013, with either PHR or THR. Patients' information was withdrawn from our local computerized database. The age-adjusted Charlson comorbidity index (ACCI) and American Society of Anesthesiologists (ASA) score were calculated for all patients. The patients were followed for 2 years after surgery. Survival and surgical re-intervention rates were compared between the two groups using a Multivariate Cox proportional hazard model. A total of 356 individuals were included in this study. At 2 years of follow-up, 221 (74.4%) of the patients with ACCI score≤7 were still alive, in contrast to only 20 (29.0%) of those with ACCI score>7. In addition, 201 (76.2%) of the patients with ASA score≤3 were still alive after 2 years, compared to 30 (32.6%) of individuals with ASA >3. Patients with the ACCI score>7, and ASA score>3 had a significant increase in all-cause 2-year mortality (adjusted hazard ratio of 3.2, 95% CI 2.2-4.6; and 3.12, 95% CI 2.2-4.5, respectively). Patients with an ASA score>3 had a quasi-significant increase in the re-intervention risk (adjusted hazard ratio 2.2, 95% CI 1.0-5.1). The sensitivity, specificity, positive predictive value and negative predictive values of ACCI in predicting 2-year mortality were 39.2%, 91.1%, 71%, and 74.4%, respectively. On the other hand, the sensitivity, specificity, positive predictive value and negative predictive values of ASA score in predicting 2-year mortality were 49.6%, 79.1%, 67.4%, and 76.1%, respectively. Both ACCI and ASA scales were able to predict the 2-year

  9. Survival and quality of life of patients with oral and oropharyngeal cancer at 1-year follow-up of tumor resection

    Directory of Open Access Journals (Sweden)

    Maria Gabriela Haye Biazevic

    2010-06-01

    Full Text Available OBJECTIVE: This study aimed to assess the survival and life quality evolution of patients subjected to surgical excision of oral and oropharyngeal squamous cell carcinoma. MATERIAL AND METHODS: Forty-seven patients treated at a Brazilian healthcare unit specialized in head and neck surgery between 2006 and 2007 were enrolled in the study. The gathering of data comprised reviewing hospital files and applying the University of Washington Quality of Life (UW-QOL questionnaire previously and 1 year after the surgery. Comparative analysis used Poisson regression to assess factors associated with survival and a paired t-test to compare preoperative and 1-year postoperative QOL ratings. RESULTS: 1 year after surgery, 7 patients were not found (dropout of the cohort; 15 had died and 25 fulfilled the UW-QOL again. The risk of death was associated with having regional metastasis previously to surgery (relative risk=2.18; 95% confidence interval=1.09-5.17 and tumor size T3 or T4 (RR=2.30; 95%CI=1.05-5.04. Survivors presented significantly (p<0.05 poorer overall and domain-specific ratings of quality of life. Chewing presented the largest reduction: from 74.0 before surgery to 34.0 one year later. Anxiety was the only domain whose average rating increased (from 36.0 to 70.7. CONCLUSIONS: The prospective assessment of survival and quality of life may contribute to anticipate interventions aimed at reducing the incidence of functional limitations in patients with oral and oropharyngeal cancer.

  10. Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the influenza A virus subtypes responsible for the 20th‐century pandemics

    Science.gov (United States)

    Pasricha, Gunisha; Mishra, Akhilesh C.; Chakrabarti, Alok K.

    2012-01-01

    Please cite this paper as: Pasricha et al. (2012) Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the Influenza A virus subtypes responsible for the 20th‐century pandemics. Influenza and Other Respiratory Viruses 7(4), 497–505. Background  PB1F2 is the 11th protein of influenza A virus translated from +1 alternate reading frame of PB1 gene. Since the discovery, varying sizes and functions of the PB1F2 protein of influenza A viruses have been reported. Selection of PB1 gene segment in the pandemics, variable size and pleiotropic effect of PB1F2 intrigued us to analyze amino acid sequences of this protein in various influenza A viruses. Methods  Amino acid sequences for PB1F2 protein of influenza A H5N1, H1N1, H2N2, and H3N2 subtypes were obtained from Influenza Research Database. Multiple sequence alignments of the PB1F2 protein sequences of the aforementioned subtypes were used to determine the size, variable and conserved domains and to perform mutational analysis. Results  Analysis showed that 96·4% of the H5N1 influenza viruses harbored full‐length PB1F2 protein. Except for the 2009 pandemic H1N1 virus, all the subtypes of the 20th‐century pandemic influenza viruses contained full‐length PB1F2 protein. Through the years, PB1F2 protein of the H1N1 and H3N2 viruses has undergone much variation. PB1F2 protein sequences of H5N1 viruses showed both human‐ and avian host‐specific conserved domains. Global database of PB1F2 protein revealed that N66S mutation was present only in 3·8% of the H5N1 strains. We found a novel mutation, N84S in the PB1F2 protein of 9·35% of the highly pathogenic avian influenza H5N1 influenza viruses. Conclusions  Varying sizes and mutations of the PB1F2 protein in different influenza A virus subtypes with pandemic potential were obtained. There was genetic divergence of the protein in various hosts which highlighted the host‐specific evolution of the virus

  11. High survival rates and associated factors among ebola virus disease patients hospitalized at donka national hospital, conakry, Guinea.

    Science.gov (United States)

    Qureshi, Adnan I; Chughtai, Morad; Bah, Elhadj Ibrahima; Barry, Moumié; Béavogui, Kézély; Loua, Tokpagnan Oscar; Malik, Ahmed A

    2015-02-01

    Anecdotal reports suggesting that survival rates among hospitalized patients with Ebola virus disease in Guinea are higher than the 29.2% rate observed in the current epidemic in West Africa. Survival after symptom onset was determined using Kaplan Meier survival methods among patients with confirmed Ebola virus disease treated in Conakry, Guinea from March 25, 2014, to August 5, 2014. We analyzed the relationship between survival and patient factors, including demographics and clinical features. Of the 70 patients analyzed [mean age ± standard deviation (SD), 34 ± 14.1; 44 were men], 42 were discharged alive with a survival rate among hospitalized patients of 60% (95% confidence interval, 41.5-78.5%). The survival rate was 28 (71.8%) among 39 patients under 34 years of age, and 14 (46.7%) among 30 patients aged 35 years or greater (p = 0.034). The rates of myalgia (3 of 42 versus 7 of 28, p = 0.036) and hiccups (1 of 42 versus 5 of 28, p = 0.023) were significantly lower among patients who survived. Our results provide insights into a cohort of hospitalized patients with Ebola virus disease in whom survival is prominently higher than seen in other cohorts of hospitalized patients.

  12. Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FEAU) and micro-PET imaging of HSV-tk gene expression in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

    2004-07-01

    Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FEAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

  13. Investigation of the multiphotonic excitation processes of the 4f2 5d configuration in LiYF4, LiLuF4 and BaY2F8 crystals doped with trivalent neodymium

    International Nuclear Information System (INIS)

    Librantz, Andre Felipe Henriques

    2004-01-01

    Ultraviolet (UV) fluorescence of Nd 3+ ions induced by multistep laser excitation was investigated in Nd-doped LiYF 4 (YLF), LiLuF 4 (LLF) and BaY 2 F 8 (BaYF) crystals using a technique of time-resolved spectroscopy. The observed UV luminescence was due to transitions between the bottom of 4f 2 5d configuration and the 4f 3 states of Nd 3+ ions. The lower excited state 4f 2 ( 3 H)5d [ 4 K 11/2 ] was reached by three stepwise absorptions of photons at 521 nm (green) and 478 nm (blue) of a short pulse laser excitation. The three sequential absorptions at 478 nm constitutes a new multiphoton excitation process of Nd 3+ in these crystals with the following excitation sequence: 4 I 9/2 + hv(480 nm)→ 2 G(1) 9/2 + hv(480 nm)→ 2 F(2) 7/2 + hv(480 nm)→ 4f 2 ( 3 H)5d [ 4 K 9/2 ] (excited state at ∼ 63000 cm -1 ). The observed UV emissions from [ 4 K 11/2 ] state have a lifetime of 35 ns (parity allowed) and are: broadband in contrast to UV emissions from 4f 3 configuration, which are also present in the luminescence investigation but having longer lifetime (8 μs) and structures composed of narrow lines. The excitation spectrum of fast UV luminescence exhibited different structure depending on the excitation geometry (σ or π) with respect to the c-axis of the crystal. It was seen two new emissions from [ 4 K 11/2 ] and 2 F(2) 5/2 states near 528 nm, which modified the branching ratio of the bottom of the 4f 2 5d configuration (∼ 55500 cm -1 for the YLF and LLF crystals and ∼-53700 cm -1 for the BaYF crystal). The equivalent cross-section of three and two excitation process was estimated at 521 nm by solving the rate equations of the system under short laser excitation, which leads us to infer that is possible to have laser action under pulsed laser pumping with intensity below the crystal damage threshold. (author)

  14. The inflammation-based Glasgow Prognostic Score predicts survival in patients with cervical cancer.

    Science.gov (United States)

    Polterauer, Stephan; Grimm, Christoph; Seebacher, Veronika; Rahhal, Jasmin; Tempfer, Clemens; Reinthaller, Alexander; Hefler, Lukas

    2010-08-01

    The Glasgow Prognostic Score (GPS) is known to reflect the degree of tumor-associated cachexia and inflammation and is associated with survival in various malignancies. We investigated the value of the GPS in patients with cervical cancer. We included 244 consecutive patients with cervical cancer in our study. The pretherapeutic GPS was calculated as follows: patients with elevated C-reactive protein serum levels (>10 mg/L) and hypoalbuminemia (L) were allocated a score of 2, and patients with 1 or no abnormal value were allocated a score of 1 or 0, respectively. The association between GPS and survival was evaluated by univariate log-rank tests and multivariate Cox regression models. The GPS was correlated with clinicopathologic parameters as shown by performing chi2 tests. In univariate analyses, GPS (P GPS (P = 0.03, P = 0.04), FIGO stage (P = 0.006, P = 0.006), and lymph node involvement (P = 0.003, P = 0.002), but not patients' age (P = 0.5, P = 0.5), histological grade (P = 0.7, P = 0.6), and histological type (P = 0.4, P = 0.6) were associated with disease-free and overall survival, respectively. The GPS was associated with FIGO stage (P GPS can be used as an inflammation-based predictor for survival in patients with cervical cancer.

  15. A Ru(II) complex with 2-(4-(methylsulfonyl)phenyl)-1H-imidazo[4,5- f][1,10]phenanthroline: Synthesis, characterization, and acid-base and DNA-binding properties

    Science.gov (United States)

    Gao, Jie; Wang, Zhi-Ping; Yuan, Cui-Li; Jia, Hai-Shun; Wang, Ke-Zhi

    2011-09-01

    A new Ru(II) complex of [Ru(bpy) 2(Hmspip)]Cl 2 {in which bpy = 2,2'-bipyridine, Hmspip = 2-(4-(methylsulfonyl)phenyl)-1 H-imidazo[4,5- f][1,10]phenanthroline} have been synthesized and characterized. The ground- and excited-state acid-base properties of [Ru(bpy) 2(Hmspip)]Cl 2 and its parent complex of [Ru(bpy) 2(Hpip)]Cl 2 {Hpip = 2-phenyl-1H-imidazo[4,5- f][1,10]phenanthroline} have been studied by UV-visible (UV-vis) and emission spectrophotometric pH titrations. [Ru(bpy) 2(Hmspip)]Cl 2 acts as a calf thymus DNA intercalators with a binding constant of 4.0 × 10 5 M -1 in buffered 50 mM NaCl, as evidenced by UV-vis and luminescence titrations, steady-state emission quenching by [Fe(CN) 6] 4-, DNA competitive binding with ethidium bromide, reverse salt titrations and viscosity measurements.

  16. [{sup 18}F]F15599, a novel 5-HT{sub 1A} receptor agonist, as a radioligand for PET neuroimaging

    Energy Technology Data Exchange (ETDEWEB)

    Lemoine, Laetitia; Verdurand, Mathieu [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Vacher, Bernard; Blanc, Elodie; Newman-Tancredi, Adrian [Centre de Recherches Pierre Fabre, Castres (France); Le Bars, Didier [CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Zimmer, Luc [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); CERMEP - Imagerie du Vivant, ANIMAGE Department, Lyon (France)

    2010-03-15

    The serotonin-1A (5-HT{sub 1A}) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT{sub 1A} receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT{sub 1A} receptors. Since all clinical PET 5-HT{sub 1A} radiopharmaceuticals are antagonists, it is of great interest to develop a{sup 18}F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{l_brace}[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl{r_brace}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT{sub 1A} receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT{sub 1A} receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [{sup 18}F]MPPF, a validated 5-HT{sub 1A} antagonist radiopharmaceutical. The chemical and radiochemical purities of [{sup 18}F]F15599 were >98%. In vitro [{sup 18}F ]F15599 binding was consistent with the known 5-HT{sub 1A} receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [{sup 18}F ]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [{sup 18}F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT{sub 1A} antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer

  17. Mutation Analysis of JAK2V617F, FLT3-ITD, NPM1, and DNMT3A in Chinese Patients with Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Min Wang

    2014-01-01

    Full Text Available Since the discovery of JAK2V617F tyrosine kinase-activating mutation, several genes have been found mutated in myeloproliferative neoplasms (MPNs. FLT3-ITD, NPM1, and DNMT3A mutations frequently occurred in AML patients and have been found conferred with myeloproliferative neoplasms in mouse model. Therefore, we sought to search for mutations in JAK2V617F, FLT3-ITD, NPM1, and DNMT3A in 129 cases including 120 classic MPN cases and 9 MDS/MPN cases. JAK2V617F mutation was found in 60% of the 120 classic MPNs. However, none of the patients displayed FLT3-ITD and NPM1 mutations; only 2 patients harbored DNMT3A R882 mutation. Further studies including whole-genome sequence will be conducted to investigate the possible involvement of these genes in MPN.

  18. Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

    International Nuclear Information System (INIS)

    Noh, Sang Jae; Chung, Myoung Ja; Moon, Woo Sung; Kang, Myoung Jae; Jang, Kyu Yun; Bae, Jun Sang; Jamiyandorj, Urangoo; Park, Ho Sung; Kwon, Keun Sang; Jung, Sung Hoo; Youn, Hyun Jo; Lee, Ho; Park, Byung-Hyun

    2013-01-01

    Nerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown. We investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma. Immunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time. This study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients

  19. 2,4,6-Triamino-1,3,5-triazine-1,3-diium aquapentafluoridoaluminate

    Directory of Open Access Journals (Sweden)

    V. Maisonneuve

    2008-04-01

    Full Text Available The title compound, (C3H8N6[AlF5(H2O], was obtained by solvothermal synthesis from the reaction of aluminium hydroxide, 1,3,5-triazine-2,4,6-triamine (melamine, aqueous HF and water at 323 K for 48 h. The structure consists of [AlF5(H2O]2− octahedra and diprotonated melaminium cations. Cohesion is ensured by a three-dimensional network of hydrogen bonds.

  20. Stat5 Exerts Distinct, Vital Functions in the Cytoplasm and Nucleus of Bcr-Abl{sup +} K562 and Jak2(V617F){sup +} HEL Leukemia Cells

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Axel [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany); Borghouts, Corina [Ganymed Pharmaceuticals AG, Mainz 55131 (Germany); Brendel, Christian [Boston Children’s Hospital, Division of Hematology/Oncology, Boston, MA 02115 (United States); Moriggl, Richard [Ludwig Boltzmann Institute for Cancer Research (LBI-CR), Vienna 1090 (Austria); Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd, E-mail: Groner@em.uni-frankfurt.de [Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Frankfurt am Main 60596 (Germany)

    2015-03-19

    Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl{sup +} K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells

  1. Survival in patients with brain metastases treated with radiotherapy holoencefalica at the National Institute of Cancerology

    International Nuclear Information System (INIS)

    Ospino, Rosalba; Cendales, Ricardo; Tria, Jaime

    2009-01-01

    Objective: To describe the overall survival among patients with brain metastases treated with whole brain radiation therapy at the Instituto Nacional de Cancerologia (INC) during 2004-2006. Methods: A survival study was conducted. All patients with brain metastases treated with whole brain radiotherapy were included. Frequencies, central tendency, and dispersion measures were used to describe discrete and continuous variables. Survival analysis was performed by the Kaplan-Meyer method. Results: 109 patients were included and the vital status was updated in 85 patients (80%). The median follow-up time was 2.76 months. 78 deaths were observed; the median survival time was 5.2 months and the cumulated one-year overall survival 25.5%. Karnofsky index, extra-cranial metastases, type of lesion, and recursive partitioning analysis (RPA) were significant prognostic factors. The overall median survival for recursive partitioning analysis class I was 7.2 months; class II 6.9 months; class III 1.8 months. Conclusion: Overall survival INC are similar than previous international series for RPA class I and III, while it was better in RPA class II.

  2. Incidence and outcome for patients with occult lymph node involvement in T1 and T2 oral squamous cell carcinoma: a prospective study

    International Nuclear Information System (INIS)

    Mücke, Thomas; Mitchell, David A; Wagenpfeil, Stefan; Ritschl, Lucas M; Wolff, Klaus-Dietrich; Kanatas, Anastasios

    2014-01-01

    The evidence base to inform the decision making process in patients with early stage oral cancer and a clinical and radiological N0 neck remains insufficient to answer the question when it is safe to “watch and wait” and when to proceed with a selective neck dissection. A total of 327 consecutive cases of histopathologically staged T 12 , N 0–1 and M 0 , but clinically N 0, squamous cell carcinoma of the tongue were prospectively analysed. Univariate and multivariate analyses were used for statistical analysis and are represented as Kaplan-Meier analyses or Cox proportional hazard regression analysis. In 61 patients (18.65%) lymph node involvement was found in the histopathological processing. The mean survival of all patients was 73.3 ± 48.6 months. The 2-year and 5-year overall survival rates of all patients were 87.5% and 68.4%, respectively. The 2-year and 5-year survival rates for stage N 0 were 89.1% and 70.7% compared to 83.3% and 62.9% in N 1 situations. The 2-year and 5-year survival rates for stage T 1 were 87.9% and 73.6% compared to 87.2% and 65.3% in stage T 2 , respectively . The time to recurrence in stage N 0 was 35.1 ± 30.5 months compared to 25.63 ± 24.6 months in cases with N 1 disease. Stage T 1 was associated with a time to recurrence of 38.1 ± 33.9 months compared with 27.2 ± 22.7 months in patients classified T 2 . Variables found to be strongly associated with survival in the univariate analysis included older age, higher tumour and N stage, and grading. Age, tumour stage (p = 0.011, 95% CI, 1.09 to 2.0), nodal stage (p = 0.038, 95% CI, 1.02 to 2.07), and recurrence were independently and significantly associated with survival in the multivariate analysis. This confirms a high overall disease free survival for patients with T1 and N0 treated with single modality surgery and in common with the literature confirms the poor impact on prognosis of the N positive neck

  3. Monitoring 5-fluorouracil in patients undergoing chemotherapy by means of F-19 MR spectroscopy

    International Nuclear Information System (INIS)

    Wolf, W.; Albright, M.J.; Silver, M.S.; Starewicz, P.M.; Weber, H.; Reichardt, U.; Saver, R.

    1986-01-01

    F-19 MR spectroscopy allows direct observation of fluorinated drugs and their metabolites in the human body without background signal from the tissue. In addition, unlike F-18, specific chemical structure information is available in vivo. The behavior of a well-known fluorinated chemotherapeutic drug, 5-fluorouracil (5-FU), and its metabolites was observed noninvasively in patients undergoing cancer chemotherapy. The time course of the drug's metabolism was examined and half-life values of the unmetabolized 5-FU in the liver were calculated from the F-19 peak intensity. Half-life values of the unmetabolized 5-FU in the liver were in the range of 15-30 minutes. Interpatient variations were correlated with the chemotherapy results. F-19 MR spectroscopy is feasible in humans and allows determination of the time course of the metabolism of fluorinated drugs in individual patients

  4. E2F-5, a new E2F family member that interacts with p130 in vivo

    NARCIS (Netherlands)

    Hijmans, E.M.; Voorhoeve, P.M.; Beijersbergen, R.L.; Veer, L.J. van 't; Bernards, R.A.

    1995-01-01

    E2F DNA binding sites are found in a number of genes whose expression is tightly regulated during the cell cycle. The activity of E2F transcription factors is regulated by association with specific repressor molecules that can bind and inhibit the E2F transactivation domain. For E2F-1, E2F-2, and

  5. A new scoring system for predicting survival in patients with non-small cell lung cancer

    International Nuclear Information System (INIS)

    Schild, Steven E; Tan, Angelina D; Wampfler, Jason A; Ross, Helen J; Yang, Ping; Sloan, Jeff A

    2015-01-01

    This analysis was performed to create a scoring system to estimate the survival of patients with non-small cell lung cancer (NSCLC). Data from 1274 NSCLC patients were analyzed to create and validate a scoring system. Univariate (UV) and multivariate (MV) Cox models were used to evaluate the prognostic importance of each baseline factor. Prognostic factors that were significant on both UV and MV analyses were used to develop the score. These included quality of life, age, performance status, primary tumor diameter, nodal status, distant metastases, and smoking cessation. The score for each factor was determined by dividing the 5-year survival rate (%) by 10 and summing these scores to form a total score. MV models and the score were validated using bootstrapping with 1000 iterations from the original samples. The score for each prognostic factor ranged from 1 to 7 points with higher scores reflective of better survival. Total scores (sum of the scores from each independent prognostic factor) of 32–37 correlated with a 5-year survival of 8.3% (95% CI = 0–17.1%), 38–43 correlated with a 5-year survival of 20% (95% CI = 13–27%), 44–47 correlated with a 5-year survival of 48.3% (95% CI = 41.5–55.2%), 48–49 correlated to a 5-year survival of 72.1% (95% CI = 65.6–78.6%), and 50–52 correlated to a 5-year survival of 84.7% (95% CI = 79.6–89.8%). The bootstrap method confirmed the reliability of the score. Prognostic factors significantly associated with survival on both UV and MV analyses were used to construct a valid scoring system that can be used to predict survival of NSCLC patients. Optimally, this score could be used when counseling patients, and designing future trials

  6. Mild hydrothermal synthesis, crystal structure, spectroscopic and magnetic properties of the [MxIIM2.5-xIII(H2O)2(HPIIIO3)y(PVO4)2-yF] [M=Fe, x=2.08, y=1.58; M=Co, Ni, x=2.5, y=2] compounds

    International Nuclear Information System (INIS)

    Orive, Joseba; Mesa, Jose L.; Legarra, Estibaliz; Plazaola, Fernando; Arriortua, Maria I.; Rojo, Teofilo

    2009-01-01

    The [M x II M 2.5-x III (H 2 O) 2 (HP III O 3 ) y (P V O 4 ) 2-y F] [M=Fe (1), x=2.08, y=1.58; M=Co (2), x=2.5, y=2; Ni (3), x=2.5, y=2] compounds have been synthesized using mild hydrothermal conditions at 170 deg. C during five days. Single-crystals of (1) and (2), and polycrystalline sample of (3) were obtained. These isostructural compounds crystallize in the orthorhombic system, space group Aba2, with a=9.9598(2), b=18.8149(4) and c=8.5751(2) A for (1), a=9.9142(7), b=18.570(1) and c=8.4920(5) A for (2) and a=9.8038(2), b=18.2453(2) and c=8.4106(1) A for (3), with Z=8 in the three phases. An X-ray diffraction study reveals that the crystal structure is composed of a three-dimensional skeleton formed by [MO 5 F] and [MO 4 F 2 ] (M=Fe, Co and Ni) octahedra and [HPO 3 ] tetrahedra, partially substituted by [PO 4 ] tetrahedra in phase (1). The IR spectra show the vibrational modes of the water molecules and those of the (HPO 3 ) 2- tetrahedral oxoanions. The thermal study indicates that the limit of thermal stability of these phases is 195 deg. C for (1) and 315 deg. C for (2) and (3). The electronic absorption spectroscopy shows the characteristic bands of the Fe(II), Co(II) and Ni(II) high-spin cations in slightly distorted octahedral geometry. Magnetic measurements indicate the existence of global antiferromagnetic interactions between the metallic centers with a ferromagnetic transition in the three compounds at 28, 14 and 21 K for (1), (2) and (3), respectively. Compound (1) exhibits a hysteresis loop with remnant magnetization and coercive field values of 0.72 emu/mol and 880 Oe, respectively. - Abstract: Polyhedral view of the crystal structure of the [M x II M 2.5-x III (H 2 O) 2 (HP III O 3 ) y (P IV O 4 ) 2-y F] [M=Fe, x=2.08, y=1.58; M=Co, Ni, x=2.5, y=2] compounds showing the sheets along the [001] direction.

  7. Postoperative Insulin-Like Growth Factor 1 Levels Reflect the Graft's Function and Predict Survival after Liver Transplantation.

    Directory of Open Access Journals (Sweden)

    Daniele Nicolini

    Full Text Available The reduction of insulin-like growth factor 1 (IGF-1 plasma levels is associated with the degree of liver dysfunction and mortality in cirrhotic patients. However, little research is available on the recovery of the IGF-1 level and its prognostic role after liver transplantation (LT.From April 2010 to May 2011, 31 patients were prospectively enrolled (25/6 M/F; mean age±SEM: 55.2±1.4 years, and IGF-1 serum levels were assessed preoperatively and at 15, 30, 90, 180 and 365 days after transplantation. The influence of the donor and recipient characteristics (age, use of extended criteria donor grafts, D-MELD and incidence of early allograft dysfunction on hormonal concentration was analyzed. The prognostic role of IGF-1 level on patient survival and its correlation with routine liver function tests were also investigated.All patients showed low preoperative IGF-1 levels (mean±SEM: 29.5±2.1, and on postoperative day 15, a significant increase in the IGF-1 plasma level was observed (102.7±11.7 ng/ml; p65 years or extended criteria donor grafts. An inverse correlation between IGF-1 and bilirubin serum levels at day 15 (r = -0.3924, p = 0.0320 and 30 (r = -0.3894, p = 0.0368 was found. After multivariate analysis, early (within 15 days IGF-1 normalization [Exp(b = 3.913; p = 0.0484] was the only prognostic factor associated with an increased 3-year survival rate.IGF-1 postoperative levels are correlated with the graft's quality and reflect liver function. Early IGF-1 recovery is associated with a higher 3-year survival rate after LT.

  8. The relation between survival and expression of HER1 and HER2 depends on the expression of HER3 and HER4

    DEFF Research Database (Denmark)

    Memon, A A; Sorensen, B S; Meldgaard, P

    2006-01-01

    significance of HER1 and HER2 receptors in bladder cancer is controversial and the effect of the expression of different combinations of these receptors on patient survival is not well understood. Therefore, we examined the mRNA expression of all four EGF receptors with real-time polymerase chain reaction......Increased expression of the epidermal growth factor (EGF) receptors, HER1 and HER2 are related to poor prognosis in most cancers studied. Recently, a high expression of the two remaining receptors of the EGF system, HER3 and HER4 has been related to a favourable prognosis. However, prognostic...... in biopsies from 88 patients with bladder cancer, where the survival was followed for a median of 38.5 months (range 1-117 months). Expression of HER1 and HER2 alone showed no correlation with survival. However, a high expression of HER1 together with high expression of HER3 and HER4 correlated to a better...

  9. The number of prehospital defibrillation shocks and 1-month survival in patients with out-of-hospital cardiac arrest.

    Science.gov (United States)

    Hasegawa, Manabu; Abe, Takeru; Nagata, Takashi; Onozuka, Daisuke; Hagihara, Akihito

    2015-04-17

    The relationship between the number of pre-hospital defibrillation shocks and treatment outcome in patients with out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF) is unknown currently. We examined the association between the number of pre-hospitalization defibrillation shocks and 1-month survival in OHCA patients. We conducted a prospective observational study using national registry data obtained from patients with OHCA between January 1, 2009 and December 31, 2012 in Japan. The study subjects were ≥ 18-110 years of age, had suffered from an OHCA before arrival of EMS personnel, had a witnessed collapse, had an initial rhythm that was shockable [VF/ventricular tachycardia (pulseless VT)], were not delivered a shock using a public automated external defibrillator (AED), received one or more shocks using a biphasic defibrillator by EMS personnel, and were transported to a medical institution between January 1, 2009 and December 31, 2012. There were 20,851 OHCA cases which met the inclusion criteria during the study period. Signal detection analysis was used to identify the cutoff point in the number of prehospital defibrillation shocks most closely related to one-month survival. Variables related to the number of defibrillations or one-month survival in OHCA were identified using multiple logistic regression analysis. A cutoff point in the number of pre-hospital defibrillation shocks most closely associated with 1-month OHCA survival was between two and three (χ(2) = 209.61, p < 0.0001). Among those patients who received two shocks or less, 34.48% survived for at least 1 month, compared with 24.75% of those who received three shocks or more. The number of defibrillations (odds ratio [OR] = 1.19, 95% CI: 1.03, 1.38), OHCA origin (OR = 2.81, 95% CI: 2.26, 3.49), use of ALS devices (OR = 0.68, 95% CI: 0.59, 0.79), use of epinephrine (OR = 0.33, 95% C: 0.28, 0.39), interval between first defibrillation and first ROSC (OR = 1.45, 95

  10. Bronchoscopic management of patients with symptomatic airway stenosis and prognostic factors for survival.

    Science.gov (United States)

    Okiror, Lawrence; Jiang, Li; Oswald, Nicola; Bille, Andrea; Rajesh, Pala; Bishay, Ehab; Steyn, Richard; Naidu, Babu; Kalkat, Maninder

    2015-05-01

    Interventional bronchoscopy is effective in the management of patients with symptomatic airway obstruction for both malignant and benign conditions. The main aim of this study is to report our experience with emergency interventional bronchoscopy in patients with symptomatic airway obstruction and identify prognostic factors for survival. This is a retrospective observational study of patients undergoing emergency interventional bronchoscopy over a 4-year period. Survival times were analyzed separately for patients with benign and malignant airway obstruction by the Kaplan-Meier method. Between June 2009 and July 2013, 168 emergency interventional bronchoscopies were performed in 112 patients for airway obstruction. The median age was 63 years (range, 20 to 86), and 91 patients (54%) patients were female. Seventy-two cases (43%) had airway obstruction due to malignant disease. There were 3 in-hospital deaths (2.7%). Median survival of the study population was 5.6 months (range, 0 to 51) with a median follow-up of 7.3 months (range, 0 to 51). Median survival for patients with malignant airway obstruction was 3.5 months (range, 0 to 21), and 9.8 months (range, 0.1 to 51) for those with benign disease. Airway intervention facilitated palliative chemotherapy in 32 patients (44%) of those with malignant airway obstruction. At multivariate analysis in patients with malignant airway obstruction, presence of stridor (hazard ratio 1.919, 95% confidence interval: 1.082 to 3.404, p = 0.026) and not receiving postprocedure chemotherapy (hazard ratio 2.05, 95% confidence interval: 1.156 to 3.636, p = 0.014) were independent prognostic factors for death. Emergency interventional bronchoscopy for airway obstruction is safe, relieved symptoms, and facilitated palliative chemotherapy, which improved survival. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  11. Fluorinated benzamide neuroleptics--III. Development of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[{sup 18}F]fluoropropyl)-2,3- dimethoxybenzamide as an improved dopamine D-2 receptor tracer

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, Jogeshwar; Zhiying, Yang; Das, Malay K; Brown, Terry

    1995-04-01

    We have prepared five new analogs (n-propyl, iso-propyl, allyl, n-butyl, and iso-butyl) of the dopamine D-2 receptor antagonist, FPMB which result from modifications of the ethyl group at the pyrrolidine nitrogen in FPMB. As expected, all new derivatives showed higher apparent lipophilicity (log k{sub w}), with iso-butyl being the most lipophilic (log k{sub w} = 2.52), followed by the allyl derivative (log k{sub w} = 2.43). The allyl group showed the largest increase in affinity (from 0.26 nM for the ethyl substituent to 0.03 nM for the allyl substituent, almost 10-fold), followed by the n-propyl substituent which showed approximately five-fold better affinity than did the ethyl substituent. Radiosynthesis of S-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[{sup 18}F]fluoropropyl)-2,3-dimethoxybenzamide ([{sup 18}F]fallypride) was carried out by nucleophilic substitution reaction of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-tosyloxypropyl)-2,3- dimethoxybenzamide with no carrier added {sup 18}F{sup -}. [{sup 18}F]Fallypride was obtained in approximately 20-40% yields (EOS/EOB, decay corrected) in specific activities of 900-1700 Ci/mmol after reverse phase HPLC purification in 60 min from EOB. High striatal uptake (upto 2.5% injected dose/g) of [{sup 18}F]fallypride in rats was observed with striatal/cerebellar ratios of 17, 42, 63 and 122 at 30, 60, 90 and 120 min post-injection, respectively. PET experiments with [{sup 18}F]fallypride in a cebus monkey showed a brain uptake of 0.10% injected dose/cc. In rhesus monkeys [{sup 18}F]fallypride showed rapid specific uptake in the striata (0.04-0.06% injected dose/cc) with striata/cerebellum ratios of approx. 3.0 at 14 min, 5.0 at 35 min and 8 at 70 min post-injection. Specifically bound [{sup 18}F]fallypride was displaced with haloperidol (1 mg/kg) with a half-life of 18 min in the rhesus monkey.

  12. EBP1 is a novel E2F target gene regulated by transforming growth factor-β.

    Directory of Open Access Journals (Sweden)

    David Judah

    2010-11-01

    Full Text Available Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1 promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.

  13. EBP1 is a novel E2F target gene regulated by transforming growth factor-β.

    Science.gov (United States)

    Judah, David; Chang, Wing Y; Dagnino, Lina

    2010-11-10

    Regulation of gene expression requires transcription factor binding to specific DNA elements, and a large body of work has focused on the identification of such sequences. However, it is becoming increasingly clear that eukaryotic transcription factors can exhibit widespread, nonfunctional binding to genomic DNA sites. Conversely, some of these proteins, such as E2F, can also modulate gene expression by binding to non-consensus elements. E2F comprises a family of transcription factors that play key roles in a wide variety of cellular functions, including survival, differentiation, activation during tissue regeneration, metabolism, and proliferation. E2F factors bind to the Erb3-binding protein 1 (EBP1) promoter in live cells. We now show that E2F binding to the EBP1 promoter occurs through two tandem DNA elements that do not conform to typical consensus E2F motifs. Exogenously expressed E2F1 activates EBP1 reporters lacking one, but not both sites, suggesting a degree of redundancy under certain conditions. E2F1 increases the levels of endogenous EBP1 mRNA in breast carcinoma and other transformed cell lines. In contrast, in non-transformed primary epidermal keratinocytes, E2F, together with the retinoblastoma family of proteins, appears to be involved in decreasing EBP1 mRNA abundance in response to growth inhibition by transforming growth factor-β1. Thus, E2F is likely a central coordinator of multiple responses that culminate in regulation of EBP1 gene expression, and which may vary depending on cell type and context.

  14. Spectrum of mutations in RARS-T patients includes TET2 and ASXL1 mutations.

    Science.gov (United States)

    Szpurka, Hadrian; Jankowska, Anna M; Makishima, Hideki; Bodo, Juraj; Bejanyan, Nelli; Hsi, Eric D; Sekeres, Mikkael A; Maciejewski, Jaroslaw P

    2010-08-01

    While a majority of patients with refractory anemia with ring sideroblasts and thrombocytosis harbor JAK2V617F and rarely MPLW515L, JAK2/MPL-negative cases constitute a diagnostic problem. 23 RARS-T cases were investigated applying immunohistochemical phospho-STAT5, sequencing and SNP-A-based karyotyping. Based on the association of TET2/ASXL1 mutations with MDS/MPN we studied molecular pattern of these genes. Two patients harbored ASXL1 and another 2 TET2 mutations. Phospho-STAT5 activation was present in one mutated TET2 and ASXL1 case. JAK2V617F/MPLW515L mutations were absent in TET2/ASXL1 mutants, indicating that similar clinical phenotype can be produced by various MPN-associated mutations and that additional unifying lesions may be present in RARS-T. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  15. Identification of time-to-peak on dynamic 18F-FET-PET as a prognostic marker specifically in IDH1/2 mutant diffuse astrocytoma.

    Science.gov (United States)

    Suchorska, Bogdana; Giese, Armin; Biczok, Annamaria; Unterrainer, Marcus; Weller, Michael; Drexler, Mark; Bartenstein, Peter; Schüller, Ulrich; Tonn, Jörg-Christian; Albert, Nathalie L

    2018-01-22

    Stratification of glioma according to isocitrate dehydrogenase 1/2 (IDH1/2) mutation and 1p/19q codeletion status has gained major importance in the new World Health Organization (WHO) classification. Parameters derived from uptake dynamics of 18F-fluoro-ethyl-tyrosine PET (18F-FET-PET) such as minimal time-to-peak (TTPmin) allow discrimination between different prognostic glioma subgroups, too. The present study is aimed at exploring whether TTPmin analysis provides prognostic information beyond the WHO classification. Three hundred patients with newly diagnosed WHO 2007 grades II-IV gliomas with 18F-FET-PET imaging at diagnosis were grouped into 4 subgroups (IDH1/2 mut-1p/19q codel; IDH1/2 mut-1p/19q non-codel; IDH1/2 wildtype WHO grade II and III tumors; and glioblastoma). Clinical and imaging factors such as age, Karnofsky performance score, treatment, TTPmin, and maximal tumor-to-brain ratio (TBRmax) were analyzed with regard to progression-free and overall survival (PFS and OS) via univariate and multivariate regression analysis. PFS and OS were longest in the IDH1/2 mut-1p/19q codel subgroup, followed by IDH1/2 mut-1p/19q non-codel, IDH1/2 wildtype, and GBM (P 17.5 minutes (P PET-derived dynamic analysis defines prognostically distinct subgroups of IDH1/2 mutant-1p/19q non-codel gliomas which cannot be distinguished as yet by molecular marker analysis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  16. Novel (1E,3E,5E-1,6-bis(Substituted phenylhexa-1,3,5-triene Analogs Inhibit Melanogenesis in B16F10 Cells and Zebrafish

    Directory of Open Access Journals (Sweden)

    Jisun Oh

    2018-04-01

    Full Text Available The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1E,3E,5E-1,6-bis(substituted phenylhexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively analyzed using three-dimensional quantitative structure-activity relationship approach. Inhibitory activities of these synthetic compounds against melanin synthesis were determined by evaluating melanin content and melanogenic regulatory enzyme expression in B16F10 cells. The anti-melanogenic activity was verified by observing body pigmentation in zebrafishes treated with these compounds. Compound #2, #4, and #6 effectively decreased melanogenesis induced by α-melanocyte-stimulating hormone. In particular, compound #2 remarkably lowered the mRNA and protein expression levels of microphthalmia-associated transcription factor (MITF, tyrosinase (TYR, tyrosinase-related protein 1 (TYRP1, and TYRP2 in B16F10 cells and substantially reduced skin pigmentation in the developed larvae of zebrafish. These findings suggest that compound #2 may be used as an anti-melanogenic agent for cosmetic purpose.

  17. Effect of PS-K on long-term survival of primary lung cancer patients treated with radiation

    International Nuclear Information System (INIS)

    Okazaki, Atsushi; Nakajima, Nobuaki; Hayakawa, Kazushige; Saito, Yoshihiro; Mitomo, Osamu; Niibe, Hideo

    1984-01-01

    The effect of PS-K on long-term survival of primary lung cancer patients irradiated over 60 Gy through 1977 to 1982 was studied. PS-K was administrated orally 3.0 g, daily or intermittently in the pattern of 2 weeks per a month on patients of positive PPD skin test. All cases irradiated over 60 Gy were 174 (Group A) containing 62 cases with PS-K (Group B) and 112 cases without PS-K (Group C). Of group B, 44 cases were administrated within a month after curative irradiation (Group B1), 7 cases were administrated on time maintaining long-term good condition after irradiation (Group B2) and 11 cases were administrated after recognition of recurrence or metastasis (Group B3). Following results were obtained. 1. Obvious prolongation of survivals was recognized in the patients with PS-K after irradiation. (1) The cumulative 5 years survival rates of Group A, B 1 and C were 11.0%, 28.8% and 4.8%, respectively. (2) The cumulative 5 years survival rates of stage I,11 were 45.7% with PS-K and 10.7% without PS-K. (3) The cumulative 5 years survival rates of 21 cases matched age, sex, stage, histological type and tumor dose with and without PS-K were 37.8% and 7.2%. (4) In Group B 2, 5 cases out of 7 cases have been alived, but in Group B 3, satisfactory long-term survivals ware not obtained. 2. The necessary conditions which obtain long-term survival with PS-K were thought to be follows. One is that the tumor is brought almost to vanish by irradiation. Another is that the condition of host is superior to that of tumor in host-tumor relationship. 3. The possibility of intermittent administration of PS-K was suggested. (author)

  18. Evaluation of early response to concomitant chemoradiotherapy by interim {sup 18}F-FDG PET/CT imaging in patients with locally advanced oesophageal carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Cuenca, Xavier; Hennequin, Christophe; Rivera, Sofia; Baruch-Hennequin, Valerie [Saint Louis Hospital, AP-HP, Department of Radiation Oncology, Paris (France); Denis Diderot University (Paris 7), Paris (France); Hindie, Elif [Saint Louis Hospital, AP-HP, Nuclear Medicine Department, Paris (France); Denis Diderot University (Paris 7), Paris (France); University of Bordeaux, Department of Nuclear Medicine, Haut-Leveque Hospital, CHU Bordeaux (France); Vercellino, Laetitia [Saint Louis Hospital, AP-HP, Nuclear Medicine Department, Paris (France); Denis Diderot University (Paris 7), Paris (France); Gornet, Jean-Marc [Saint Louis Hospital, AP-HP, Gastroenterology Department, Paris (France); Denis Diderot University (Paris 7), Paris (France); Cattan, Pierre; Chirica, Mircea [Saint Louis Hospital, AP-HP, Surgery Department, Paris (France); Denis Diderot University (Paris 7), Paris (France); Quero, Laurent [Saint Louis Hospital, AP-HP, Department of Radiation Oncology, Paris (France); Denis Diderot University (Paris 7), Paris (France)

    2013-04-15

    The best way to assess the response to chemoradiotherapy of locally advanced oesophageal carcinomas is not known. We used {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to evaluate the metabolic response during chemoradiotherapy and tried to correlate this response to survival. Patients with biopsy-proven oesophageal carcinoma underwent FDG PET/CT with evaluation of the standardized uptake value (SUV) before any treatment (SUV1) and during chemoradiotherapy after two cycles of 5-fluorouracil (FU)/cisplatin and 20 Gy (SUV2). Metabolic response was defined as 1-(SUV2/SUV1). Surgery was discussed after 40 Gy and three cycles of chemotherapy. Results of interim PET were not considered for the therapeutic decision. Among 72 patients who underwent a first FDG PET/CT before any treatment, 59 (82 %) could receive the second FDG PET/CT examination. Median survival was 22.2 months with 1-year and 2-year survivals of 70 and 46 %, respectively. Nineteen patients (32 %) underwent surgery. Mean SUV1 and SUV2 were 12.3 {+-} 6.2 and 6 {+-} 4.1, respectively (p < 0.001). Using a cut-off for metabolic response of 50 %, sensitivity and specificity for survival were 0.7 and 0.58. The 2-year overall survival of good responders was 62 % as compared to 27 % for poor metabolic responders. A multivariate analysis was performed, including T and N stages, surgery, histology and metabolic response: only metabolic response was significantly (p = 0.009) associated with 2-year survival. Early evaluation of metabolic response had a great prognostic value and could help identify good responders to chemoradiotherapy. (orig.)

  19. Estimation of patient dose in 18 F-FDG and 18 F-FDOPA PET/CT examinations

    Directory of Open Access Journals (Sweden)

    Aruna Kaushik

    2013-01-01

    Full Text Available Purpose: To estimate specific organ and effective doses to patients resulting from the 18 F-FDG ( 18 F-2-deoxy-D-glucose and 18 F-FDOPA (6-fluoro-( 18 F-L-3, 4-dihydroxyphenylalanine PET/CT examinations for whole body and brain. Materials and Methods: Three protocols for whole body and three for brain PET/CT were used. The CTDI values were measured using standard head and body CT phantoms and also computed using a software CT-Expo for dose evaluation from the CT component. OLINDA software based on MIRD method was used for estimating doses from the PET component of the PET/CT examination. Results: The organ doses from 18 F-FDG and 18 F-FDOPA whole body and brain PET/CT studies were estimated. The total effective dose from a typical protocol of whole body PET/CT examination was 14.4 mSv for females and 11.8 mSv for male patients from 18 F-FDG, whereas it was 11 mSv for female and 9.1 mSv for male patients from 18 F-FDOPA. The total effective doses from a typical protocol for PET/CT studies of brain was 6.5 mSv for females and 5.1 mSv for males from 18 F-FDG whereas it was 3.7 mSv for females and 2.8 mSv for males from 18 F-FDOPA. Conclusions: The effective radiation doses from whole body PET/CT examination was approximately 4-8 times higher than the background radiation dose from both 18 F-FDG and 18 F-FDOPA scans, while it was 1-3 times the background radiation dose from PET/CT scans of brain.

  20. Long-term follow-up and salvage surgery in patients with T2N0M0 squamous cell carcinoma of the glottic larynx who received concurrent chemoradiation therapy with carboplatin (CBDCA) - AUC 1.5 vs AUC 2.0.

    Science.gov (United States)

    Furusaka, Tohru; Matsuda, Hiroshi; Saito, Tsutomu; Katsura, Yoshihisa; Ikeda, Minoru

    2012-11-01

    Patients who received concurrent chemoradiation therapy with carboplatin were followed up on a long-term basis. In 25 patients treated with carboplatin at an AUC of 2.0 mg/ml, the complete response (CR), 10-year survival, and 10-year larynx preservation rates were 96.0%, 91.1%, and 75.2%, respectively, and the safety margin for partial laryngectomy was 4 mm from the gross tumor. To perform long-term follow-up of the therapeutic outcomes of concurrent chemoradiation therapy and salvage surgery to determine the additive and synergistic effects of anticancer drugs combined with chemoradiotherapy. Fifty male patients (aged 33-76 years) with untreated T2N0M0 squamous cell carcinoma of the glottic larynx were included. Carboplatin was intravenously administered once a week for 4 weeks. Radiotherapy was delivered by an external beam of 4 MV linac X-ray (total = 66 Gy). The AUC 1.5 combination group showed overall response, CR, 5-year survival, 10-year survival, 5-year larynx preservation, and 10-year larynx preservation rates of 100.0%, 68.0%, 83.4%, 77.0%, 75.2%, and 75.2%, respectively. The AUC 2.0 combination group showed corresponding rates of 100%, 96.0%, 95.7%, 91.1%, 82.9%, and 72.7%, respectively. The most common side effects of grade 3 or more were leukopenia, neutropenia, and mucositis (stomatitis), and all were reversible. Thirteen patients (52.0%) in the AUC 1.5 combination group and nine patients (36.0%) in the AUC 2.0 combination group required salvage surgery. Histologically, concurrent chemoradiation therapy with carboplatin caused more severe cancer tissue degeneration. Pathological examinations indicated that the safety margin for partial laryngectomy was 4 mm from the gross tumor.

  1. Long non-coding RNA TUG1 contributes to tumorigenesis of human osteosarcoma by sponging miR-9-5p and regulating POU2F1 expression.

    Science.gov (United States)

    Xie, Chu-Hai; Cao, Yan-Ming; Huang, Yan; Shi, Qun-Wei; Guo, Jian-Hong; Fan, Zi-Wen; Li, Ju-Gen; Chen, Bin-Wei; Wu, Bo-Yi

    2016-11-01

    Recent studies have shown that long non-coding RNAs (lncRNAs) have critical roles in tumorigenesis, including osteosarcoma. The lncRNA taurine-upregulated gene 1 (TUG1) was reported to be involved in the progression of osteosarcoma. Here, we investigated the role of TUG1 in osteosarcoma cells and the underlying mechanism. TUG1 expression was measured in osteosarcoma cell lines and human normal osteoblast cells by quantitative real-time PCR (qRT-PCR). The effects of TUG1 on osteosarcoma cells were studied by RNA interference in vitro and in vivo. The mechanism of competing endogenous RNA (ceRNA) was determined using bioinformatic analysis and luciferase assays. Our data showed that TUG1 knockdown inhibited cell proliferation and colony formation, and induced G0/G1 cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in vivo. Besides, we found that TUG1 acted as an endogenous sponge to directly bind to miR-9-5p and downregulated miR-9-5p expression. Moreover, TUG1 overturned the effect of miR-9-5p on the proliferation, colony formation, cell cycle arrest, and apoptosis in osteosarcoma cells, which involved the derepression of POU class 2 homeobox 1 (POU2F1) expression. In conclusion, our study elucidated a novel TUG1/miR-9-5p/POU2F1 pathway, in which TUG1 acted as a ceRNA by sponging miR-9-5p, leading to downregulation of POU2F1 and facilitating the tumorigenesis of osteosarcoma. These findings may contribute to the lncRNA-targeted therapy for human osteosarcoma.

  2. Stereotactic body radiation therapy versus conventional radiation therapy in patients with early stage non-small cell lung cancer - An updated retrospective study on local failure and survival rates

    International Nuclear Information System (INIS)

    Jeppesen, Stefan S.; Schytte, Tine; Hansen, Olfred; Jensen, Henrik R.; Brink, Carsten

    2013-01-01

    Introduction: Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is now an accepted and patient friendly treatment, but still controversy exists about its comparability to conventional radiation therapy (RT). The purpose of this single-institutional report is to describe survival outcome for medically inoperable patients with early stage NSCLC treated with SBRT compared with high dose conventional RT. Material and methods: From August 2005 to June 2012, 100 medically inoperable patients were treated with SBRT at Odense Univ. Hospital. The thoracic RT consisted of 3 fractions (F) of 15-22 Gy delivered in nine days. For comparison a group of 32 medically inoperable patients treated with conventional RT with 80 Gy/35-40 F (5 F/week) in the period of July 1998 to August 2011 were analyzed. All tumors had histological or cytological proven NSCLC T1-2N0M0. Results: The median overall survival was 36.1 months versus 24.4 months for SBRT and conventional RT, respectively (p = 0.015). Local failure-free survival rates at one year were in SBRT group 93 % versus 89 % in the conventional RT group and at five years 69 % versus 66 %, SBRT and conventional RT respectively (p = 0.99). On multivariate analysis, female gender and performance status of 0-1 and SBRT predicted improved prognosis. Conclusion: In a cohort of patients with NSCLC there was a significant difference in overall survival favoring SBRT. Performance status of 0-1, female gender and SBRT predicted improved prognosis. However, staging procedure, confirmation procedure of recurrence and technical improvements of radiation treatment is likely to influence outcomes. However, SBRT seems to be as efficient as conventional RT and is a more convenient treatment for the patients

  3. Intratumoral heterogeneity of 18F-FLT uptake predicts proliferation and survival in patients with newly diagnosed gliomas

    International Nuclear Information System (INIS)

    Mitamura, Katsuya; Yamamoto, Yuka; Kudomi, Nobuyuki; Norikane, Takashi; Miyake, Keisuke; Nishiyama, Yoshihiro; Maeda, Yukito

    2017-01-01

    The nucleoside analog 3'-deoxy-3'- 18 F-fluorothymidine (FLT) has been investigated for evaluating tumor proliferating activity in brain tumors. We evaluated FLT uptake heterogeneity using textural features from the histogram analysis in patients with newly diagnosed gliomas and examined correlation of the results with proliferative activity and patient prognosis, in comparison with the conventional PET parameters. FLT PET was investigated in 37 patients with newly diagnosed gliomas. The conventional parameters [tumor-to-contralateral normal brain tissue (T/N) ratio and metabolic tumor volume (MTV)] and textural parameters (standard deviation, skewness, kurtosis, entropy, and uniformity) were derived from FLT PET images. Linear regression analysis was used to compare PET parameters and the proliferative activity as indicated by the Ki-67 index. The associations between parameters and overall survival (OS) were tested by Cox regression analysis. Median OS was 662 days. For the conventional parameters, linear regression analysis indicated a significant correlation between T/N ratio and Ki-67 index (p = 0.02) and MTV and Ki-67 index (p = 0.02). Among textural parameters, linear regression analysis indicated a significant correlation for kurtosis (p = 0.003), entropy (p < 0.001), and uniformity (p < 0.001) as compared to Ki-67 index, exceeding those of the conventional parameters. The results of univariate analysis suggested that skewness and kurtosis were associated with OS (p = 0.03 and 0.02, respectively). Mean survival for patients with skewness values less than 0.65 was 1462 days, compared with 917 days for those with values greater than 0.65 (p = 0.02). Mean survival for patients with kurtosis values less than 6.16 was 1616 days, compared with 882 days for those with values greater than 6.16 (p = 0.006). Based on the results of this preliminary study in a small patient population, textural features reflecting heterogeneity on FLT PET images seem to be

  4. 5-tert-Butyl-2-(4'-[{sup 18}F]fluoropropynylphenyl)-1,3-dithiane oxides: potential new GABA{sub A} receptor radioligands

    Energy Technology Data Exchange (ETDEWEB)

    Li Xuehe; Jung, Yong-Woon; Snyder, Scott E.; Blair, Joseph; Sherman, Philip S.; Desmond, Timothy; Frey, Kirk A. [Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States); Kilbourn, Michael R. [Department of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109 (United States)], E-mail: mkilbour@umich.edu

    2008-07-15

    As potential new ligands targeting the binding site of {gamma}-aminobutyric acid (GABA) receptor ionophore, trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1-dioxo-1, 3-dithiane (1) and cis/trans-5-tert-butyl-2-(4'-fluoropropynylphenyl)-2-methyl-1,1,3, 3-tetroxo-1,3-dithiane (2) were selected for radiolabeling and initial evaluation as in vivo imaging agents for positron emission tomography (PET). Both compounds exhibited identical high in vitro binding affinities (K{sub i}=6.5 nM). Appropriate tosylate-substituted ethynyl precursors were prepared by multistep syntheses involving stepwise sulfur oxidation and chromatographic isolation of desired trans isomers. Radiolabeling was accomplished in one step using nucleophilic [{sup 18}F]fluorination. In vivo biodistribution studies with trans-[{sup 18}F]1 and trans-[{sup 18}F]2 showed significant initial uptake into mouse brain and gradual washout, with heterogeneous regional brain distributions and higher retention in the cerebral cortex and cerebellum and lower retention in the striatum and pons-medulla. These regional distributions of the new radioligands correlated with in vitro and ex vivo measures of standard radioligands binding to the ionophore- and benzodiazepine-binding sites of GABA{sub A} receptor in rodent brain. A comparison of these results with previously prepared radiotracers for other neurochemical targets, including successes and failures as in vivo radioligands, suggests that higher-affinity compounds with increased retention in target brain tissues will likely be needed before a successful radiopharmaceutical for human PET imaging can be identified.

  5. [Long term effect of hepatitis B and C virus infection on the survival of kidney transplant patients].

    Science.gov (United States)

    Corrêa, José Roberto Missel; Rocha, Fabrício Domingos; Peres, Alessandro Afonso; Gonçalves, Luiz Felipe; Manfro, Roberto Ceratti

    2003-01-01

    To evaluate the impact of HCV (hepatitis C virus) and HBV (hepatitis B virus) infection on long-term graft and patient survival in renal transplantation. One hundred and nine kidney allograft recipients were evaluated regarding the presence of antibodies against HCV and hepatitis B surface antigen. Patients were divided into four groups according to their serologic status and followed for ten years for survival analysis. Age, gender, renal failure etiology, length of previous dialysis and post transplantation periods were evaluated. Length on dialysis time was significantly longer in the anti-HCV positive group. There was also a higher number of patients with re-transplants in the HBV and HCV groups. There were no significant differences in 10-year patient survival in the anti-HCV positive group (71.0%; relative risk: 1.13; CI: 0.86-1.47) and in the HBV infected group (77.8%; relative risk: 1.03; CI: 0.7-1.5) compared to the not infected group (80%). However, the group of patients infected with both viruses presented a significantly lower 10-year patient survival (37.5%; relative risk: 2.13; CI: 0.86-5.28) compared to the index group. There were no significant differences on graft survival among the groups. In the present study renal transplant patients infected concomitantly with HBV and HCV present a significantly lower long-term patient survival.

  6. Bi[NC5H3(CO2)2](OH2)xF (x=1 and 2): New one-dimensional Bi-coordination materials—Reversible hydration and topotactic decomposition to α-Bi2O3

    International Nuclear Information System (INIS)

    Jeon, Hye Rim; Lee, Dong Woo; Ok, Kang Min

    2012-01-01

    Two one-dimensional bismuth-coordination materials, Bi[NC 5 H 3 (CO 2 ) 2 ](OH 2 ) x F (x=1 and 2), have been synthesized by hydrothermal reactions using Bi 2 O 3 , 2,6-NC 5 H 3 (CO 2 H) 2 , HF, and water at 180 °C. Structures of the two materials were determined by single-crystal X-ray diffraction. Although they have different crystal structures, both Bi-organic materials shared a common structural motif, a one-dimensional chain structure consisting of Bi 3+ cations and pyridine dicarboxylate linkers. Detailed structural analyses include infrared spectroscopy, thermogravimetric analysis, and reversible hydration reactions for the coordinated water molecules were reported. Also, thermal decomposition of the rod-shaped Bi[NC 5 H 3 (CO 2 ) 2 ](OH 2 )F single crystals at 800 °C led to α-Bi 2 O 3 that maintained the same morphology of the original crystals. - Graphical abstract: Calcination of the Bi[NC 5 H 3 (CO 2 ) 2 ](OH 2 )F single crystals at 800 °C results in the α-Bi 2 O 3 rods that maintain the original morphology of the crystals. Highlights: ► Synthesis of one-dimensional chain Bi-organic frameworks. ► Reversible hydration reactions of Bi[NC 5 H 3 (CO 2 ) 2 ](OH 2 )F. ► Topotactic decomposition maintaining the same morphology of the original crystals.

  7. Primary localization and tumor thickness as prognostic factors of survival in patients with mucosal melanoma.

    Directory of Open Access Journals (Sweden)

    Tarun Mehra

    Full Text Available Data on survival with mucosal melanoma and on prognostic factors of are scarce. It is still unclear if the disease course allows for mucosal melanoma to be treated as primary cutaneous melanoma or if differences in overall survival patterns require adapted therapeutic approaches. Furthermore, this investigation is the first to present 10-year survival rates for mucosal melanomas of different anatomical localizations.116 cases from Sep 10 1984 until Feb 15 2011 retrieved from the Comprehensive Cancer Center and of the Central Register of the German Dermatologic Society databases in Tübingen were included in our analysis. We recorded anatomical location and tumor thickness, and estimated overall survival at 2, 5 and 10 years and the mean overall survival time. Survival times were analyzed with the Kaplan-Meier method. The log-rank test was used to compare survival times by localizations and by T-stages.We found a median overall survival time of 80.9 months, with an overall 2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%. The 10-year survival rates for patients with T1, T2, T3 or T4 stage tumors were 100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non-vulva mucosal melanomas.Survival times differed significantly between patients with melanomas of the vulva compared to the rest (p = 0.0006. It also depends on T-stage at the time of diagnosis (p < 0.0001.

  8. Reduction of hydrogen desorption temperature of ball-milled MgH2 by NbF5 addition

    International Nuclear Information System (INIS)

    Recham, N.; Bhat, V.V.; Kandavel, M.; Aymard, L.; Tarascon, J.-M.; Rougier, A.

    2008-01-01

    Enhanced sorption properties of ball-milled MgH 2 are reported by adding NbF 5 . Among various catalyst amounts, 2 mol% of NbF 5 reveals to be the optimum concentration leading to significant reduction of the desorption temperature as well as faster kinetics of ball-milled MgH 2 . At 200 deg. C, temperature at which MgH 2 does not show any activity, MgH 2NbF 5 /2mol% composite desorbs 3.2 wt.% of H 2 in 50 mins. Interestingly, the addition of NbF 5 is also associated with an increase in the desorption pressure. At 300 deg. C, MgH 2NbF 5 /2mol% composite starts to desorb hydrogen at 600 mbar in comparison with 1 mbar for MgH 2 . Further improvements were successfully achieved by pre-grinding NbF 5 prior to ball-milling the catalyst with MgH 2 . Such pre-ground NbF 5 catalyzed MgH 2 composite desorbs 3 wt.% of H 2 at 150 deg. C. Improved properties are associated with smaller activation energies down to values close to the enthalpy of formation of MgH 2 . Finally, the mechanism at the origin of the enhancement is discussed in terms of catalyst stability, MgF 2 formation and electronic density localization

  9. Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib

    Directory of Open Access Journals (Sweden)

    Lee SH

    2015-04-01

    Full Text Available Sangheun Lee,1,* Beom Kyung Kim,25,* Seung Up Kim,25 Jun Yong Park,25 Do Young Kim,25 Sang Hoon Ahn,2–6 Kwang-Hyub Han2–6 1Department of Internal Medicine, International St Mary’s Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea; 2Department of Internal Medicine, 3Institute of Gastroenterology, 4Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea; 6Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea.   *These authors contributed equally to this work Background: It is not clear whether tumor marker responses can predict survival during sorafenib treatment in hepatocellular carcinoma (HCC. We investigated whether the α-fetoprotein (AFP response is associated with survival in patients with advanced HCC treated with sorafenib. Methods: We retrospectively reviewed the records of 126 patients with advanced HCC treated with sorafenib between 2007 and 2012. An AFP response was defined as >20% decrease from baseline. At 6–8 weeks after commencing sorafenib, AFP and radiological responses were assessed by modified Response Evaluation Criteria in Solid Tumors. Results: The median overall survival (OS and progression-free survival (PFS were 6.2 and 3.5 months, respectively. Of the study population, a partial response (PR was identified in 5 patients (4.0%, stable disease (SD in 65 patients (51.6%, and progressive disease (PD in 57 patients (44.4%, respectively. AFP non-response was an independent prognostic factor for poor OS (median 10.9 months for AFP response vs 5.2 months for AFP non-response, together with Child-Pugh B, tumor diameter ≥10 cm, and portal vein invasion (all P<0.05, and PFS (median 5.3 months for AFP response vs 2.9 months for AFP non-response, together with tumor diameter ≥10 cm and portal vein invasion (all P<0.05. SD or PR was more frequently found

  10. Intravoxel Incoherent Motion Metrics as Potential Biomarkers for Survival in Glioblastoma.

    Directory of Open Access Journals (Sweden)

    Josep Puig

    Full Text Available Intravoxel incoherent motion (IVIM is an MRI technique with potential applications in measuring brain tumor perfusion, but its clinical impact remains to be determined. We assessed the usefulness of IVIM-metrics in predicting survival in newly diagnosed glioblastoma.Fifteen patients with glioblastoma underwent MRI including spin-echo echo-planar DWI using 13 b-values ranging from 0 to 1000 s/mm2. Parametric maps for diffusion coefficient (D, pseudodiffusion coefficient (D*, and perfusion fraction (f were generated for contrast-enhancing regions (CER and non-enhancing regions (NCER. Regions of interest were manually drawn in regions of maximum f and on the corresponding dynamic susceptibility contrast images. Prognostic factors were evaluated by Kaplan-Meier survival and Cox proportional hazards analyses.We found that fCER and D*CER correlated with rCBFCER. The best cutoffs for 6-month survival were fCER>9.86% and D*CER>21.712 x10-3mm2/s (100% sensitivity, 71.4% specificity, 100% and 80% positive predictive values, and 80% and 100% negative predictive values; AUC:0.893 and 0.857, respectively. Treatment yielded the highest hazard ratio (5.484; 95% CI: 1.162-25.88; AUC: 0.723; P = 0.031; fCER combined with treatment predicted survival with 100% accuracy.The IVIM-metrics fCER and D*CER are promising biomarkers of 6-month survival in newly diagnosed glioblastoma.

  11. Targeting to 5-HT1F Receptor Subtype for Migraine Treatment

    DEFF Research Database (Denmark)

    Mitsikostas, Dimos D; Tfelt-Hansen, Peer

    2012-01-01

    attacks with efficacy in the same range as oral sumatriptan 100mg, the gold standard for triptans. The LY334370 project withdrew because of toxicity in animals, while lasmiditan is still testing. In this review we present all the available preclinical and clinical data on the 5-HT1F agonists...... inhibited markers associated with electrical stimulation of the TG. Thus 5-HT1F receptor represents an ideal target for anti-migraine drugs. So far two selective 5-HT1F agonists have been tested in human trials for migraine: LY334370 and lasmiditan. Both molecules were efficient in attenuating migraine...

  12. E2F1 regulates cellular growth by mTORC1 signaling.

    Directory of Open Access Journals (Sweden)

    Sebastian Real

    2011-01-01

    Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

  13. Survival in Patients Receiving Prolonged Ventilation: Factors that Influence Outcome

    Directory of Open Access Journals (Sweden)

    A. James Mamary

    2011-01-01

    Full Text Available Background Prolonged mechanical ventilation is increasingly common. It is expensive and associated with significant morbidity and mortality. Our objective is to comprehensively characterize patients admitted to a Ventilator Rehabilitation Unit (VRU for weaning and identify characteristics associated with survival. Methods 182 consecutive patients over 3.5 years admitted to Temple University Hospital (TUH VRU were characterized. Data were derived from comprehensive chart review and a prospectively collected computerized database. Survival was determined by hospital records and social security death index and mailed questionnaires. Results Upon admission to the VRU, patients were hypoalbuminemic (albumin 2.3 ± 0.6 g/dL, anemic (hemoglobin 9.6 ± 1.4 g/dL, with moderate severity of illness (APACHE II score 10.7 + 4.1, and multiple comorbidities (Charlson index 4.3 + 2.3. In-hospital mortality (19% was related to a higher Charlson Index score ( P = 0.006; OR 1.08-1.6, and APACHE II score ( P = 0.016; OR 1.03-1.29. In-hospital mortality was inversely related to admission albumin levels ( P = 0.023; OR 0.17-0.9. The presence of COPD as a comorbid illness or primary determinant of respiratory failure and higher VRU admission APACHE II score predicted higher long-term mortality. Conversely, higher VRU admission hemoglobin was associated with better long term survival (OR 0.57-0.90; P = 0.0006. Conclusion Patients receiving prolonged ventilation are hypoalbuminemic, anemic, have moderate severity of illness, and multiple comorbidities. Survival relates to these factors and the underlying illness precipitating respiratory failure, especially COPD.

  14. Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency.

    Science.gov (United States)

    Diekman, Eugene F; de Koning, Tom J; Verhoeven-Duif, Nanda M; Rovers, Maroeska M; van Hasselt, Peter M

    2014-02-01

    The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. MEDLINE, EMBASE, and Cochrane databases between January 1960 and December 2012. Studies that described patients with severe MTHFR deficiency who received betaine treatment. We identified 15 case reports and case series, totaling 36 patients. Data included the following: (1) families with 2 or more patients with severe MTHFR deficiency, of whom at least 1 received betaine, or (2) single patients with severe MTHFR deficiency treated with betaine. To define severe MTHFR deficiency, methionine, homocysteine, MTHFR enzyme activity in fibroblasts, or mutations (in the MTHFR gene) had to be described as well as the effect of treatment (survival and/or psychomotor development). We compared the outcome in treated vs untreated patients and early- vs late-treated patients. Sensitivity analysis was performed to address definition of early treatment. To further assess the impact of treatment on mortality, we performed a subanalysis in families with at least 1 untreated deceased patient. Survival and psychomotor development. Eleven of 36 patients (31%) died. All deaths occurred in patients who did not receive treatment or in patients in whom treatment was delayed. In contrast, all 5 early-treated patients survived. Subgroup analysis of patients with deceased siblings-their genotypically identical controls-revealed that betaine treatment prevented mortality (P = .002). In addition, psychomotor development in surviving patients treated with betaine was normal in all 5 early-treated patients but in none of the 19 surviving patients with delayed treatment (P psychomotor development in patients with severe MTHFR deficiency, highlighting the importance of timely recognition through newborn screening.

  15. 2-Methylsulfanyl-5,6-dihydro-2H-1,3-dithiolo[4,5-b][1,4]dioxin-2-ium tetrafluoroborate

    Directory of Open Access Journals (Sweden)

    Guoquan Zhou

    2012-04-01

    Full Text Available The title compound, C6H7O2S3+·BF4−, consists of a planar 2-thioxo-1,3-dithiol-4,5-yl unit [maximum deviation from the ring plane = 0.020 (3 Å], with an ethylenedioxy group fused at the 4,5-positions; the ethylenedioxy C atoms are disordered over two positions with site-occupancy factors of 0.5. The 1,4-dioxine ring has a twist-chair conformation. Weak cation–anion S...F interactions [3.022 (4–3.095 (4 Å] and an S...O [3.247 (4 Å] interaction are present.

  16. {sup 18}F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with {sup 90}Y microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Haug, Alexander R. [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany); Klinikum Grosshadern, Department of Nuclear Medicine, Munich (Germany); Heinemann, Volker [Ludwig-Maximilians-University, Department of Internal Medicine III, Munich (Germany); Bruns, Christiane J. [Ludwig-Maximilians-University, Department of Surgery, Munich (Germany); Hoffmann, Ralf; Jakobs, Tobias [Ludwig-Maximilians-University, Institute of Clinical Radiology, Munich (Germany); Bartenstein, Peter; Hacker, Marcus [Ludwig-Maximilians-University, Department of Nuclear Medicine, Munich (Germany)

    2011-06-15

    {sup 90}Y radioembolization has emerged as a valuable therapy for intrahepatic cholangiocellular carcinomas (ICC). We aimed to evaluate the prognostic power of FDG PET/CT and that of pretherapeutic scintigraphy with {sup 99m}Tc-labelled macroagglutinated albumin (MAA), an index of tumour vascularization. The study group comprised 26 consecutive patients suffering from nonresectable ICC. Before treatment with radioembolization, all patients underwent MRI of the liver, as well as MAA scintigraphy, which was followed immediately by SPECT(/CT) to quantify the liver-lung shunt fraction. Using image fusion, regions of interest were drawn around the tumours and the entire liver, and the tumour-to-liver quotient was calculated. In addition, FDG PET/CT was performed at baseline and 3 months after radioembolization, and the percentage changes in peak ({delta}SUV{sub max}) and mean ({delta}SUV{sub mean}) FDG uptake and in metabolic tumour volume ({delta}Vol{sub 2SD}) relative to baseline were calculated. Treatment response at 3 months was also assessed using contrast-enhanced MRI and CT on the basis of standard criteria. Of 23 patients in whom follow-up MRI was available, 5 (22%) showed a partial response, 15 (65%) stable disease and 3 (13%) progressive disease. The change in all FDG values significantly predicted survival by Kaplan-Meier analysis after radioembolization; {delta}Vol{sub 2SD} responders had a median survival of 97 weeks versus 30 weeks in nonresponders (P = 0.02), whereas {delta}SUV{sub max} and {delta}SUV{sub mean} responders had a median survival of 114 weeks (responder) versus 19 weeks (nonresponder) and 69 weeks in patients with stable disease (P < 0.05). Pretherapeutic MAA scintigraphy or MRI did not predict survival, nor did the presence of extrahepatic metastases, or prior therapies. Only {delta}Vol{sub 2SD} was significantly associated with survival by univariate analysis (hazard ratio 0.25; P = 0.04) and multivariate analysis (hazard ratio 0.20, P = 0

  17. Secretory Phospholipase A(2)-IIA and Cardiovascular Disease

    NARCIS (Netherlands)

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; Van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, Andre G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Pare, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. Background Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not

  18. The validity of EORTC GBM prognostic calculator on survival of GBM patients in the West of Scotland.

    Science.gov (United States)

    Teo, Mario; Clark, Brian; MacKinnon, Mairi; Stewart, Willie; Paul, James; St George, Jerome

    2014-06-01

    It is now accepted that the addition of temozolomide to radiotherapy in the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) significantly improves survival. In 2008, a subanalysis of the original study data was performed, and an online "GBM Calculator" was made available on the European Organisation for Research and Treatment of Cancer (EORTC) website allowing users to estimate patients' survival outcomes. We tested this calculator against actual local survival data to validate its use in our patients. Prospectively collected clinical data were analysed on 105 consecutive patients receiving concurrent chemoradiotherapy following surgical treatment of GBM between December 2004 and February 2009. Using the EORTC online calculator, survival outcomes were generated for these patients and compared with their actual survival. The median overall survival for the entire cohort was 15.3 months (range 2.8-50.5 months), with 1-year and 2-year overall survival of 65.7% and 19%, respectively. This is in comparison to the median overall predictive survival of 21.3 months, with 1-year and 2-year survival of 95% and 39.5%, respectively. Case by case analysis also showed that the survival was overestimated in nearly 80% of patients. Subgroup analyses showed similar overestimation of patients' survival, except calculator Model 3 which utilised MGMT status. Use of the EORTC GBM prognostic calculator would have overestimated the survival of the majority of our patients with GBM. Uncertainty exists as to the cause of overestimation in the cohort although local socioeconomic factors might play a role. The different calculator models yielded different outcomes and the "best" predictor of survival for the cohort under study utilised the tumour MGMT status. We would strongly encourage similar local studies of validity testing prior to employing the online prognostic calculator for other population groups.

  19. Preoperative Comorbidity Correlates Inversely with Survival after Intestinal and Multivisceral Transplantation in Adults

    Directory of Open Access Journals (Sweden)

    Rajesh Sivaprakasam

    2013-01-01

    Full Text Available We investigated the relationship between preoperative comorbidity and postoperative survival after intestinal transplantation. Each patient received a score for preoperative comorbidity. Each comorbidity was given a score based on the degree it impaired function (score range 0–3. A total score was derived from the summation of individual comorbidity scores. Patients (72 adults (M : F, 33 : 39 received an isolated intestinal graft (27 or a cluster graft (45. Mean (standard deviation survival was 1501 (1444 days. The Kaplan-Meier analysis revealed a significant inverse association between survival and comorbidity score (logrank test for trend, . Patients grouped into comorbidity scores of 0 and 1, 2 and 3, 4 and 5, 6, and above had hazard ratios (95% confidence intervals for death (compared to group 0 + 1, which increased with comorbidity scores: 1.945 (0.7622–5.816, 5.075 (3.314–36.17, and 13.77 (463.3–120100, respectively, (. Receiver-operator curves at 1, 3, 5, and 10 years postoperative had “C” statistics of 0.88, 0.85, 0.88, and 0.92, respectively. When evaluating patients for transplantation, the degree of comorbidity should be considered as a major factor influencing postoperative survival.

  20. {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography for grading and estimation of prognosis in patients with intracranial gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Gempt, Jens, E-mail: jens.gempt@tum.de [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Bette, Stefanie; Ryang, Yu-Mi; Buchmann, Niels; Peschke, Patrick [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Pyka, Thomas; Wester, Hans-Jürgen; Förster, Stefan [Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Meyer, Bernhard; Ringel, Florian [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany)

    2015-05-15

    . Results: One hundred fifty-two patients (39 WHO II, 26 WHO III, 87 WHO IV) were included. The median T/N ratio was 2.81 (1.1–8.1). The median T/N ratio of low-grade glioma patients was 1.65 (1.1–3.7), and 3.14 (1.61–8.1, p < 0.001) in high-grade glioma patients. The median survival for patients with WHO III tumors was 22.8 months (95% CI: 15.87%–NA) and 13.23 months (95% CI: 10.83–15.6.%) for patients with WHO IV tumors (p = 0.0001). For T/N ≤ 1.6, no deaths were recorded; for 1.6 < T/N ≤ 3, median survival was 25.6 months (95% CI: 16.5%–NA), while for T/N > 3, median survival was 14.0 months (95% CI: 11.7–16.2%, p < 0.001). The test of the maximally selected log-rank statistic resulted in a T/N ratio of 1.88 as the cut-off value, with the greatest difference in overall survival between patients with longer and shorter survival. The ROC curve for differentiation of low- vs. high-grade tumors with regard to the T/N ratio showed an area under the curve (AUC) of 0.903. Regarding the prognostic validity for overall survival ROC-curves for 12-month, 24-month and 48-month survival display a higher validity for the WHO-classification than for the imaging modalities though with an AUC of 0.847 for the 48-month survival T/N ratio and MRI contrast-enhancement have a high prognostic value as well. Conclusion: Our study suggests that FET-PET can predict prognosis and survival in patients harboring intracranial gliomas and serves as a valuable tool to supplement the established clinical and histopathological parameters.

  1. Spectrum of mutations in RARS-T patients includes TET2 and ASXL1 mutations

    OpenAIRE

    Szpurka, Hadrian; Jankowska, Anna M.; Makishima, Hideki; Bodo, Juraj; Bejanyan, Nelli; Hsi, Eric D.; Sekeres, Mikkael A.; Maciejewski, Jaroslaw P.

    2010-01-01

    While a majority of patients with refractory anemia with ring sideroblasts and thrombocytosis harbor JAK2V617F and rarely MPLW515L, JAK2/MPL-negative cases constitute a diagnostic problem. 23 RARS-T cases were investigated applying immunohistochemical phospho-STAT5, sequencing and SNP-A-based karyotyping. Based on the association of TET2/ASXL1 mutations with MDS/MPN we studied molecular pattern of these genes. Two patients harbored ASXL1 and another 2 TET2 mutations. Phospho-STAT5 activation ...

  2. Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Maklad AM

    2016-10-01

    Full Text Available Ahmed Marzouk Maklad,1,2 Yasser Bayoumi,2,3 Mohamed Abdalazez Senosy Hassan,2,4 AbuSaleh A Elawadi,5,6 Hussain AlHussain,2 Ashraf Elyamany,7,8 Saleh F Aldhahri,9 Khalid Hussain Al-Qahtani,10 Mubarak AlQahtani,11 Mutahir A Tunio12 1Clinical Oncology, Sohag University, Sohag, Egypt; 2Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 3Radiation Oncology, NCI, Cairo University, Cairo, 4Radiation Oncology, Minia Oncology Center, Minia, 5Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 6Medical Physics, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 7Medical Oncology, SECI-Assiut University, Assiut, Egypt; 8Medical Oncology, Comprehensive Cancer Center, King Fahad Medical City, 9Department of Otolaryngology, Head and Neck Surgery, King Saud University, 10Department of Otolaryngology-Head and Neck Surgery, College of Medicine, King Saud University, 11Department of ENT, King Fahad Medical City, 12Radiation Oncology, King Fahad Medical City, Riyadh, Saudi Arabia Background: We aimed to investigate the patterns of failure (locoregional and distant metastasis, associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT combined with chemotherapy. Patients and methods: From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume, and 50.4–56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results: The median follow-up time was 52.2 months (range: 11–87 months. Epstein–Barr virus infection was positive in 63.2% of

  3. Prognostic relevance at 5 years of the early monitoring of neoadjuvant chemotherapy using 18F-FDG PET in luminal HER2-negative breast cancer

    International Nuclear Information System (INIS)

    Humbert, Olivier; Brunotte, Francois; Berriolo-Riedinger, Alina; Toubeau, Michel; Dygai-Cochet, Inna; Cochet, Alexandre; Gauthier, Melanie; Charon-Barra, Celine; Guiu, Severine; Desmoulins, Isabelle; Fumoleau, Pierre; Coutant, Charles

    2014-01-01

    The objective of this study was to evaluate, in the luminal human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype, the prognostic value of tumour glucose metabolism at baseline and of its early changes during neoadjuvant chemotherapy (NAC). This prospective study included 61 women with hormone-sensitive HER2-negative breast cancer treated with NAC. 18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed at baseline. Hepatic activity was used as a reference to distinguish between low metabolic and hypermetabolic tumours. In hypermetabolic tumours, a PET exam was repeated after the first course of NAC. The relative change in the maximum standardized uptake value of the tumour (∇SUV) was calculated. Nineteen women had low metabolic luminal breast cancers at baseline, correlated with low proliferation indexes. Forty-two women had hypermetabolic tumours, corresponding to more proliferative breast cancers with higher Ki-67 expression (p = 0.017) and higher grade (p = 0.04). The median follow-up period was 64.2 months (range 11.5-93.2). Thirteen women developed recurrent disease, nine of whom died. Worse overall survival was associated with larger tumour size [>5 cm, hazard ratio (HR) = 6.52, p = 0.009] and with hypermetabolic tumours achieving a low metabolic response after one cycle of NAC (ΔSUV < 16 %, HR = 10.63, p = 0.004). Five-year overall survival in these poor responder patients was 49.2 %. Overall survival in women with low metabolic tumours or hypermetabolic/good response tumours was 100 and 96.15 %, respectively. In luminal HER2-negative breast tumours, tumour metabolism at baseline and changes after the first course of NAC are early surrogate markers of patients' survival. A subgroup of women with hypermetabolic/poorly responding tumours, correlated with poor prognosis at 5 years, can be identified early. These results may guide future studies by tailoring the NAC regimen to the metabolic response. (orig.)

  4. Survival of Patients with Oral Cavity Cancer in Germany

    Science.gov (United States)

    Listl, Stefan; Jansen, Lina; Stenzinger, Albrecht; Freier, Kolja; Emrich, Katharina; Holleczek, Bernd; Katalinic, Alexander; Gondos, Adam; Brenner, Hermann

    2013-01-01

    The purpose of the present study was to describe the survival of patients diagnosed with oral cavity cancer in Germany. The analyses relied on data from eleven population-based cancer registries in Germany covering a population of 33 million inhabitants. Patients with a diagnosis of oral cavity cancer (ICD-10: C00-06) between 1997 and 2006 are included. Period analysis for 2002–2006 was applied to estimate five-year age-standardized relative survival, taking into account patients' sex as well as grade and tumor stage. Overall five-year relative survival for oral cavity cancer patients was 54.6%. According to tumor localization, five-year survival was 86.5% for lip cancer, 48.1% for tongue cancer and 51.7% for other regions of the oral cavity. Differences in survival were identified with respect to age, sex, tumor grade and stage. The present study is the first to provide a comprehensive overview on survival of oral cavity cancer patients in Germany. PMID:23349710

  5. Copy number variations of E2F1: a new genetic risk factor for testicular cancer.

    Science.gov (United States)

    Rocca, Maria Santa; Di Nisio, Andrea; Marchiori, Arianna; Ghezzi, Marco; Opocher, Giuseppe; Foresta, Carlo; Ferlin, Alberto

    2017-03-01

    Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years, many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer. E2F1 is a transcription factor that plays an important role in regulating cell growth, differentiation, apoptosis and response to DNA damage. Therefore, deficiency or overexpression of this protein might significantly influence fundamental biological processes involved in cancer development and progression, including TGCT. We analyzed E2F1 CNVs in 261 cases with TGCT and 165 controls. We found no CNVs in controls, but 17/261 (6.5%) cases showed duplications in E2F1 Blot analysis demonstrated higher E2F1 expression in testicular samples of TGCT cases with three copies of the gene. Furthermore, we observed higher phosphorylation of Akt and mTOR in samples with E2F1 duplication. Interestingly, normal, non-tumoral testicular tissue in patient with E2F1 duplication showed lower expression of E2F1 and lower AKT/mTOR phosphorylation with respect to adjacent tumor tissue. Furthermore, increased expression of E2F1 obtained in vitro in NTERA-2 testicular cell line induced increased AKT/mTOR phosphorylation. This study suggests for the first time an involvement of E2F1 CNVs in TGCT susceptibility and supports previous preliminary data on the importance of AKT/mTOR signaling pathway in this cancer. © 2017 Society for Endocrinology.

  6. Failure-free survival following brachytherapy alone or external beam irradiation alone for T1-2 prostate tumors in 2222 patients: results from a single practice

    International Nuclear Information System (INIS)

    Brachman, David G.; Thomas, Theresa; Hilbe, Joseph; Beyer, David C.

    2000-01-01

    Purpose: To evaluate failure-free survival (FFS) for brachytherapy (BT) alone compared to external beam radiotherapy (EBRT) alone for Stage T1-2 Nx-No Mo patients over the same time period by a single community-based practice in the prostate-specific antigen (PSA) era. Materials and Methods: The database of Arizona Oncology Services (a multiphysician radiation oncology practice in the Phoenix metropolitan area) was reviewed for patients meeting the following criteria: (1) T1 or T2 Nx-No Mo prostate cancer; (2) no prior or concurrent therapy including hormones; (3) treatment period 12/88-12/95; and (4) treatment with either EBRT alone or BT alone ( 125 I or 103 Pd). This yielded 1527 EBRT and 695 BT patients; no patients meeting the above criteria were excluded from analysis. Median follow-up for EBRT patients was 41.3 months and, for BT patients, 51.3 months. Patients were not randomized to either therapy but rather received EBRT or BT based upon patient, treating, and/or referring physician preference. PSA failure was defined according to the ASTRO consensus guidelines. The median patient age was 74 years for both groups. Results: Failure-free survival at 5 years for EBRT and BT are 69% and 71%, respectively (p = 0.91). For T stage, no significant difference in FFS at 5 years is observed between EBRT and BT for either T1 (78% vs. 83%, p = 0.47) or T2 (67% vs. 67%, p = 0.89) tumors. Analysis by Gleason score shows superior outcomes for Gleason 8-10 lesions treated with EBRT vs. BT (5-year FFS 52% vs. 28%, p = 0.04); outcomes for lower grade lesions (Gleason 4-6) when analyzed by Gleason score alone do not significantly differ according to treatment received. Patients with initial PSA values of 10-20 ng/dL have an improved FFS with EBRT vs. BT at 5 years (70% vs. 53%, p = 0.001); outcomes for patients with initial PSA ranges of 0-4 ng/dL, of > 4-10 ng/dL, and > 20 ng/dL did not differ significantly by treatment received. FFS was also determined for presenting

  7. Factors affecting 30-month survival in lung cancer patients.

    Science.gov (United States)

    Mahesh, P A; Archana, S; Jayaraj, B S; Patil, Shekar; Chaya, S K; Shashidhar, H P; Sunitha, B S; Prabhakar, A K

    2012-10-01

    Age adjusted incidence rate of lung cancer in India ranges from 7.4 to 13.1 per 100,000 among males and 3.9 to 5.8 per 100,000 among females. The factors affecting survival in lung cancer patients in India are not fully understood. The current study was undertaken to evaluate the factors affecting survival in patients diagnosed with lung cancer attending a tertiary care cancer institute in Bangalore, Karnataka, India. Consecutive patients with primary lung cancer attending Bangalore Institute of Oncology, a tertiary care centre at Bangalore, between 2006 and 2009 were included. Demographic, clinical, radiological data were collected retrospectively from the medical records. A total of 170 consecutive subjects (128 males, 42 females) diagnosed to have lung cancer; 151 non-small cell lung cancer (NSCLC) and 19 small cell lung cancer (SCLC) were included. A higher proportion of never-smokers (54.1%) were observed, mostly presenting below the age of 60 yr. Most subjects were in stage IV and III at the time of diagnosis. More than 50 per cent of patients presented with late stage lung cancer even though the duration of symptoms is less than 2 months. The 30-month overall survival rates for smokers and never-smokers were 32 and 49 per cent, respectively. No significant differences were observed in 30 month survival based on age at presentation, gender and type of lung cancer. Cox proportional hazards model identified never-smokers and duration of symptoms less than 1 month as factors adversely affecting survival. Our results showed that lung cancer in Indians involved younger subjects and associated with poorer survival as compared to other ethnic population. Studies on large sample need to be done to evaluate risk factors in lung cancer patients.

  8. CALR, JAK2 and MPL mutation status in Argentinean patients with BCR-ABL1- negative myeloproliferative neoplasms.

    Science.gov (United States)

    Ojeda, Mara Jorgelina; Bragós, Irma Margarita; Calvo, Karina Lucrecia; Williams, Gladis Marcela; Carbonell, María Magdalena; Pratti, Arianna Flavia

    2018-05-01

    To establish the frequency of JAK2, MPL and CALR mutations in Argentinean patients with BCR-ABL1-negative  myeloproliferative neoplasms (MPN) and to compare their clinical and haematological features. Mutations of JAK2V617F, JAK2 exon 12, MPL W515L/K and CALR were analysed in 439 Argentinean patients with BCR-ABL1-negative MPN, including 176 polycythemia vera (PV), 214 essential thrombocythemia (ET) and 49 primary myelofibrosis (PMF). In 94.9% of PV, 85.5% ET and 85.2% PMF, we found mutations in JAK2, MPL or CALR. 74.9% carried JAK2V617F, 12.3% CALR mutations, 2.1% MPL mutations and 10.7% were triple negative. In ET, nine types of CALR mutations were identified, four of which were novel. PMF patients were limited to types 1 and 2, type 2 being more frequent. In ET, patients with CALR mutation were younger and had higher platelet counts than those with JAK2V617F and triple negative. In addition, JAK2V617F patients had high leucocyte and haemoglobin values compared with CALR-mutated and triple-negative patients. In PMF, patients with mutant CALR were associated with higher platelet counts. Our study underscores the importance of JAK2, MPL and CALR genotyping for accurate diagnosis of patients with BCR-ABL1-negative MPN.

  9. Effect of postoperative adjuvant transarterial chemoembolization on postoperative survival of patients with liver cancer and related influencing factors for prognosis

    Directory of Open Access Journals (Sweden)

    XING Zhixiang

    2017-12-01

    Full Text Available ObjectiveTo investigate the effect of postoperative adjuvant transarterial chemoembolization (TACE on the survival of patients with hepatocellular carcinoma (HCC, as well as influencing factors for prognosis. MethodsA retrospective analysis was performed for the clinical data of 215 HCC patients who were admitted to Renmin Hospital of Wuhan University from January 2007 to December 2012. According to whether TACE was given after hepatectomy, these patients were divided into single group with 95 patients and combination group with 120 patients. A comparative analysis was performed for the two groups. The patients in the single group were given hepatectomy alone, and those in the combination group were given hepatectomy followed by TACE at one month after surgery. General status, treatment condition, and related clinical indices were recorded for both groups, and the two groups were compared in terms of the 1-, 3-, and 5-year survival rates and disease-free survival rates after surgery. The independent samples t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used for comparison of survival rates between groups, and univariate analysis and Cox multivariate regression analysis were used to investigate the influencing factors for prognosis after hepatectomy. ResultsIn the combination group, the 1-, 3-, and 5-year survival rates were 96.5%, 67.0%, and 51.0%, respectively, with a median survival time of 51 months; in the single group, the 1-, 3-, and 5-year survival rates were 84.0%,49.5%, and 36.5%, respectively, with a median survival time of 39 months; there was a significant difference in survival rates between the two groups (χ2=5.540, P=0.018. The 1-, 3-, and 5-year disease-free survival rates were 91.7%, 62.5%, and 37.5%, respectively, in the combination group and 84.0%, 42.1%, and 26.3%, respectively, in the single

  10. A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro; Okagawa, Yutaka; Osuga, Takahiro; Hayashi, Tsuyoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Takimoto, Rishu [Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo (Japan); Sagawa, Tamotsu [Division of Gastroenterology, Hokkaido Cancer Center, Sapporo (Japan); Hori, Masakazu; Someya, Masanori; Nakata, Kensei; Sakata, Koh-ichi [Department of Radiology, Sapporo Medical University School of Medicine, Sapporo (Japan); Takayama, Tetsuji [Department of Gastroenterology and Oncology, University of Tokushima, Tokushima (Japan); Kato, Junji, E-mail: jkato@sapmed.ac.jp [Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo (Japan)

    2015-10-01

    Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m{sup 2}) and nedaplatin (50 mg/m{sup 2}) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m{sup 2}/day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m{sup 2}. In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC.

  11. A Phase 1/2 Study of Definitive Chemoradiation Therapy Using Docetaxel, Nedaplatin, and 5-Fluorouracil (DNF-R) for Esophageal Cancer

    International Nuclear Information System (INIS)

    Ohnuma, Hiroyuki; Sato, Yasushi; Hirakawa, Masahiro; Okagawa, Yutaka; Osuga, Takahiro; Hayashi, Tsuyoshi; Sato, Tsutomu; Miyanishi, Koji; Kobune, Masayoshi; Takimoto, Rishu; Sagawa, Tamotsu; Hori, Masakazu; Someya, Masanori; Nakata, Kensei; Sakata, Koh-ichi; Takayama, Tetsuji; Kato, Junji

    2015-01-01

    Purpose: Patient survival in esophageal cancer (EC) remains poor. The purpose of this study was to investigate a regimen of definitive chemoradiation therapy (CRT) that exerts good local control of EC. We performed a phase 1/2 study to assess the safety and efficacy of CRT with docetaxel, nedaplatin, and 5-fluorouracil (DNF-R). Methods and Materials: Eligible patients presented with stage IB to IV EC. Patients received 2 cycles of docetaxel (20, 30, or 40 mg/m 2 ) and nedaplatin (50 mg/m 2 ) on days 1 and 8 and a continuous infusion of 5-fluorouracil (400 mg/m 2 /day) on days 1 to 5 and 8 to 12, every 5 weeks, with concurrent radiation therapy (59.4 Gy/33 fractions). The recommended dose (RD) was determined using a 3 + 3 design. Results: In the phase 1 study, the dose-limiting toxicities were neutropenia and thrombocytopenia. The RD of docetaxel was determined to be 20 mg/m 2 . In the phase 2 study, grade 3 to 4 acute toxicities included neutropenia (42.8%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3 to 4 late radiation toxicity included esophagostenosis (10.7%). The complete response rate was 82.1% (95% confidence interval: 67.9-96.3%). Both the median progression-free survival and overall survival were 41.2 months. Conclusions: DNF-R showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for EC

  12. Multiple neoplasms, single primaries, and patient survival

    International Nuclear Information System (INIS)

    Amer, Magid H

    2014-01-01

    Multiple primary neoplasms in surviving cancer patients are relatively common, with an increasing incidence. Their impact on survival has not been clearly defined. This was a retrospective review of clinical data for all consecutive patients with histologically confirmed cancer, with emphasis on single versus multiple primary neoplasms. Second primaries discovered at the workup of the index (first) primary were termed simultaneous, if discovered within 6 months of the index primary were called synchronous, and if discovered after 6 months were termed metachronous. Between 2005 and 2012, of 1,873 cancer patients, 322 developed second malignancies; these included two primaries (n=284), and three or more primaries (n=38). Forty-seven patients had synchronous primaries and 275 had metachronous primaries. Patients with multiple primaries were predominantly of Caucasian ancestry (91.0%), with a tendency to develop thrombosis (20.2%), had a strong family history of similar cancer (22.3%), and usually presented with earlier stage 0 through stage II disease (78.9%). When compared with 1,551 patients with a single primary, these figures were 8.9%, 15.6%, 18.3%, and 50.9%, respectively (P≤0.001). Five-year survival rates were higher for metachronous cancers (95%) than for synchronous primaries (59%) and single primaries (59%). The worst survival rate was for simultaneous concomitant multiple primaries, being a median of 1.9 years. The best survival was for patients with three or more primaries (median 10.9 years) and was similar to the expected survival for the age-matched and sex-matched general population (P=0.06991). Patients with multiple primaries are usually of Caucasian ancestry, have less aggressive malignancies, present at earlier stages, frequently have a strong family history of similar cancer, and their cancers tend to have indolent clinical behavior with longer survival rates, possibly related to genetic predisposition

  13. Survival of patients with Ewing's sarcoma in Yazd-Iran.

    Science.gov (United States)

    Akhavan, Ali; Binesh, Fariba; Shamshiri, Hadi; Ghanadi, Fazllolah

    2014-01-01

    The Ewing's sarcoma family is a group of small round cell tumors which accounts for 10-15% of all primary bone neoplasms. The aim of this study was to evaluate the survival of Ewing's sarcoma patients in our province and to determine of influencing factors. All patients with documented Ewing's sarcoma/ primitive neuroectodermal tumor(PNET) family pathology were enrolled in this study during a period of eight years. For all of them local and systemic therapy were carried out. Overall and event free survival and prognostic factors were evaluated. Thirty two patients were enrolled in the study. The median age was 17.5 years. Twenty (65.2%) were male and 9 (28.1%) were aged 14 years or less. Mean disease free survival was 26.8 (95%CI; 13.8-39.9) months and five year disease free survival was 26%. Mean overall survival was 38.7 months (95%CI; 25.9-50.6) and median overall survival was 24 months. Five year overall survival was 25%. From the variables evaluated , only presence of metastatic disease at presentation (p value=0. 028) and complete response (p value =0. 006) had significant relations to overall survival. Survival of Ewing's sarcoma in our province is disappointing. It seems to be mostly due to less effective treatment. Administration of adequate chemotherapy dosage, resection of tumor with negative margins and precise assessment of irradiation volume may prove helpful.

  14. Clinical characteristics and survival of lung cancer patients associated with multiple primary malignancies.

    Directory of Open Access Journals (Sweden)

    Shan Shan

    Full Text Available To investigate the characteristics and survival of lung cancer patients with additional malignant primary cancers.Records of lung cancer patients newly diagnosed in Shanghai Pulmonary Hospital between January 2000 and January 2010 were retrospectively reviewed. Patients with second primary lung cancer and those with lung cancer only were included for detailed analysis.Of 27642 newly diagnosed lung cancer patients, 283 patients (1.02% suffered previous additional primary cancers. Compared with single primary lung cancer, patients with secondary lung cancer associated other primary cancers were more often women (female to male ratio 1:1.72 vs 1:2.58, P = 0.018, older (64.2 vs 60.5 years old, P<0.001, more squamous cell type (30.7% vs 20.5%, P = 0.004, less small cell (3.9% vs 15.5%, P<0.001 type, at earlier stages (17.7% vs 11.0% for stage I, P = 0.014, and more frequently with family history of cancers (7.8% vs 3.9%, P = 0.038. The most common previous primary cancers observed were colorectal (22.0%, breast (18.4%, gastric (14.4% and larynx cancers (11.9%. Approximately 42.9% of patients were diagnosed with lung cancer 2 to 6 years after diagnosis of initial primary cancers. The survival of patients with secondary lung cancer associated other malignancies was not significantly different from those with single lung cancer (P = 0.491, while synchronous multiple primary malignancies showed worse prognosis compared with those with metachronous ones or single lung cancer (p = 0.012.The possibility of second primary lung cancer should always be considered during the follow-up of related cancer types, especially those with family history of cancers. Patients with secondary lung cancer associated other primary malignancies have non-inferior survival than those with single lung cancer.

  15. Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases.

    Directory of Open Access Journals (Sweden)

    Patrick N Harter

    Full Text Available The multifunctional molecule netrin-1 is upregulated in various malignancies and has recently been presented as a major general player in tumorigenesis leading to tumor progression and maintenance in various animal models. However, there is still a lack of clinico-epidemiological data related to netrin-1 expression. Therefore, the aim of our study was to elucidate the association of netrin-1 expression and patient survival in brain metastases since those constitute one of the most limiting factors for patient prognosis. We investigated 104 brain metastases cases for netrin-1 expression using in-situ hybridization and immunohistochemistry with regard to clinical parameters such as patient survival and MRI data. Our data show that netrin-1 is strongly upregulated in most cancer subtypes. Univariate analyses revealed netrin-1 expression as a significant factor associated with poor patient survival in the total cohort of brain metastasis patients and in sub-entities such as non-small cell lung carcinomas. Interestingly, many cancer samples showed a strong nuclear netrin-1 signal which was recently linked to a truncated netrin-1 variant that enhances tumor growth. Nuclear netrin-1 expression was associated with poor patient survival in univariate as well as in multivariate analyses. Our data indicate both total and nuclear netrin-1 expression as prognostic factors in brain metastases patients in contrast to other prognostic markers in oncology such as patient age, number of brain metastases or Ki67 proliferation index. Therefore, nuclear netrin-1 expression constitutes one of the first reported molecular biomarkers for patient survival in brain metastases. Furthermore, netrin-1 may constitute a promising target for future anti-cancer treatment approaches in brain metastases.

  16. Dynamic contrast-enhanced MRI, diffusion-weighted MRI and {sup 18}F-FDG PET/CT for the prediction of survival in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ng, Shu-Hang [Chang Gung University, Molecular Imaging Center, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Liao, Chun-Ta [Chang Gung University, Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Lin, Chien-Yu; Chang, Joseph Tung-Chieh; Fan, Kang-Hsing [Chang Gung University, Department of Radiation Oncology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chan, Sheng-Chieh; Yen, Tzu-Chen [Chang Gung University, Molecular Imaging Center, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Lin, Yu-Chun [Chang Gung University, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Ko, Sheung-Fat [Chang Gung University, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Wang, Hung-Ming [Chang Gung University, Department of Medical Oncology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Yang, Lan-Yan [Chang Gung University, Biostatistics and Informatics Unit, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Wang, Jiun-Jie [Chang Gung University, Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung Memorial Hospital, Neuroscience Research Center, Taoyuan (China); Chang Gung Memorial Hospital, Department of Diagnostic Radiology, Keelung (China); Chang Gung University / Chang Gung Memorial Hospital, Linkou, Medical Imaging Research Center, Institute for Radiological Research, Taoyuan (China)

    2016-11-15

    We prospectively investigated the roles of pretreatment dynamic contrast-enhanced MR imaging (DCE-MRI), diffusion-weighted MR imaging (DWI) and {sup 18}F-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG PET)/CT for predicting survival of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) patients treated with chemoradiation. Patients with histologically proven OHSCC and neck nodal metastases scheduled for chemoradiation were eligible. Clinical variables as well as DCE-MRI-, DWI- and {sup 18}F-FDG PET/CT-derived parameters of the primary tumours and metastatic neck nodes were analysed in relation to 3-year progression-free survival (PFS) and overall survival (OS) rates. Eighty-six patients were available for analysis. Multivariate analysis identified the efflux rate constant (K{sub ep})-tumour < 3.79 min{sup -1} (P = 0.001), relative volume of extracellular extravascular space (V{sub e})-node < 0.23 (P = 0.004) and SUV{sub max}-tumour > 19.44 (P = 0.025) as independent risk factors for both PFS and OS. A scoring system based upon the sum of each of the three imaging parameters allowed stratification of our patients into three groups (patients with 0/1 factor, patients with 2 factors and patients with 3 factors, respectively) with distinct PFS (3-year rates = 72 %, 38 % and 0 %, P < 0.0001) and OS (3-year rates = 81 %, 46 % and 20 %, P < 0.0001). K{sub ep}-tumour, V{sub e}-node and SUV{sub max}-tumour were independent prognosticators for OHSCC treated with chemoradiation. Their combination helped survival stratification. (orig.)

  17. IGF-1 and Survival in ESRD

    Science.gov (United States)

    Jia, Ting; Gama Axelsson, Thiane; Heimbürger, Olof; Bárány, Peter; Stenvinkel, Peter; Qureshi, Abdul Rashid

    2014-01-01

    Summary Background and objectives IGF-1 deficiency links to malnutrition in CKD patients; however, it is not clear to what extent it associates with survival among these patients. Design, setting, participants, & measurements Serum IGF-1 and other biochemical, clinical (subjective global assessment), and densitometric (dual energy x-ray absorptiometry) markers of nutritional status and mineral and bone metabolism were measured in a cohort of 365 Swedish clinically stable CKD stage 5 patients (median age of 53 years) initiating dialysis between 1994 and 2009; in 207 patients, measurements were also taken after 1 year of dialysis. Deaths were registered during a median follow-up of 5 years. Associations of mortality with baseline IGF-1 and changes of IGF-1 after 1 year of dialysis were evaluated by Cox models. Results At baseline, IGF-1 concentrations associated negatively with age, diabetes mellitus, cardiovascular disease, poor nutritional status, IL-6, and osteoprotegerin and positively with body fat mass, bone mineral density, serum phosphate, calcium, and fibroblast growth factor-23. At 1 year, IGF-1 had increased by 33%. In multivariate regression, low age, diabetes mellitus, and high serum phosphate and calcium associated with IGF-1 at baseline, and in a mixed model, these factors, together with high fat body mass, associated with changes of IGF-1 during the first 1 year of dialysis. Adjusting for calendar year of inclusion, age, sex, diabetes mellitus, cardiovascular disease, IL-6, and poor nutritional status, a 1 SD higher level of IGF-1 at baseline associated with lower mortality risk (hazard ratio, 0.57; 95% confidence interval, 0.32 to 0.98). Persistently low or decreasing IGF-1 levels during the first 1 year on dialysis predicted worse survival (adjusted hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.50). Conclusion In incident dialysis patients, low serum IGF-1 associates with body composition and markers of mineral and bone metabolism, and it

  18. [11C]Choline PET/CT predicts survival in hormone-naive prostate cancer patients with biochemical failure after radical prostatectomy

    International Nuclear Information System (INIS)

    Giovacchini, Giampiero; Incerti, Elena; Mapelli, Paola; Gianolli, Luigi; Picchio, Maria; Kirienko, Margarita; Briganti, Alberto; Gandaglia, Giorgio; Montorsi, Francesco

    2015-01-01

    Over the last decade, PET/CT with radiolabelled choline has been shown to be useful for restaging patients with prostate cancer (PCa) who develop biochemical failure. The limitations of most clinical studies have been poor validation of [ 11 C]choline PET/CT-positive findings and lack of survival analysis. The aim of this study was to assess whether [ 11 C]choline PET/CT can predict survival in hormone-naive PCa patients with biochemical failure. This retrospective study included 302 hormone-naive PCa patients treated with radical prostatectomy who underwent [ 11 C]choline PET/CT from 1 December 2004 to 31 July 2007 because of biochemical failure (prostate-specific antigen, PSA, >0.2 ng/mL). Median PSA was 1.02 ng/mL. PCa-specific survival was estimated using Kaplan-Meier curves. Cox regression analysis was used to evaluate the association between clinicopathological variables and PCa-specific survival. The coefficients of the covariates included in the Cox regression analysis were used to develop a novel nomogram. Median follow-up was 7.2 years (1.4 - 18.9 years). [ 11 C]Choline PET/CT was positive in 101 of 302 patients (33 %). Median PCa-specific survival after prostatectomy was 14.9 years (95 % CI 9.7 - 20.1 years) in patients with positive [ 11 C]choline PET/CT. Median survival was not achieved in patients with negative [ 11 C]choline PET/CT. The 15-year PCa-specific survival probability was 42.4 % (95 % CI 31.7 - 53.1 %) in patients with positive [ 11 C]choline PET/CT and 95.5 % (95 % CI 93.5 - 97.5 %) in patients with negative [ 11 C]choline PET/CT. In multivariate analysis, [ 11 C]choline PET/CT (hazard ratio 6.36, 95 % CI 2.14 - 18.94, P < 0.001) and Gleason score >7 (hazard ratio 3.11, 95 % CI 1.11 - 8.66, P = 0.030) predicted PCa-specific survival. An internally validated nomogram predicted 15-year PCa-specific survival probability with an accuracy of 80 %. Positive [ 11 C]choline PET/CT after biochemical failure predicts PCa-specific survival in hormone

  19. Magnesium hexafluoridozirconates MgZrF{sub 6}.5H{sub 2}O, MgZrF{sub 6}.2H{sub 2}O, and MgZrF{sub 6}. Structures, phase transitions, and internal mobility of water molecules

    Energy Technology Data Exchange (ETDEWEB)

    Gerasimenko, Andrey V.; Gaivoronskaya, Kseniya A.; Slobodyuk, Arseny B.; Didenko, Nina A. [Institute of Chemistry, Russian Academy of Sciences, Vladivostok (Russian Federation)

    2017-12-04

    The MgZrF{sub 6}.nH{sub 2}O (n = 5, 2 and 0) compounds were studied by the methods of X-ray diffraction and {sup 19}F, MAS {sup 19}F, and {sup 1}H NMR spectroscopy. At room temperature, the compound MgZrF{sub 6}.5H{sub 2}O has a monoclinic C-centered unit cell and is composed of isolated chains of edge-sharing ZrF{sub 8} dodecahedra reinforced with MgF{sub 2}(H{sub 2}O){sub 4} octahedra and uncoordinated H{sub 2}O molecules and characterized by a disordered system of hydrogen bonds. In the temperature range 259 to 255 K, a reversible monoclinic <-> two-domain triclinic phase transition is observed. The phase transition is accompanied with ordering of hydrogen atoms positions and the system of hydrogen bonds. The structure of MgZrF{sub 6}.2H{sub 2}O comprises a three-dimensional framework consisting of chains of edge-sharing ZrF{sub 8} dodecahedra linked to each other through MgF{sub 4}(H{sub 2}O){sub 2} octahedra. The compound MgZrF{sub 6} belongs to the NaSbF{sub 6} type and is built from regular ZrF{sub 6} and MgF{sub 6} octahedra linked into a three-dimensional framework through linear Zr-F-Mg bridges. The peaks in {sup 19}F MAS spectra were attributed to the fluorine structural positions. The motions of structural water molecules were studied by variable-temperature {sup 1}H NMR spectroscopy. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  20. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

    Science.gov (United States)

    Onofriescu, Mihai; Siriopol, Dimitrie; Voroneanu, Luminita; Hogas, Simona; Nistor, Ionut; Apetrii, Mugurel; Florea, Laura; Veisa, Gabriel; Mititiuc, Irina; Kanbay, Mehmet; Sascau, Radu; Covic, Adrian

    2015-01-01

    Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered. A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort). In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30-3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72-4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12-3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60-4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56-3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29-5

  1. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

    Directory of Open Access Journals (Sweden)

    Mihai Onofriescu

    Full Text Available Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered.A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE, by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup. Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO: 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort.In the entire study population, patients considered overhydrated (using both cut-offs had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30-3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72-4.78 for RFO>17.4%, respectively and multivariate (HR = 1.87, 95%CI = 1.12-3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60-4.63 for RFO>17.4%, respectively Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56-3.87 for RFO >15% and HR = 3

  2. Older age impacts on survival outcome in patients receiving curative surgery for solid cancer

    Directory of Open Access Journals (Sweden)

    Chang-Hsien Lu

    2018-07-01

    Full Text Available Summary: Background: Given the global increase in aging populations and cancer incidence, understanding the influence of age on postoperative outcome after cancer surgery is imperative. This study aimed to evaluate the impact of age on survival outcome in solid cancer patients receiving curative surgery. Methods: A total of 37,288 patients receiving curative surgeries for solid cancers between 2007 and 2012 at four affiliated Chang Gung Memorial Hospital were included in the study. All patients were categorized into age groups by decades for survival analysis. Results: The percentages of patient populations aged <40 years, 40–49 years, 50–59 years, 60–69 years, 70–79 years, and ≥80 years were 9.7%, 17.7%, 27.8%, 22.1%, 16.9%, and 5.7%, respectively. The median follow-up period was 38.9 months (range, 22.8–60.4 months and the overall, cancer-specific, and noncancer-specific mortality rates were 26.0%, 17.6%, and 8.5%, respectively. The overall mortality rate of patients in different age groups were 18.5%, 21.1%, 22.0%, 25.3%, 35.3%, and 49.0%, respectively. Compared to patients aged <40 years, more significant decrease in long-term survival were observed in aging patients. Multivariate analysis showed higher postoperative short-term mortality rates in patients older than 70 years, and the adjusted odds ratio of mortality risk ranged from 1.47 to 1.74 and 2.26 to 3.03 in patients aged 70–79 years and ≥80 years, respectively, compared to those aged <40 years. Conclusion: Aging was a negative prognostic factor of survival outcome in solid cancer patients receiving curative surgery. After adjustment of other clinicopathologic factors, the influence of age on survival outcome was less apparent in the elderly. Keywords: Age, Solid cancer, Surgical resection, Prognosis

  3. Influence of gender and age on the survival of patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Xiao, Guangli; Cao, Yabing; Qiu, Xibin; Wang, Weihua; Wang, Yufeng

    2013-01-01

    The prognostic value of gender and age in the survival of nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT) is unclear. Several studies have suggested a female advantage in the prognosis of solid tumors. We investigated the relationship between gender differences and disease outcome in NPC patients treated with IMRT in South China. A total of 299 patients with non-disseminated NPC were analyzed retrospectively. IMRT was delivered with a simultaneous modulated, accelerated radiotherapy boost technique at prescribed doses of 70 Gy/30 fractions/6 weeks to the primary tumor (GTVp) and positive neck nodes (GTVn), 60Gy (2.0 Gy/day) to the clinical target volume (CTV) and upper neck region and 54 Gy (1.8 Gy/day) to the clinically negative low neck. A median boost dose of 9.2 Gy (4–20 Gy) was administered to patients with persistent disease at the primary site. With a median follow-up of 52 months, the male patients had a significantly unfavorable 5-year OS (70.7% compared to 94.1%, P < 0.001), DPFS (71.5% compared to 87.3%, P = 0.029) and DMFS (77.2% compared to 89.7%, P = 0.036) than the female patients. In patients younger than 45, the male patients had a poorer 5-year OS (66.8% compared to 91.2%, P = 0.008), DPFS (59.9% compared to 91.2%, P = 0.005) and DMFS (66.4% compared to 94.0%, P = 0.004) than the female patients. For patients older than 45, only the 5-year OS (72.2% compared to 96.0%, P = 0.001) was significantly different. Gender and age are strong independent prognostic factors for NPC in this study. We are the first to report that younger male patients were more likely to have distant metastases and exhibited inferior overall survival and disease progression-free survival rates compared to other patients

  4. Antibody guided targeting of non-small cell lung cancer using 111In-labeled HMFG1 F(ab')2 fragments

    International Nuclear Information System (INIS)

    Kalofonos, H.P.; Sivolapenko, G.B.; Courtenay-Luck, N.S.

    1988-01-01

    Immunoscintigraphy using F(ab')2 fragments of tumor-associated monoclonal antibody HMFG1 was performed in 14 patients with primary and metastatic non-small cell carcinoma of lung cancer. The antibody was conjugated with diethylenetriamine pentaacetic acid and labeled with 111 In. Quality control studies showed efficient incorporation of 111 In onto antibody (5 mCi/mg), no significant loss of immunoreactivity, and in vitro and in vivo stability. The optimal time for imaging was between 48 and 72 h. Following i.v. administration, serum activity fell rapidly (t1/2a = 2.5 +/- 1.3 (SD) h; t1/2b = 42 +/- 4.5 h). The majority of the radioactivity was associated with the plasma and not with the blood cells. All patients had a significant concentration of 111 In in the liver (approximately 20% of the injected dose, 48 h postadministration). No toxicity was encountered. No human antimurine-IgG antibody was detected in any of the patients within 4 months of follow-up, even in patients receiving two administrations of F(ab')2 fragments. Localization of all primary lesions and the majority (80%) of metastatic lesions was achieved. Seven of 14 patients were also studied using a 111 In-labeled nonspecific antibody (Fab')2 fragment (4C4). In three patients the specificity index was higher than the other four (P less than 0.05). We conclude that although successful targeting of 111 In-labeled (Fab')2 fragments of HMFG1 can be achieved in patients with non-small cell carcinoma of lung, observable tumor localization can also be achieved using a nonspecific antibody

  5. E2F1-mediated transcriptional inhibition of the plasminogen activator inhibitor type 1 gene

    DEFF Research Database (Denmark)

    Koziczak, M; Müller, H; Helin, K

    2001-01-01

    but independent of binding to pocket-binding proteins, suggesting a novel mechanism for E2F-mediated negative gene regulation [Koziczak, M., Krek, W. & Nagamine, Y. (2000) Mol. Cell. Biol. 20, 2014-2022]. However, it remains to be seen whether endogenous E2F can exert a similar effect. We report here that down....... These results all indicate that endogenous E2F can directly repress the PAI-1 gene. DNase I hypersensitive-site analysis of the PAI-1 promoter suggested the involvement of conformation changes in chromatin structure of the PAI-1 promoter. 5' deletion analysis of the PAI-1 promoter showed that multiple sites...

  6. Epitaxial growth of lithium fluoride on the (1 1 1) surface of CaF 2

    Science.gov (United States)

    Klumpp, St; Dabringhaus, H.

    1999-08-01

    Growth of lithium fluoride by molecular beam epitaxy on the (1 1 1) surface of calcium fluoride crystals was studied by TEM and LEED for crystal temperatures from 400 to 773 K and impinging lithium fluoride fluxes from 3×10 11 to 3×10 14 cm -2 s -1. Growth starts, usually, at the steps on the (1 1 1) surface of CaF 2. For larger step distances and at later growth stages also growth on the terraces between the steps is found. Preferably, longish, roof-like crystallites are formed, which can be interpreted by growth of LiF(2 0 1¯)[0 1 0] parallel to CaF 2(1 1 1)[ 1¯ 0 1]. To a lesser extent square crystallites, i.e. growth with LiF(0 0 1), and, rarely, three-folded pyramidal crystallites, i.e. growth with LiF(1 1 1) parallel to CaF 2(1 1 1), are observed. While the pyramidal crystallites show strict epitaxial orientation with LiF[ 1¯ 0 1]‖CaF 2[ 1¯ 0 1] and LiF[ 1¯ 0 1]‖CaF 2[1 2¯ 1], only about 80% of the square crystallites exhibit an epitaxial alignment, where LiF[1 0 0]‖CaF 2[ 1¯ 0 1] is preferred to LiF[1 1 0]‖CaF 2[ 1¯ 0 1]. The epitaxial relationships are discussed on the basis of theoretically calculated adsorption positions of the lithium fluoride monomer and dimer on the terrace and at the steps of the CaF 2(1 1 1) surface.

  7. Methylated DNMT1 and E2F1 are targeted for proteolysis by L3MBTL3 and CRL4DCAF5 ubiquitin ligase.

    Science.gov (United States)

    Leng, Feng; Yu, Jiekai; Zhang, Chunxiao; Alejo, Salvador; Hoang, Nam; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-04-24

    Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4 DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4 DCAF5 . Mouse L3MBTL3/MBT-1 deletion causes accumulation of DNMT1 protein, increased genomic DNA methylation, and late embryonic lethality. DNMT1 contains a consensus methylation motif shared by many non-histone proteins including E2F1, a key transcription factor for S phase. We show that the methylation-dependent E2F1 degradation is also controlled by L3MBTL3-CRL4 DCAF5 . Our studies elucidate for the first time a novel mechanism by which the stability of many methylated non-histone proteins are regulated.

  8. Survival period after tube feeding in bedridden older patients.

    Science.gov (United States)

    Kosaka, Yoichi; Nakagawa-Satoh, Takuma; Ohrui, Takashi; Fujii, Masahiko; Arai, Hiroyuki; Sasaki, Hidetada

    2012-04-01

    We prospectively studied survival periods after tube feeding. Participants were 163 bedridden older patients suffering from dysphagia. A wide range of survival periods after tube feeding were observed within half a year without tube feeding after being bedridden. After this initial period, survival periods after tube feeding were limited to approximately half a year. Survival periods after tube feeding were positively proportional to the length of time patients were free from pneumonia after tube feeding. After tube feeding, patients died from pneumonia within half a year, and the frequency of pneumonia was 3.1 ± 2.7 times (mean ± SD) before death. Survival periods after tube feeding for less than 1 year were primarily determined by being bedridden for more than half a year without tube feeding and once pneumonia occurred; patients who were tube fed did not survive for more than half a year. © 2012 Japan Geriatrics Society.

  9. Serum levels of IGF-1 and IGF-BP3 are associated with event-free survival in adult Ewing sarcoma patients treated with chemotherapy

    Directory of Open Access Journals (Sweden)

    de Groot S

    2017-06-01

    Full Text Available Stefanie de Groot,1 Hans Gelderblom,1 Marta Fiocco,2,3 Judith VMG Bovée,4 Jacobus JM van der Hoeven,1 Hanno Pijl,5 Judith R Kroep1 1Department of Medical Oncology, 2Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, 3Mathematical Department, Leiden University, 4Department of Pathology, 5Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands Background: Activation of the insulin-like growth factor 1 (IGF-1 pathway is involved in cell growth and proliferation and is associated with tumorigenesis, tumor progression, and therapy resistance in solid tumors. We examined whether variability in serum levels of IGF-1, IGF-2, and IGF-binding protein 3 (IGF-BP3 can predict event-free survival (EFS and overall survival (OS in Ewing sarcoma patients treated with chemotherapy.Patients and methods: Serum levels of IGF-1, IGF-2, and IGF-BP3 of 22 patients with localized or metastasized Ewing sarcoma treated with six cycles of vincristine/ifosfamide/doxorubicin/etoposide (VIDE chemotherapy were recorded. Baseline levels were compared with presixth cycle levels using paired t-tests and were tested for associations with EFS and OS. Continuous variables were dichotomized according to the Contal and O’Quigley procedure. Survival analyses were performed using Cox regression analysis.Results: High baseline IGF-1 and IGF-BP3 serum levels were associated with EFS (hazard ratio [HR] 0.075, 95% confidence interval [CI] 0.009–0.602 and HR 0.090, 95% CI 0.011–0.712, respectively in univariate and multivariate analyses (HR 0.063, 95% CI 0.007–0.590 and HR 0.057, 95% CI 0.005–0.585, respectively. OS was improved, but this was not statistically significant. IGF-BP3 and IGF-2 serum levels increased during treatment with VIDE chemotherapy (P=0.055 and P=0.023, respectively.Conclusion: High circulating serum levels of IGF-1 and IGF-BP3 and the molar ratio of IGF-1:IGF-BP3 serum levels were associated

  10. Longevity of Patients With Cystic Fibrosis in 2000 to 2010 and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry

    Science.gov (United States)

    MacKenzie, Todd; Gifford, Alex H.; Sabadosa, Kathryn A.; Quinton, Hebe B.; Knapp, Emily A.; Goss, Christopher H.; Marshall, Bruce C.

    2015-01-01

    Background Advances in treatments for cystic fibrosis (CF) continue to extend survival. An updated estimate of survival is needed for better prognostication and to anticipate evolving adult care needs. Objective To characterize trends in CF survival between 2000 and 2010 and to project survival for children born and diagnosed with the disease in 2010. Design Registry-based study. Setting 110 Cystic Fibrosis Foundation–accredited care centers in the United States. Patients All patients represented in the Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2000 and 2010. Measurements Survival was modeled with respect to age, age at diagnosis, gender, race or ethnicity, F508del mutation status, and symptoms at diagnosis. Results Between 2000 and 2010, the number of patients in the CFFPR increased from 21 000 to 26 000, median age increased from 14.3 to 16.7 years, and adjusted mortality decreased by 1.8% per year (95% CI, 0.5% to 2.7%). Males had a 19% (CI, 13% to 24%) lower adjusted risk for death than females. Median survival of children born and diagnosed with CF in 2010 is projected to be 37 years (CI, 35 to 39 years) for females and 40 years (CI, 39 to 42 years) for males if mortality remains at 2010 levels and more than 50 years if mortality continues to decrease at the rate observed between 2000 and 2010. Limitations The CFFPR does not include all patients with CF in the United States, and loss to follow-up and missing data were observed. Additional analyses to address these limitations suggest that the survival projections are conservative. Conclusion Children born and diagnosed with CF in the United States in 2010 are expected to live longer than those born earlier. This has important implications for prognostic discussions and suggests that the health care system should anticipate greater numbers of adults with CF. Primary Funding Source Cystic Fibrosis Foundation. PMID:25133359

  11. Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma.

    Science.gov (United States)

    Kent, Lindsey N; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K; Ridolfi, Elisa; Miller, Grace C; Zorko, Sarah M; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J; Pohar, Kamal S; Pipas, James M; Leone, Gustavo

    2017-03-01

    Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

  12. Immunoscintigraphy of adenocarcinomas by means of 111In-labelled F(ab')2 fragments of anti-CEA monoclonal antibody F023C5

    International Nuclear Information System (INIS)

    Riva, P.; Paganelli, G.; Callegaro, L.

    1988-01-01

    F(ab') 2 fragments of F023C5, an anti-CEA monoclonal antibody, were conjugated to diethylenetriamine pentaacetic acid (DTPA) and converted into a ready to use reagent for instant 111 In-labelling. The resulting 111 In radiopharmaceutical was administered intravenously and tested for its ability to image (at 48-72 h after administration) 31 primary and 85 metastatic carcinoma lesions in 70 adenocarcinoma patients (26 gastrointestinal, 18 breast and 26 lung tumour patients) whose serum CEA was elevated in 43 cases and normal in the other 27. (author)

  13. Synthesis and evaluation of 18F-labeled 5-HT2A receptor agonists as PET ligands

    DEFF Research Database (Denmark)

    Herth, Matthias M; Petersen, Ida Nymann; Hansen, Hanne Demant

    2016-01-01

    INTRODUCTION: The serotonin 2A receptor (5-HT2AR) is the most abundant excitatory 5-HT receptor in the human brain and implicated in various brain disorders such as schizophrenia, depression, and Alzheimer's disease. Positron emission tomography (PET) can be used to image specific proteins...... to be potent 5-HT2A agonists. (18)F-labeling of the appropriate precursors was performed using [(18)F]FETos, typically yielding 0.2-2.0GBq and specific activities of 40-120GBq/μmol. PET studies in Danish landrace pigs revealed that [(18)F]1 displayed brain uptake in 5-HT2AR rich regions. However, high uptake...

  14. Oxidative stress in Complex Regional Pain Syndrome (CRPS): no systemically elevated levels of malondialdehyde, F2-isoprostanes and 8OHdG in a selected sample of patients.

    Science.gov (United States)

    Fischer, Sigrid G L; Perez, Roberto S G M; Nouta, Jan; Zuurmond, Wouter W A; Scheffer, Peter G

    2013-04-10

    Exaggerated inflammation and oxidative stress are involved in the pathogenesis of Complex Regional Pain Syndrome (CRPS). However, studies assessing markers for oxidative stress in CRPS patients are limited. In this study, markers for lipid peroxidation (malondialdehyde and F2-isoprostanes) and DNA damage (8-hydroxy-2-deoxyguanosine) were measured in nine patients (mean age 50.1 ± 17.1 years) with short term CRPS-1 (median 3 months) and nine age and sex matched healthy volunteers (mean age 49.3 ± 16.8 years) to assess and compare the level of oxidative stress. No differences were found in plasma between CRPS patients and healthy volunteers for malondialdehyde (5.2 ± 0.9 µmol/L vs. 5.4 ± 0.5 µmol/L) F2-isoprostanes (83.9 ± 18.7 pg/mL vs. 80.5 ± 12.3 pg/mL) and 8-hydroxy-2-deoxyguanosine (92.6 ± 25.5 pmol/L vs. 86.9 ± 19.0 pmol/L). Likewise, in urine, no differences were observed between CRPS patients and healthy volunteers for F2-isoprostanes (117 ng/mmol, IQR 54.5-124.3 vs. 85 ng/mmol, IQR 55.5-110) and 8-hydroxy-2-deoxyguanosine (1.4 ± 0.7 nmol/mmol vs. 1.4 ± 0.5 nmol/mmol). Our data show no elevation of systemic markers of oxidative stress in CRPS patients compared to matched healthy volunteers. Future research should focus on local sampling methods of oxidative stress with adequate patient selection based on CRPS phenotype and lifestyle.

  15. The Impact of Chemoembolization Endpoints on Survival in Hepatocellular Carcinoma Patients

    Science.gov (United States)

    Jin, Brian; Wang, Dingxin; Lewandowski, Robert J.; Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Larson, Andrew C.; Salem, Riad; Omary, Reed A.

    2010-01-01

    OBJECTIVE To investigate the relationship between angiographic embolic endpoints of transarterial chemoembolization (TACE) and survival in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This study retrospectively assessed 105 patients with surgically unresectable HCC who underwent TACE. Patients were classified according to a previously established subjective angiographic chemoembolization endpoint (SACE) scale. Only one patient was classified as SACE level 1 and thus excluded from all subsequent analysis. Survival was evaluated with Kaplan-Meier analysis. Multivariate analysis with Cox’s proportional hazard regression model was used to determine independent prognostic risk factors of survival. RESULTS Overall median survival was 21.1 months (95% confidence interval [CI], 15.9–26.4). Patients embolized to SACE levels 2 and 3 were aggregated and had a significantly higher median survival (25.6 months; 95% CI, 16.2–35.0) than patients embolized to SACE level 4 (17.1 months; 95% CI, 13.3–20.9) (p = 0.035). Multivariate analysis indicated that SACE level 4 (Hazard ratio [HR], 2.49; 95% CI, 1.41–4.42; p = 0.002), European Cooperative Oncology Group performance status > 0 (HR, 1.97; 95% CI, 1.15–3.37; p = 0.013), American Joint Committee on Cancer stage 3 or 4 (HR, 2.42; 95% CI, 1.27–4.60; p = 0.007), and Child-Pugh class B (HR, 1.94; 95% CI, 1.09–3.46; p = 0.025) were all independent negative prognostic indicators of survival. CONCLUSION Embolization to an intermediate, sub-stasis endpoint (SACE levels 2 and 3) during TACE improves survival compared to embolization to a higher, stasis endpoint (SACE level 4). Interventional oncologists should consider targeting these intermediate, sub-stasis angiographic endpoints during TACE. PMID:21427346

  16. Multiple neoplasms, single primaries, and patient survival

    Directory of Open Access Journals (Sweden)

    Amer MH

    2014-03-01

    Full Text Available Magid H Amer Department of Medicine, St Rita's Medical Center, Lima, OH, USA Background: Multiple primary neoplasms in surviving cancer patients are relatively common, with an increasing incidence. Their impact on survival has not been clearly defined. Methods: This was a retrospective review of clinical data for all consecutive patients with histologically confirmed cancer, with emphasis on single versus multiple primary neoplasms. Second primaries discovered at the workup of the index (first primary were termed simultaneous, if discovered within 6 months of the index primary were called synchronous, and if discovered after 6 months were termed metachronous. Results: Between 2005 and 2012, of 1,873 cancer patients, 322 developed second malignancies; these included two primaries (n=284, and three or more primaries (n=38. Forty-seven patients had synchronous primaries and 275 had metachronous primaries. Patients with multiple primaries were predominantly of Caucasian ancestry (91.0%, with a tendency to develop thrombosis (20.2%, had a strong family history of similar cancer (22.3%, and usually presented with earlier stage 0 through stage II disease (78.9%. When compared with 1,551 patients with a single primary, these figures were 8.9%, 15.6%, 18.3%, and 50.9%, respectively (P≤0.001. Five-year survival rates were higher for metachronous cancers (95% than for synchronous primaries (59% and single primaries (59%. The worst survival rate was for simultaneous concomitant multiple primaries, being a median of 1.9 years. The best survival was for patients with three or more primaries (median 10.9 years and was similar to the expected survival for the age-matched and sex-matched general population (P=0.06991. Conclusion: Patients with multiple primaries are usually of Caucasian ancestry, have less aggressive malignancies, present at earlier stages, frequently have a strong family history of similar cancer, and their cancers tend to have indolent

  17. Establishing the anion recognition correlation of the 2-(2-methoxyphenyl)-1H-imidazo [4, 5-f][1,10] phenanthroline and its Ru(bipy){sub 2}{sup 2+} complex via fluorimetry

    Energy Technology Data Exchange (ETDEWEB)

    Alreja, Priya; Kaur, Navneet, E-mail: neet_chem@yahoo.co.in

    2016-11-15

    2-(2-methoxyphenyl)-1H-imidazo [4, 5-f][1, 10] phenanthroline (1) and its Ru(bipy){sub 2}{sup 2+} complex (2) were synthesized and the anion sensing properties of the two were well evaluated and compared by fluorescence titration experiments. Both 1 and 2 were fluorescent in DMSO solution and possessed an anion binding imidazole N–H site to interact with the anions. 1 did not exhibit any fluorescent changes with even most basic anions in DMSO solution but on introduction of Ru metal center via synthesis of its Ru(bipy){sub 2}{sup 2+} complex (2), the N–H acidity enhanced appreciably and it could detect acetate even at very low concentrations (LOD=5.25×10{sup −7}). The fluorescence intensity of 2 was almost completely quenched and its fluorescent red orange color disappeared with the addition of acetate ions. The spatial arrangement of receptor 2 fits well for the triangular shape of AcO{sup −} ion, hence making it the most preferred anion for binding. Both {sup 1}H NMR titrations and DFT computational calculations supported the deprotonation mechanism.

  18. 18F-FDG PET/CT在复发宫颈癌疗效评价及预后预测中的价值%Value of 18F-FDG PET/CT in the evaluation of treatment response and prognosis for patients with recurrent uterine cervical cancer

    Institute of Scientific and Technical Information of China (English)

    陈丹丹; 吴湖炳; 王全师; 韩彦江; 周文兰; 李洪生; 田颖

    2015-01-01

    Objective To investigate the value of 18F-FDG PET/CT in the evaluation of treatment response and prognosis for patients.with recurrent uterine cervical cancer.Methods Forty-five patients with recurrent uterine cervical cancer underwent 18F-FDG PET/CT before and after treatment from October 2004 to December 2014,and their PET/CT results were retrospectively analyzed.Treatment response was categorized as complete metabolic response (CMR),partial metabolic response (PMR),stable metabolic disease (SMD) and progressive metabolic disease (PMD) according to PET response criteria in solid tumors (PERCIST).Kaplan-Meier survival analysis was used.The difference of progression-free survival (PFS) between patients with and without PMD was compared by x2 test.The PFS difference among patients with different SUVmax on pretreatment PET/CT was also compared byx2 test.Results After treatment,22.2% (10/45) of patients were categorized as CMR,22.2%(10/45) as PMR,4.4%(2/45) as SMD and 51.1% (23/45) as PMD by post-treatment 18F-FDG PET/CT.Thirty-two patients had long-term (6-64 months) clinical follow-up.The PFS was 1-64 months and the median PFS was 5 months.The patients without PMD had a significantly better PFS than those with PMD(12.2 vs 4.2 months,x2 =7.223,P<0.01).Patients with lesion SUVmax<7.5 on pretreatment PET/CT had a better PFS than those with SUVmax ≥7.5 (16.3 vs 5.9 months,x2 =5.415,P<0.05).Conclusion 18F-FDG PET/CT is useful forthe evaluation of treatment response and prognosis in patients with recurrent cancer of the uterine cervix.%目的 探讨18F-FDG PET/CT在复发宫颈癌疗效评价及预后预测中的作用.方法 回顾性分析2004年10月至2014年12月45例宫颈癌复发患者的治疗前、后18F-FDG PET

  19. 3D skeletal uptake of 18F sodium fluoride in PET/CT images is associated with overall survival in patients with prostate cancer

    DEFF Research Database (Denmark)

    Lindgren Belal, Sarah; Sadik, May; Kaboteh, Reza

    2017-01-01

    /CT and investigate its correlation to the bone scan index (BSI) and overall survival (OS) in a group of patients with prostate cancer. Methods: NaF PET/CT and bone scans were studied in 48 patients with prostate cancer. Automated segmentation of the thoracic and lumbar spines, sacrum, pelvis, ribs, scapulae...

  20. STING-Dependent 2'-5' Oligoadenylate Synthetase-Like Production Is Required for Intracellular Mycobacterium leprae Survival.

    Science.gov (United States)

    de Toledo-Pinto, Thiago Gomes; Ferreira, Anna Beatriz Robottom; Ribeiro-Alves, Marcelo; Rodrigues, Luciana Silva; Batista-Silva, Leonardo Ribeiro; Silva, Bruno Jorge de Andrade; Lemes, Robertha Mariana Rodrigues; Martinez, Alejandra Nóbrega; Sandoval, Felipe Galvan; Alvarado-Arnez, Lucia Elena; Rosa, Patrícia Sammarco; Shannon, Edward Joseph; Pessolani, Maria Cristina Vidal; Pinheiro, Roberta Olmo; Antunes, Sérgio Luís Gomes; Sarno, Euzenir Nunes; Lara, Flávio Alves; Williams, Diana Lynn; Ozório Moraes, Milton

    2016-07-15

    Cytosolic detection of nucleic acids elicits a type I interferon (IFN) response and plays a critical role in host defense against intracellular pathogens. Herein, a global gene expression profile of Mycobacterium leprae-infected primary human Schwann cells identified the genes differentially expressed in the type I IFN pathway. Among them, the gene encoding 2'-5' oligoadenylate synthetase-like (OASL) underwent the greatest upregulation and was also shown to be upregulated in M. leprae-infected human macrophage cell lineages, primary monocytes, and skin lesion specimens from patients with a disseminated form of leprosy. OASL knock down was associated with decreased viability of M. leprae that was concomitant with upregulation of either antimicrobial peptide expression or autophagy levels. Downregulation of MCP-1/CCL2 release was also observed during OASL knock down. M. leprae-mediated OASL expression was dependent on cytosolic DNA sensing mediated by stimulator of IFN genes signaling. The addition of M. leprae DNA enhanced nonpathogenic Mycobacterium bovis bacillus Calmette-Guerin intracellular survival, downregulated antimicrobial peptide expression, and increased MCP-1/CCL2 secretion. Thus, our data uncover a promycobacterial role for OASL during M. leprae infection that directs the host immune response toward a niche that permits survival of the pathogen. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  1. Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy

    International Nuclear Information System (INIS)

    Choi, Yunseon; Ahn, Ki Jung; Park, Sung Kwang; Cho, Heung Lae; Lee, Ji Young

    2017-01-01

    This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m2 (range, 17.7 to 35.9 kg/m2). The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m2) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes

  2. Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yunseon; Ahn, Ki Jung; Park, Sung Kwang; Cho, Heung Lae; Lee, Ji Young [Inje University Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2017-03-15

    This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m2 (range, 17.7 to 35.9 kg/m2). The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m2) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes.

  3. Prognostic relevance at 5 years of the early monitoring of neoadjuvant chemotherapy using {sup 18}F-FDG PET in luminal HER2-negative breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Humbert, Olivier; Brunotte, Francois [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); CHU Le Bocage, Imaging Department, Dijon (France); Universite de Bourgogne, UMR CNRS 5158, Dijon (France); Berriolo-Riedinger, Alina; Toubeau, Michel; Dygai-Cochet, Inna [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); Cochet, Alexandre [Centre GF Leclerc, Department of Nuclear Medicine, Dijon (France); Universite de Bourgogne, UMR CNRS 5158, Dijon (France); Gauthier, Melanie [Centre GF Leclerc, Biostatistics and Quality of Life Unit, EA 4184, Dijon (France); Charon-Barra, Celine [Centre GF Leclerc, Department of Pathology, Dijon (France); Guiu, Severine; Desmoulins, Isabelle; Fumoleau, Pierre [Centre GF Leclerc, Department of Medical Oncology, Dijon (France); Coutant, Charles [Centre GF Leclerc, Department of Surgery, Dijon (France)

    2014-03-15

    The objective of this study was to evaluate, in the luminal human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype, the prognostic value of tumour glucose metabolism at baseline and of its early changes during neoadjuvant chemotherapy (NAC). This prospective study included 61 women with hormone-sensitive HER2-negative breast cancer treated with NAC. {sup 18}F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed at baseline. Hepatic activity was used as a reference to distinguish between low metabolic and hypermetabolic tumours. In hypermetabolic tumours, a PET exam was repeated after the first course of NAC. The relative change in the maximum standardized uptake value of the tumour (∇SUV) was calculated. Nineteen women had low metabolic luminal breast cancers at baseline, correlated with low proliferation indexes. Forty-two women had hypermetabolic tumours, corresponding to more proliferative breast cancers with higher Ki-67 expression (p = 0.017) and higher grade (p = 0.04). The median follow-up period was 64.2 months (range 11.5-93.2). Thirteen women developed recurrent disease, nine of whom died. Worse overall survival was associated with larger tumour size [>5 cm, hazard ratio (HR) = 6.52, p = 0.009] and with hypermetabolic tumours achieving a low metabolic response after one cycle of NAC (ΔSUV < 16 %, HR = 10.63, p = 0.004). Five-year overall survival in these poor responder patients was 49.2 %. Overall survival in women with low metabolic tumours or hypermetabolic/good response tumours was 100 and 96.15 %, respectively. In luminal HER2-negative breast tumours, tumour metabolism at baseline and changes after the first course of NAC are early surrogate markers of patients' survival. A subgroup of women with hypermetabolic/poorly responding tumours, correlated with poor prognosis at 5 years, can be identified early. These results may guide future studies by tailoring the NAC regimen to the metabolic response

  4. Functional analysis of two PLA2G2A variants associated with secretory phospholipase A2-IIA levels.

    Directory of Open Access Journals (Sweden)

    Holly J Exeter

    Full Text Available Secretory phospholipase A2 group IIA (sPLA2-IIA has been identified as a biomarker of atherosclerosis in observational and animal studies. The protein is encoded by the PLA2G2A gene and the aim of this study was to test the functionality of two PLA2G2A non-coding SNPs, rs11573156 C>G and rs3767221 T>G where the rare alleles have been previously associated with higher and lower sPLA2-IIA levels respectively.Luciferase assays, electrophoretic mobility shift assays (EMSA, and RNA expression by RT-PCR were used to examine allelic differences. For rs3767221 the G allele showed ∼55% lower luciferase activity compared to the T allele (T = 62.1 (95% CI 59.1 to 65.1 G = 27.8 (95% CI 25.0 to 30.6, p = 1.22×10⁻³⁵, and stronger EMSA binding of a nuclear protein compared to the T-allele. For rs11573156 C >G there were no luciferase or EMSA allelic differences seen. In lymphocyte cell RNA, from individuals of known rs11573156 genotype, there was no allelic RNA expression difference for exons 5 and 6, but G allele carriers (n = 7 showed a trend to lower exon 1-2 expression compared to CC individuals. To take this further, in the ASAP study (n = 223, an rs11573156 proxy (r² = 0.91 showed ∼25% higher liver expression of PLA2G2A (1.67×10⁻¹⁷ associated with the G allele. However, considering exon specific expression, the association was greatly reduced for exon 2 (4.5×10⁻⁵ compared to exons 3-6 (10⁻¹⁰ to 10⁻²⁰, suggesting rs11573156 G allele-specific exon 2 skipping.Both SNPs are functional and provide useful tools for Mendelian Randomisation to determine whether the relationship between sPLA2-IIA and coronary heart disease is causal.

  5. Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients.

    Science.gov (United States)

    Wright, Adam; Mahaut-Smith, Martyn; Symon, Fiona; Sylvius, Nicolas; Ran, Shaun; Bafadhel, Mona; Muessel, Michelle; Bradding, Peter; Wardlaw, Andrew; Vial, Catherine

    2016-06-15

    Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported in bronchoalveolar lavage fluids of asthmatic patients. Although eosinophils are known to express several subtypes of P2 receptors for extracellular nucleotides, their function and contribution to asthma remain unclear. In this article, we show that transcripts for P2X1, P2X4, and P2X5 receptors were expressed in healthy and asthmatic eosinophils. The P2X receptor agonist α,β-methylene ATP (α,β-meATP; 10 μM) evoked rapidly activating and desensitizing inward currents (peak 18 ± 3 pA/pF at -60 mV) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 μM) (3 ± 2 pA/pF). α,β-meATP-evoked currents were smaller in eosinophils from asthmatic patients (8 ± 2 versus 27 ± 5 pA/pF for healthy) but were enhanced following treatment with a high concentration of the nucleotidase apyrase (17 ± 5 pA/pF for 10 IU/ml and 11 ± 3 pA/pF for 0.32 IU/ml), indicating that the channels are partially desensitized by extracellular nucleotides. α,β-meATP (10 μM) increased the expression of CD11b activated form in eosinophils from healthy, but not asthmatic, donors (143 ± 21% and 108 ± 11% of control response, respectively). Furthermore, α,β-meATP increased healthy (18 ± 2% compared with control 10 ± 1%) but not asthmatic (13 ± 1% versus 10 ± 0% for control) eosinophil adhesion. Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil αMβ2 integrin-dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared with healthy eosinophils, probably as the result of an increase in extracellular nucleotide concentration. Copyright © 2016 by The American Association of Immunologists, Inc.

  6. Convection enhanced delivery of panobinostat (LBH589-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

    Directory of Open Access Journals (Sweden)

    Singleton WG

    2017-02-01

    Full Text Available WG Singleton,1,2 AM Collins,3 AS Bienemann,1 CL Killick-Cole,1 HR Haynes,4 DJ Asby,1 CP Butts,5 MJ Wyatt,1 NU Barua,1,2 SS Gill1,2 1Functional Neurosurgery Research Group, School of Clinical Sciences, University of Bristol, 2Department of Neurosurgery, North Bristol NHS Trust, 3Bristol Centre for Functional Nanomaterials, School of Physics, HH Wills Physics Laboratory, 4Brain Tumour Research Group, School of Clinical Sciences, 5School of Chemistry, University of Bristol, Bristol, UKBackground: The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood–brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED.Materials and methods: The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls.Results: Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of

  7. Preparation and biological evaluation of 18F-MPPF as a 5-HT1A imaging agent

    International Nuclear Information System (INIS)

    Wu Chunying; Lin Xiangtong; Zhang Zhengwei; Liu Ping; Xue Fangping; Lu Chunxiong; Zou Meifen; Chen Zhengping; Jiang Quanfu; Fu Ronggeng; Wang Songpei; Zhang Tongxing; Li Xiaomin; Zhu Junqing

    2004-01-01

    Objective: To develop and evaluate 4- 18 F-fluoro-N-2-[1-(2-methoxyphenyl)-1-piperazinyl] ethyl-N-2-pyridinyl-benzamide ( 18 F-MPPF) as a 5-hydroxytryptamine (5-HT 1A ) imaging agent. Methods: Nucleophilic substitution of fluoro replacement reaction was proceeding in dimethyl sulfoxide (DMSO) solution by oil-bath heating. Radiochemical purity (RCP) was determined by high pressure liquid chromatography (HPLC). Biological evaluations were performed in rats and mice. Results: RCP determined by HPLC was over 95% and were stable within 3 h. Biodistribution studies in rats showed that the initial uptake of 18 F-MPPF in the brain was high [(0.621±0.010)%ID/organ at 2 min]. The specific binding [(T/CB)-1] in hippocampus reaches its peak value of 2.70 at 30 min postinjection. (T/CB)-1 in hippocampus were significantly reduced to 0.89, 0.74 and 1.93 by pretreatment with 8-hydroxy-2-N, N-(di-n-propyl) aminotetralin (8-OH-DPAT), 4-(2'-methoxy-phenyl)-1-{2'-[n-(2 ) -pyridinyl]-cyclohexanecarboxamido}-ethyl piperazine (WAY100635) and spiperone at 30 min postinjection, respectively. The rat brain autoradiography and analysis showed that there was high 131 I-4-(2'-methoxy-phenyl)-1-{2'-[n-(2 ) -pyridinyl]-p-iodobenzamido}-ethyl piperazine (MPPI) uptake in hippocampus, the hippocampus/cerebellum ratio was significantly reduced from 13.98±0.87 to 1.96±0.46 by pretreatment with 8-OH-DPAT at 30 min postinjection. Conclusions: 18 F-MPPF can be specifically accumulated in hippocampus. It suggests that 18 F-MPPF might be a useful imaging agent for the studies of localization, function and modulation of 5-HT 1A receptor in the brain

  8. Unsuspected muscle metastases detected with "1"8F-FDG PET/CT

    International Nuclear Information System (INIS)

    San Román, J.; Hovsepian, M.

    2017-01-01

    Objective: To assess the prevalence of unsuspected muscle metastases (MM) in patients with known malignant disease, examined with "1"8F-fluorodeoxyglucose positron emission tomography integrated with computed tomography ("1"8F-FDG PET/CT). Materials and methods: A total of 2,953 "1"8F-FDG PET/CT examinations were retrospectively analysed, looking for cases with MM. Primary neoplasm, number and location of MM and SUV max were recorded on each patient. Oncology patients with known histology and multiple secondary lesions were included. The "1"8F-FDG PET/CT was the reference method for detection of metastases. Results: MM were observed in 33 patients (prevalence: 1.12%) aged between 18 and 88 years. The primary tumours included: kidney in 7 cases, breast in 5, melanoma in 4, lung in 3, ovary in 3, thyroid in 3, sarcomas in 3, colorectal in 2, bladder in 2, and endometrial in 1. A total of 96 MM were observed in 33 patients, and located in: thigh muscles 24, gluteal 15, chest wall 13, iliopsoas 10, paravertebral muscles 10, abdominal wall 7, leg 7, arm 4, and other locations 6 (pelvis, neck, etc.). MM affected only one muscle in 22/33 patients and several muscles in 11/33. Hypermetabolic focus was the most frequent uptake pattern, with SUV max between 1.5 and 34. Discussion: Our series has a significant number of cases, and is consistent with other authors on the incidence and location of MM. Conclusion: MM are uncommon and may be overlooked. MM may be detected with "1"8F-FDG PET/CT as single or multiple hypermetabolic foci. (authors) [es

  9. The OsO(3)F(+) and mu-F(OsO(3)F)(2)(+) cations: their syntheses and study by Raman and (19)F NMR spectroscopy and electron structure calculations and X-ray crystal structures of [OsO(3)F][PnF(6)] (Pn = As, Sb), [OsO(3)F][HF](2)[AsF(6)], [OsO(3)F][HF][SbF(6)], and [OsO(3)F][Sb(3)F(16)].

    Science.gov (United States)

    Gerken, Michael; Dixon, David A; Schrobilgen, Gary J

    2002-01-28

    The fluoride ion donor properties of OsO(3)F(2) have been investigated. The salts [OsO(3)F][AsF(6)], [OsO(3)F][HF](2)[AsF(6)], mu-F(OsO(3)F)(2)[AsF(6)], [OsO(3)F][HF](2)[SbF(6)], and [OsO(3)F][HF][SbF(6)] have been prepared by reaction of OsO(3)F(2) with AsF(5) and SbF(5) in HF solvent and have been characterized in the solid state by Raman spectroscopy. The single-crystal X-ray diffraction studies of [OsO(3)F][AsF(6)] (P2(1)/n, a = 7.0001(11) A, c = 8.8629(13) A, beta = 92.270(7) degrees, Z = 4, and R(1) = 0.0401 at -126 degrees C), [OsO(3)F][SbF(6)] (P2(1)/c, a = 5.4772(14) A, b = 10.115(3) A, c = 12.234(3) A, beta = 99.321(5) degrees, Z = 4, and R(1) = 0.0325 at -173 degrees C), [OsO(3)F][HF](2)[AsF(6)] (P2(1)/n, a = 5.1491(9) A, b = 8.129(2) A, c = 19.636(7) A, beta = 95.099(7) degrees, Z = 4, and R(1) = 0.0348 at -117 degrees C), and [OsO(3)F][HF][SbF(6)] (Pc, a = 5.244(4) A, b = 9.646(6) A, c = 15.269(10) A, beta = 97.154(13) degrees, Z = 4, and R(1) = 0.0558 at -133 degrees C) have shown that the OsO(3)F(+) cations exhibit strong contacts to the anions and HF solvent molecules giving rise to cyclic, dimeric structures in which the osmium atoms have coordination numbers of 6. The reaction of OsO(3)F(2) with neat SbF(5) yielded [OsO(3)F][Sb(3)F(16)], which has been characterized by (19)F NMR spectroscopy in SbF(5) and SO(2)ClF solvents and by Raman spectroscopy and single-crystal X-ray diffraction in the solid state (P4(1)m, a = 10.076(6) A, c = 7.585(8) A, Z = 2, and R(1) = 0.0858 at -113 degrees C). The weak fluoride ion basicity of the Sb(3)F(16)(-) anion resulted in an OsO(3)F(+) cation (C(3)(v) point symmetry) that is well isolated from the anion and in which the osmium is four-coordinate. The geometrical parameters and vibrational frequencies of OsO(3)F(+), ReO(3)F, mu-F(OsO(3)F)(2)(+), (FO(3)Os--FPnF(5))(2), and (FO(3)Os--(HF)(2)--FPnF(5))(2) (Pn = As, Sb) have been calculated using density functional theory methods.

  10. Identification of a High-Risk Group Among Patients With Oral Cavity Squamous Cell Carcinoma and pT1-2N0 Disease

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Chun-Ta [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Lin, Chien-Yu [Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences of Chang Gung University, Taoyuan, Taiwan (China); Fan, Kang-Hsing [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital and Graduate Institute of Clinical Medical Sciences of Chang Gung University, Taoyuan, Taiwan (China); Wang, Hung-Ming [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Hema-Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Ng, Shu-Hang [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Diagnostic Radiology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Lee, Li-Yu; Hsueh, Chuen [Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Chen, I-How; Huang, Shiang-Fu; Kang, Chung-Jan [Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan (China); and others

    2012-01-01

    Purpose: In the American Joint Committee on Cancer 2010 classification system, pT1-2N0 oral cavity squamous cell carcinoma (OSCC) is considered an early-stage cancer treatable with surgery alone (National Comprehensive Cancer Network 2010 guidelines). Our aim was to evaluate the feasibility of surgery alone for pT1-2N0 OSCC patients. Methods and Materials: Among 1279 previously untreated OSCC patients referred to our hospital between January 1996 and May 2008, we identified 457 consecutive patients with pT1-2N0 disease. All had radical tumor excision with neck dissection. A total of 387 patients showing pathologic margins greater than 4 mm and treated by surgery alone were included in the final analysis. All were followed up for at least 24 months after surgery or until death. The 5-year rates of control, distant metastasis, and survival were the main outcome measures. Results: The 5-year rates in the entire group of pT1-2N0 patients were as follows: local control, 91%; neck control, 92%; distant metastases, 1%; disease-free survival, 85%; disease-specific survival, 93%; and overall survival, 84%. Multivariate analysis identified poor differentiation and pathologic tumor depth of 4 mm or greater as independent risk factors for neck control, disease-free survival, and disease-specific survival. A scoring system using poor differentiation and tumor depth was formulated to define distinct prognostic groups. The presence of both poorly differentiated tumors and a tumor depth of 4 mm or greater resulted in significantly poorer 5-year neck control (p < 0.0001), disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p = 0.0046) rates. Conclusion: The combination of poor differentiation and pathologic tumor depth of 4 mm or greater identified a subset of pT1-2N0 OSCC patients with poor outcome, who may have clinical benefit from postoperative adjuvant radiotherapy.

  11. Secretory phospholipase A2 in dromedary tears: a host defense against staphylococci and other gram-positive bacteria.

    Science.gov (United States)

    Ben Bacha, Abir; Abid, Islem

    2013-03-01

    The best known physiologic function of secreted phospholipase A2 (sPLA2) group IIA (sPLA2-IIA) is defense against bacterial infection through hydrolytic degradation of bacterial membrane phospholipids. In fact, sPLA2-IIA effectively kills Gram-positive bacteria and to a lesser extent Gram-negative bacteria and is considered a major component of the eye's innate immune defense system. The antibacterial properties of sPLA2 have been demonstrated in rabbit and human tears. In this report, we have analyzed the bactericidal activity of dromedary tears and the subsequently purified sPLA2 on several Gram-positive bacteria. Our results showed that the sPLA2 displays a potent bactericidal activity against all the tested bacteria particularly against the Staphylococcus strains when tested in the ionic environment of tears. There is a synergic action of the sPLA2 with lysozyme when added to the bacteria culture prior to sPLA2. Interestingly, lysozyme purified from dromedary tears showed a significant bactericidal activity against Listeria monocytogene and Staphylococcus epidermidis, whereas the one purified from human tears displayed no activity against these two strains. We have also demonstrated that Ca(2+) is crucial for the activity of dromedary tear sPLA2 and to a less extent Mg(2+) ions. Given the presence of sPLA2 in tears and intestinal secretions, this enzyme may play a substantial role in innate mucosal and systemic bactericidal defenses against Gram-positive bacteria.

  12. Metabolomic NMR fingerprinting to identify and predict survival of patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Bertini, Ivano; Cacciatore, Stefano; Jensen, Benny V

    2012-01-01

    Earlier detection of patients with metastatic colorectal cancer (mCRC) might improve their treatment and survival outcomes. In this study, we used proton nuclear magnetic resonance ((1)H-NMR) to profile the serum metabolome in patients with mCRC and determine whether a disease signature may exist...... survival (HR, 3.4; 95% confidence interval, 2.06-5.50; P = 1.33 × 10(-6)). A number of metabolites concurred with the (1)H-NMR fingerprint of mCRC, offering insights into mCRC metabolic pathways. Our findings establish that (1)H-NMR profiling of patient serum can provide a strong metabolomic signature of m...

  13. 18F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients

    International Nuclear Information System (INIS)

    D'Angelillo, Rolando M.; Sciuto, Rosa; Ramella, Sara; Papalia, Rocco; Jereczek-Fossa, Barbara A.; Trodella, Luca E.; Fiore, Michele; Gallucci, Michele; Maini, Carlo L.; Trodella, Lucio

    2014-01-01

    Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic 18 F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, 18 F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity

  14. Expression of Aurora-B and FOXM1 predict poor survival in patients with nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Pei-Yu; Luo, Dong-Hua; Mai, Hai-Qiang [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Sun Yat-sen University Cancer Center, Department of Nasopharyngeal Carcinoma, Guangzhou (China); Li, Yan; Zeng, Ting-Ting; Li, Meng-Qing [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Hou, Xue; Zhang, Li [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Sun Yat-sen University Cancer Center, Department of Medical Oncology, Guangzhou (China)

    2015-08-15

    The purpose of this work was to investigate the relationship between Aurora-B, FOXM1, and clinical outcomes in patients with nasopharyngeal carcinoma (NPC) who were treated with a combination of induction chemotherapy and radiotherapy. The expression of Aurora-B and FOXM1 were investigated by immunohistochemistry using a tissue microarray (TMA) containing samples from 166 NPC patients who were treated with cisplatin (DDP) + fluorouracil (5-FU) induction chemotherapy and radiotherapy between 1999 and 2005. The relationship of Aurora-B, FOXM1, and survival of these NPC patients was analyzed. Informative TMA results were obtained in 91 tumor cases for Aurora-B and 93 tumor cases for FOXM1. The 8-year failure-free survival rate (FFS) for the Aurora-B-negative and Aurora-B-positive group was 65.6 and 37.3 %, respectively (p = 0.024), and the 8-year distant FFS (D-FFS) rate was 65.6 and 41.5 %, respectively (p = 0.047). The 8-year overall survival (OS) in the FOXM1-negative group was moderately higher than in the FOXM1-positive group (58.4 vs 39.1 %, p = 0.081). Cox regression analysis revealed that for FFS, Aurora-B expression was a significant prognostic factor (p = 0.025), while for D-FFS, Aurora-B expression was a marginally significant prognostic factor (p = 0.056). When FOXM1 expression was analyzed, the Cox regression analyses showed that FOXM1 expression was a marginally significant prognostic factor (p = 0.056) for OS. Correlation analysis showed that Aurora-B and FOXM1 expression had no significant correlation. Aurora-B and FOXM1 were both adverse prognostic markers for NPC patients treated with chemoradiotherapy. However, the two markers had no significant correlation. (orig.) [German] Ziel war die Untersuchung der Beziehung zwischen Aurora-B, FOXM1 und den klinischen Ergebnissen bei Patienten mit nasopharyngealem Karzinom (NPC), die mit einer Kombinationstherapie aus Induktionschemotherapie und Radiotherapie behandelt wurden. Die Expression von Aurora-B und

  15. Bonded versus vacuum-formed retainers: a randomized controlled trial. Part 1: stability, retainer survival, and patient satisfaction outcomes after 12 months.

    Science.gov (United States)

    Forde, Katherine; Storey, Madeleine; Littlewood, Simon J; Scott, Paul; Luther, Friedy; Kang, Jing

    2017-10-20

    There is a shortage of evidence on the best type of retainer. Evaluate upper and lower bonded retainers (BRs) versus upper and lower vacuum-formed retainers (VFRs) over 12 months, in terms of stability, retainer survival, and patient satisfaction. Two-arm parallel group multi-centre randomized controlled clinical trial. Sixty consecutive patients completing fixed appliance therapy and requiring retainers were recruited from 3 hospital departments. They were randomly allocated to either upper and lower labial segment BRs (n = 30) or upper and lower full-arch VFRs (n = 30). Primary outcome was stability. Secondary outcomes were retainer survival and patient satisfaction. A random sequence of treatment allocation was computer-generated and implemented by sealing in sequentially numbered opaque sealed envelopes independently prepared in advance. Patients, operators and outcome could not be blinded due to the nature of the intervention. Thirty patients received BRs (median [Mdn] age 16 years, inter-quartile range [IQR] = 2) and 30 received VFRs (Mdn age 17 years, IQR = 4). Baseline characteristics were similar between groups. At 12 months, there were no statistically significant inter-group differences in post-treatment change of maxillary labial segment alignment (BR = 1.1 mm, IQR = 1.56, VFR = 0.76 mm, IQR = 1.55, P = 0.61); however, there was greater post-treatment change in the mandibular VFR group (BR = 0.77 mm, IQR = 1.46, VFR = 1.69mm, IQR = 2.00, P = 0.008). The difference in maxillary retainer survival rates were statistically non-significant, P = 0.34 (BR = 63.6%, 239.3 days, 95% confidence interval [CI] = 191.1-287.5, VFR = 73.3%, 311.1 days, 95% CI = 278.3-344.29). The mandibular BR had a lower survival rate (P = 0.01) at 12 months (BR = 50%, 239.3 days 95% CI = 191.1-287.5, VFR = 80%, 324.9 days 95% CI = 295.4-354.4). More subjects with VFRs reported discomfort (P = 0.002) and speech difficulties (P = 0.004) but found them easier to clean than those with

  16. A pilot study for texture analysis of {sup 18}F-FDG and {sup 18}F-FLT-PET/CT to predict tumor recurrence of patients with colorectal cancer who received surgery

    Energy Technology Data Exchange (ETDEWEB)

    Nakajo, Masatoyo; Tani, Atsushi; Jinguji, Megumi; Yoshiura, Takashi [Kagoshima University, Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima (Japan); Kajiya, Yoriko; Nakajo, Masayuki [Nanpuh Hospital, Department of Radiology, Kagoshima (Japan); Kitazono, Masaki [Nanpuh Hospital, Department of Surgery, Kagoshima (Japan)

    2017-12-15

    This retrospective study was done to examine whether the heterogeneity in primary tumor F-18-fluorodeoxyglucose ({sup 18}F-FDG) and {sup 18}F-3'-fluoro-3'-deoxythymidine ({sup 18}F-FLT) distribution can predict prognosis of patients with colorectal cancer who received surgery. The enrolled 32 patients with colorectal cancer underwent both {sup 18}F-FDG- and {sup 18}F-FLT-PET/CT studies before surgery. Clinicopathological factors, stage, SUVmax, SUVmean, metabolic tumor volume (SUV ≥ 2.5), total lesion glycolysis, total lesion proliferation and seven texture heterogeneity parameters (coefficient of variation, local parameters: entropy, homogeneity, and dissimilarity; and regional parameters: intensity variability [IV], size-zone variability [SZV], and zone percentage [ZP]) were obtained. Progression free survival (PFS) was calculated by the Kaplan-Meier method. Prognostic significance was assessed by Cox proportional hazards analysis. Eight patients had eventually come to progression, and 24 patients were alive without progression during clinical follow-up [mean follow-up PFS; 55.9 months (range, 1-72)]. High stage (p = 0.004), high {sup 18}F-FDG-IV (p = 0.015), high {sup 18}F-FDG-SZV (p = 0.013) and high {sup 18}F-FLT-entropy (p = 0.015) were significant in predicting poor 5-year PFS. Other parameters did not predict the disease outcome. At bivariate analysis, disease event hazards ratios for {sup 18}F-FDG-IV and {sup 18}F-FDG-SZV remained significant when adjusted for stage and {sup 18}F-FLT-entropy ({sup 18}F-FDG-IV; p = 0.004 [adjusted for stage], 0.007 [adjusted for {sup 18}F-FLT-entropy]; {sup 18}F-FDG-SZV; p = 0.028 [adjusted for stage], 0.040 [adjusted for {sup 18}F-FLT-entropy]). {sup 18}F-FDG PET heterogeneity parameters, IV and SZV, have a potential to be strong prognostic factors to predict PFS of patients with surgically resected colorectal cancer and are more useful than {sup 18}F-FLT-PET/CT heterogeneity parameters. (orig.)

  17. Atmospheric histories and growth trends of C4F10, C5F12, C6F14, C7F16 and C8F18

    Directory of Open Access Journals (Sweden)

    R. F. Weiss

    2012-05-01

    Full Text Available Atmospheric observations and trends are presented for the high molecular weight perfluorocarbons (PFCs: decafluorobutane (C4F10, dodecafluoropentane (C5F12, tetradecafluorohexane (C6F14, hexadecafluoroheptane (C7F16 and octadecafluorooctane (C8F18. Their atmospheric histories are based on measurements of 36 Northern Hemisphere and 46 Southern Hemisphere archived air samples collected between 1973 to 2011 using the Advanced Global Atmospheric Gases Experiment (AGAGE "Medusa" preconcentration gas chromatography-mass spectrometry systems. A new calibration scale was prepared for each PFC, with estimated accuracies of 6.8% for C4F10, 7.8% for C5F12, 4.0% for C6F14, 6.6% for C7F16 and 7.9% for C8F18. Based on our observations the 2011 globally averaged dry air mole fractions of these heavy PFCs are: 0.17 parts-per-trillion (ppt, i.e., parts per 1012 for C4F10, 0.12 ppt for C5F12, 0.27 ppt for C6F14, 0.12 ppt for C7F16 and 0.09 ppt for C8F18. These atmospheric mole fractions combine to contribute to a global average radiative forcing of 0.35 mW m−2, which is 6% of the total anthropogenic PFC radiative forcing (Montzka and Reimann, 2011; Oram et al., 2012. The growth rates of the heavy perfluorocarbons were largest in the late 1990s peaking at 6.2 parts per quadrillion (ppq, i.e., parts per 1015 per year (yr for C4F10, at 5.0 ppq yr−1 for C5F12 and 16.6 ppq yr−1 for C6F14 and in the early 1990s for C7F16 at 4.7 ppq yr−1 and in the mid 1990s for C8F18 at 4.8 ppq yr−1. The 2011 globally averaged mean atmospheric growth rates of these PFCs are subsequently lower at 2.2 ppq yr−1 for C4F10, 1.4 ppq yr−1 for C5F12, 5.0 ppq yr−1 for C6F14, 3.4 ppq yr−1 for C7F16 and 0.9 ppq yr−1 for C8F18. The more recent slowdown in the growth rates suggests that emissions are declining as compared to the 1980s and 1990s.

  18. Rac1 selective activation improves retina ganglion cell survival and regeneration.

    Directory of Open Access Journals (Sweden)

    Erika Lorenzetto

    Full Text Available In adult mammals, after optic nerve injury, retinal ganglion cells (RGCs do not regenerate their axons and most of them die by apoptosis within a few days. Recently, several strategies that activate neuronal intracellular pathways were proposed to prevent such degenerative processes. The rho-related small GTPase Rac1 is part of a complex, still not fully understood, intracellular signaling network, mediating in neurons many effects, including axon growth and cell survival. However, its role in neuronal survival and regeneration in vivo has not yet been properly investigated. To address this point we intravitreally injected selective cell-penetrating Rac1 mutants after optic nerve crush and studied the effect on RGC survival and axonal regeneration. We injected two well-characterized L61 constitutively active Tat-Rac1 fusion protein mutants, in which a second F37A or Y40C mutation confers selectivity in downstream signaling pathways. Results showed that, 15 days after crush, both mutants were able to improve survival and to prevent dendrite degeneration, while the one harboring the F37A mutation also improved axonal regeneration. The treatment with F37A mutant for one month did not improve the axonal elongation respect to 15 days. Furthermore, we found an increase of Pak1 T212 phosphorylation and ERK1/2 expression in RGCs after F37A treatment, whereas ERK1/2 was more activated in glial cells after Y40C administration. Our data suggest that the selective activation of distinct Rac1-dependent pathways could represent a therapeutic strategy to counteract neuronal degenerative processes in the retina.

  19. Synthesis of New Unsymmetrical 4,5-Dihydroxy-2-imidazolidinones. Dynamic NMR Spectroscopic Study of the Prototropic Tautomerism in 1-(2-Benzimidazolyl-3-phenyl-4,5-dihydroxy-2-imidazolidinone

    Directory of Open Access Journals (Sweden)

    Farshid Salimi

    2006-10-01

    Full Text Available The acid-catalyzed cyclocondensation in refluxing acetonitrile of aqueousglyoxal with N-heteroaryl-N'-phenylureas 4a-f (heteroaryl = 2-thiazolyl, 2-pyrimidinyl,2-pyrazinyl, 2-pyridinyl, 3-pyridinyl and 2-benzimidazolyl led to the formation of thecorresponding 1-heteroaryl-3-phenyl-4,5-dihydroxy-2-imidazolidinones 5a-f. All theproducts were characterized by elemental and spectroscopic analyses. The free-energybarrier (∆GP≠ for prototropic tautomerism in 1-(2-benzimidazolyl-3-phenyl-4,5-dihydroxy-2-imidazolidinone (5f was determined by dynamic NMR studies to be 81 ± 2KJ molP-1

  20. Cultural Considerations for Security Cooperation Operations in South Sudan: Understanding the Sudan People’s Liberation Army (SPLA)

    Science.gov (United States)

    2012-04-01

    relationships among people, living and dead, animals, plants, and natural and supernatural phenomena. “Fatalism, the belief that life is destined...thoughts persist today. According to quotes from militiamen in one of 14 Nenad Marinkovic’s articles , “Almost all South Sudan militias claim...foreign threats. He utilized these very arms to wage war against the SPLA and supply the government backed militias.63 In an article in the Small War

  1. Hydriding and dehydriding rates of Mg, Mg-10TaF5, and Mg-10NbF5 prepared via reactive mechanical grinding

    Science.gov (United States)

    Song, Myoung Youp; Kwak, Young Jun; Lee, Seong Ho; Park, Hye Ryoung

    2015-01-01

    In this work, TaF5 and NbF5 were chosen as additives to enhance the hydriding and dehydriding rates of Mg. Mg, Mg-10TaF5, and Mg-10NbF5 samples were prepared by reactive mechanical grinding. The hydriding and dehydriding properties of the samples were then examined. Mg-10TaF5 had the largest amount of hydrogen absorbed for 30 min and the highest initial dehydriding rate after incubation period, followed in order by Mg-10NbF5, and Mg. At 593 K under 12 bar H2 at the first cycle, Mg-10TaF5 absorbed 3.63 wt% H for 5 min and 4.53 wt% H for 30 min. At 593 K under 1.0 bar H2 at the first cycle, Mg-10TaF5 desorbed 0 wt% H for 2.5 min, 0.59 wt% H for 5 min, 3.42 wt% H for 30 min, and 4.24 wt% H for 60 min. The reactive mechanical grinding of Mg with TaF5 or NbF5 is believed to have facilitated the nucleation and to have decreased the diffusion distances of hydrogen atoms. These two effects are believed to have increased the hydriding and dehydriding rates of Mg. The MgF2 and Ta2H formed in Mg-10TaF5, and the MgF2, NbH2, and NbF3 formed in Mg-10NbF5 are considered to have enhanced both of these effects.

  2. Data of evolutionary structure change: 1RAAA-3GD5F [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1RAAA-3GD5F 1RAA 3GD5 A F ANPLYQKHIISINDLSRDDLNLVLATAAKLKANPQPELL...ARGAHILYTDVWTHR---LQLFEQ----YQINAALLNCAAAEAIVLHCLPAHRGEEITDEVMEGPRSRIWDEAENRLHAQK...ex> 1RAA A 1RAAA DML...> A 1RAAA PLPRV--DEIA...dbChain> 1RAAA TEFSGNVPVLN HHHH

  3. E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

    Science.gov (United States)

    Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

    2016-11-01

    Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

  4. Investigation of the multiphotonic excitation processes of the 4f{sup 2} 5d configuration in LiYF{sub 4}, LiLuF{sub 4} and BaY{sub 2}F{sub 8} crystals doped with trivalent neodymium; Investigacao dos processos de excitacao multifotonica da configuracao 4f{sup 2} 5d nos cristais de LiYF{sub 4}, LiLuF{sub 4} e BaY{sub 2}F{sub 8} dopados com neodimio trivalente

    Energy Technology Data Exchange (ETDEWEB)

    Librantz, Andre Felipe Henriques

    2004-07-01

    Ultraviolet (UV) fluorescence of Nd{sup 3+} ions induced by multistep laser excitation was investigated in Nd-doped LiYF{sub 4} (YLF), LiLuF{sub 4} (LLF) and BaY{sub 2}F{sub 8} (BaYF) crystals using a technique of time-resolved spectroscopy. The observed UV luminescence was due to transitions between the bottom of 4f{sup 2} 5d configuration and the 4f{sup 3} states of Nd{sup 3+} ions. The lower excited state 4f {sup 2}({sup 3}H)5d [{sup 4}K{sub 11/2}] was reached by three stepwise absorptions of photons at 521 nm (green) and 478 nm (blue) of a short pulse laser excitation. The three sequential absorptions at 478 nm constitutes a new multiphoton excitation process of Nd{sup 3+} in these crystals with the following excitation sequence: {sup 4}I{sub 9/2} + hv(480 nm){yields} {sup 2}G(1){sub 9/2} + hv(480 nm){yields} {sup 2}F(2){sub 7/2} + hv(480 nm){yields} 4f {sup 2}({sup 3}H)5d [{sup 4}K{sub 9/2}] (excited state at {approx} 63000 cm{sup -1}). The observed UV emissions from [{sup 4}K{sub 11/2}] state have a lifetime of 35 ns (parity allowed) and are: broadband in contrast to UV emissions from 4f{sup 3} configuration, which are also present in the luminescence investigation but having longer lifetime (8 {mu}s) and structures composed of narrow lines. The excitation spectrum of fast UV luminescence exhibited different structure depending on the excitation geometry ({sigma} or {pi}) with respect to the c-axis of the crystal. It was seen two new emissions from [{sup 4}K{sub 11/2}] and {sup 2}F(2){sub 5/2} states near 528 nm, which modified the branching ratio of the bottom of the 4f{sup 2} 5d configuration ({approx} 55500 cm{sup -1} for the YLF and LLF crystals and {approx}-53700 cm{sup -1} for the BaYF crystal). The equivalent cross-section of three and two excitation process was estimated at 521 nm by solving the rate equations of the system under short laser excitation, which leads us to infer that is possible to have laser action under pulsed laser pumping with

  5. Low PIP4K2B expression in human breast tumors correlates with reduced patient survival: A role for PIP4K2B in the regulation of E-cadherin expression.

    Science.gov (United States)

    Keune, Willem-Jan; Sims, Andrew H; Jones, David R; Bultsma, Yvette; Lynch, James T; Jirström, Karin; Landberg, Goran; Divecha, Nullin

    2013-12-01

    Phosphatidylinositol-5-phosphate (PtdIns5P) 4-kinase β (PIP4K2B) directly regulates the levels of two important phosphoinositide second messengers, PtdIns5P and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P2]. PIP4K2B has been linked to the regulation of gene transcription, to TP53 and AKT activation, and to the regulation of cellular reactive oxygen accumulation. However, its role in human tumor development and on patient survival is not known. Here, we have interrogated the expression of PIP4K2B in a cohort (489) of patients with breast tumor using immunohistochemical staining and by a meta-analysis of gene expression profiles from 2,999 breast tumors, both with associated clinical outcome data. Low PIP4K2B expression was associated with increased tumor size, high Nottingham histological grade, Ki67 expression, and distant metastasis, whereas high PIP4K2B expression strongly associated with ERBB2 expression. Kaplan-Meier curves showed that both high and low PIP4K2B expression correlated with poorer patient survival compared with intermediate expression. In normal (MCF10A) and tumor (MCF7) breast epithelial cell lines, mimicking low PIP4K2B expression, using short hairpin RNA interference-mediated knockdown, led to a decrease in the transcription and expression of the tumor suppressor protein E-cadherin (CDH1). In MCF10A cells, knockdown of PIP4K2B enhanced TGF-β-induced epithelial to mesenchymal transition (EMT), a process required during the development of metastasis. Analysis of gene expression datasets confirmed the association between low PIP4K2B and low CDH1expression. Decreased CDH1 expression and enhancement of TGF-β-induced EMT by reduced PIP4K2B expression might, in part, explain the association between low PIP4K2B expression and poor patient survival.

  6. Long-term survival of patients with primary oral squamous cell carcinoma. Comparison of two treatment protocols in a prospective study; 5-Jahres-Ueberlebenswahrscheinlichkeit von Patienten mit primaeren Plattenepithelkarzinomen der Mundhoehle. Vergleich von zwei Behandlungsstrategien in einer prospektiven Studie

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, P.; Bloch-Birkholz, A.; Neukam, F.W. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Mund-, Kiefer-, Gesichtschirurgie; Grabenbauer, G.; Sauer, R. [Erlangen-Nuernberg Univ., Erlangen (Germany). Klinik und Poliklinik fuer Strahlentherapie; Leher, A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Medizininformatik, Biometrie und Epidemiologie; Vairaktaris, E. [Univ. of Athens Medical School (Greece). Dept. of Maxillofacial Surgery

    2007-04-15

    Background and Purpose: In recent years, different concepts for the treatment of oral squamous cell carcinomas (OSCC) have been developed; these include preoperative simultaneous neoadjuvant radiochemotherapy and one-stage surgery with tumor ablation and reconstruction. When considering long-term survival, there is substantial evidence that multimodality treatment based on a neoadjuvant radiochemotherapy is superior to adjuvant therapy concepts based on a surgical approach with postoperative irradiation. The aim of this study was to discuss the 5-year survival rate in a neoadjuvant and an adjuvant combination treatment in patients with primary OSCC. Patients and Methods: This nonrandomized longitudinal study prospectively evaluates the long-term tumor-free survival in 128 patients with oral cancer. Two groups consisting of 74 neoadjuvantly and 54 primarily surgically treated patients were formed. 99 patients suffered from stage III and IV disease according to the UICC criteria. Long-term survival was estimated according to the Kaplan-Meier assumption. Results: The neoadjuvant treatment increases the prospect of a long-term tumor-free survival. According to Kaplan-Meier assumption the estimation for a 5-year tumor-free survival in OSCC in category T1 is 83.1% in neoadjuvant, and 70.1% in adjuvant treatment, in T2 79.6% and 57.7%, in T3 68.2% and 33.2%, in T4 51.4% and 30.5%, respectively. Significance (p < 0.05) could be proven for T1 (p = 0.002), T2 (p = 0.028), and T4 (p < 0.0001) tumors. The effectiveness of the preoperative radiochemotherapy was demonstrated in the pathohistological result of tumor-free resection specimens in 28 patients of the neoadjuvant treatment group (37.8%). On the other hand, four patients died during the preoperative combination therapy. 64.8% of the patients in the adjuvant and 71.6% in the neoadjuvant treatment group survived the observation period. Conclusion: Neoadjuvant therapy is highly effective and results in a better 5-year

  7. Opioid growth factor improves clinical benefit and survival in patients with advanced pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jill P Smith

    2010-03-01

    Full Text Available Jill P Smith1, Sandra I Bingaman1, David T Mauger2, Harold H Harvey1, Laurence M Demers3, Ian S Zagon41Departments of Medicine, 2Public Health Sciences, 3Pathology, and 4Neurosciences and Anatomy, Pennsylvania State University, College of Medicine, Hershey Medical Center, Hershey, PA, USABackground: Advanced pancreatic cancer carries the poorest prognosis of all gastrointestinal malignancies. Once the tumor has spread beyond the margins of the pancreas, chemotherapy is the major treatment modality offered to patients; however, chemotherapy does not significantly improve survival.Objective: Opioid growth factor (OGF; [Met5]-enkephalin is a natural peptide that has been shown to inhibit growth of pancreatic cancer in cell culture and in nude mice. The purpose of this study was to evaluate the effects of OGF biotherapy on subjects with advanced pancreatic cancer who failed chemotherapy.Methods: In a prospective phase II open-labeled clinical trial, 24 subjects who failed standard chemotherapy for advanced pancreatic cancer were treated weekly with OGF 250 μg/kg intravenously. Outcomes measured included clinical benefit, tumor response by radiographic imaging, quality of life, and survival.Results: Clinical benefit response was experienced by 53% of OGF-treated patients compared to historical controls of 23.8% and 4.8% for gemcitabine and 5-fluorouracil (5-FU, respectively. Of the subjects surviving more than eight weeks, 62% showed either a decrease or stabilization in tumor size by computed tomography. The median survival time for OGF-treated patients was three times that of untreated patients (65.5 versus 21 days, p < 0.001. No adverse effects on hematologic or chemistry parameters were noted, and quality of life surveys suggested improvement with OGF. Limitations: Measurements other than survival were not allowed in control patients, and clinical benefit comparisons were made to historical controls.Conclusion: OGF biotherapy improves the

  8. Pet imaging of human pituitary 5-HT2 receptors with F-18 setoperone

    Energy Technology Data Exchange (ETDEWEB)

    Fischman, A.J.; Bonab, A.A.; Babich, J.W. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1995-05-01

    Serotonin (5-HT) receptors play an important role in the regulation of pituitary function. In particular, 5HT agonists stimulate ACTH, {beta}-endorphin, prolactin and growth hormone secretion but inhibit TSH release. 5-HT binding sites have been identified by autoradiographic studies of rat and human pituitary. In the present investigation, we used PET with F-18 setoperone to image 5-HT2 receptors in normal humans. Setoperone, a piperidine derivative with potent 5-HT2 receptor blocking properties was labelled with F-18 by nucleophilic substitution on the nitro derivative. After HPLC purification, specific activity was between 10,000 and 15,000 mCi/{mu} mole and radiochemical purity was >98%. Six healthy male volunteers were injected with 5-7 mCi of F-18. Setoperone and serial PET images and arterial blood samples were collected over 2 hrs. Specific binding to 5-HT2 receptors in the frontal cortex (FC), striatum (ST) and pituitary (P) was quantitated using the cerebellum (C) as reference. The tracer showed clear retention in FC, ST and P (known to contain a high density of 5-HT2 receptors) relative to C (known to be devoid of 5-HT2 receptors). In all subjects, FC/C, ST/C and P/C ratios increased during the first hr. and remained stable thereafter. For FC and ST, the ratios reached similar values; 3.92{plus_minus}0.73 and 3.53{plus_minus}0.32. For pituitary, a significantly higher ratio, was measured at all times; 6.53{plus_minus}1.82 (p<0.01). These results indicate that F-18 setoperone is an effective PET radiopharmaceutical for imaging 5-HT2 receptors in the human pituitary. Future applications of this agent could provide important new insights into neuroendocrine function.

  9. Socioeconomic Status, Not Race, Is Associated With Reduced Survival in Esophagectomy Patients.

    Science.gov (United States)

    Erhunmwunsee, Loretta; Gulack, Brian C; Rushing, Christel; Niedzwiecki, Donna; Berry, Mark F; Hartwig, Matthew G

    2017-07-01

    Black patients with esophageal cancer have worse survival than white patients. This study examines this racial disparity in conjunction with socioeconomic status (SES) and explores whether race-based outcome differences exist using a national database. The associations between race and SES with overall survival of patients treated with esophagectomy for stages I to III esophageal cancer between 2003 and 2011 in the National Cancer Data Base were investigated using the Kaplan-Meier method and proportional hazards analyses. Median income by zip code and proportion of the zip code residents without a high school diploma were grouped into income and education quartiles, respectively and used as surrogates for SES. The association between race and overall survival stratified by SES is explored. Of 11,599 esophagectomy patients who met study criteria, 3,503 (30.2%) were in the highest income quartile, 2,847 (24.5%) were in the highest education quartile, and 610 patients (5%) were black. Before adjustment for SES, black patients had worse overall survival than white patients (median survival 23.0 versus 34.7 months, log rank p race was not. Prior studies have suggested that survival of esophageal cancer patients after esophagectomy is associated with race. Our study suggests that race is not significantly related to overall survival when adjusted for other prognostic variables. Socioeconomic status, however, remains significantly related to overall survival in our model. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Characteristics of 49 patients who survived for 5 years following radical radiation therapy for non-small cell lung cancer: the potential for cure

    International Nuclear Information System (INIS)

    Mac Manus, Michael P.; Wada, Morikatsu; Matthews, Jane P.; Ball, David L.

    2000-01-01

    Purpose: To investigate the long-term curative potential of radical radiation therapy (RT) for non-small cell lung cancer (NSCLC) by studying characteristics of patients from a large prospective database who survived > 5 years after RT, and by analyzing survival beyond 5 years. Methods and Materials: Five-year survivors were identified from a database containing information on 488 patients given radical RT following presentation to the Peter MacCallum Cancer Institute with NSCLC between 1984 and 1990. Additional data were obtained from case notes of survivors. RT was computed tomography (CT)-planned, conventionally-fractionated, and given without chemotherapy. Results: Actuarial survival for 49 5-year survivors was 65% at 10 years. Five 5-year survivors had documented disease progression within the first 5 years and subsequently died. Of 44 patients free-from-progression (FFP) at 5 years, an estimated 81% remained FFP in the second 5 years. Age and histology were not significant prognostic factors, and only 22 patients (4.5%) had weight loss > 10%. For 277 patients who had not undergone thoracotomy, median RT dose was 60 Gy and survival at 5 and 10 years was 7% and 3%, respectively. For 207 patients who received radical RT post-thoracotomy, median dose was 60 Gy and survival at 5 and 10 years was 24% and 18%, respectively. Five-year survivors of post-thoracotomy RT had been treated for gross residual disease (n = 10), positive-margin (n = 6), or probable microscopic residual disease (n = 17). Failure to regain ECOG performance status = 0 post-thoracotomy was associated with reduced survival (p 5 years after radical RT for NSCLC remained FFP in the following 5 years and were apparently cured. RT alone can cure small but significant numbers of patients. Long-term results of combined chemotherapy/RT protocols, which are associated with increased median survival, are awaited for comparison

  11. Clinical and survival impact of FDG PET in patients with suspicion of recurrent cervical carcinoma

    International Nuclear Information System (INIS)

    Pallardy, Amandine; Testard, Aude; Resche, Isabelle; Bridji, Boumediene; Bodet-Milin, Caroline; Oudoux, Aurore; Ansquer, Catherine; Campion, Loic; Bourbouloux, Emmanuelle; Sagan, Christine; Kraeber-Bodere, Francoise; Rousseau, Caroline

    2010-01-01

    The aim of this retrospective study was to evaluate the contribution of 18 F-FDG PET to the clinical management and survival outcome of patients suspected of recurrent cervical carcinoma and in line with the hypothesis that early diagnosis of recurrent cervical cancer may improve overall survival. A total of 40 patients underwent conventional imaging (CI) and FDG PET/CT for suspected cervical cancer. Clinical management decisions were recorded with CI and additional PET/CT. Discordances and concordances between CI and PET/CT results were compared to the final diagnosis as based on histopathology analysis or follow-up considered as the gold standard. The final diagnosis was established pathologically (n=25) or by median clinical follow-up for 48 months after the PET (n=15). The PET/CT was positive in 76% (20/26) of patients compared to 19% (6/26) with CI. Globally PET/CT modified the treatment plan in 55% (22/40) of patients and in 75% (18/24) when the CI was negative prior to PET/CT. These changes led to the use of previously unplanned therapeutic procedures in 37.5% (15/40). When FDG PET was positive for recurrence (>3 foci), the median overall survival was 12 months (2-70) compared to patients with PET findings with ≤1 focus for which the median survival was not attained (p=0.007). A multivariate analysis of prognostic factors demonstrated that abnormal FDG uptake (>3 foci) was the most significant factor (p<0.03) for death from cervical cancer. FDG PET is a valuable tool in the case of suspected recurrence of cervical cancer on account of its impact on treatment planning and especially in predicting patient outcome. (orig.)

  12. Survival significance of epidermal growth factor receptor tyrosine kinase inhibitors and current staging system for survival after recurrence in patients with completely resected lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Saji H

    2017-08-01

    Full Text Available Hisashi Saji,1,2 Hiroki Sakai,1 Hiroyuki Kimura,1 Tomoyuki Miyazawa,1 Hideki Marushima,1 Haruhiko Nakamura1 1Department of Chest Surgery, St Marianna University School of Medicine, Miyamae-ku, Kawasaki, Kanagawa, Japan; 2Department of Thoracic Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan Objective: We previously reported that the staging system and epidermal growth factor receptor (EGFR mutation status are key factors for treatment strategy and predicting survival. However, the significance of these factors as predictors of overall survival (OS and postoperative recurrence survival (PRS has not been sufficiently elucidated. The objective here was to investigate EGFR mutation status and p-stage, which affect PRS and OS in patients with completely resected lung adenocarcinoma, using a different database.Patients and methods: We retrospectively reviewed 56 consecutive lung adenocarcinoma patients with disease recurrence in St. Marianna University Hospital between January 2010 and December 2014.Results: EGFR mutants (M were detected in 16/56 patients (29%. The patients with EGFR M had a better OS than those with EGFR wild-type (WT status (5-year survival: 50.3% vs 43.1, P=0.133. There was no significant difference in the 3-year recurrence-free survival rate between patients with M and WT (6.3% vs 7.7%, P=0.656, and the patients with EGFR M had a significantly better 3-year PRS than those with WT (77.4% vs 51.7%, P=0.033. The 3-year PRS rate for patients with M/pathologic stage (p-stage I–II (87.5% was better than that for patients with M/p-stage III (60.0%, WT/p-stage I–II (52.7%, and WT/p-stage III (43.8%. There was a significant difference between patients with M/p-stage I and WT/p-stage I–II or WT/p-stage III (P=0.021 and 0.030, respectively. During the study period, of the 16 patients with mutants, 12 patients (75% received EGFR-tyrosine kinase inhibitor (TKI therapy and among the 40 patients with WT, no patient received

  13. Bee Venom Phospholipase A2: Yesterday's Enemy Becomes Today's Friend.

    Science.gov (United States)

    Lee, Gihyun; Bae, Hyunsu

    2016-02-22

    Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases including asthma, Parkinson's disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of bee venom group III sPLA2 because this enzyme is known to be the major allergen of bee venom that can cause anaphylactic shock. For many decades, efforts have been made to avoid its adverse effects. At high concentrations, exposure to bee venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of bee venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of bee venom group III sPLA2 in regulating various immune responses and physiopathological changes.

  14. A novel mechanism of E2F1 regulation via nucleocytoplasmic shuttling: determinants of nuclear import and export.

    Science.gov (United States)

    Ivanova, Iordanka A; Vespa, Alisa; Dagnino, Lina

    2007-09-01

    E2F1 is a transcription factor central for cell survival, proliferation, and repair following genomic insult. Depending on the cell type and conditions, E2F1 can induce apoptosis in transformed cells, behaving as a tumour suppressor, or impart growth advantages favouring tumour formation. The pleiotropic functions of E2F1 are a likely consequence of its ability to transcriptionally control a wide variety of target genes, and require tight regulation of its activity at multiple levels. Although sequestration of proteins to particular cellular compartments is a well-established regulatory mechanism, virtually nothing is known about its contribution to modulation of E2F1 target gene expression. We have examined the subcellular trafficking of E2F1 and, contrary to the widely held notion that this factor is constitutively nuclear, we now demonstrate that it is subjected to continuous nucleocytoplasmic shuttling. We have also defined two nuclear localization domains and a nuclear export region, which mediates CRM1-dependent transit out of the nucleus. The predominant subcellular location of E2F1 is likely determined by the balance between the activity of nuclear import and export domains, and can be modulated by differentiation stimuli in epidermal cells. Thus, we have identified a hitherto unrecognized mechanism to control E2F1 function through modulation of its subcellular localization.

  15. E2F3a gene expression has prognostic significance in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Wang, Kai-Ling; Mei, Yan-Yan; Cui, Lei; Zhao, Xiao-Xi; Li, Wei-Jing; Gao, Chao; Liu, Shu-Guang; Jiao, Ying; Liu, Fei-Fei; Wu, Min-Yuan; Ding, Wei; Li, Zhi-Gang

    2014-10-01

    To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia (ALL). We quantified E2F3a expression at diagnosis in 148 children with ALL by real-time PCR. In the test cohort (n = 48), receiver operating characteristic (ROC) curve was used to find the best cut-off point to divide the patients into E2F3a low- and high-expression groups. The prognostic significance of E2F3a expression was investigated in the test cohort and confirmed in the validation cohort (n = 100). The correlations of E2F3a expression with the clinical features and treatment outcome of these patients were analyzed. ROC curve analysis indicated that the best cut-off point of E2F3a expression was 0.3780. In the test cohort, leukemia-free survival (LFS) and event-free survival (EFS) of the low-expression group were lower than those of the high-expression group (log rank: P = 0.026 for both). This finding was verified in the validation cohort. LFS, EFS, and overall survival were also lower in the low-expression group than in the high-expression group (log rank, P = 0.015, 0.008, and 0.002 respectively). E2F3a low expression was correlated with the existence of BCR-ABL fusion. An algorithm composed of E2F3a expression and minimal residual disease (MRD) could predict relapse or induction failure more precisely than current risk stratification. These results were still significant in the ALL patients without BCR-ABL fusion. Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. ASXL2 mutations are frequently found in pediatric AML patients with t(8;21)/ RUNX1-RUNX1T1 and associated with a better prognosis.

    Science.gov (United States)

    Yamato, Genki; Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Hara, Yusuke; Ohki, Kentaro; Okubo, Jun; Okuno, Haruna; Chiba, Kenichi; Tanaka, Hiroko; Kinoshita, Akitoshi; Moritake, Hiroshi; Kiyokawa, Nobutaka; Tomizawa, Daisuke; Park, Myoung-Ja; Sotomatsu, Manabu; Taga, Takashi; Adachi, Souichi; Tawa, Akio; Horibe, Keizo; Arakawa, Hirokazu; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

    2017-05-01

    ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric acute myeloid leukemia (AML) patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0-17 years). We identified 9 (2.4%) ASXL1 and 17 (4.6%) ASXL2 mutations in 25 patients. These mutations were more common in patients with t(8;21)(q22;q22)/RUNX1-RUNX1T1 (ASXL1, 6/9, 67%, P = 0.02; ASXL2, 10/17, 59%, P = 0.01). Among these 25 patients, 4 (27%) of 15 patients with t(8;21) and 6 (60%) of 10 patients without t(8;21) relapsed. However, most patients with relapse were rescued using stem cell transplantation irrespective of t(8;21). The overall survival (OS) and event-free survival (EFS) rates showed no differences among pediatric AML patients with t(8;21) and ASXL1 or ASXL2 mutations and ASXL wild-type (5-year OS, 75% vs. 100% vs. 91% and 5-year EFS, 67% vs. 80% vs. 67%). In 106 patients with t(8;21) AML, the coexistence of mutations in tyrosine kinase pathways and chromatin modifiers and/or cohesin complex component genes had no effect on prognosis. These results suggest that ASXL1 and ASXL2 mutations play key roles as cooperating mutations that induce leukemogenesis, particularly in pediatric AML patients with t(8;21), and these mutations might be associated with a better prognosis than that reported previously. © 2017 Wiley Periodicals, Inc.

  17. Prognostic significance of mediastinal {sup 18}F-FDG uptake in PET/CT in advanced ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bats, Anne-Sophie; Lecuru, Fabrice [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Universite Paris Descartes, Sorbonne Paris Cite, INSERM UMR-S 747, Paris (France); Hugonnet, Florent; Faraggi, Marc [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France); Huchon, Cyrille [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Bensaid, Cherazade [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Pierquet-Ghazzar, Nadia [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France)

    2012-03-15

    To evaluate the prognostic significance of increased mediastinal {sup 18}F-FDG uptake in PET/CT for the staging of advanced ovarian cancer. We retrospectively evaluated patients managed for FIGO stage III/IV ovarian cancer between 1 January 2006 and 1 June 2009. Patients were included if they had undergone {sup 18}F-FDG PET/CT and surgery for initial staging. Exclusion criteria were age younger than 18 years, inability to undergo general anaesthesia, recurrent ovarian cancer, and borderline or nonepithelial malignancy. Whole-body PET/CT was performed after intravenous {sup 18}F-FDG injection. The location of abnormal hot spots and {sup 18}F-FDG maximal standard uptake values (SUV{sub max}) were recorded. We compared the complete cytoreduction and survival rates in groups defined based on mediastinal {sup 18}F-FDG uptake and SUV{sub max} values. Kaplan-Meier curves of overall survival and disease-free survival were compared using the log-rank test. Hazard ratios with their 95% confidence intervals were computed. Adjusted hazard ratios were obtained using a multivariate Cox model. We included 53 patients, of whom 17 (32%) had increased mediastinal {sup 18}F-FDG uptake. Complete cytoreduction was achieved in 14 (87.5%) of the 16 patients managed with primary surgery and in 21 (75%) of the 28 patients managed with interval surgery. Complete cytoreduction was achieved significantly more often among patients without increased mediastinal {sup 18}F-FDG uptake (80.6% vs. 35.3%; p = 0.001). Disease-free survival was comparable between the two groups. By univariate analysis, overall mortality was significantly higher among patients with increased mediastinal {sup 18}F-FDG uptake (hazard ratio 5.70, 95% confidence interval 1.74-18.6). The only factor significantly associated with overall survival by multivariate analysis was complete cytoreduction (adjusted hazard ratio 0.24, 95% confidence interval 0.07-0.89). Increased mediastinal {sup 18}F-FDG uptake was common in patients

  18. Activation of the 2-5OAS/RNase L pathway in CVB1 or HAV/18f infected FRhK-4 cells does not require induction of OAS1 or OAS2 expression

    International Nuclear Information System (INIS)

    Kulka, Michael; Calvo, Mona S.; Ngo, Diana T.; Wales, Samantha Q.; Goswami, Biswendu B.

    2009-01-01

    The latent, constitutively expressed protein RNase L is activated in coxsackievirus and HAV strain 18f infected FRhK-4 cells. Endogenous oligoadenylate synthetase (OAS) from uninfected and virus infected cell extracts synthesizes active forms of the triphosphorylated 2-5A oligomer (the only known activator of RNase L) in vitro and endogenous 2-5A is detected in infected cell extracts. However, only the largest OAS isoform, OAS3, is readily detected throughout the time course of infection. While IFNβ treatment results in an increase in the level of all three OAS isoforms in FRhK-4 cells, IFNβ pretreatment does not affect the temporal onset or enhancement of RNase L activity nor inhibit virus replication. Our results indicate that CVB1 and HAV/18f activate the 2-5OAS/RNase L pathway in FRhK-4 cells during permissive infection through endogenous levels of OAS, but contrary to that reported for some picornaviruses, CVB1 and HAV/18f replication is insensitive to this activated antiviral pathway.

  19. Stomatin-like protein 2 is overexpressed in epithelial ovarian cancer and predicts poor patient survival

    International Nuclear Information System (INIS)

    Sun, Fei; Ding, Wen; He, Jie-Hua; Wang, Xiao-Jing; Ma, Ze-Biao; Li, Yan-Fang

    2015-01-01

    Stomatin-like protein 2 (SLP-2, also known as STOML2) is a stomatin homologue of uncertain function. SLP-2 overexpression has been suggested to be associated with cancer progression, resulting in adverse clinical outcomes in patients. Our study aim to investigate SLP-2 expression in epithelial ovarian cancer cells and its correlation with patient survival. SLP-2 mRNA and protein expression levels were analysed in five epithelial ovarian cancer cell lines and normal ovarian epithelial cells using real-time PCR and western blotting analysis. SLP-2 expression was investigated in eight matched-pair samples of epithelial ovarian cancer and adjacent noncancerous tissues from the same patients. Using immunohistochemistry, we examined the protein expression of paraffin-embedded specimens from 140 patients with epithelial ovarian cancer, 20 cases with borderline ovarian tumours, 20 cases with benign ovarian tumours, and 20 cases with normal ovarian tissues. Statistical analyses were applied to evaluate the clinicopathological significance of SLP-2 expression. SLP-2 mRNA and protein expression levels were significantly up-regulated in epithelial ovarian cancer cell lines and cancer tissues compared with normal ovarian epithelial cells and adjacent noncancerous ovarian tissues. Immunohistochemistry analysis revealed that the relative overexpression of SLP-2 was detected in 73.6 % (103/140) of the epithelial ovarian cancer specimens, 45.0 % (9/20) of the borderline ovarian specimens, 30.0 % (6/20) of the benign ovarian specimens and none of the normal ovarian specimens. SLP-2 protein expression in epithelial ovarian cancer was significantly correlated with the tumour stage (P < 0.001). Epithelial ovarian cancer patients with higher SLP-2 protein expression levels had shorter progress free survival and overall survival times compared to patients with lower SLP-2 protein expression levels. Multivariate analyses showed that SLP-2 expression levels were an independent prognostic

  20. Benefit of adjuvant chemotherapy after resection of stage II (T1-2N1M0) non-small cell lung cancer in elderly patients.

    Science.gov (United States)

    Berry, Mark F; Coleman, Brooke K; Curtis, Lesley H; Worni, Mathias; D'Amico, Thomas A; Akushevich, Igor

    2015-02-01

    We evaluated the use and efficacy of adjuvant chemotherapy after resection of T1-2N1M0 non-small cell lung cancer (NSCLC) in elderly patients. Factors associated with the use of adjuvant chemotherapy in patients older than 65 years of age who underwent surgical resection of T1-2N1M0 NSCLC without induction chemotherapy or radiation in the Surveillance, Epidemiology, and End Results-Medicare database from 1992 to 2006 were assessed using a multivariable logistic regression model that included treatment, patient, tumor, and census tract characteristics. Overall survival (OS) was analyzed using the Kaplan-Meier approach and inverse probability weight-adjusted Cox proportional hazard models. Overall, 2,781 patients who underwent surgical resection as the initial treatment for T1-2N1M0 NSCLC and survived at least 31 days after surgery were identified, with adjuvant chemotherapy given to 784 patients (28.2 %). Factors that predicted adjuvant chemotherapy use were younger age and higher T status. The 5-year OS was significantly better for patients who received adjuvant chemotherapy compared with patients not given adjuvant chemotherapy: 35.8 % (95 % confidence interval [CI] 31.9-39.6) vs. 28.0 % (95 % CI 25.9-30.0) (p = 0.008). In the inverse probability weight-adjusted Cox proportional hazard regression model, adjuvant chemotherapy use predicted significantly improved survival (hazard ratio 0.84; 95 % CI 0.76-0.92; p = 0.0002). Adjuvant chemotherapy after resection of T1-2N1M0 NSCLC is associated with significantly improved survival in patients older than 65 years. These data can be used to provide elderly patients with realistic expectations of the potential benefits when considering adjuvant chemotherapy in this setting.

  1. Are pretreatment 18F-FDG PET tumor textural features in non-small cell lung cancer associated with response and survival after chemoradiotherapy?

    Science.gov (United States)

    Cook, Gary J R; Yip, Connie; Siddique, Muhammad; Goh, Vicky; Chicklore, Sugama; Roy, Arunabha; Marsden, Paul; Ahmad, Shahreen; Landau, David

    2013-01-01

    There is evidence in some solid tumors that textural features of tumoral uptake in (18)F-FDG PET images are associated with response to chemoradiotherapy and survival. We have investigated whether a similar relationship exists in non-small cell lung cancer (NSCLC). Fifty-three patients (mean age, 65.8 y; 31 men, 22 women) with NSCLC treated with chemoradiotherapy underwent pretreatment (18)F-FDG PET/CT scans. Response was assessed by CT Response Evaluation Criteria in Solid Tumors (RECIST) at 12 wk. Overall survival (OS), progression-free survival (PFS), and local PFS (LPFS) were recorded. Primary tumor texture was measured by the parameters coarseness, contrast, busyness, and complexity. The following parameters were also derived from the PET data: primary tumor standardized uptake values (SUVs) (mean SUV, maximum SUV, and peak SUV), metabolic tumor volume, and total lesion glycolysis. Compared with nonresponders, RECIST responders showed lower coarseness (mean, 0.012 vs. 0.027; P = 0.004) and higher contrast (mean, 0.11 vs. 0.044; P = 0.002) and busyness (mean, 0.76 vs. 0.37; P = 0.027). Neither complexity nor any of the SUV parameters predicted RECIST response. By Kaplan-Meier analysis, OS, PFS, and LPFS were lower in patients with high primary tumor coarseness (median, 21.1 mo vs. not reached, P = 0.003; 12.6 vs. 25.8 mo, P = 0.002; and 12.9 vs. 20.5 mo, P = 0.016, respectively). Tumor coarseness was an independent predictor of OS on multivariable analysis. Contrast and busyness did not show significant associations with OS (P = 0.075 and 0.059, respectively), but PFS and LPFS were longer in patients with high levels of each (for contrast: median of 20.5 vs. 12.6 mo, P = 0.015, and median not reached vs. 24 mo, P = 0.02; and for busyness: median of 20.5 vs. 12.6 mo, P = 0.01, and median not reached vs. 24 mo, P = 0.006). Neither complexity nor any of the SUV parameters showed significant associations with the survival parameters. In NSCLC, baseline (18)F

  2. [Determinants of survival in HIV patients receiving antiretroviral therapy in Goma, Democratic Republic of Congo].

    Science.gov (United States)

    Akilimali, P Z; Mutombo, P B; Kayembe, P K; Kaba, D K; Mapatano, M A

    2014-06-01

    The study aimed to identify factors associated with the survival of patients receiving antiretroviral therapy. A historic cohort of HIV patients from two major hospitals in Goma (Democratic Republic of Congo) was followed from 2004 to 2012. The Kaplan-Meier method was used to describe the probability of survival as a function of time since inclusion into the cohort. The log-rank test was used to compare survival curves based on determinants. The Cox regression model identified the determinants of survival since treatment induction. The median follow-up time was 3.56 years (IQR=2.22-5.39). The mortality rate was 40 deaths per 1000 person-years. Male gender (RR: 2.56; 95 %CI 1.66-4.83), advanced clinical stage (RR: 2.12; 95 %CI 1.15-3.90), low CD4 count (CD4 < 50) (RR: 2.05; 95 %CI : 1.22-3.45), anemia (RR: 3.95; 95 %CI 2.60-6.01), chemoprophylaxis with cotrimoxazole (RR: 4.29, 95 % CI 2.69-6.86) and period of treatment initiation (2010-2011) (RR: 3.34; 95 %CI 1.24-8.98) were statistically associated with short survival. Initiation of treatment at an early stage of the disease with use of less toxic molecules and an increased surveillance especially of male patients are recommended to reduce mortality. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  3. Intraductal papillary components in invasive ductal carcinoma of the pancreas are associated with long-term survival of patients.

    Science.gov (United States)

    Fukushima, N; Sakamoto, M; Mukai, K; Kanai, Y; Shimada, K; Kosuge, T; Hirohashi, S

    2001-08-01

    Most patients with pancreatic ductal carcinoma have a poor prognosis. However, in certain cases, 5-year survival can be achieved after surgical resection. Analysis of the pathologic findings associated with good survival rates will assist in identifying the optimum treatment. The clinicopathologic features of 67 patients who underwent surgical resection of ductal adenocarcinoma of the pancreas between 1990 and 1996 were reviewed and correlated with survival rates. There were 42 men and 25 women, with a mean age of 62.1 years (range, 44 to 82 years). The mean greatest diameter of the tumor was 4.3 cm (range, 1.5 to 11 cm). Nineteen patients (29.4%) survived more than 3 years, and 9 (13.2%) survived more than 5 years after surgical resection. The intraductal papillary component (IDPC) of the carcinoma was the main focus of the pathologic observations. IDPC was defined as intraductal papillary proliferative lesions seen in the tumor nodule with proliferative cells consistent with carcinomatous cellular atypia. IDPC was clearly present (++) in 24 patients and vaguely present (+) in 9 patients. Using the Mantel-Cox test, a statistically significant correlation was found between the presence of IDPC (either + or ++) and postoperative patient survival (P =.002). IDPC is a morphologic feature associated with longer patient survival and should be taken into consideration in assessing the pathway of tumor progression.

  4. Resolution of bone marrow fibrosis in a patient receiving JAK1/JAK2 inhibitor treatment with ruxolitinib.

    Science.gov (United States)

    Wilkins, Bridget S; Radia, Deepti; Woodley, Claire; Farhi, Sarah El; Keohane, Clodagh; Harrison, Claire N

    2013-12-01

    Ruxolitinib, a JAK1/JAK2 inhibitor, is currently the only pharmacological agent approved for the treatment of myelofibrosis. Approval was based on findings from two phase 3 trials comparing ruxolitinib with placebo (COMFORT-I) and with best available therapy (COMFORT-II) for the treatment of primary or secondary myelofibrosis. In those pivotal trials, ruxolitinib rapidly improved splenomegaly, disease-related symptoms, and quality of life and prolonged survival compared with both placebo and conventional treatments. However, for reasons that are currently unclear, there were only modest histomorphological changes in the bone marrow, and only a subset of patients had significant reductions in JAK2 V617F clonal burden. Here we describe a patient with post-polycythemia vera myelofibrosis who received ruxolitinib at our institution (Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom) as part of the COMFORT-II study. While on treatment, the patient had dramatic improvements in splenomegaly and symptoms shortly after starting ruxolitinib. With longer treatment, the patient had marked reductions in JAK2 V617F allele burden, and fibrosis of the bone marrow resolved after approximately 3 years of ruxolitinib treatment. To our knowledge, this is the first detailed case report of resolution of fibrosis with a JAK1/JAK2 inhibitor. ClinicalTrials.gov Identifier: NCT00934544.

  5. Cannabinoid receptor-2 immunoreactivity is associated with survival in squamous cell carcinoma of the head and neck.

    Science.gov (United States)

    Klein Nulent, Thomas J W; Van Diest, Paul J; van der Groep, Petra; Leusink, Frank K J; Kruitwagen, Cas L J J; Koole, Ronald; Van Cann, Ellen M

    2013-10-01

    The prediction of progression of individual tumours, prognosis, and survival in squamous cell carcinoma (SCC) of the head and neck is difficult. Cannabinoid-1 (CB1) and cannabinoid-2 (CB2) receptor expression is related to survival in several types of cancer, and the aim of this study was to find out whether the expression of CB1 and CB2 receptors is associated with survival in primary SCC of the head and neck. We made immunohistochemical analyses of the cannabinoid receptors on tissue arrays from 240 patients with the disease. Receptor immunoreactivity was classified as none, weak, moderate, or strong staining. Overall survival and disease-specific survival were plotted using Kaplan-Meier survival curves. A multivariate Cox proportional hazard model was created with all the relevant clinical and pathological features. Strong immunoreactivity of the CB2 receptor was significantly associated with reduced disease-specific survival (p=0.007). Cox-proportional hazard ratio (HR) showed that CB2 receptor immunoreactivity contributed to the prediction of survival (HR 3.6, 95% CI 1.5-8.7, p=0.004). Depth of invasion (HR 2.2, 95% CI 1.2-4.2, p=0.01) and vascular invasion (HR 2.5, 95% CI 1.4-4.5, p=0.001) were also associated with survival. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  6. Role of Pre-therapeutic 18F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    Teik Hin Tan

    2016-07-01

    Full Text Available Objective(s: The present study aimed to evaluate the role of pretherapeutic 18fluorine-fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PET-CT and maximum standardized uptake value (SUVmax in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of thepatients.Methods: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy, who underwent pre-operative 18F-FDG PET-CTstaging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted 18F-FDG PET-CT evaluations.The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan–Meier product-limit method.Results: In a total of 40 patients, 18F-FDG PET-CT scan led to changes in disease stage in 26n (65.0% cases, with upstaging and downstaging reported in 10n (25.0% and 16n (40.0% patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the18F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0n (95 % CI 3.0-5.0 months, whereas the median survival in the curative group has not been reached, based on the 12-month followup.Selection of treatment strategy on the basis of 18F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03 and marginally significant at 12 months (P=0.05. On the basisof SUVmax, the relation between survival and SUVmax was not statistically significant.Conclusion: 18F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre

  7. Evaluation of F-18-labeled 5-iodocytidine ({sup 18}F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Pei-Chia; Wu, Chun-Yi; Chang, Wen-Yi; Chang, Wei-Ting [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Alauddin, Mian [Department of Experimental Diagnostic Imaging, MD Anderson Cancer Center, University of Texas, TX, 77054 (United States); Liu, Ren-Shan [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Department of Nuclear Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan (China); Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, 11217, Taiwan (China); Lin, Wuu-Jyh [Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, 32546, Taiwan (China); Chen, Fu-Du [College of Health and Leisure Science, TransWorld University, Yunlin, 64063, Taiwan (China); Chen, Chuan-Lin, E-mail: clchen2@ym.edu.tw [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Wang, Hsin-Ell, E-mail: hewang@ym.edu.tw [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China)

    2011-10-15

    Objective: Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[{sup 18}F]fluoro-{beta}-D-arabinofuranosyl)-5-iodocytosine ({sup 18}F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ({sup 18}F-FIAU) and 2'-deoxy-2'-[{sup 18}F]fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil({sup 18}F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model. Methods: A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of {sup 18}F-FIAC, {sup 18}F-FIAU and {sup 18}F-FEAU were conducted to characterize the biological properties of these tracers. Results: Highly specific uptake of {sup 18}F-FIAC, {sup 18}F-FIAU and {sup 18}F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6{+-}25.1, 76.3{+-}18.2 and 247.2{+-}37.2, respectively. In biodistribution studies, {sup 18}F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with {sup 18}F-FIAU (15.8) but lower than {sup 18}F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor. Conclusion: Our findings suggested that the cytidine analogue {sup 18}F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. {sup 18}F-FIAC may be regarded as the prodrug of {sup 18}F-FIAU in vivo.

  8. Three enzymatically active neurotoxins of Clostridium botulinum strain Af84: BoNT/A2, /F4, and /F5.

    Science.gov (United States)

    Kalb, Suzanne R; Baudys, Jakub; Smith, Theresa J; Smith, Leonard A; Barr, John R

    2014-04-01

    Botulinum neurotoxins (BoNTs) are produced by various species of clostridia and are potent neurotoxins which cause the disease botulism, by cleaving proteins needed for successful nerve transmission. There are currently seven confirmed serotypes of BoNTs, labeled A-G, and toxin-producing clostridia typically only produce one serotype of BoNT. There are a few strains (bivalent strains) which are known to produce more than one serotype of BoNT, producing either both BoNT/A and /B, BoNT/A and /F, or BoNT/B and /F, designated as Ab, Ba, Af, or Bf. Recently, it was reported that Clostridium botulinum strain Af84 has three neurotoxin gene clusters: bont/A2, bont/F4, and bont/F5. This was the first report of a clostridial organism containing more than two neurotoxin gene clusters. Using a mass spectrometry based proteomics approach, we report here that all three neurotoxins, BoNT/A2, /F4, and /F5, are produced by C. botulinum Af84. Label free MS(E) quantification of the three toxins indicated that toxin composition is 88% BoNT/A2, 1% BoNT/F4, and 11% BoNT/F5. The enzymatic activity of all three neurotoxins was assessed by examining the enzymatic activity of the neurotoxins upon peptide substrates, which mimic the toxins' natural targets, and monitoring cleavage of the substrates by mass spectrometry. We determined that all three neurotoxins are enzymatically active. This is the first report of three enzymatically active neurotoxins produced in a single strain of Clostridium botulinum.

  9. Identification of a High-Risk Group Among Patients With Oral Cavity Squamous Cell Carcinoma and pT12N0 Disease

    International Nuclear Information System (INIS)

    Liao, Chun-Ta; Lin, Chien-Yu; Fan, Kang-Hsing; Wang, Hung-Ming; Ng, Shu-Hang; Lee, Li-Yu; Hsueh, Chuen; Chen, I-How; Huang, Shiang-Fu; Kang, Chung-Jan

    2012-01-01

    Purpose: In the American Joint Committee on Cancer 2010 classification system, pT12N0 oral cavity squamous cell carcinoma (OSCC) is considered an early-stage cancer treatable with surgery alone (National Comprehensive Cancer Network 2010 guidelines). Our aim was to evaluate the feasibility of surgery alone for pT12N0 OSCC patients. Methods and Materials: Among 1279 previously untreated OSCC patients referred to our hospital between January 1996 and May 2008, we identified 457 consecutive patients with pT12N0 disease. All had radical tumor excision with neck dissection. A total of 387 patients showing pathologic margins greater than 4 mm and treated by surgery alone were included in the final analysis. All were followed up for at least 24 months after surgery or until death. The 5-year rates of control, distant metastasis, and survival were the main outcome measures. Results: The 5-year rates in the entire group of pT12N0 patients were as follows: local control, 91%; neck control, 92%; distant metastases, 1%; disease-free survival, 85%; disease-specific survival, 93%; and overall survival, 84%. Multivariate analysis identified poor differentiation and pathologic tumor depth of 4 mm or greater as independent risk factors for neck control, disease-free survival, and disease-specific survival. A scoring system using poor differentiation and tumor depth was formulated to define distinct prognostic groups. The presence of both poorly differentiated tumors and a tumor depth of 4 mm or greater resulted in significantly poorer 5-year neck control (p < 0.0001), disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p = 0.0046) rates. Conclusion: The combination of poor differentiation and pathologic tumor depth of 4 mm or greater identified a subset of pT12N0 OSCC patients with poor outcome, who may have clinical benefit from postoperative adjuvant radiotherapy.

  10. Preparation, photoluminescent properties and luminescent dynamics of BaAlF5:Eu2+ nanophosphors

    International Nuclear Information System (INIS)

    Zhang, Wei; Hua, Ruinian; Liu, Tianqing; Zhao, Jun; Na, Liyan; Chen, Baojiu

    2014-01-01

    Graphical abstract: Rice-shaped BaAlF 5 :Eu 2+ nanophosphors were synthesized via one-pot hydrothermal process. The as-prepared BaAlF 5 :Eu 2+ are composed of many particles with an average diameter of 40 nm. When excited at 260 nm, the sharp line emission located at 361 nm of Eu 2+ was observed. The optimum doping concentration of Eu 2+ was confirmed to be 5 mol%. The strong ultraviolet emission of Eu 2+ ions in BaAlF 5 :Eu 2+ nanoparticles suggests that these nanoparticles may have potential applications for sensing, solid-state lasers and spectrometer calibration. - Highlights: • BaAlF 5 :Eu 2+ nanophosphors were synthesized via a mild hydrothermal process. • The Van and Huang models were used to research the mechanism of concentration quenching. • The optimum doping concentration of Eu2+ was confirmed to be 5 mol%. - Abstract: Eu 2+ -doped BaAlF 5 nanophosphors were synthesized via a facile one-pot hydrothermal method. The final products were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and photoluminescence (PL) spectroscopy. XRD results showed that the prepared samples are single-phase. The FE-SEM and TEM images indicated that the prepared BaAlF 5 :Eu 2+ nanophosphors are composed of many rice-shaped particles with an average diameter of 40 nm. When excited at 260 nm, BaAlF 5 :Eu 2+ nanophosphors exhibit the sharp line emissions of Eu 2+ at room temperature. The optimum doping concentration of Eu 2+ was confirmed to be 5 mol%. The Van and Huang models were used to study the mechanism of concentration quenching and the electric dipole–dipole interaction between Eu 2+ can be deduced to be a dominant for quenching fluorescence in BaAlF 5 :Eu 2+ nanophosphors. The strong ultraviolet emission of Eu 2+ in BaAlF 5 :Eu 2+ nanophosphors suggests that these nanoparticles may have potential applications for sensing, spectrometer calibration and solid-state lasers

  11. RECQ1 A159C Polymorphism Is Associated With Overall Survival of Patients With Resected Pancreatic Cancer: A Replication Study in NRG Oncology Radiation Therapy Oncology Group 9704

    Energy Technology Data Exchange (ETDEWEB)

    Li, Donghui, E-mail: dli@mdanderson.org [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Moughan, Jennifer [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Crane, Christopher [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hoffman, John P. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, Maryland (United States); Abrams, Ross A. [Rush University Medical Center, Chicago, Illinois (United States); Safran, Howard [Brown University Oncology Group, Providence, Rhode Island (United States); Liu, Chang; Chang, Ping [Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Freedman, Gary M. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Winter, Kathryn A. [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Guha, Chandan [Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York (United States); Abbruzzese, James L. [Duke University Medical Center, Durham, North Carolina (United States)

    2016-03-01

    Purpose: To confirm whether a previously observed association between RECQ1 A159C variant and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population prospectively treated with postoperative chemoradiation. Methods and Materials: Patients were selected, according to tissue availability, from eligible patients with resected pancreatic cancer who were enrolled on the NRG Oncology Radiation Therapy Oncology Group 9704 trial of 5-fluorouacil (5-FU)-based chemoradiation preceded and followed by 5-FU or gemcitabine. Deoxyribonucleic acid was extracted from paraffin-embedded tissue sections, and genotype was determined using the Taqman method. The correlation between genotype and overall survival was analyzed using a Kaplan-Meier plot, log-rank test, and multivariate Cox proportional hazards models. Results: In the 154 of the study's 451 eligible patients with evaluable tissue, genotype distribution followed Hardy-Weinberg equilibrium (ie, 37% had genotype AA, 43% AC, and 20% CC). The RECQ1 variant AC/CC genotype carriers were associated with being node positive compared with the AA carrier (P=.03). The median survival times (95% confidence interval [CI]) for AA, AC, and CC carriers were 20.6 (16.3-26.1), 18.8 (14.2-21.6), and 14.2 (10.3-21.0) months, respectively. On multivariate analysis, patients with the AC/CC genotypes were associated with worse survival than patients with the AA genotype (hazard ratio [HR] 1.54, 95% CI 1.07-2.23, P=.022). This result seemed slightly stronger for patients on the 5-FU arm (n=82) (HR 1.64, 95% CI 0.99-2.70, P=.055) than for patients on the gemcitabine arm (n=72, HR 1.46, 95% CI 0.81-2.63, P=.21). Conclusions: Results of this study suggest that the RECQ1 A159C genotype may be a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant 5-FU before and after 5-FU-based chemoradiation. Further study is

  12. SURVIVAL OF LUNG CANCER PATIENTS RESIDING IN TOMSK REGION (2004–2013

    Directory of Open Access Journals (Sweden)

    E. L. Choynzonov

    2017-01-01

    Full Text Available A 10-year survival of 3482 lung cancer patients residing in Tomsk region was studied. Based on the populationbased cancer registry data, the observed, corrected and relative survival rates were calculated by the actuarial method taking into consideration age, sex, disease stage and place of residence of the patients. Survival rates were lower in males than in females: the difference in the overall observed survival (OS rate was from 5.1 % (8-year OS to 7.3 % (2-year OS. An inverse relationship between survival and cancer spread was observed. Survival rates were higher for urban populations than for rural populations. The analysis indicated that most lung cancer cases were diagnosed at an advanced stage. Survival rates demonstrated relatively equal levels of cancer care in different regions of Russia. When comparing survival rates in Tomsk region with those in Europe and the USA, it was shown that one-year survival was lower in Tomsk region than in Europe and the USA, thus indicating more effective cancer screening programs in European countries and the USA.

  13. Bi[NC5H3(CO2)2](OH2)xF (x=1 and 2): New one-dimensional Bi-coordination materials—Reversible hydration and topotactic decomposition to α-Bi2O3

    Science.gov (United States)

    Jeon, Hye Rim; Lee, Dong Woo; Ok, Kang Min

    2012-03-01

    Two one-dimensional bismuth-coordination materials, Bi[NC5H3(CO2)2](OH2)xF (x=1 and 2), have been synthesized by hydrothermal reactions using Bi2O3, 2,6-NC5H3(CO2H)2, HF, and water at 180 °C. Structures of the two materials were determined by single-crystal X-ray diffraction. Although they have different crystal structures, both Bi-organic materials shared a common structural motif, a one-dimensional chain structure consisting of Bi3+ cations and pyridine dicarboxylate linkers. Detailed structural analyses include infrared spectroscopy, thermogravimetric analysis, and reversible hydration reactions for the coordinated water molecules were reported. Also, thermal decomposition of the rod-shaped Bi[NC5H3(CO2)2](OH2)F single crystals at 800 °C led to α-Bi2O3 that maintained the same morphology of the original crystals.

  14. Salvage brachytherapy (BT) of 85 T1 T2 oral cavity second head and neck primaries (SHNP) in previously irradiated patients

    International Nuclear Information System (INIS)

    Peiffert, D; Hoffstetter, S; Pernot, M.; Aletti, P.; Luporsi, E.; Kozminski, P.; Lapeyre, M.; Dartois, D.; Bey, P.

    1996-01-01

    The occurrence of a SNHP (20%) represents a major therapeutic dilemma for salvage treatment. BT achieves a local conservative treatment but neglects the node areas. The aim of the study is to evaluate the local control, the late complications, and the survival. Materials and Methods. From 1976 to 1994, 85 patients were treated by salvage BT for a T1 T2 SHNP (38 mobile tongues and 47 floors of mouth). All of them had been previously irradiated for a first head and neck primary by external beam irradiation (80 patients, mean dose = 55 Gy) and/or BT (31 patients, mean dose 39 Gy). A tumour resection had been performed in 33 patients. Results: They were 81 males and 4 females, their mean age was 59 (range 40-80). 78 had infiltrative squamous cell carcinomas, and 7 micro-invasive or intra-epithelial carcinomas. They were 20 T1N0, 17 T2 N0 and 1 T2 N1 mobile tongue, and 39 T1 N0, 8 T2 N0 floor of mouth tumours. The mean follow-up was 46 months (range 1-130). The BT used Ir 192 wires, at low dose rate (mean = 0.58 Gy/h, range 0.3-1.1), and delivered a mean dose of 62 Gy (range 26-70) in the 85% ref. isodose of the Paris System. For the tongue and the floor respectively, the 5 years overall survival was 41% and 26%, and the 5 years specific survival 74% and 94%. The causes of death were respectively the tumour for 32% and 5%, and another primary for 42% and 66%. The local relapse rate was respectively 18% and 8.5%, half of them occurring in the first year of follow-up, the nodal relapses were 8% and 4%. Only one patient developed a distant metastasis. 5 patients developed osteoradionecrosis (3 grade 3 with fracture and/or mandible resection) and 19 soft tissue necrosis (2 grade 3 treated by local excision, and 9 grade 2 treated by hyperbaric 02). 47 patients developed other primaries, especially in the oesophagus (18 patients) explaining the low overall survival. Conclusion: Salvage BT is a useful treatment for T1 T2 oral cavity SHNP occurring in previous irradiated

  15. Haptoglobin 2-2 Genotype, Patient, and Graft Survival in Renal Transplant Recipients

    DEFF Research Database (Denmark)

    Dupont, Laust; Eide, Ivar Anders; Hartmann, Anders

    2017-01-01

    Background: Cardiovascular disease is the leading cause of death in renal transplant recipients. An association between haptoglobin genotype 2-2 and cardiovascular disease has been found in patients with diabetes mellitus and liver transplant recipients. To date, the role of haptoglobin genotype...... after renal transplantation has not been studied. Methods: In this single-center retrospective cohort study of 1975 adult Norwegian transplant recipients, who underwent transplantation between 1999 and 2011, we estimated the risk of all-cause and cardiovascular mortality and overall and death...... transplant recipients, we could not demonstrate any association between haptoglobin 2-2 genotype and patient or graft survival after renal transplantation....

  16. Conditional survival in patients with chronic myeloid leukemia in chronic phase in the era of tyrosine kinase inhibitors.

    Science.gov (United States)

    Sasaki, Koji; Kantarjian, Hagop M; Jain, Preetesh; Jabbour, Elias J; Ravandi, Farhad; Konopleva, Marina; Borthakur, Gautam; Takahashi, Koichi; Pemmaraju, Naveen; Daver, Naval; Pierce, Sherry A; O'Brien, Susan M; Cortes, Jorge E

    2016-01-15

    Tyrosine kinase inhibitors (TKIs) significantly improve survival in patients with chronic myeloid leukemia in chronic phase (CML-CP). Conditional probability provides survival information in patients who have already survived for a specific period of time after treatment. Cumulative response and survival data from 6 consecutive frontline TKI clinical trials were analyzed. Conditional probability was calculated for failure-free survival (FFS), transformation-free survival (TFS), event-free survival (EFS), and overall survival (OS) according to depth of response within 1 year of the initiation of TKIs, including complete cytogenetic response, major molecular response, and molecular response with a 4-log or 4.5-log reduction. A total of 483 patients with a median follow-up of 99.4 months from the initiation of treatment with TKIs were analyzed. Conditional probabilities of FFS, TFS, EFS, and OS for 1 additional year for patients alive after 12 months of therapy ranged from 92.0% to 99.1%, 98.5% to 100%, 96.2% to 99.6%, and 96.8% to 99.7%, respectively. Conditional FFS for 1 additional year did not improve with a deeper response each year. Conditional probabilities of TFS, EFS, and OS for 1 additional year were maintained at >95% during the period. In the era of TKIs, patients with chronic myeloid leukemia in chronic phase who survived for a certain number of years maintained excellent clinical outcomes in each age group. Cancer 2016;122:238-248. © 2015 American Cancer Society. © 2015 American Cancer Society.

  17. Transcriptional regulation of human RANK ligand gene expression by E2F1

    International Nuclear Information System (INIS)

    Hu Yan; Sun Meng; Nadiminty, Nagalakshmi; Lou Wei; Pinder, Elaine; Gao, Allen C.

    2008-01-01

    Receptor activator of nuclear factor kappa B ligand (RANKL) is a critical osteoclastogenic factor involved in the regulation of bone resorption, immune function, the development of mammary gland and cardiovascular system. To understand the transcriptional regulation of RANKL, we amplified and characterized a 1890 bp 5'-flanking sequence of human RANKL gene (-1782 bp to +108 bp relative to the transcription start site). Using a series of deletion mutations of the 1890 bp RANKL promoter, we identified a 72 bp region (-172 to -100 bp) mediating RANKL basal transcriptional activity. Sequence analysis revealed a putative E2F binding site within this 72 bp region in the human RANKL promoter. Overexpression of E2F1 increased RANKL promoter activity, while down-regulation of E2F1 expression by small interfering RNA decreased RANKL promoter activity. RT-PCR and enzyme linked immunosorbent assays (ELISA) further demonstrated that E2F1 induced the expression of RANKL. Electrophoretic gel mobility shift assays (EMSA) and antibody competition assays confirmed that E2F1 proteins bind to the consensus E2F binding site in the RANKL promoter. Mutation of the E2F consensus binding site in the RANKL promoter profoundly reduced the basal promoter activity and abolished the transcriptional modulation of RANKL by E2F1. These results suggest that E2F1 plays an important role in regulating RANKL transcription through binding to the E2F consensus binding site

  18. Inhibition of Secretory Phospholipase A(2) in Patients with Acute Coronary Syndromes: Rationale and Design of the Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16) Trial

    NARCIS (Netherlands)

    Nicholls, Stephen J.; Cavender, Matthew A.; Kastelein, John J. P.; Schwartz, Gregory; Waters, David D.; Rosenson, Robert S.; Bash, Dianna; Hislop, Colin

    2012-01-01

    Background The action of secretory phospholipase A(2) (sPLA(2)) on lipoproteins may render them more susceptible to oxidation, thereby promoting vascular inflammation and increasing cardiovascular risk. Patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events

  19. Synthesis of carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine derivatives as new potential PET tracers for imaging of p38α mitogen-activated protein kinase.

    Science.gov (United States)

    Wang, Min; Gao, Mingzhang; Zheng, Qi-Huang

    2014-08-15

    The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10b) and corresponding precursors 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic acid in multiple steps with moderate to excellent yields. The target tracer [(11)C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10a) and [(11)C]methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10b) were prepared from their corresponding precursors with [(11)C]CH3OTf under basic condition through O-[(11)C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields at end of bombardment (EOB) with 185-555 GBq/μmol specific activity at end of synthesis (EOS). Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Metabolic tumor burden quantified on [{sup 18}F]FDG PET/CT improves TNM staging of lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Lapa, Paula; Isidoro, Jorge; Costa, Gracinda [Centro Hospitalar e Universitario de Coimbra, Nuclear Medicine Department, Coimbra (Portugal); Oliveiros, Barbara [University of Coimbra, Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine, Coimbra (Portugal); University of Coimbra, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, Coimbra (Portugal); Marques, Margarida [University of Coimbra, Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine, Coimbra (Portugal); Centro Hospitalar e Universitario de Coimbra, Technology and Information Systems Department, Coimbra (Portugal); Caseiro Alves, Filipe [Centro Hospitalar e Universitario de Coimbra, Radiology Department, Coimbra (Portugal); Nascimento Costa, J.M. [University of Coimbra, University Oncology Clinic, Faculty of Medicine, Coimbra (Portugal); Lima, Joao Pedroso de [Centro Hospitalar e Universitario de Coimbra, Nuclear Medicine Department, Coimbra (Portugal); University of Coimbra, Institute of Nuclear Sciences Applied to Health-ICNAS, Coimbra (Portugal)

    2017-12-15

    The purpose of our study was to test a new staging algorithm, combining clinical TNM staging (cTNM) with whole-body metabolic active tumor volume (MATV-WB), with the goal of improving prognostic ability and stratification power. Initial staging [{sup 18}F]FDG PET/CT of 278 non-small cell lung cancer (NSCLC) patients, performed between January/2011 and April/2016, 74(26.6%) women, 204(73.4%) men; aged 34-88 years (mean ± SD:66 ± 10), was retrospectively evaluated, and MATV-WB was quantified. Each patient's follow-up time was recorded: 0.7-83.6 months (mean ± SD:25.1 ± 20.3). MATV-WB was an independent and statistically-significant predictor of overall survival (p < 0.001). The overall survival predictive ability of MATV-WB (C index: mean ± SD = 0.7071 ± 0.0009) was not worse than cTNM (C index: mean ± SD = 0.7031 ± 0.007) (Z = -0.143, p = 0.773). Estimated mean survival times of 56.3 ± 3.0 (95%CI:50.40-62.23) and 21.7 ± 2.2 months (95%CI:17.34-25.98) (Log-Rank = 77.48, p < 0.001), one-year survival rate of 86.8% and of 52.8%, and five-year survival rate of 53.6% and no survivors, were determined, respectively, for patients with MATV-WB < 49.5 and MATV-WB ≥ 49.5. Patients with MATV-WB ≥ 49.5 had a mortality risk 2.9-5.8 times higher than those with MATV-WB < 49.5 (HR = 4.12, p < 0.001). MATV-WB cutoff points were also determined for each cTNM stage: 23.7(I), 49.5(II), 52(III), 48.8(IV) (p = 0.029, p = 0.227, p = 0.025 and p = 0.001, respectively). At stages I, III and IV there was a statistically-significant difference in the estimated mean overall survival time between groups of patients defined by the cutoff points (p = 0.007, p = 0.004 and p < 0.001, respectively). At stage II (p = 0.365), there was a clinically-significant difference of about 12 months between the groups. In all cTNM stages, patients with MATV-WB ≥ cutoff points had lower survival rates. Combined clinical TNM-PET staging (cTNM-P) was then tested: Stage I < 23.7; Stage I

  1. Survival of Idiopathic Pulmonary Arterial Hypertension Patients in the Modern Era in Australia and New Zealand.

    Science.gov (United States)

    Strange, Geoff; Lau, Edmund M; Giannoulatou, Eleni; Corrigan, Carolyn; Kotlyar, Eugene; Kermeen, Fiona; Williams, Trevor; Celermajer, David S; Dwyer, Nathan; Whitford, Helen; Wrobel, Jeremy P; Feenstra, John; Lavender, Melanie; Whyte, Kenneth; Collins, Nicholas; Steele, Peter; Proudman, Susanna; Thakkar, Vivek; Keating, Dominic; Keogh, Anne

    2017-09-20

    Epidemiology and treatment strategies continue to evolve in pulmonary arterial hypertension (PAH). We sought to define the characteristics and survival of patients with idiopathic, heritable and drug-induced PAH in the current management era. Consecutive cases of idiopathic, heritable and drug-induced PAH were prospectively enrolled into an Australian and New Zealand Registry. Between January 2012 and December 2016, a total of 220 incident cases were enrolled (mean age 57.2±18.7years, female 69.5%) and followed for a median duration of 26 months (IQR17-39). Co-morbidities were common such as obesity (34.1%), systemic hypertension (30.5%), coronary artery disease (16.4%) and diabetes mellitus (19.5%). Initial combination therapy was used in 54 patients (dual, n=50; triple, n=4). Estimated survival rates at 1-year, 2-years and 3-years were 95.6% (CI 92.8-98.5%), 87.3% (CI 82.5-92.4%) and 77.0% (CI 70.3-84.3%), respectively. Multivariate analysis showed that male sex and lower 6-minute distance at diagnosis independently predicted worse survival, whereas obesity was associated with improved survival. Co-morbidities other than obesity did not impact survival. Initial dual oral combination therapy was associated with a trend towards better survival compared with initial oral monotherapy (adjusted HR=0.27, CI 0.06-1.18, p=0.082) CONCLUSIONS: The epidemiology and survival of patients with idiopathic PAH in Australia and New Zealand are similar to contemporary registries reported in Europe and North America. Male sex and poorer exercise capacity are predictive of mortality whereas obesity appears to exert a protective effect. Despite current therapies, PAH remains a life-threatening disease associated with significant early mortality. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

  2. Factors associated with improved survival among older colorectal cancer patients in the US: a population-based analysis

    Directory of Open Access Journals (Sweden)

    Earle Craig C

    2009-07-01

    Full Text Available Abstract Background The purpose of this study was to estimate the relative impact of changes in demographics, stage at detection, treatment mix, and medical technology on 5-year survival among older colorectal cancer (CRC patients. Methods We selected older patients diagnosed with CRC between 1992 and 2000 from the SEER-Medicare database and followed them through 2005. Trends in demographic characteristics, stage at detection and initial treatment mix were evaluated descriptively. Separate multivariate logistic regression models for colon (CC and rectal cancer (RC patients were estimated to isolate the independent effects of these factors along with technological change (proxied by cohort year on 5-year survival. Results Our sample included 37,808 CC and 13,619 RC patients (combined mean ± SD age: 77.2 ± 7.0 years; 55% female; 87% white. In recent years, more CC patients were diagnosed at Stage I and fewer at Stages II and IV, and more RC patients were diagnosed at Stage I and fewer at Stages II and III. CC and RC patients diagnosed in later years were slightly older with somewhat better Charlson scores and were more likely to be female, from the Northeast, and from areas with higher average education levels. Surgery alone was more common in later years for CC patients while combined surgery, chemotherapy, and radiotherapy was more common for RC patients. Between 1992 and 2000, 5-year observed survival improved from 43.0% to 46.3% for CC patients and from 39.4% to 42.2% for RC patients. Multivariate logistic regressions indicate that patients diagnosed in 2000 had significantly greater odds of 5-year survival than those diagnosed in 1992 (OR: 1.35 for CC, 1.38 for RC. Our decomposition suggests that early detection had little impact on survival; rather, technological improvements (e.g., new medical technologies or more effective use of existing technologies and changing demographics were responsible for the largest share of the change in 5

  3. Survival affects decision making for fenestrated and branched endovascular aortic repair.

    Science.gov (United States)

    Beach, Jocelyn M; Rajeswaran, Jeevanantham; Parodi, F Ezequiel; Kuramochi, Yuki; Brier, Corey; Blackstone, Eugene; Eagleton, Matthew J

    2018-03-01

    Repair options for complex abdominal and thoracoabdominal aortic aneurysms (TAAAs) are evolving with increased experience and availability of less invasive endovascular techniques. Identifying risk factors for mortality after fenestrated and branched endovascular aortic repair (F/B-EVAR) could improve patient selection and facilitate decision making regarding who may benefit from prophylactic F/B-EVAR. We evaluated 1091 patients in a prospective investigational device exemption trial who underwent F/B-EVAR from August 2001 to June 2015 for complex aortic aneurysms (CAAs). Multivariable analysis of risk factors for death was performed using a nonproportional hazards model and a nonparametric analysis using random survival forest technology. Operative mortality after F/B-EVAR was low (3.7%), with high CAA-related survival at 30 day and 5 years (96.8% and 94.0%, respectively). All-cause 5-year survival, however, was 46.2% and older age, heart failure, chronic obstructive pulmonary disease, renal disease, anemia, and coagulation disorders were risk factors. Risk was highest for those undergoing type I/II TAAA repairs and those with larger aneurysms. Patients with multiple comorbidities and those undergoing type I or II TAAA repair are at greatest risk of mortality; however, in this high-risk population, F/B-EVAR offers greater survival compared with that reported for the natural history of untreated aneurysms. Operative and early mortality is lower than the best-reported open repair outcomes, even in this high-risk population, suggesting a potential benefit in extending the use of F/B-EVAR to low-to-average risk CAA patients. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  4. Ho3+/Yb3+ co-doped TeO2-BaF2-Y2O3 glasses for ∼1.2 μm laser applications

    Science.gov (United States)

    Wang, Shunbin; Li, Chengzhi; Yao, Chuanfei; Jia, Shijie; Jia, Zhixu; Qin, Guanshi; Qin, Weiping

    2017-02-01

    Intense ∼1.2 μm fluorescence is observed in Ho3+/Yb3+ co-doped TeO2-BaF2-Y2O3 glasses under 915 nm laser diode excitation. The 1.2 μm emission can be ascribed to the transition 5I6→5I8 of Ho3+. With the introducing of BaF2, the content of OH in the glasses drops markedly, and the 1.2 μm emission intensity increases gradually as increasing the concentration percentage of BaF2. Furthermore, microstructured fibers based on the TeO2-BaF2-Y2O3 glasses are fabricated by using a rod-in-tube method, and a relative positive gain of ∼9.42 dB at 1175.3 nm is obtained in a 5 cm long fiber.

  5. Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): Phase 2 study results.

    Science.gov (United States)

    Amin, Asim; Dudek, Arkadiusz Z; Logan, Theodore F; Lance, Raymond S; Holzbeierlein, Jeffrey M; Knox, Jennifer J; Master, Viraj A; Pal, Sumanta K; Miller, Wilson H; Karsh, Lawrence I; Tcherepanova, Irina Y; DeBenedette, Mark A; Williams, W Lee; Plessinger, Douglas C; Nicolette, Charles A; Figlin, Robert A

    2015-01-01

    AGS-003 is an autologous immunotherapy prepared from fully matured and optimized monocyte-derived dendritic cells, which are co-electroporated with amplified tumor RNA plus synthetic CD40L RNA. AGS-003 was evaluated in combination with sunitinib in an open label phase 2 study in intermediate and poor risk, treatment naïve patients with metastatic clear cell renal cell carcinoma (mRCC). Twenty-one intermediate and poor risk patients were treated continuously with sunitinib (4 weeks on, 2 weeks off per 6 week cycle). After completion of the first cycle of sunitinib, patients were treated with AGS-003 every 3 weeks for 5 doses, then every 12 weeks until progression or end of study. The primary endpoint was to determine the complete response rate. Secondary endpoints included clinical benefit, safety, progression free survival (PFS) and overall survival (OS). Immunologic response was also monitored. Thirteen patients (62%) experienced clinical benefit (9 partial responses, 4 with stable disease); however there were no complete responses in this group of intermediate and poor risk mRCC patients and enrollment was terminated early. Median PFS from registration was 11.2 months (95% CI 6.0, 19.4) and the median OS from registration was 30.2 months (95% CI 9.4, 57.1) for all patients. Seven (33%) patients survived for at least 4.5 years, while five (24%) survived for more than 5 years, including 2 patients who remain progression-free with durable responses for more than 5 years at the time of this report. AGS-003 was well tolerated with only mild injection-site reactions. The most common adverse events were related to expected toxicity from sunitinib therapy. In patients who had sequential samples available for immune monitoring, the magnitude of the increase in the absolute number of CD8(+) CD28(+) CD45RA(-) effector/memory T cells (CTLs) after 5 doses of AGS-003 relative to baseline, correlated with overall survival. AGS-003 in combination with sunitinib was

  6. CYB5D2 requires heme-binding to regulate HeLa cell growth and confer survival from chemotherapeutic agents.

    Directory of Open Access Journals (Sweden)

    Anthony Bruce

    Full Text Available The cytochrome b5 domain containing 2 (CYB5D2; Neuferricin protein has been reported to bind heme, however, the critical residues responsible for heme-binding are undefined. Furthermore, the relationship between heme-binding and CYB5D2-mediated intracellular functions remains unknown. Previous studies examining heme-binding in two cytochrome b5 heme-binding domain-containing proteins, damage-associated protein 1 (Dap1; Saccharomyces cerevisiae and human progesterone receptor membrane component 1 (PGRMC1, have revealed that conserved tyrosine (Y 73, Y79, aspartic acid (D 86, and Y127 residues present in human CYB5D2 may be involved in heme-binding. CYB5D2 binds to type b heme, however, only the substitution of glycine (G at D86 (D86G within its cytochrome b5 heme-binding (cyt-b5 domain abolished its heme-binding ability. Both CYB5D2 and CYB5D2(D86G localize to the endoplasmic reticulum. Ectopic CYB5D2 expression inhibited cell proliferation and anchorage-independent colony growth of HeLa cells. Conversely, CYB5D2 knockdown and ectopic CYB5D2(D86G expression increased cell proliferation and colony growth. As PGRMC1 has been reported to regulate the expression and activities of cytochrome P450 proteins (CYPs, we examined the role of CYB5D2 in regulating the activities of CYPs involved in sterol synthesis (CYP51A1 and drug metabolism (CYP3A4. CYB5D2 co-localizes with cytochrome P450 reductase (CYPOR, while CYB5D2 knockdown reduced lanosterol demethylase (CYP51A1 levels and rendered HeLa cells sensitive to mevalonate. Additionally, knockdown of CYB5D2 reduced CYP3A4 activity. Lastly, CYB5D2 expression conferred HeLa cell survival from chemotherapeutic agents (paclitaxel, cisplatin and doxorubicin, with its ability to promote survival being dependent on its heme-binding ability. Taken together, this study provides evidence that heme-binding is critical for CYB5D2 in regulating HeLa cell growth and survival, with endogenous CYB5D2 being required to

  7. Survival of patients with hepatocellular carcinoma in the San Joaquin Valley: a comparison with California Cancer Registry data.

    Science.gov (United States)

    Atla, Pradeep R; Sheikh, Muhammad Y; Mascarenhas, Ranjan; Choudhury, Jayanta; Mills, Paul

    2012-01-01

    Variation in the survival of patients with hepatocellular carcinoma (HCC) is related to racial differences, socioeconomic disparities and treatment options among different populations. A retrospective review of the data from medical records of patients diagnosed with HCC were analyzed at an urban tertiary referral teaching hospital and compared to patients in the California Cancer Registry (CCR) - a participant in the Survival Epidemiology and End Results (SEER)program of the National Cancer Institute (NCI). The main outcome measure was overall survival rates. 160 patients with the diagnosis of HCC (M/F=127/33), mean age 59.7±10 years, 32% white, 49% Hispanic, 12% Asian and 6% African American. Multivariate analysis identified tumor size, model for end-stage liver disease (MELD) score, portal vein invasion and treatment offered as the independent predictors of survival (p <0.05). Survival rates across racial groups were not statistically significant. 5.6% received curative treatments (orthotopic liver transplantation, resection, rediofrequency ablation) (median survival 69 months), 34.4% received nonsurgical treatments (trans-arterial chemoembolization, systemic chemotherapy) (median survival 9 months), while 60% received palliative or no treatment (median survival 3 months) (p <0.001). There was decreased survival in our patient population with HCC beyond 2 years. 60% of our study population received only palliative or no treatment suggesting a possible lack of awareness of chronic liver disease as well as access to appropriate surveillance modalities. Ethnic disparities such as Hispanic predominance in this study in contrast to the CCR/SEER database may have been a contributing factor for poorer outcome.

  8. Trastuzumab and survival of patients with metastatic breast cancer.

    Science.gov (United States)

    Kast, Karin; Schoffer, Olaf; Link, Theresa; Forberger, Almuth; Petzold, Andrea; Niedostatek, Antje; Werner, Carmen; Klug, Stefanie J; Werner, Andreas; Gatzweiler, Axel; Richter, Barbara; Baretton, Gustavo; Wimberger, Pauline

    2017-08-01

    Prognosis of Her2-positive breast cancer has changed since the introduction of trastuzumab for treatment in metastatic and early breast cancer. It was described to be even better compared to prognosis of Her2-negative metastatic breast cancer. The purpose of this study was to evaluate the effect of trastuzumab in our cohort. Besides the effect of adjuvant pretreatment with trastuzumab on survival of patients with metastatic Her2-positive breast cancer was analyzed. All patients with primary breast cancer of the Regional Breast Cancer Center Dresden diagnosed during the years 2001-2013 were analyzed for treatment with or without trastuzumab in the adjuvant and in the metastatic treatment setting using Kaplan-Meier survival estimation and Cox regression. Age and tumor stage at time of first diagnosis of breast cancer as well as hormone receptor status, grading, time, and site of metastasis at first diagnosis of distant metastatic disease were analyzed. Of 4.481 female patients with primary breast cancer, 643 presented with metastatic disease. Her2-positive status was documented in 465 patients, including 116 patients with primary or secondary metastases. Median survival of patients with Her2-positive primary metastatic disease was 3.0 years (95% CI 2.3-4.0). After adjustment for other factors, survival was better in patients with Her2-positive breast cancer with trastuzumab therapy compared to Her2-negative metastatic disease (HR 2.10; 95% CI 1.58-2.79). Analysis of influence of adjuvant therapy with and without trastuzumab by Kaplan-Meier showed a trend for better survival in not pretreated patients. Median survival was highest in hormone receptor-positive Her2-positive (triple-positive) primary metastatic breast cancer patients with 3.3 years (95% CI 2.3-4.6). Prognosis of patients with Her2-positive metastatic breast cancer after trastuzumab treatment is more favorable than for Her2-negative breast cancer. The role of adjuvant chemotherapy with or without

  9. Molecular and functional characterisation of E2F-5, a new member of the E2F family

    NARCIS (Netherlands)

    Buck, V.; Allen, K.E.; Sørensen, T.; Bybee, A.; Hijmans, E.M.; Voorhoeve, P.M.; Bernards, R.A.; Thangue, N.B. La

    1995-01-01

    The transcription factor DRTF1/E2F is implicated in the control of cellular proliferation due to its interaction with key regulators of cell cycle progression, such as the retinoblastoma tumour suppressor gene product and related pocket proteins, cyclins and cyclin-dependent kinases. DRTF1/E2F DNA

  10. Prognostic Value of Metabolic Activity Measured by 18F-FDG PET/CT in Patients with Advanced Endometrial Cancer

    International Nuclear Information System (INIS)

    Kim, Hyun Jeong; Choi, Jiyoun; Jeong, Yong Hyu; Jo, Kwan Hyeong; Lee, Jaehoon; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Young Tae; Kang, Won Jun

    2013-01-01

    We evaluated the potential prognostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with stage IIIC/IV endometrial cancer. Patients with stage IIIC/IV endometrial cancer who had undergone FDG PET/CT workup for staging were enrolled. Maximum standardized uptake values (SUV max ) measured from regions of interest (ROIs) of the primary tumor (SUVt) and lymph nodes (SUVn) were correlated with overall survival (OS). The SUVn was defined as the highest SUV max of the metastatic lymph nodes. Survival probability was assessed using the Kaplan-Meier method. A total of 42 patients with a median age of 55.5 years (range 32-76 years) were included. Twenty-nine percent (n =12) of patients were premenopausal and 71 % (n =30) were postmenopausal. The average SUVt was 12.9 (range 1.8-36.5), and the average SUVn was 7.3 (range 2.0-22.5). Median follow-up time was 25.9 months (range 1.84 months). Using a SUVt of 9.5 as a cutoff value, two groups with different rates were determined (P=0.026). In addition, patients with a low SUVn had significantly better OS than those with a high SUVn (P=0.003). Patients in the International Federation of Obstetrics and Gynecology (FIGO) stage IV group with SUVt≥9.5 or SUVn≥7.3 showed a significantly longer OS than the other groups. FDG uptake of primary endometrial cancer and lymph nodes might be a prognostic factor in advanced endometrial cancer. More aggressive therapy could be considered in patients with stage IV endometrial cancer and high SUVt and/or high SUVn

  11. Survival Pattern of Hodgkin Lymphoma Patients in the Last 25 Years in Lebanon.

    Science.gov (United States)

    Massoud, Marcel; Kerbage, Fouad; Nehme, Joseph; Sakr, Riwa; Rached, Layale; Zeghondy, Jean; Nasr, Fady; Chahine, Georges

    2017-07-01

    After the emergence of combination chemotherapy in 1960s, survival of patients with Hodgkin lymphoma (HL) has dramatically improved worldwide. We lack studies that document the favorable evolution of survival regarding this disease in Lebanon. To compare the overall survival in HL over 3 different decades in Lebanon. We retrospectively reviewed the charts of 196 patients diagnosed with HL, treated and followed from 1990 to 2015 in our center. Patients were divided into 3 groups according to period of analysis: group A (1990-1999), group B (2000-2009), and group C (2010-2015). We studied the characteristics and survival patterns of patients in each group. The male-to-female sex ratio was 1.06. The median age at diagnosis was 33 years in group A, 30.4 in group B, and 33.12 in group C (P = .6). Results showed variations in the subtypes of the disease according to the following: nodular-sclerosis HL 59.5% in group A, 76.2% in group B, and 85.4% in group C. Mixed cellularity HL 21.6% in group A, 2.4% in group B, and 73.7% in group C (P = .0001). Patients presented with localized disease in 58.6%, 73.7%, and 56.4% in groups A, B, and C, respectively (P = .173). Complete remission was achieved in 76.5% in group A, 85.3% in group B, and 69.5% in group C (P = .007). The survival rate at 5 years in group A was 91%, 94% in group B, and 100% in group C. The survival of patients with HL has dramatically improved over the past 25 years in Lebanon. These results resemble those achieved in Western countries due to the fast adoption of new molecular imaging technologies at diagnosis and follow-up and the rapid approval of new drugs for relapse in the Lebanese market. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Comparison of survival of patients with metastases from known versus unknown primaries: survival in metastatic cancer

    Directory of Open Access Journals (Sweden)

    Riihimäki Matias

    2013-01-01

    Full Text Available Abstract Background Cancer of unknown primary site (CUP is considered an aggressive metastatic disease but whether the prognosis differs from metastatic cancers of known primary site is not known. Such data may give insight into the biology of CUP and the metastatic process in general. Methods 6,745 cancer patients, with primary metastatic cancer at diagnosis, were identified from the Swedish Cancer Registry, and were compared with 2,881 patients with CUP. Patients were diagnosed and died between 2002 and 2008. The influence of the primary site, known or unknown, on survival in patients with metastases at specific locations was investigated. Hazard ratios (HRs of death were estimated for several sites of metastasis, where patients with known primary sites were compared with CUP patients. Results Overall, patients with metastatic cancers with known primary sites had decreased hazards of death compared to CUP patients (HR = 0.69 [95% CI = 0.66–0.72]. The exceptions were cancer of the pancreas (1.71 [1.54–1.90], liver (1.58 [1.36–1.85], and stomach (1.16 [1.02–1.31]. For individual metastatic sites, patients with liver or bone metastases of known origin had better survival than those with CUP of the liver and bone. Patients with liver metastases of pancreatic origin had an increased risk of death compared with patients with CUP of the liver (1.25 [1.06–1.46]. The median survival time of CUP patients was three months. Conclusions Patients with CUP have poorer survival than patients with known primaries, except those with brain and respiratory system metastases. Of CUP sites, liver metastases had the worst prognosis. Survival in CUP was comparable to that in metastatic lung cancer. The aggressive behavior of CUP may be due to initial immunosuppression and immunoediting which may allow accumulation of mutations. Upon escape from the suppressed state an unstoppable tumor spread ensues. These novel data on the epidemiology of the

  13. Secretory Phospholipase A2-IIA and Cardiovascular Disease: A Mendelian Randomization Study

    NARCIS (Netherlands)

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, André G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Paré, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is

  14. 5-year survival and rehospitalization due to stroke recurrence among patients with hemorrhagic or ischemic strokes in Singapore.

    Science.gov (United States)

    Sun, Yan; Lee, Sze Haur; Heng, Bee Hoon; Chin, Vivien S

    2013-10-03

    Stroke is the 4th leading cause of death and 1st leading cause of disability in Singapore. However the information on long-term post stroke outcomes for Singaporean patients was limited. This study aimed to investigate the post stroke outcomes of 5-year survival and rehospitalization due to stroke recurrence for hemorrhagic and ischemic stroke patients in Singapore. The outcomes were stratified by age, ethnic group, gender and stroke types. The causes of death and stroke recurrence were also explored in the study. A multi-site retrospective cohort study. Patients admitted for stroke at any of the three hospitals in the National Healthcare Group of Singapore were included in the study. All study patients were followed up to 5 years. Kaplan-Meier was applied to study the time to first event, death or rehospitalization due to stroke recurrence. Cox proportional hazard model was applied to study the time to death with adjustment for stroke type, age, sex, ethnic group, and admission year. Cumulative incidence model with competing risk was applied for comparing the risks of rehospitalization due to stroke recurrence with death as the competing risk. Totally 12,559 stroke patients were included in the study. Among them, 59.3% survived for 5 years; 18.4% were rehospitalized due to stroke recurrence in 5 years. The risk of stroke recurrence and mortality increased with age in all stroke types. Gender, ethnic group and admitting year were not significantly associated with the risk of mortality or stroke recurrence in hemorrhagic stroke. Male or Malay patient had higher risk of stroke recurrence and mortality in ischemic stroke. Hemorrhagic stroke had higher early mortality while ischemic stroke had higher recurrence and late mortality. The top cause of death among died stroke patients was cerebrovascular diseases, followed by pneumonia and ischemic heart diseases. The recurrent stroke was most likely to be the same type as the initial stroke among rehospitalized stroke

  15. RETINOBLASTOMA IN INDIA: Clinical Presentation and Outcome in 1,457 Patients (2,074 Eyes).

    Science.gov (United States)

    Kaliki, Swathi; Patel, Anamika; Iram, Sadiya; Ramappa, George; Mohamed, Ashik; Palkonda, Vijay A R

    2017-11-23

    To study the clinical presentation, treatment, and outcome of patients with retinoblastoma (RB) in India. Retrospective study of 1,457 patients with RB (2,074 eyes). The mean age at presentation of RB was 29 months (median, 24 months; range, presentation of RB in 57% (n = 834) and bilateral in 43% (n = 623). Familial RB was present in 4% (n = 55). The most common presenting complaints included leukocoria (n = 1,100; 75%), proptosis (n = 91; 6%), strabismus (n = 77; 5%), and red eye (n = 68; 5%). Most (n = 1,889; 91%) tumors were intraocular in location, and 185 (n = 185; 9%) had extraocular tumor extension at presentation. The most common modalities of primary treatment-included systemic chemotherapy (n = 1,171; 60%) and enucleation (n = 674; 35%). At a mean follow-up period of 44 months (median, 30 months; range, 3-234 months), 92% (n = 1,206) were alive, and 108 (8%) patients died because of RB. Based on Kaplan-Meier analysis, the survival at 1, 3, 5, and 10 years was 94%, 91%, 90%, and 89%, respectively. The most common presenting signs of RB in Asian Indian population are leukocoria and proptosis. With appropriate treatment, the survival rate is favorable at 92%.

  16. Radical prostatectomy and adjuvant radioactive gold seed placement: Results of treatment at 5 and 10 years for clinical stages A2, B1 and B2 cancer of the prostate

    International Nuclear Information System (INIS)

    Kwon, E.D.; Loening, S.A.; Hawtrey, C.E.

    1991-01-01

    Between 1977 and 1988, 131 patients with adenocarcinoma of the prostate underwent combined radical prostatectomy and intraoperative radioactive gold seed placement. Of these 131 patients 80 were clinically assessed as having stage A2 (12), B1 (43) or B2 (25) cancer and they are the subject of this review. The average dose of radioactivity administered to each patient was 96.6 mCi, and mean followup was 65 months (median 64 months). No patient in this series received any other form of adjuvant therapy until disease recurrence was demonstrated. Local recurrences were observed in 2 patients (2.5%) in this series while distant recurrences were observed in 10 (12.5%). Cancer specific survival free of disease at 5 years was 100% for clinical stage A2, 91% for B1 and 75% for B2 cancers. The 10-year survival free of disease was 100% for clinical stage A2, 82% for B1 and 68% for B2 cancers. Covariants of clinical stage and seminal vesicle involvement influenced survival free of disease in a statistically significant manner (p less than 0.05) while pathological stage and degree of tumor differentiation did not. Mild to severe complications were observed in 12 patients (15%). Intraoperative placement of radioactive gold seeds into unresected pelvic tissues surrounding the site of prostatectomy offers a theoretical advantage in treatment by delivering tumoricidal levels of irradiation to residual foci of cancer not appreciated at the time of surgery. Our results suggest that increases in cancer specific survival free of disease over that previously reported for prostatectomy alone may be achieved through this combined treatment regimen. Furthermore, it is our opinion that therapeutic gains can be achieved without the attendant increases in morbidity and treatment delay often associated with adjuvant external beam radiotherapy

  17. Electric conductivity of double fluorides in the systems M1F-Th(U)F4(M1=K, Tl) and M2F2-ThF4(M2=Ca, Sr, Ba)

    International Nuclear Information System (INIS)

    Murin, I.V.; Andreev, A.M.; Amelin, Yu.V.

    1982-01-01

    The temperature dependence of electric conductivity of some double fluorides formed in the systems M 1 F-Th(U)F 4 (M 1 =K, Tl) and M 2 F 2 -ThF 4 (M 2 =Ca, Sr, Ba) as well as UF 3 in a wide temperature range is studied. It is shown that the values of electric conductivity and activation energy of these fluorides depend on the compound structure and cation nature. The temperature electric conductivity dependence for double fluorides with the tysonite structure is close to the lanthanum fluoride dependence. Taking into account low electron electric conductivity component the conclusion is drawn that the investigated compounds can be used as solid electrolytes

  18. Exponential Decay Nonlinear Regression Analysis of Patient Survival Curves: Preliminary Assessment in Non-Small Cell Lung Cancer

    Science.gov (United States)

    Stewart, David J.; Behrens, Carmen; Roth, Jack; Wistuba, Ignacio I.

    2010-01-01

    Background For processes that follow first order kinetics, exponential decay nonlinear regression analysis (EDNRA) may delineate curve characteristics and suggest processes affecting curve shape. We conducted a preliminary feasibility assessment of EDNRA of patient survival curves. Methods EDNRA was performed on Kaplan-Meier overall survival (OS) and time-to-relapse (TTR) curves for 323 patients with resected NSCLC and on OS and progression-free survival (PFS) curves from selected publications. Results and Conclusions In our resected patients, TTR curves were triphasic with a “cured” fraction of 60.7% (half-life [t1/2] >100,000 months), a rapidly-relapsing group (7.4%, t1/2=5.9 months) and a slowly-relapsing group (31.9%, t1/2=23.6 months). OS was uniphasic (t1/2=74.3 months), suggesting an impact of co-morbidities; hence, tumor molecular characteristics would more likely predict TTR than OS. Of 172 published curves analyzed, 72 (42%) were uniphasic, 92 (53%) were biphasic, 8 (5%) were triphasic. With first-line chemotherapy in advanced NSCLC, 87.5% of curves from 2-3 drug regimens were uniphasic vs only 20% of those with best supportive care or 1 drug (p<0.001). 54% of curves from 2-3 drug regimens had convex rapid-decay phases vs 0% with fewer agents (p<0.001). Curve convexities suggest that discontinuing chemotherapy after 3-6 cycles “synchronizes” patient progression and death. With postoperative adjuvant chemotherapy, the PFS rapid-decay phase accounted for a smaller proportion of the population than in controls (p=0.02) with no significant difference in rapid-decay t1/2, suggesting adjuvant chemotherapy may move a subpopulation of patients with sensitive tumors from the relapsing group to the cured group, with minimal impact on time to relapse for a larger group of patients with resistant tumors. In untreated patients, the proportion of patients in the rapid-decay phase increased (p=0.04) while rapid-decay t1/2 decreased (p=0.0004) with increasing

  19. Marital status and survival in patients with rectal cancer: A population-based STROBE cohort study.

    Science.gov (United States)

    Li, Zhuyue; Wang, Kang; Zhang, Xuemei; Wen, Jin

    2018-05-01

    To examine the impact of marital status on overall survival (OS) and rectal cancer-specific survival (RCSS) for aged patients.We used the Surveillance, Epidemiology and End Results database to identify aged patients (>65 years) with early stage rectal cancer (RC) (T1-T4, N0, M0) in the United States from 2004 to 2010. Propensity score matching was conducted to avoid potential confounding factors with ratio at 1:1. We used Kaplan-Meier to compare OS and RCSS between the married patients and the unmarried, respectively. We used cox proportion hazard regressions to obtain hazard rates for OS, and proportional subdistribution hazard model was performed to calculate hazard rates for RCSS.Totally, 5196 patients were included. The married (2598 [50%]) aged patients had better crude 5-year overall survival rate (64.2% vs 57.3%, P vs 75.9%, P unmarried (2598 (50%)), respectively. In multivariate analyses, married patients had significantly lower overall death than unmarried patients (HR = 0.77, 95% CI = 0.71-0.83, P married patients had no cancer-specific survival benefit versus the unmarried aged patients (HR = 0.92, 95% CI = 0.81-1.04, P = .17).Among old population, married patients with early stage RC had better OS than the unmarried, while current evidence showed that marital status might have no protective effect on cancer-specific survival.

  20. Incidence, treatment and survival of patients with craniopharyngioma in the surveillance, epidemiology and end results program

    Science.gov (United States)

    Zacharia, Brad E.; Bruce, Samuel S.; Goldstein, Hannah; Malone, Hani R.; Neugut, Alfred I.; Bruce, Jeffrey N.

    2012-01-01

    Craniopharyngioma is a rare primary central nervous system neoplasm. Our objective was to determine factors associated with incidence, treatment, and survival of craniopharyngiomas in the United States. We used the surveillance, epidemiology and end results program (SEER) database to identify patients who received a diagnosis of craniopharyngioma during 2004–2008. We analyzed clinical and demographic information, including age, race, sex, tumor histology, and treatment. Age-adjusted incidence rates and age, sex, and race-adjusted expected survival rates were calculated. We used Cox proportional hazards models to determine the association between covariates and overall survival. We identified 644 patients with a diagnosis of craniopharyngioma. Black race was associated with an age-adjusted relative risk for craniopharyngioma of 1.26 (95% confidence interval [CI], 0.98–1.59), compared with white race. One- and 3-year survival rates of 91.5% (95% CI, 88.9%–93.5%), and 86.2% (95% CI, 82.7%–89.0%) were observed for the cohort; relative survival rates were 92.1% (95% CI, 89.5%–94.0%) and 87.6% (95% CI, 84.1%–90.4%) for 1- and 3-years, respectively. In the multivariable model, factors associated with prolonged survival included younger age, smaller tumor size, subtotal resection, and radiation therapy. Black race, on the other hand, was associated with worse overall survival in the final model. We demonstrated that >85% of patients survived 3 years after diagnosis and that subtotal resection and radiation therapy were associated with prolonged survival. We also noted a higher incidence rate and worse 1- and 3-year survival rates in the black population. Future investigations should examine these racial disparities and focus on evaluating the efficacy of emerging treatment paradigms. PMID:22735773

  1. Cyclisation versus 1,1-Carboboration: Reactions of B(C6F5)3 with Propargyl Amides.

    Science.gov (United States)

    Melen, Rebecca L; Hansmann, Max M; Lough, Alan J; Hashmi, A Stephen K; Stephan, Douglas W

    2013-09-02

    A series of propargyl amides were prepared and their reactions with the Lewis acidic compound B(C6F5)3 were investigated. These reactions were shown to afford novel heterocycles under mild conditions. The reaction of a variety of N-substituted propargyl amides with B(C6F5)3 led to an intramolecular oxo-boration cyclisation reaction, which afforded the 5-alkylidene-4,5-dihydrooxazolium borate species. Secondary propargyl amides gave oxazoles in B(C6F5)3 mediated (catalytic) cyclisation reactions. In the special case of disubstitution adjacent to the nitrogen atom, 1,1-carboboration is favoured as a result of the increased steric hindrance (1,3-allylic strain) in the 5-alkylidene-4,5-dihydrooxazolium borate species. Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

    International Nuclear Information System (INIS)

    Blackstock, A. William; Farmer, Michael R.; Lovato, James; Mishra, Girish; Melin, Susan A.; Oaks, Timothy; Aklilu, Mabea; Clark, Paige B.; Levine, Edward A.

    2006-01-01

    Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligible because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival

  3. Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-[3-(1-adamantyl)-4-substituted-5-thioxo-1,2,4-triazolin-1-yl] acetic acids, 2-[3-(1-adamantyl)-4-substituted-5-thioxo-1,2,4-triazolin-1-yl]propionic acids and related derivatives.

    Science.gov (United States)

    Al-Deeb, Omar A; Al-Omar, Mohamed A; El-Brollosy, Nasser R; Habib, Elsayed E; Ibrahim, Tarek M; El-Emam, Ali A

    2006-01-01

    The reaction of 3-(1-adamantyl)-4-substituted-1,2,4-triazoline-5-thiones 3a-g with sodium chloroacetate, in ethanolic sodium hydroxide yielded the corresponding N1-acetic acid derivatives 4a-g. The interaction of 3a-g with ethyl 2-bromopropionate in acetone, in the presence of potassium carbonate, yielded the corresponding N1-ethyl propionate derivatives 5a-g, which upon hydrolysis with aqueous sodium hydroxide afforded the corresponding propionic acid derivatives 6a-g. Similarly, the reaction of 3-(1-adamantyl)-4-amino-1,2,4-triazoline-5-thione 7 with sodium chloroacetate in ethanolic sodium hydroxide yielded the corresponding N1-acetic acid derivative 8. On the other hand, the reaction of 2-(1-adamantyl)-1,3,4-oxadiazoline-5-thione 9 with sodium chloroacetate yielded the corresponding S-acetic acid derivative 10. Compounds 4a-g, 5b, 5c, 5g, 6a-g, 8 and 10 were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several derivatives produced good or moderate activities particularly against Bacillus subtilis. In addition, the in vivo anti-inflammatory activities of these compounds were determined using the carrageenin-induced paw oedema method in rats. Compounds 4a, 4b, 4e, 4f, 6f, 6g and 10 produced good dose-dependent anti-inflammatory activities.

  4. Prognostic value of {sup 18}F-FDG uptake by regional lymph nodes on pretreatment PET/CT in patients with resectable colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Byung Hyun; Lim, Ilhan; Kim, Byung Il; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Department of Nuclear Medicine, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Moon, Sun Mi; Shin, Ui Sup [Korea Institute of Radiological and Medical Sciences (KIRAMS), Surgery, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2014-12-15

    We evaluated the ability of pretreatment {sup 18}F-FDG uptake by regional lymph nodes to predict the survival of patients with resectable colorectal cancer. The records of 78 patients with AJCC stage III colorectal cancer (pathologically confirmed node-positive disease without evidence of distant metastasis) treated with surgery and adjuvant chemotherapy were retrospectively reviewed. The maximum standardized uptake values of the primary tumor (SUVp) and regional lymph nodes (SUVn) were measured by pretreatment {sup 18}F-FDG PET/CT. The ROC curve analyses and the Cox proportional hazard model were used to analyze whether SUVp, SUVn, and clinicopathologic parameters could predict disease-free survival. Although there were no significant differences between the median SUVp in the event group and that in the non-event group, the median SUVn was significantly higher in the event group (1.7) than in the non-event group (0.8, p = 0.023). Based on the ROC curve analysis, SUVn predicted the event for disease-free survival (AUC = 0.668, p = 0.02) with the optimal criterion, sensitivity, specificity, and accuracy of > 1.2, 71 %, 63 %, and 65 %, respectively. However, SUVp did not predict disease-free survival (AUC = 0.570, p = 0.349). Univariate analysis revealed that SUVn (p = 0.011) and venous invasion (p = 0.016) were associated with disease-free survival, but pathologic N stage was not (p = 0.09). By multivariate analysis, only SUVn > 1.2 independently shortened the disease-free survival (relative risk, 2.97; 95 % CI, 1.14-7.74, p = 0.026). SUVn before surgery may be a useful prognostic marker in patients with AJCC stage III colorectal cancer. (orig.)

  5. Impact of "1"8F-FDG-PET/CT on surgical management in patients with advanced melanoma: an outcome based analysis

    International Nuclear Information System (INIS)

    Forschner, Andrea; Keim, Ulrike; Eigentler, Thomas Kurt; Garbe, Claus; Olthof, Susann-Cathrin; Gueckel, Brigitte; Nikolaou, Konstantin; Pfannenberg, Christina; Martus, Peter; Vach, Werner; Fougere, Christian la

    2017-01-01

    To evaluate the influence of "1"8F-FDG-PET/CT on clinical decision making and outcome in advanced melanoma patients planned for radical metastasectomy. A cohort of 333 patients with mainly stage III/IV melanoma having a PET/CT for clinical reasons was prospectively enrolled in our oncologic PET/CT registry between 2013 and 2015. Referring physicians completed questionnaires regarding their intended management for each patient before and after PET/CT. Management changes after PET/CT were classified as major and minor changes. A subgroup of 107 patients (stage I, N = 5; stage II, N = 3; stage III, N = 42; stage IV, N = 57) was planned for complete metastasectomy initially, based on conventional imaging. Management changes and outcome were evaluated by linkage with the information obtained from patients' medical records. In 28 of 107 patients (26%), the surgical treatment plan remained unchanged after PET/CT. In 24 patients (22%), minor changes were performed, such as enlargement or reduction of the surgical field. In 55 patients (51%, 95% CI 42%-61%) major changes of the intended treatment plan occurred; of those, 20 patients (19%) were classified to be tumor-free with PET/CT, 32 patients (30%) were found to have multiple previously unrecognized metastases and had to be treated by systemic therapy, three patients (3%) had to be changed to palliative radiotherapy or isolated extremity perfusion. The 1-year and 2-year overall survival (OS) in patients with complete metastasectomy (N = 52) was 90% and 79%, respectively. Systemically treated patients (N = 32) resulted in 1-year OS of 72% and 2-year OS of 61%. Eleven of 32 patients (34%) with systemic therapy experienced a complete response. Until December 2016, all 20 patients classified as tumor-free by PET/CT were alive. The study confirms the high impact of PET/CT on clinical management in patients with advanced melanoma planned for radical metastasectomy. PET/CT resulted in frequent management changes, preventing

  6. NbF5 and TaF5: Assignment of 19F NMR resonances and chemical bond analysis from GIPAW calculations

    International Nuclear Information System (INIS)

    Biswal, Mamata; Body, Monique; Legein, Christophe; Sadoc, Aymeric; Boucher, Florent

    2013-01-01

    The 19 F isotropic chemical shifts (δ iso ) of two isomorphic compounds, NbF 5 and TaF 5 , which involve six nonequivalent fluorine sites, have been experimentally determined from the reconstruction of 1D 19 F MAS NMR spectra. In parallel, the corresponding 19 F chemical shielding tensors have been calculated using the GIPAW method for both experimental and DFT-optimized structures. Furthermore, the [M 4 F 20 ] units of NbF 5 and TaF 5 being held together by van der Waals interactions, the relevance of Grimme corrections to the DFT optimization processes has been evaluated. However, the semi-empirical dispersion correction term introduced by such a method does not show any significant improvement. Nonetheless, a complete and convincing assignment of the 19 F NMR lines of NbF 5 and TaF 5 is obtained, ensured by the linearity between experimental 19 F δ iso values and calculated 19 F isotropic chemical shielding σ iso values. The effects of the geometry optimizations have been carefully analyzed, confirming among other matters, the inaccuracy of the experimental structure of NbF 5 . The relationships between the fluorine chemical shifts, the nature of the fluorine atoms (bridging or terminal), the position of the terminal ones (opposite or perpendicular to the bridging ones), the fluorine charges, the ionicity and the length of the M–F bonds have been established. Additionally, for three of the 19 F NMR lines of NbF 5 , distorted multiplets, arising from 1 J-coupling and residual dipolar coupling between the 19 F and 93 Nb nuclei, were simulated yielding to values of 93 Nb– 19 F 1 J-coupling for the corresponding fluorine sites. - Graphical abstract: The complete assignment of the 19 F NMR lines of NbF 5 and TaF 5 allow establishing relationships between the 19 F δ iso values, the nature of the fluorine atoms (bridging or terminal), the position of the terminal ones (opposite or perpendicular to the bridging ones), the fluorine charges, the ionicity and the

  7. Origin and evolution of group XI secretory phospholipase A2 from flax (Linum usitatissimum) based on phylogenetic analysis of conserved domains.

    Science.gov (United States)

    Gupta, Payal; Saini, Raman; Dash, Prasanta K

    2017-07-01

    Phospholipase A 2 (PLA 2 ) belongs to class of lipolytic enzymes (EC 3.1.1.4). Lysophosphatidic acid (LPA) and free fatty acids (FFAs) are the products of PLA 2 catalyzed hydrolysis of phosphoglycerides at sn-2 position. LPA and FFA that act as second mediators involved in the development and maturation of plants and animals. Mining of flax genome identified two phospholipase A 2 encoding genes, viz., LusPLA 2 I and LusPLA 2 II (Linum usitatissimum secretory phospholipase A 2 ). Molecular simulation of LusPLA 2 s with already characterized plant sPLA 2 s revealed the presence of conserved motifs and signature domains necessary to classify them as secretory phospholipase A 2 . Phylogenetic analysis of flax sPLA 2 with representative sPLA 2 s from other organisms revealed that they evolved rapidly via gene duplication/deletion events and shares a common ancestor. Our study is the first report of detailed phylogenetic analysis for secretory phospholipase A 2 in flax. Comparative genomic analysis of two LusPLA 2 s with earlier reported plant sPLA 2 s, based on their gene architectures, sequence similarities, and domain structures are presented elucidating the uniqueness of flax sPLA 2 .

  8. 5-[{sup 18}F]Fluoroalkyl pyrimidine nucleosides: probes for positron emission tomography imaging of herpes simplex virus type 1 thymidine kinase gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Chacko, Ann-Marie [Institute for Environmental Medicine, Targeted Therapeutics Program, University of Pennsylvania, Philadelphia, PA 19104 (United States); Blankemeyer, Eric; Lieberman, Brian P.; Qu, Wenchao [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Kung, Hank F. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States)], E-mail: kunghf@gmail.com

    2009-01-15

    Introduction: The preliminary in vivo evaluation of novel 5-[{sup 18}F]fluoroalkyl-2'-deoxyuridines ([{sup 18}F]FPrDU, [{sup 18}F]FBuDU, [{sup 18}F]FPeDU; [{sup 18}F]1a-c, respectively) and 2'-fluoro-2'-deoxy-5-[{sup 18}F]fluoroalkyl-1-{beta}-D-arabinofuranosyl uracils ([{sup 18}F]FFPrAU, [{sup 18}F]FFBuAU, [{sup 18}F]FFPeAU; [{sup 18}F]1d-f, respectively) as probes for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene expression is described. Methods: [{sup 18}F]1a-f were successfully synthesized by a rapid and efficient two-step one-pot nucleophilic fluorination reaction using 5-O-mesylate precursors and [{sup 18}F]F{sup -}. For in vivo studies, tumor xenografts were grown in nude mice by implanting RG2 cells stably expressing HSV1-tk (RG2TK+) and wild-type cells (RG2). Results: Biodistribution studies at 2 h pi revealed that the uptake of [{sup 18}F]1a-b and [{sup 18}F]1d-e in RG2TK+ tumors was not significantly different from control tumors. However, [{sup 18}F]1c and [{sup 18}F]1f had an average 1.6- and 1.7-fold higher uptake in RG2TK+ tumors than control RG2 tumors. Blood activity curves for [{sup 18}F]1c and [{sup 18}F]1f highlight rapid clearance of radioactivity in the blood. Dynamic small animal PET (A-PET) imaging studies of tumor-bearing mice with [{sup 18}F]1c and [{sup 18}F]1f showed higher initial uptake (3.5- and 1.4-fold, respectively) in RG2TK+ tumors than in control tumors, with continued washout of activity from both tumors over time. Conclusions: Biological evaluations suggest that [{sup 18}F]1c and [{sup 18}F]1f may have limited potential for imaging HSV1-tk gene expression due to fast washout of activity from the blood, thus significantly decreasing sensitivity and specificity of tracer accumulation in HSV1-tk-expressing tumors.

  9. Benzene-1,3-dicarboxylic acid 2,5-dimethylpyrrole derivatives as multiple inhibitors of bacterial Mur ligases (MurC-MurF).

    Science.gov (United States)

    Perdih, Andrej; Hrast, Martina; Barreteau, Hélène; Gobec, Stanislav; Wolber, Gerhard; Solmajer, Tom

    2014-08-01

    Enzymes catalyzing the biosynthesis of bacterial peptidoglycan represent traditionally a collection of highly selective targets for novel antibacterial drug design. Four members of the bacterial Mur ligase family-MurC, MurD, MurE and MurF-are involved in the intracellular steps of peptidoglycan biosynthesis, catalyzing the synthesis of the peptide moiety of the Park's nucleotide. In our previous virtual screening campaign, a chemical class of benzene-1,3-dicarboxylic acid 2,5-dimethylpyrrole derivatives exhibiting dual MurD/MurE inhibition properties was discovered. In the present study we further investigated this class of compounds by performing inhibition assays on all four Mur ligases (MurC-MurF). Furthermore, molecular dynamics (MD) simulation studies of one of the initially discovered compound 1 were performed to explore its geometry as well as its energetic behavior based on the Linear Interaction Energy (LIE) method. Further in silico virtual screening (VS) experiments based on the parent active compound 1 were conducted to optimize the discovered series. Selected hits were assayed against all Escherichia coli MurC-MurF enzymes in biochemical inhibition assays and molecules 10-14 containing benzene-1,3-dicarboxylic acid 2,5-dimethylpyrrole coupled with five member-ring rhodanine moiety were found to be multiple inhibitors of the whole MurC-MurF cascade of bacterial enzymes in the micromolar range. Steady-state kinetics studies suggested this class to act as competitive inhibitors of the MurD enzyme towards d-Glu. These compounds represent novel valuable starting point in the development of novel antibacterial agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Survival and prognosticators of node-positive cervical cancer patients treated with radical hysterectomy and systematic lymphadenectomy

    International Nuclear Information System (INIS)

    Hosaka, Masayoshi; Watari, Hidemichi; Mitamura, Takashi; Konno, Yousuke; Odagiri, Tetsuji; Kato, Tatsuya; Takeda, Mahito; Sakuragi, Noriaki

    2011-01-01

    Lymph node metastasis (LNM) is known to be the most important prognostic factor in cervical cancer. We analyzed the number of positive lymph nodes and other clinicopathological factors as prognostic factors for survival in node-positive patients with cervical cancer. Node-positive cervical cancer patients (n=108) who underwent radical hysterectomy and systematic lymphadenectomy in Hokkaido University Hospital from 1982 to 2002 were enrolled. Clinicopathological data including age, stage, histologic subtype, and the number of LNM sites were collected. The main outcome was the overall survival (OS) rate for Stage Ib-IIb patients treated with surgery and postoperative radiotherapy. The 5-year OS rate of patients with 1 positive node was 93.3%, that for 2 nodes was 77.3%, for 3 nodes it was 33.3%, and for 4 or more it was 13.8%. The OS rate of patients with 1 or 2 LNM sites was significantly better than that for patients with more than 2 LNM sites. The OS rate of patients with adenocarcinoma (Ad) (28.6%) was significantly lower than that for patients with other histologic subtypes (squamous cell carcinoma; 66.7%, adenosquamous carcinoma; 75.0%, p=0.0003). Multivariate analysis revealed that >2 LNM sites and Ad were independent prognostic factors for survival. The 5-year OS rate of patients with 1 or 2 LNM sites was 86.8%, a more favorable prognosis than the OS rates in other reports. More than two LNM sites and adenocarcinoma were independent prognostic factors for node-positive patients with cervical cancer. (author)

  11. The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis?

    Directory of Open Access Journals (Sweden)

    Dimitar Divchev

    2008-06-01

    Full Text Available Dimitar Divchev, Bernhard SchiefferDepartment of Cardiology and Angiology, Medizinische Hochschule Hannover, GermanyAbstract: Inflammation, lipid peroxidation and chronic activation of the renin–angiotensin system (RAS are hallmarks of the development of atherosclerosis. Recent studies have suggested the involvement of the pro-inflammatory secretory phospholipase A2 (sPLA2-IIA in atherogenesis. This enzyme is produced by different cell types through stimulation by proinflammatory cytokines. It is detectable in the intima and in media smooth muscle cells, not only in atherosclerotic lesions but also in the very early stages of atherogenesis. sPLA2-IIA can hydrolyse the phospholipid monolayers of low density lipoproteins (LDL. Such modified LDL show increased affinity to proteoglycans. The modified particles have a greater tendency to aggregate and an enhanced ability to insert cholesterol into cells. This modification may promote macrophage LDL uptake leading to the formation of foam cells. Furthermore, sPLA2-IIA is not only a mediator for localized inflammation but may be also used as an independent predictor of adverse outcomes in patients with stable coronary artery disease or acute coronary syndromes. An interaction between activated RAS and phospholipases has been indicated by observations showing that inhibitors of sPLA2 decrease angiotensin (Ang II-induced macrophage lipid peroxidation. Meanwhile, various interactions between Ang II and oxLDL have been demonstrated suggesting a central role of sPLA2-IIA in these processes and offering a possible target for treatment. The role of sPLA2-IIA in the perpetuation of atherosclerosis appears to be the missing link between inflammation, activated RAS and lipidperoxidation.Keywords: secretory phospholipase A2, lipoproteins, renin-angiotensin system, inflammation, atherosclerosis

  12. EPIDEMIOLOGY AND SURVIVAL OF PATIENTS WITH MALIGNANT TUMORS OF CONNECTIVE AND SOFT TISSUE

    Directory of Open Access Journals (Sweden)

    V. M. Merabishvili

    2015-01-01

    Full Text Available Introduction. Malignant tumors of connective and soft tissue are met relatively rare, although in general in Russia each year more than 1.500 new cases are registered. On five administrative territories of Russia during a year there are recorded less than 5 new cases of malignant tumors of connective and soft tissue (Yamal-Nenets A.R. – 4; Tuva Republic – 0, Magadan Region – 3; Chukotka A.R. – 0; Jewish A.R. – 4. More seldom data on these patients’ survival are published. Purpose of study. To estimate dynamics of incidence of malignant tumors of connective and soft tissue on the basis of public reporting, to calculate the index accuracy and observed and relative survival rates by histological forms, including sarcomas. Material and methods. To perform a detailed study there were selected, for two periods of observation, respectively 1054 patients (1995–2001 and 919 patients (2002–2008. Estimation of survival was carried out using software, which had been developed together with Ltd. «Novel» (Director – T.L.Tsvetkova, Ph.D.. results of study. The most typical incidence rate for of malignant tumors of connective and soft tissue (S47, 49 that are presented by  cancer registries of different countries is from 1.5 to 2.5 0/   in men and 1.52.0 0/   in women. Dynamics  of morbidity of the Russian population, Moscow and St. Petersburg indicates that the level of standardized  incidence rates is in the range of 2.0 0/   in men and within 1.5 0/   in women. The mortality rate in 2013  was respectively for men and women in Russia in total 1.7 0/   and 1.13 0/   , in Moscow – 1.42 0/   and  1.24 0/   , in St. Petersburg – 1.88 0/   and 1.26 0/   . The index accuracy for both sexes in Russia is 0.88,  in Moscow – 1.2; in St. Petersburg – 1.4. This index should be used for the site of these diseases with high fatality. According to official data a one-year lethality of patients with tumors of connective and soft

  13. trans-Diaquabis(1,1,1,5,5,5-hexafluoropentane-2,4-dionato-κ2O,O′cobalt(II dihydrate

    Directory of Open Access Journals (Sweden)

    Takumi Tominaga

    2017-01-01

    Full Text Available The CoII atom in the mononuclear title compound, [Co(C5HF6O22(H2O22H2O, is situated on an inversion centre and exhibits a slightly distorted octahedral coordination sphere. In the crystal, molecules are arranged in layers parallel to (100, held together by O—H...O and O—H...F hydrogen bonds.

  14. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

    International Nuclear Information System (INIS)

    Ma, Junliang; Liu, Lunxu; Che, Guowei; Yu, Nanbin; Dai, Fuqiang; You, Zongbing

    2010-01-01

    Tumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC), TAMs' anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function) and M2 (with pro-tumor function) forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient's survival time. Fifty patients with an average of 1-year survival (short survival group) and 50 patients with an average of 5-year survival (long survival group) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical double-staining of CD68/HLA-DR (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded fashion. The M1 and M2 macrophage densities in the tumor islets, stroma, or islets and stroma were determined using computer-aided microscopy. Correlation of the macrophage densities and patient's survival time was analyzed using the Statistical Package for the Social Sciences. Approximately 70% of TAMs were M2 macrophages and the remaining 30% were M1 macrophages in NSCLC. The M2 macrophage densities (approximately 78 to 113 per mm 2 ) in the tumor islets, stroma, or islets and stroma were not significantly different between the long survival and short survival groups. The M1 macrophage densities in the tumor islets (approximately 70/mm 2 ) and stroma (approximately 34/mm 2 ) of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets (approximately 7/mm 2 ) and stroma (13/mm 2 ) of the short survival group (P < 0.001 and P < 0.05, respectively). The M2 macrophage densities were not associated with patient's survival time. The M1 macrophage densities in the tumor islets, stroma, or islets and stroma

  15. Molecular details of secretory phospholipase A2 from flax (Linum usitatissimum L.) provide insight into its structure and function.

    Science.gov (United States)

    Gupta, Payal; Dash, Prasanta K

    2017-09-11

    Secretory phospholipase A 2 (sPLA 2 ) are low molecular weight proteins (12-18 kDa) involved in a suite of plant cellular processes imparting growth and development. With myriad roles in physiological and biochemical processes in plants, detailed analysis of sPLA 2 in flax/linseed is meagre. The present work, first in flax, embodies cloning, expression, purification and molecular characterisation of two distinct sPLA 2 s (I and II) from flax. PLA 2 activity of the cloned sPLA 2 s were biochemically assayed authenticating them as bona fide phospholipase A 2 . Physiochemical properties of both the sPLA 2 s revealed they are thermostable proteins requiring di-valent cations for optimum activity.While, structural analysis of both the proteins revealed deviations in the amino acid sequence at C- & N-terminal regions; hydropathic study revealed LusPLA 2 I as a hydrophobic protein and LusPLA 2 II as a hydrophilic protein. Structural analysis of flax sPLA 2 s revealed that secondary structure of both the proteins are dominated by α-helix followed by random coils. Modular superimposition of LusPLA 2 isoforms with rice sPLA 2 confirmed monomeric structural preservation among plant phospholipase A 2 and provided insight into structure of folded flax sPLA 2 s.

  16. Hospitalization and survival in patients using epoprostenol for injection in the PROSPECT observational study.

    Science.gov (United States)

    Frantz, Robert P; Schilz, Robert J; Chakinala, Murali M; Badesch, David B; Frost, Adaani E; McLaughlin, Vallerie V; Barst, Robyn J; Rosenberg, Daniel M; Miller, Dave P; Hartline, Brian K; Benton, Wade W; Farber, Harrison W

    2015-02-01

    Few studies have prospectively reported outcomes in patients with pulmonary arterial hypertension (PAH) treated with epoprostenol in the modern-day era of oral therapy and combination treatments. The Registry to Prospectively Describe Use of Epoprostenol for Injection (Veletri, prolonged room temperature stable-epoprostenol [RTS-Epo]) in Patients with Pulmonary Arterial Hypertension (PROSPECT) was established to prospectively describe the course of PAH in patients prescribed RTS-Epo. PROSPECT is a multicenter, US-based drug registry of primarily group 1 patients with PAH treated with RTS-Epo who were parenteral-naive or parenteral-transitioned at enrollment. Patients were followed until discontinuation of RTS-Epo, withdrawal, loss to follow-up, death, or end of study (maximum 1 year). One-year freedom from hospitalization (FH) and survival estimates were summarized by prostacyclin history (parenteral-naive or parenteral-transitioned), sex, and chronic renal insufficiency (CRI). A total of 336 patients were included. The overall 1-year FH estimate was 51.0% ± 2.8% and was lower in parenteral-naive patients than parenteral-transitioned patients (42.8% ± 4.3% vs 57.1% ± 3.7%, respectively; P = .002). FH estimates were lower in male patients than female patients (38.3% ± 5.9% vs 54.6% ± 3.2%, respectively; P < .015) and in patients with CRI than patients without CRI (17.0% ± 8.4% vs 53.7% ± 2.9%, respectively; P < .001). The overall 1-year survival estimate was 84.0% ± 2.1%. Survival was poorer in parenteral-naive patients, male patients, and patients with CRI. Risk of hospitalization and mortality remain high in patients with PAH. In particular, patients who are parenteral-naive at initiation of RTS-Epo therapy, male patients, and patients with CRI require close monitoring and aggressive clinical management.

  17. Conditional survival of cancer patients: an Australian perspective

    Directory of Open Access Journals (Sweden)

    Yu Xue

    2012-10-01

    Full Text Available Abstract Background Estimated conditional survival for cancer patients diagnosed at different ages and disease stage provides important information for cancer patients and clinicians in planning follow-up, surveillance and ongoing management. Methods Using population-based cancer registry data for New South Wales Australia, we estimated conditional 5-year relative survival for 11 major cancers diagnosed 1972–2006 by time since diagnosis and age and stage at diagnosis. Results 193,182 cases were included, with the most common cancers being prostate (39,851, female breast (36,585 and colorectal (35,455. Five-year relative survival tended to increase with increasing years already survived and improvement was greatest for cancers with poor prognosis at diagnosis (lung or pancreas and for those with advanced stage or older age at diagnosis. After surviving 10 years, conditional 5-year survival was over 95% for 6 localised, 6 regional, 3 distant and 3 unknown stage cancers. For the remaining patient groups, conditional 5-year survival ranged from 74% (for distant stage bladder cancer to 94% (for 4 cancers at different stages, indicating that they continue to have excess mortality 10–15 years after diagnosis. Conclusion These data provide important information for cancer patients, based on age and stage at diagnosis, as they continue on their cancer journey. This information may also be used by clinicians as a tool to make more evidence-based decisions regarding follow-up, surveillance, or ongoing management according to patients' changing survival expectations over time.

  18. Factors predicting survival in amyotrophic lateral sclerosis patients on non-invasive ventilation.

    Science.gov (United States)

    Gonzalez Calzada, Nuria; Prats Soro, Enric; Mateu Gomez, Lluis; Giro Bulta, Esther; Cordoba Izquierdo, Ana; Povedano Panades, Monica; Dorca Sargatal, Jordi; Farrero Muñoz, Eva

    2016-01-01

    Non invasive ventilation (NIV) improves quality of life and extends survival in amyotrophic lateral sclerosis (ALS) patients. However, few data exist about the factors related to survival. We intended to assess the predictive factors that influence survival in patients after NIV initiation. Patients who started NIV from 2000 to 2014 and were tolerant (compliance ≥ 4 hours) were included; demographic, disease related and respiratory variables at NIV initiation were analysed. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. 213 patients were included with median survival from NIV initiation of 13.5 months. In univariate analysis, the identified risk factors for mortality were severity of bulbar involvement (HR 2), Forced Vital Capacity (FVC) % (HR 0.99) and ALSFRS-R (HR 0.97). Multivariate analysis showed that bulbar involvement (HR 1.92) and ALSFRS-R (HR 0.97) were independent predictive factors of survival in patients on NIV. In our study, the two prognostic factors in ALS patients following NIV were the severity of bulbar involvement and ALSFRS-R at the time on NIV initiation. A better assessment of bulbar involvement, including evaluation of the upper airway, and a careful titration on NIV are necessary to optimize treatment efficacy.

  19. Transthoracic versus transhiatal esophagectomy – influence on patient survival

    Directory of Open Access Journals (Sweden)

    Mariusz Łochowski

    2016-12-01

    Full Text Available Aim: To evaluate the survival of patients after surgery of the esophagus/cardia using the transthoracic and transhiatal methods. Material and methods : In the years 2007–2011, 102 patients were radically treated for cancer of the esophagus/cardia: 24 women and 78 men at the average age of 59.5. There were 38 transthoracic procedures and 64 transhiatal procedures. All patients had a conduit made from the stomach, led through lodges in the esophagus and combined with the stump of the esophagus in the neck following the Collard method. Two-pole lymphadenectomies were performed in all patients. Results: Patients after transthoracic procedures had statistically more (p < 0.05 lymph nodes removed than patients after transhiatal procedures. The 5-year survival rates in transhiatal and transthoracic procedures did not statistically differ, being 8% and 0% respectively. The length of patient survival was influenced by metastases in the nearby lymph nodes (p < 0.0001 and the presence of adenocarcinoma. Conclusions : Surgical access (transhiatal and transthoracic surgery does not affect the 5-year survival rates. Transhiatal surgery allows a greater number of lymph nodes to be removed. The main factor influencing the 5-year survival rate is the presence of metastases in the nearby lymph nodes.

  20. Goblet cell carcinoids: characteristics of a Danish cohort of 83 patients.

    Directory of Open Access Journals (Sweden)

    Ingrid Holst Olsen

    Full Text Available Appendiceal goblet cell carcinoids (GCCs exhibit neuroendocrine and adenocarcinoma features.Analysis of demography, pathology, prognostic markers, treatment and survival in 83 GCC patients (f/m: 56/27 diagnosed 1992-2013.Median age for f/m was 59/58 years, respectively, and similar for localized and disseminated disease. At diagnosis 54 patients had localized appendiceal disease (f/m: 29/25. According to TNM 24% had Stage I, 70% had Stage II and 6% had Stage III. Twenty-nine patients had disseminated disease (f/m: 27/2. Chromogranin A, synaptophysin and p53 were positive in >90%. Serotonin was positive in 70%. Median Ki67 index was 32% (6-75% and higher in Tang group C (50% compared to group A (30%; p<0.0001, and group B (30%; p<0.004. All patients had surgery. Sixty-three (76% had radical resections including all patients with localized disease. Median OS was 83 months. The 1-, 5- and 10-year survival rates were 90%, 58%, and 38%, respectively. For localized disease OS was 164 months and 1-, 5- and 10-year survival rates were 100%, 80%, and 55%, respectively. For disseminated disease OS was 19 months and 1-, 5- and 10-year survival rates were 73%, 18% and 6%, respectively. The 1-, 5- and 10 year-survival rates for f/m were 87%/96%, 49%/76% and 31%/57%, respectively (p = 0.02. According to the Tang classification group A, B, and C OS was 118, 83 and 20 months, respectively (p = 0.0002.The Tang classification was found to be a significant prognostic factor, while the Ki67 index was not. Localized GCCs occurred equally in males and females, while disseminated GCCs were mostly seen in females. Median age of patients with localized disease and disseminated disease was identical. Cox regression analysis found Stage IV, focally positive synaptophysin and non-radical surgery as strongest negative prognostic factors.

  1. Atmospheric chemistry of n-CxF2x+1CHO (x = 1, 2, 3, 4)

    DEFF Research Database (Denmark)

    Hurley, M. D.; Ball, J. C.; Wallington, T. J.

    2006-01-01

    Smog chamber/FTIR techniques were used to study the atmospheric fate of n-C(x)F(2)(x)(+1)C(O) (x = 1, 2, 3, 4) radicals in 700 Torr O(2)/N(2) diluent at 298 +/- 3 K. A competition is observed between reaction with O(2) to form n-C(x)()F(2)(x)()(+1)C(O)O(2) radicals and decomposition to form n-C(x...... to the atmospheric chemistry of n-C(x)F(2)(x)(+1)C(O) radicals and their possible role in contributing to the formation of perfluorocarboxylic acids in the environment....

  2. Influence of socioeconomic status on allograft and patient survival following kidney transplantation.

    Science.gov (United States)

    Ward, Frank L; O'Kelly, Patrick; Donohue, Fionnuala; ÓhAiseadha, Coilin; Haase, Trutz; Pratschke, Jonathan; deFreitas, Declan G; Johnson, Howard; Conlon, Peter J; O'Seaghdha, Conall M

    2015-06-01

    Whether socioeconomic status confers worse outcomes after kidney transplantation is unknown. Its influence on allograft and patient survival following kidney transplantation in Ireland was examined. A retrospective, observational cohort study of adult deceased-donor first kidney transplant recipients from 1990 to 2009 was performed. Those with a valid Irish postal address were assigned a socioeconomic status score based on the Pobal Hasse-Pratschke deprivation index and compared in quartiles. Cox proportional hazards models and Kaplan-Meier survival analysis were used to investigate any significant association of socioeconomic status with patient and allograft outcomes. A total of 1944 eligible kidney transplant recipients were identified. The median follow-up time was 8.2 years (interquartile range 4.4-13.3 years). Socioeconomic status was not associated with uncensored or death-censored allograft survival (hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.99-1.00, P = 0.33 and HR 1.0, 95% CI 0.99-1.00, P = 0.37, respectively). Patient survival was not associated with socioeconomic status quartile (HR 1.0, 95% CI 0.93-1.08, P = 0.88). There was no significant difference among quartiles for uncensored or death-censored allograft survival at 5 and 10 years. There was no socioeconomic disparity in allograft or patient outcomes following kidney transplantation, which may be partly attributable to the Irish healthcare model. This may give further impetus to calls in other jurisdictions for universal healthcare and medication coverage for kidney transplant recipients. © 2015 Asian Pacific Society of Nephrology.

  3. [Postoperative complications and survival analysis of 1 118 cases of open splenectomy and azygoportal disconnection in the treatment of portal hypertension].

    Science.gov (United States)

    Qi, R Z; Zhao, X; Wang, S Z; Zhang, K; Chang, Z Y; Hu, X L; Wu, M L; Zhang, P R; Yu, L X; Xiao, C H; Shi, X J; Li, Z W

    2018-06-01

    Objective: To analyze the recent postoperative and long-term postoperative complications of open-splenectomy and disconnection in patients with portal hypertension. Methods: There were 1 118 cases with portal hypertension who underwent open splenectomy and azygoportal disconnection from April 2010 to September 2015 at Department of Surgery, People's Liberation Army 302 Hospital. Retrospective case investigation and telephone follow-up were conducted in October 2016. All patients had history of upper gastrointestinal bleeding before operation. Short-term complications after surgery were recorded including secondary laparotomy of postoperative abdominal hemostasis, severe infection, intake disorders, liver insufficiency, postoperative portal vein thrombosis and perioperative mortality. Long-term data including postoperative upper gastrointestinal rebleeding, postoperative survival rate and incidence of postoperative malignancy were recorded, too. GraphPad Prism 5 software for data survival analysis and charting. Results: Postoperative short-term complications in 1 118 patients included secondary laparotomy of postoperative abdominal hemostasis(1.8%, 21/1 118), severe infection(2.9%, 32/1 118), intake disorders(1.0%, 11/1 118), liver dysfunction (1.6%, 18/1 118), postoperative portal vein thrombosis(47.1%, 526/1 118)and perioperative mortality(0.5%, 5/1 118). After phone call following-up, 942 patients' long-term data were completed including 1, 3, 5 years postoperative upper gastrointestinal rebleeding rate(4.4%, 12.1%, 17.2%), 1, 3, 5-year postoperative survival rate(97.0%, 93.5%, 90.3%); the incidence of postoperative malignant tumors in 1, 3 and 5 years were 1.7%, 4.4% and 6.2%. Conclusions: Reasonable choosing of surgical indications and timing, proper performing the surgery process, effective conducting perioperative management of portal hypertension are directly related to the patient's short-term prognosis after portal hypertension. Surgical intervention can

  4. Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer

    International Nuclear Information System (INIS)

    Dahl, Edgar; Dunn, Sandra E; Mertens, Peter R; En-Nia, Abdelaziz; Wiesmann, Frank; Krings, Renate; Djudjaj, Sonja; Breuer, Elisabeth; Fuchs, Thomas; Wild, Peter J; Hartmann, Arndt

    2009-01-01

    Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival). Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample

  5. HYPERDIRE. HYPERgeometric functions DIfferential REduction. MATHEMATICA based packages for differential reduction of generalized hypergeometric functions pFp-1, F1, F2, F3, F4

    International Nuclear Information System (INIS)

    Bytev, Vladimir V.; Kalmykov, Mikhail Yu.; Kniehl, Bernd A.

    2013-05-01

    HYPERDIRE is a project devoted to the creation of a set of Mathematica based programs for the differential reduction of hypergeometric functions. The current version includes two parts: one, pfq, is relevant for manipulations of hypergeometric functions p+1 F p , and the second one, AppellF1F4, for manipulations with Appell hypergeometric functions F 1 , F 2 , F 3 , F 4 of two variables.

  6. Effect of integrated surgery + radiotherapy + chemotherapy treatment on survival status and serum indexes in patients with gallbladder carcinoma

    Directory of Open Access Journals (Sweden)

    Zhi-Li Wei

    2016-12-01

    Full Text Available Objective: To study the effect of integrated surgery + radiotherapy + chemotherapy treatment on the survival status and serum indexes in patients with gallbladder carcinoma. Methods: A total of 68 patients with gallbladder carcinoma were divided into observation group (received integrated surgery + radiotherapy + chemotherapy treatment and control group (received surgery + radiotherapy according to different treatments. Differences in the content of tumor markers, growth factors and adhesion molecules in serum as well as the median survival time and survival rate in 5 years of follow-up were compared between the two groups 1 month after treatment. Results: Tumor markers β2-MG, CA19-9, CA242, CA125, CA724, CEA and AFP content in serum of observation group after treatment were significantly lower than those of control group; growth factors VEGF, FGF, EGFR and HER2 content in serum were significantly lower than those of control group while IGFBP-2 and IGFBP-3 content were significantly higher than those of control group; adhesion molecules E-selectin, ICAM-1, VCAM-1 and sE-Cd content in serum were significantly lower than those of control group; the median survival time of 5-year follow-up as well as 1-, 3- and 5-year survival rate were significantly greater than those of control group. Conclusions: Integrated treatment of surgery + radiotherapy + chemotherapy can optimize the short-term and long-term curative effect in patients with gallbladder carcinoma.

  7. Survival and Prognostic Factors for Metachronous Peritoneal Metastasis in Patients with Colon Cancer.

    Science.gov (United States)

    Nagata, Hiroshi; Ishihara, Soichiro; Hata, Keisuke; Murono, Koji; Kaneko, Manabu; Yasuda, Koji; Otani, Kensuke; Nishikawa, Takeshi; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Kawai, Kazushige; Nozawa, Hiroaki; Watanabe, Toshiaki

    2017-05-01

    The clinical course of metachronous peritoneal metastasis of colorectal origin is poorly understood. In this retrospective study, we aimed to elucidate survival and prognostic factors for metachronous peritoneal metastasis. Patients with metachronous peritoneal metastasis after curative resection for stage I-III colon cancer were retrospectively reviewed, and the incidence and prognosis of metachronous peritoneal metastasis were investigated. Prognostic factors were identified by univariate and multivariate analyses. Among 1582 surgically resected stage I-III colon cancer patients, 65 developed metachronous peritoneal metastasis. The 5-year cumulative incidence rate was 4.5%, and the median survival after diagnosis of peritoneal metastasis was 29.6 months. None of the patients underwent peritonectomy or intraperitoneal chemotherapy. Independent prognostic factors included right colon cancer [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.26-5.64; p = 0.011], time to metachronous peritoneal metastasis of Cancer Index (PCI) >10 (HR 3.68, 95% CI 1.37-8.99; p = 0.012), concurrent metastases (HR 4.09, 95% CI 2.02-8.23; p colon cancer patients with metachronous peritoneal metastasis may benefit from combined peritoneal nodule resection and systemic chemotherapy. Right colon cancer, early peritoneal metastasis, a high PCI, and concurrent metastases negatively affected prognosis in patients with metachronous peritoneal metastasis.

  8. Detection of MPL exon10 mutations in 103 Chinese patients with JAK2V617F-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Chen, Xiuhua; Qi, Xiling; Tan, Yanhong; Xu, Zhifang; Xu, Aining; Zhang, Linlin; Wang, Hongwei

    2011-06-15

    JAK2V617F mutation has been reported in 90% of patients with polycythemia vera (PV) and about 50% of patients with essential thromobocythemia (ET) and primary myelofibrosis (PMF). Recently, acquired mutations in the transmembrane-juxtamembrane region of MPL (MPLW515 mutations) have been reported in approximately 5% of JAK2V617F-negative PMF and about 1% of all cases of ET. MPL is the receptor for thrombopoietin that regulates the production of platelets by bone marrow. It is likely that some mutations more closely related to ET in MPL exon10 may have been missed by current assays. We inferred that there might be other mutations in MPL exon10 for MPN patients in addition to MPLW515 mutations. To investigate its mutation types and prevalence in Chinese patients with myeloproliferative neoplasms (MPN), we performed mutation detection on MPL exon10 in 103 JAK2V617F-negative MPN patients by single strand conformation polymorphism (SSCP) and allele-specific PCR (AS-PCR) combined with sequencing. As a result, one previously unrecognized MPL mutation (12-bp in-frame insertion) was identified in one patient with ET in addition to an MPLW515K mutation identified in one PMF patient. This confirms our hypothesis that BCR/ABL negative and JAK2V617F-negative MPN patients have other mutations besides W515 mutation in MPL exon10 and mutations other than single nucleotide exchange also exist. In addition, MPL mutation was associated with Chinese MPN patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Imaging malignant melanoma with {sup 18}F-5-FPN

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

    2016-01-15

    Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

  10. Geographic Variation in Oxaliplatin Chemotherapy and Survival in Patients With Colon Cancer.

    Science.gov (United States)

    Panchal, Janki M; Lairson, David R; Chan, Wenyaw; Du, Xianglin L

    2016-01-01

    Geographic disparity in colon cancer survival has received less attention, despite the fact that health care delivery varied across regions. To examine geographic variation in colon cancer survival and explore factors affecting this variation, including the use of oxaliplatin chemotherapy, we studied cases with resected stage-III colon cancer in 2004-2009, identified from the Surveillance, Epidemiology and End Results-Medicare linked database. Cox proportional hazard model was used to estimate the effect of oxaliplatin-containing chemotherapy on survival across regions. Propensity score adjustments were made to control for potential selection bias and confounding. Rural regions showed lowest 3-year survival, whereas big metro regions showed better 3-year survival rate than any other region (67.3% in rural regions vs. 69.5% in big metro regions). Hazard ratio for patients residing in metro region was comparable with those residing in big metro region (1.27, 95% confidence interval: 0.90-1.80). However, patients residing in urban area were exhibiting lower mortality than those in other regions, although not statistically significant. Patients who received oxaliplatin chemotherapy were 23% significantly less likely to die of cancer than those received 5-fluorouracil only chemotherapy (adjusted hazard ratio = 0.77, 95% confidence interval: 0.63-0.95). In conclusion, there were some differences in survival across geographic regions, which were not statistically significant after adjusting for sociodemographic, tumor, chemotherapy, and other treatment characteristics. Oxaliplatin chemotherapy was associated with improved survival outcomes compared with 5-fluorouracil only chemotherapy across regions. Further studies may evaluate other factors and newer chemotherapy regimens on mortality/survival of older patients.

  11. Implantable cardioverter-defibrillators improve survival after coronary artery bypass grafting in patients with severely impaired left ventricular function

    Directory of Open Access Journals (Sweden)

    Pasque Michael K

    2007-01-01

    Full Text Available Abstract Objective Patients with severe left ventricular (LV dysfunction have a poor long term survival despite complete surgical revascularization. Recent data suggests that the use of Implantable Cardioverter-Defibrillator (ICD improves survival in patients with severe LV dysfunction. We compared the survival impact of ICD implantation in patients with severe LV dysfunction who underwent CABG. Methods Between January 1996 and August 2004, 305 patients with LV ejection fraction (EF ≤25% had CABG surgery at our institution. Demographics of patients who had received an ICD (ICD+ in the post -operative period was compared to those without ICD (ICD-. Survival was evaluated by the Kaplan-Meier method. Results Of the entire group, 35 (11.5% patients received an ICD with a median of 2 (+/-2 years after CABG. Indication for ICD implantation was clinical evidence of non sustained ventricular tachycardia (NSVT. There were no differences between the 2 groups with respect to age, gender, NYHA classification, number of bypasses, or other co-morbidities. Survival at 1, 3 and 5 years was 88%, 79%, and 67% for the ICD- group compared to 94%, 89% and 83% for the ICD+ group, respectively (figure, p Conclusion Implantation of ICD after CABG confers improved short and long term survival benefit to patients with severe LV dysfunction. Prophylactic ICD implantation in the setting of severe LV dysfunction and CABG surgery should be considered.

  12. Analysis of 5 year survival of esophageal cancer treated by radiotherapy

    International Nuclear Information System (INIS)

    Takegawa, Yoshihiro; Ohgushi, Ikuyo; Hiraki, Yoshio; Honke, Yoshifumi; Matsuki, Tsutomu; Yokoyama, Takashi; Yoshida, Mineo.

    1987-01-01

    Since 1984, a total of 1,419 patients with carcinoma of the esophagus were treated at the Department of Radiology of 17 hospitals in Chugoku-Shikoku province. The five year survival rate was 7.3 % (42/578 cases). Thirty-nine out of the forty-two cases were analyzed according to the tumor extent, localization and types of the X-ray findings. In addition, 95 patients (67 had been reported in other journals and 28 in this report) who have survived more than 5 years after radical radiotherapy were analyzed. (author)

  13. Synthesis, radiofluorination and first evaluation of [{sup 18}F]fluorophenylsulfonyl- and [{sup 18}F]fluorophenylsulfinyl-piperidines as serotonin 5-HT{sub 2A} receptor antagonists for PET

    Energy Technology Data Exchange (ETDEWEB)

    Muehlhausen, Ute; Sihver, Wiebke [Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany); Ermert, Johannes, E-mail: j.ermert@fz-juelich.d [Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany); Coenen, Heinz H. [Institute of Neuroscience and Medicine, INM-5: Nuclear Chemistry, Forschungszentrum Juelich GmbH, 52425 Juelich (Germany)

    2010-07-15

    In psychiatric disorders, 5-HT{sub 2A} receptors play an important role. In order to study these receptors in vivo by positron emission tomography (PET), there is an increasing interest for subtype selective and high affinity radioligands. Up to now, no optimal radiotracer is available. Thus, 1-(2,4-difluorophenethyl)-4-(4-fluorophenylsulfonyl)piperidine (9), possessing high affinity and sufficient subtype selectivity for 5-HT{sub 2A} receptors, and 1-(2,4-difluorophenethyl)-4-(4-fluorophenylsulfinyl)piperidine (15) have been {sup 18}F-labelled by a nucleophilic one-step reaction. Both radiotracers could be prepared and isolated within 45 min, [{sup 18}F]9 in a radiochemical yield (RCY) of 34.5{+-}8% and [{sup 18}F]15 of 9.5{+-}2.5%. The K{sub i} values of 9 and 15 at 5-HT{sub 2A} receptors towards [{sup 3}H]ketanserin were determined to be 1.9{+-}0.6 and 198{+-}8 nM, respectively. Autoradiography with [{sup 18}F]9 and [{sup 18}F]15 on rat brain sections showed a very high nonspecific binding of >80% for [{sup 18}F]9 and 30% to 40% nonspecific binding for [{sup 18}F]15; however, it is still too high in order to compensate for its lower affinity. Even though the affinity of 9 is more promising compared with 15, the high nonspecific binding of both radiofluorinated tracers in rat brain does not recommend those as an in vivo PET imaging agent for serotonin 5-HT{sub 2A} receptors in humans.

  14. Prognostic Value of Metabolic Activity Measured by {sup 18}F-FDG PET/CT in Patients with Advanced Endometrial Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Jeong; Choi, Jiyoun; Jeong, Yong Hyu; Jo, Kwan Hyeong; Lee, Jaehoon; Cho, Arthur; Yun, Mijin; Lee, Jong Doo; Kim, Young Tae; Kang, Won Jun [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    We evaluated the potential prognostic value of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with stage IIIC/IV endometrial cancer. Patients with stage IIIC/IV endometrial cancer who had undergone FDG PET/CT workup for staging were enrolled. Maximum standardized uptake values (SUV{sub max}) measured from regions of interest (ROIs) of the primary tumor (SUVt) and lymph nodes (SUVn) were correlated with overall survival (OS). The SUVn was defined as the highest SUV{sub max} of the metastatic lymph nodes. Survival probability was assessed using the Kaplan-Meier method. A total of 42 patients with a median age of 55.5 years (range 32-76 years) were included. Twenty-nine percent (n =12) of patients were premenopausal and 71 % (n =30) were postmenopausal. The average SUVt was 12.9 (range 1.8-36.5), and the average SUVn was 7.3 (range 2.0-22.5). Median follow-up time was 25.9 months (range 1.84 months). Using a SUVt of 9.5 as a cutoff value, two groups with different rates were determined (P=0.026). In addition, patients with a low SUVn had significantly better OS than those with a high SUVn (P=0.003). Patients in the International Federation of Obstetrics and Gynecology (FIGO) stage IV group with SUVt≥9.5 or SUVn≥7.3 showed a significantly longer OS than the other groups. FDG uptake of primary endometrial cancer and lymph nodes might be a prognostic factor in advanced endometrial cancer. More aggressive therapy could be considered in patients with stage IV endometrial cancer and high SUVt and/or high SUVn.

  15. Preclinical validation of the hypoxia tracer 2-(2-nitroimidazol-1-yl)-N-(3,3,3-[18F]trifluoropropyl)acetamide, [18F]EF3

    International Nuclear Information System (INIS)

    Mahy, P.; De Bast, M.; Gregoire, V.; Leveque, P.H.; Gillart, J.; Labar, D.; Marchand, J.

    2004-01-01

    The 2-nitroimidazole derivative 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a marker which forms adducts into hypoxic cells. Radiosynthesis of [ 18 F]EF3 was recently performed by our group. Our aim was to study the pharmacokinetics, biodistribution, metabolism and specificity for hypoxia of [ 18 F]EF3. MCa-4, SCC VII, NFSA, FSA, FSA II or Sa-NH tumour-bearing C3H mice were injected intravenously with [ 18 F]EF3 and allowed to breathe air, 10% O 2 or carbogen until sacrifice 5-770 min after injection. Radioactivity was measured ex vivo in various organs, including urine and faeces. Selected organs were additionally processed to measure tracer metabolites with high-performance liquid chromatography. The half-life in blood was 73.9 min. [ 18 F]EF3 was eliminated mainly via the kidneys, with 75% of the injected activity found in the urine by 12 h 50 min. The biodistribution was fast and homogeneous except in the brain and the bone, where it was significantly lower, and in the liver and the kidney, where it was significantly higher. In most organs, the exceptions being the gastrointestinal and urinary tract, tissue-to-blood ratios were below or close to unity. In tumours, a relative accumulation of the tracer was observed with time, which, at 220 min after injection, depended on tumour strain and oxygenation conditions, i.e. 10% O 2 significantly increased the tumour-to-muscle ratio whereas carbogen decreased it. [ 18 F]EF3 was rapidly metabolised in the kidney and the liver. [ 18 F]EF3 is a promising tracer for detection of tumour hypoxia. A phase I study in head and neck cancer patients is in progress at our institution. (orig.)

  16. MALIGNANT TUMORS OF BONES. MORBIDITY, MORTALITY, INDEX ACCURACY, SURVIVAL OF PATIENTS ACCORDING TO HISTOLOGICAL FORMS

    Directory of Open Access Journals (Sweden)

    V. M. Merabishvili

    2015-01-01

    Full Text Available Introduction. Standardized (world standard incidence of malignant tumors of bones (S40,41 does not have has significant fluctuations. According to IARC among male population the most common incidence rates range from 1 to 2 cases per 100.000 and among female population – from 0.5 to 1.0 among women.  Purpose of study. To study dynamics of morbidity and mortality from malignant tumors of bones, the quality of estimation, observed and relative survival of patients according to histological forms. The work of this level is held in Russia for the first time. Material and methods of study. There were used an open world and domestic sources to estimate the prevalence of malignant tumors of bones, databases of population-based cancer registers, classical methods of population-based estimation of the prevalence of malignant tumors of bones. results of study. The basis of this work is data from the Population-based Cancer Registry of St. Petersburg and special studies being held before its establishing in 1993. Annually in St. Petersburg there are registered 40–60 primary cases of malignant tumors of bones (S40, 41. The level of morphological verification of these malignancies in Russia is 82.1 %, in St. Petersburg – 84.9 %. There is a high rate of undefined stage: in Russia – 19.7 %, in St. Petersburg – 24.5 %, in Moscow – 23.5 %. During the first year of observation 27.3 % of patients die in Russia, 21.7 % in St. Petersburg, and 11.1 % in Moscow. In comparison with the average data (Eurocare program the relative survival of patients in St. Petersburg is significantly lower: in men (St. Petersburg – 42.2–48.2 %, (Eurocare-3,4 – 55–58 %, in women (St. Petersburg – 32.2–54.6 % (Eurocare – 59–63 %. conclusion. Thus, in this work for the first time in Russia it is showed dynamics of absolute and relative incidence rates of malignant tumors of bones since 1980 by sex and age-specific indicators. It is presented a set of

  17. Distinct enzymatic and cellular characteristics of two secretory phospholipases A2 in the filamentous fungus Aspergillus oryzae.

    Science.gov (United States)

    Nakahama, Tomoyuki; Nakanishi, Yoshito; Viscomi, Arturo R; Takaya, Kohei; Kitamoto, Katsuhiko; Ottonello, Simone; Arioka, Manabu

    2010-04-01

    Microbial secretory phospholipases A(2) (sPLA(2)s) are among the last discovered and least known members of this functionally diverse family of enzymes. We analyzed here two sPLA(2)s, named sPlaA and sPlaB, of the filamentous ascomycete Aspergillus oryzae. sPlaA and sPlaB consist of 222 and 160 amino acids, respectively, and share the conserved Cys and catalytic His-Asp residues typical of microbial sPLA(2)s. Two sPLA(2)s differ in pH optimum, Ca(2+) requirement and expression profile. The splaA mRNA was strongly upregulated in response to carbon starvation, oxidative stress and during conidiation, while splaB was constitutively expressed at low levels and was weakly upregulated by heat shock. Experiments with sPLA(2) overexpressing strains demonstrated that two enzymes produce subtly different phospholipid composition variations and also differ in their subcellular localization: sPlaA is most abundant in hyphal tips and secreted to the medium, whereas sPlaB predominantly localizes to the ER-like intracellular compartment. Both sPLA(2) overexpressing strains were defective in conidiation, which was more pronounced for sPlaB overexpressors. Although no major morphological abnormality was detected in either DeltasplaA or DeltasplaB mutants, hyphal growth of DeltasplaB, but not that of DeltasplaA, displayed increased sensitivity to H(2)O(2) treatment. These data indicate that two A. oryzae sPLA(2) enzymes display distinct, presumably non-redundant, physiological functions.

  18. PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma.

    Science.gov (United States)

    Nguyen, Bella Hai; Montgomery, Renn; Fadia, Mitali; Wang, Jiali; Ali, Sayed

    2018-02-01

    There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome. Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity. Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484). Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time. © 2017 John Wiley & Sons Australia, Ltd.

  19. Chemoembolization With Doxorubicin-Eluting Beads for Unresectable Hepatocellular Carcinoma: Five-Year Survival Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Malagari, Katerina, E-mail: kmalag@otonet.gr [University of Athens, Second Department of Radiology (Greece); Pomoni, Mary [University of Athens, Imaging and Research Unit (Greece); Moschouris, Hippocrates, E-mail: hipmosch@gmail.com [Tzanion Hospital, Department of Radiology (Greece); Bouma, Evanthia [University of Athens, Imaging and Research Unit (Greece); Koskinas, John [Ippokration Hospital, University of Athens, Department of Internal Medicine and Hepatology (Greece); Stefaniotou, Aspasia [University of Athens, Imaging and Research Unit (Greece); Marinis, Athanasios [Tzanion Hospital, Department of Surgery (Greece); Kelekis, Alexios; Alexopoulou, Efthymia [University of Athens, Second Department of Radiology (Greece); Chatziioannou, Achilles [University of Athens, First Department of Radiology (Greece); Chatzimichael, Katerina [University of Athens, Second Department of Radiology (Greece); Dourakis, Spyridon [Ippokration Hospital, University of Athens, Department of Internal Medicine and Hepatology (Greece); Kelekis, Nikolaos [University of Athens, Second Department of Radiology (Greece); Rizos, Spyros [Tzanion Hospital, Department of Surgery (Greece); Kelekis, Dimitrios [University of Athens, Imaging and Research Unit (Greece)

    2012-10-15

    Purpose: The purpose of this study was to report on the 5-year survival of hepatocellular carcinoma (HCC) patients treated with DC Bead loaded with doxorubicin (DEB-DOX) in a scheduled scheme in up to three treatments and thereafter on demand. Materials and Methods: 173 HCC patients not suitable for curable treatments were prospectively enrolled (mean age 70.4 {+-} 7.4 years). Child-Pugh (Child) class was A/B (102/71 [59/41 %]), Okuda stage was 0/1/2 (91/61/19 [53.2/35.7/11.1 %]), and mean lesion diameter was 7.6 {+-} 2.1 cm. Lesion morphology was one dominant {<=}5 cm (22 %), one dominant >5 cm (41.6 %), multifocal {<=}5 (26 %), and multifocal >5 (10.4 %). Results: Overall survival at 1, 2, 3, 4, and 5 years was 93.6, 83.8, 62, 41.04, and 22.5 %, with higher rates achieved in Child class A compared with Child class B patients (95, 88.2, 61.7, 45, and 29.4 % vs. 91.5, 75, 50.7, 35.2, and 12.8 %). Mean overall survival was 43.8 months (range 1.2-64.8). Cumulative survival was better for Child class A compared with Child class B patients (p = 0.029). For patients with dominant lesions {<=}5 cm 1-, 2-, 3-, 4-, and 5-year survival rates were 100, 95.2, 71.4, 66.6, and 47.6 % for Child class A and 94.1, 88.2, 58.8, 41.2, 29.4, and 23.5 % for Child class B patients. Regarding DEB-DOX treatment, multivariate analysis identified number of lesions (p = 0.033), lesion vascularity (p < 0.0001), initially achieved complete response (p < 0.0001), and objective response (p = 0.046) as significant and independent determinants of 5-year survival. Conclusion: DEB-DOX results, with high rates of 5-year survival for patients, not amenable to curative treatments. Number of lesions, lesion vascularity, and local response were significant independent determinants of 5-year survival.

  20. Chemoembolization With Doxorubicin-Eluting Beads for Unresectable Hepatocellular Carcinoma: Five-Year Survival Analysis

    International Nuclear Information System (INIS)

    Malagari, Katerina; Pomoni, Mary; Moschouris, Hippocrates; Bouma, Evanthia; Koskinas, John; Stefaniotou, Aspasia; Marinis, Athanasios; Kelekis, Alexios; Alexopoulou, Efthymia; Chatziioannou, Achilles; Chatzimichael, Katerina; Dourakis, Spyridon; Kelekis, Nikolaos; Rizos, Spyros; Kelekis, Dimitrios

    2012-01-01

    Purpose: The purpose of this study was to report on the 5-year survival of hepatocellular carcinoma (HCC) patients treated with DC Bead loaded with doxorubicin (DEB-DOX) in a scheduled scheme in up to three treatments and thereafter on demand. Materials and Methods: 173 HCC patients not suitable for curable treatments were prospectively enrolled (mean age 70.4 ± 7.4 years). Child-Pugh (Child) class was A/B (102/71 [59/41 %]), Okuda stage was 0/1/2 (91/61/19 [53.2/35.7/11.1 %]), and mean lesion diameter was 7.6 ± 2.1 cm. Lesion morphology was one dominant ≤5 cm (22 %), one dominant >5 cm (41.6 %), multifocal ≤5 (26 %), and multifocal >5 (10.4 %). Results: Overall survival at 1, 2, 3, 4, and 5 years was 93.6, 83.8, 62, 41.04, and 22.5 %, with higher rates achieved in Child class A compared with Child class B patients (95, 88.2, 61.7, 45, and 29.4 % vs. 91.5, 75, 50.7, 35.2, and 12.8 %). Mean overall survival was 43.8 months (range 1.2–64.8). Cumulative survival was better for Child class A compared with Child class B patients (p = 0.029). For patients with dominant lesions ≤5 cm 1-, 2-, 3-, 4-, and 5-year survival rates were 100, 95.2, 71.4, 66.6, and 47.6 % for Child class A and 94.1, 88.2, 58.8, 41.2, 29.4, and 23.5 % for Child class B patients. Regarding DEB-DOX treatment, multivariate analysis identified number of lesions (p = 0.033), lesion vascularity (p < 0.0001), initially achieved complete response (p < 0.0001), and objective response (p = 0.046) as significant and independent determinants of 5-year survival. Conclusion: DEB-DOX results, with high rates of 5-year survival for patients, not amenable to curative treatments. Number of lesions, lesion vascularity, and local response were significant independent determinants of 5-year survival.

  1. Clinical significance of incidental focal "1"8F-FDG uptake in the spinal cord of patients with cancer

    International Nuclear Information System (INIS)

    Lim, Chae Hong; Hyun, Seung Hyup; Moon, Seung Hwan; Cho, Young Seok; Choe, Yearn Seong; Lee, Kyung Han; Kim, Byung Tae; Choi, Joon Young

    2017-01-01

    We investigated the incidence, location, and clinical significance of focal "1"8F-FDG uptake of the spinal cord in patients with cancer. We reviewed the medical records of 22,937 consecutive adult patients with known or suspicious malignancy who underwent "1"8F-FDG PET/CT. PET/CT scans with incidental focal spinal cord uptake were selected and retrospectively reviewed to determine the presence, location, number, and maximum standardized uptake value (SUV_m_a_x) of any focal hypermetabolic lesions of the spinal cord. In subjects with focal spinal uptake, clinical characteristics and clinical follow-up results, including follow-up PET/CT, were reviewed. Incidental focal spinal cord uptake was observed in 69 of 22,937 adult patients (incidence = 0.3%; M:F = 31:38; age, 55.8 ± 14.7 years). Seventy-eight focal hypermetabolic lesions on spinal cord in the PET/CT scans of the 69 study subjects were analyzed. The most common sites of focal spinal cord uptake were the T12 vertebra (47/78; 60.3%) and L1 vertebra (20/78; 25.6%). Multifocal cord uptake was found in 8 of 69 patients (11.6%). The average SUVmax for cord uptake was 2.5 ± 0.5 (range, 1.4∼3.9). There was no clinical or imaging evidence of abnormalities in the spinal cord, both at the time of PET/CT and during clinical follow-up. Although incidental focal "1"8F-FDG uptake of the spinal cord is rare in patients with cancer, it may be physiological or benign, but it should not be considered as malignant involvement. Common sites for the uptake were in the T12 and L1 spine levels

  2. Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho; Kim, So Yeon [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Ramaiya, Nikhil H.; Tirumani, Sree Harsha [Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, MA (United States); Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    To evaluate the prognostic value of CT to predict recurrence-free and overall survival in patients with pancreatic neuroendocrine neoplasms (PanNENs). Between January 2004 and December 2012, 161 consecutive patients who underwent preoperative triphasic CT and surgical resection with curative intent for PanNENs were identified. The tumour consistency, margin, presence of calcification, pancreatic duct dilatation, bile duct dilatation, vascular invasion, and hepatic metastases were evaluated. The tumour size, arterial enhancement ratio, and portal enhancement ratio were measured. The Cox proportional hazard model was used to determine the association between CT features and recurrence-free survival and overall survival. By multivariate analysis, tumour size (>3 cm) (hazard ratio, 3.314; p = 0.006), portal enhancement ratio (≤1.1) (hazard ratio, 2.718; p = 0.006), and hepatic metastases (hazard ratio, 4.374; p = 0.003) were independent significant variables for worse recurrence-free survival. Portal enhancement ratio (≤1.1) (hazard ratio, 5.951; p = 0.001) and hepatic metastases (hazard ratio, 4.122; p = 0.021) were independent significant variables for worse overall survival. Portal enhancement ratio (≤1.1) and hepatic metastases assessed on CT were common independent prognostic factors for worse recurrence-free survival and overall survival in patients with PanNENs. (orig.)

  3. Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho; Kim, So Yeon; Song, Ki Byung; Ramaiya, Nikhil H.; Tirumani, Sree Harsha; Hong, Seung-Mo

    2016-01-01

    To evaluate the prognostic value of CT to predict recurrence-free and overall survival in patients with pancreatic neuroendocrine neoplasms (PanNENs). Between January 2004 and December 2012, 161 consecutive patients who underwent preoperative triphasic CT and surgical resection with curative intent for PanNENs were identified. The tumour consistency, margin, presence of calcification, pancreatic duct dilatation, bile duct dilatation, vascular invasion, and hepatic metastases were evaluated. The tumour size, arterial enhancement ratio, and portal enhancement ratio were measured. The Cox proportional hazard model was used to determine the association between CT features and recurrence-free survival and overall survival. By multivariate analysis, tumour size (>3 cm) (hazard ratio, 3.314; p = 0.006), portal enhancement ratio (≤1.1) (hazard ratio, 2.718; p = 0.006), and hepatic metastases (hazard ratio, 4.374; p = 0.003) were independent significant variables for worse recurrence-free survival. Portal enhancement ratio (≤1.1) (hazard ratio, 5.951; p = 0.001) and hepatic metastases (hazard ratio, 4.122; p = 0.021) were independent significant variables for worse overall survival. Portal enhancement ratio (≤1.1) and hepatic metastases assessed on CT were common independent prognostic factors for worse recurrence-free survival and overall survival in patients with PanNENs. (orig.)

  4. Bee Venom Phospholipase A2: Yesterday’s Enemy Becomes Today’s Friend

    Science.gov (United States)

    Lee, Gihyun; Bae, Hyunsu

    2016-01-01

    Bee venom therapy has been used to treat immune-related diseases such as arthritis for a long time. Recently, it has revealed that group III secretory phospholipase A2 from bee venom (bee venom group III sPLA2) has in vitro and in vivo immunomodulatory effects. A growing number of reports have demonstrated the therapeutic effects of bee venom group III sPLA2. Notably, new experimental data have shown protective immune responses of bee venom group III sPLA2 against a wide range of diseases including asthma, Parkinson’s disease, and drug-induced organ inflammation. It is critical to evaluate the beneficial and adverse effects of bee venom group III sPLA2 because this enzyme is known to be the major allergen of bee venom that can cause anaphylactic shock. For many decades, efforts have been made to avoid its adverse effects. At high concentrations, exposure to bee venom group III sPLA2 can result in damage to cellular membranes and necrotic cell death. In this review, we summarized the current knowledge about the therapeutic effects of bee venom group III sPLA2 on several immunological diseases and described the detailed mechanisms of bee venom group III sPLA2 in regulating various immune responses and physiopathological changes. PMID:26907347

  5. A New Alternative for Difficult Ureter in Adult Patients: No Need to Dilate Ureter via a Balloon or a Stent with the Aid of 4.5F Semirigid Ureteroscope.

    Science.gov (United States)

    Söylemez, Haluk; Yıldırım, Kadir; Utangac, Mehmet Mazhar; Aydoğan, Tahsin Batuhan; Ezer, Mehmet; Atar, Murat

    2016-06-01

    To investigate the effectivity of 4.5F ultrathin ureteroscope (UT-URS) without any need for active or passive dilation in the treatment of adult patient population in whom ureteral orifices cannot be engaged using conventional URS. Among a total of 512 adult patients who had undergone URS between April 2012 and November 2015 in our department for diagnostic or therapeutic purposes, 43 (8.4%) patients required ureteral dilation because we could not engage ureteral orifice. In adult patients in whom we could not engage ureteral orifice with 7.5F and 8F semirigid URS, we tried to complete the operation using 4.5F UT-URS without resorting to dilation. Age and gender of the patients, indication for operation, stone size, location, operative times, laterality of stone(s), stone-free rates, length of hospital stay, and complications were recorded. Mean age of the patients was 34.5 ± 11.2 (21-66) years. The patients had undergone operations for ureteral stone (n = 39), unexplained hydronephrosis (n = 2), and ureteral stenosis (n = 2). Mean stone size was 8.2 ± 2.3 (4-18) mm. Mean operative time was 64.2 ± 13.5 minutes. In 37 of 39 patients, a complete stone-free rate (94.8%) was achieved. Mean length of hospital stay was 8.9 ± 5.8 hours. It has been demonstrated that in an adult patient population in whom ureteral orifices cannot be engaged using conventional URS, ureteral access could be achieved with 4.5F UT-URS without any need for dilation. At the same time, use of 4.5F UT-URS resulted in an acceptable treatment success and lower complication rates in most of these patients without the need for a second session.

  6. High level of APOBEC3F/3G editing in HIV-2 DNA vif and pol sequences from antiretroviral-naive patients.

    Science.gov (United States)

    Bertine, Mélanie; Charpentier, Charlotte; Visseaux, Benoit; Storto, Alexandre; Collin, Gilles; Larrouy, Lucile; Damond, Florence; Matheron, Sophie; Brun-Vézinet, Françoise; Descamps, Diane

    2015-04-24

    In HIV-1, hypermutation introduced by APOBEC3F/3G cytidine deaminase activity leads to defective viruses. In-vivo impact of APOBEC3F/3G editing on HIV-2 sequences remains unknown. The objective of this study was to assess the level of APOBEC3F/3G editing in HIV-2-infected antiretroviral-naive patients. Direct sequencing of vif and pol regions was performed on HIV-2 proviral DNA from antiretroviral-naive patients included in the French Agence Nationale de Recherches sur le SIDA et les hépatites virales CO5 HIV-2 cohort. Hypermutated sequences were identified using Hypermut2.0 program. HIV-1 proviral sequences from Genbank were also assessed. Among 82 antiretroviral-naive HIV-2-infected patients assessed, 15 (28.8%) and five (16.7%) displayed Vif proviral defective sequences in HIV-2 groups A and B, respectively. A lower proportion of defective sequences was observed in protease-reverse transcriptase region. A higher median number of G-to-A mutations was observed in HIV-2 group B than in group A, both in Vif and protease-reverse transcriptase regions (P = 0.02 and P = 0.006, respectively). Compared with HIV-1 Vif sequences, a higher number of Vif defective sequences was observed in HIV-2 group A (P = 0.00001) and group B sequences (P = 0.013). We showed for the first time a high level of APOBEC3F/3G editing in HIV-2 sequences from antiretroviral-naive patients. Our study reported a group effect with a significantly higher level of APOBEC3F/3G editing in HIV-2 group B than in group A sequences.

  7. PD-L1 Expression and Survival among Patients with Advanced Non-Small Cell Lung Cancer Treated with Chemotherapy

    DEFF Research Database (Denmark)

    Sørensen, Steffen Filskov; Zhou, Wei; Dolled-Filhart, Marisa

    2016-01-01

    with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy are inconsistent. MATERIAL AND METHODS: We evaluated the relationship between PD-L1 expression and overall survival (OS) among 204 patients with advanced NSCLC treated at Aarhus University Hospital, Aarhus, Denmark, from 2007 to 2012. PD......-positive tumors, and 50% had PD-L1 weak-positive tumors. No statistically significant association was found between PD-L1 expression and survival; adjusted hazard ratio of 1.34 (95% confidence interval, 0.88-2.03; median OS, 9.0 months) for the PD-L1 strong-positive group and 1.07 (0.74-1.55; median OS, 9...... by immunohistochemistry to be frequently expressed in patients with advanced NSCLC. However, PD-L1 expression is not a strong prognostic marker in patients with advanced NSCLC treated with chemotherapy....

  8. Identification and analytical characterization of six synthetic cannabinoids NNL-3, 5F-NPB-22-7N, 5F-AKB-48-7N, 5F-EDMB-PINACA, EMB-FUBINACA, and EG-018.

    Science.gov (United States)

    Liu, Cuimei; Jia, Wei; Hua, Zhendong; Qian, Zhenhua

    2017-08-01

    Clinical and forensic toxicology laboratories are continuously confronted by analytical challenges when dealing with the new psychoactive substances phenomenon. The number of synthetic cannabinoids, the chemical diversity, and the speed of emergence make this group of compounds particularly challenging in terms of detection, monitoring, and responding. Three indazole 7N positional isomer synthetic cannabinoids, two ethyl 2-amino-3-methylbutanoate-type synthetic cannabinoids, and one 9H-carbazole substituted synthetic cannabinoid were identified in seized materials. These six synthetic cannabinoid derivatives included: 1H-benzo[d] [1,2,3]triazol-1-yl 1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (NNL-3, 1), quinolin-8-yl 1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate (5F-NPB-22-7N, 2), N-((1 s,3 s)-adamantan-1-yl)-1-(5-fluoropentyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide (5F-AKB-48-7N, 3), ethyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (5F-EDMB-PINACA, 4), ethyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate (EMB-FUBINACA, 5), and naphthalen-1-yl(9-pentyl-9H-carbazol-3-yl)methanone (EG-018, 6). The identification was based on ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UHPLC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy (NMR). The analytical characterization of these six synthetic cannabinoids was described, so as to assist forensic laboratories in identifying these compounds or other substances with similar structure in their case work. To our knowledge, no analytical data about the compounds 1-5 have appeared until now, making this the first report on these compounds. The GC-MS data of 6 has been reported, but this study added the LC-MS, NMR, and Fourier transform infrared (FTIR), data to render the analytical data collection process more complete. Copyright © 2017 John Wiley & Sons, Ltd

  9. Relation between hypermetabolism, cachexia, and survival in cancer patients: a prospective study in 390 cancer patients before initiation of anticancer therapy.

    Science.gov (United States)

    Vazeille, Clara; Jouinot, Anne; Durand, Jean-Philippe; Neveux, Nathalie; Boudou-Rouquette, Pascaline; Huillard, Olivier; Alexandre, Jérôme; Cynober, Luc; Goldwasser, François

    2017-05-01

    Background: Cachexia is a major cause of death in cancer patients. The role of hypermetabolism in cancer cachexia remains unclear. Objective: We studied the relation between resting energy expenditure (REE), the estimated energy balance, clinical and biological markers of cachexia, and survival. Design: REE was measured with the use of indirect calorimetry in cancer patients before the initiation of anticancer therapies. Hypermetabolic, normometabolic, and hypometabolic patients were identified with the use of Boothby's standard. Weight loss, performance status (PS), C-reactive protein (CRP), albumin, the nutritional risk index, daily energy intake, energy balance (equal to daily energy intakes minus the REE), and survival were recorded. Results: Of 390 enrolled patients, 49% of subjects were hypermetabolic, 30% of subjects were normometabolic, and 21% of subjects were hypometabolic. Mean daily energy intakes did not differ significantly between the 3 groups. Hypermetabolic patients, compared with normometabolic patients, were more likely to have a negative energy balance [45% compared with 32%, respectively; OR: 1.74 (95% CI: 1.05, 2.91); P = 0.024], weight loss >5% [48% compared with 34%, respectively; OR: 1.83 (95% CI: 1.11, 3.04); P = 0.013], PS ≥2 [40% compared with 29%, respectively; OR: 1.70 (95% CI: 1.01, 2.88); P = 0.038], and CRP concentrations ≥10 mg/L [52% compared with 33%, respectively; OR: 2.2 (95% CI: 1.33, 3.66); P = 0.001]. In metastatic patients, compared with normometabolism, hypermetabolism was associated with a reduced median survival [14.6 compared with 21.4 mo, respectively; OR: 1.48 (95% CI: 1.01, 2.17); P = 0.044]. Conclusions: Hypermetabolism is correlated with clinical and biological markers of cancer cachexia and is associated with a shorter survival in metastatic cancer patients. The development of therapeutic strategies that aim to blunt hypermetabolism appears warranted. This trial was registered at www.controlled-trials.com as

  10. Factors influencing local control and survival for patients undergoing stereotactic radiosurgery for intracranial metastases

    International Nuclear Information System (INIS)

    Suh, John H.; Barnett, Gene H.; Sohn, Jason W.; Fernandez-Vicioso, Eduardo; Kupelian, Patrick A.

    1996-01-01

    PURPOSE: To identify factors affecting local control and survival for patients undergoing stereotactic radiosurgery for intracranial metastases. MATERIALS AND METHODS: From 3/90-10/95, 99 patients (median age 58, range 29-83; 44 women, 55 men) with asymptomatic or mildly symptomatic intracranial metastases measuring < 4 cm in diameter and ≥ 1 cm from optic chiasm and Karnofsky Performance Status (KPS) ≥ 70 underwent modified linear accelerator-based stereotactic radiosurgery (SRS). Patients characteristics included 20 with recurrent disease, 66 with solitary lesions, and 42 with systemic disease. Forty six patients underwent surgical resection prior to SRS (16 biopsy, 3 subtotal resection (STR), and 21 gross total resection (GTR)). Eighty of 99 patients underwent whole brain radiation treatments (median 4005 cGy/15 fx, range 2200-6000 cGy). A total of 154 lesions were treated with 143 being evaluable on follow-up CT or MRI scans. Radiosurgery parameters (median) were the following: volume 2.8 cc (range 0.1-38 cc) and a peripheral dose of 1700 cGy (range 500-2400 cGy) with normalization to the 80% line (range 50-90%). Survival was measured from the date of SRS. Local control was defined as stabilization or decrease in size of the intracranial lesion(s). RESULTS: The following factors were analyzed with respect to local control and survival: 1) solitary vs. multiple lesions, 2) Age < or ≥ 60, 3) sex, 4) radiosensitive vs. radioresistant (renal cell and melanoma) histologies, 5) recurrent vs. newly diagnosed lesions, 6) KPS (70-80 vs. 90-100), 7) extent of surgery (biopsy vs. STR/GTR), 8) use of whole brain radiation treatments, 9) absence or presence of systemic disease, 10) dose (< or ≥ 1500 cGy) and 11) volume (< or ≥ 3 cc). On univariate analysis, survival was significantly influenced by female sex, presence of solitary lesion, absence of systemic disease, and extent of surgery. On multivariate analysis, female sex (p=0.0037), absence of systemic disease

  11. Pre-treatment hemodynamic features involved with long-term survival of cirrhotic patients after embolization of gastric fundal varices

    International Nuclear Information System (INIS)

    Maruyama, Hitoshi; Okugawa, Hidehiro; Kobayashi, Satoshi; Yoshizumi, Hiroaki; Yokosuka, Osamu

    2010-01-01

    Purpose: To clarify the pre-treatment hemodynamic features involved in the long-term survival of cirrhotic patients with gastric fundal varices (FV) after balloon-occluded retrograde transvenous obliteration (B-RTO). Materials and methods: Eighty-one cirrhotic patients with medium- or large-grade FV treated by B-RTO were enrolled in this retrospective study. Pre-treatment flow volume ratio between gastric vein and portal trunk (GP-R) was obtained by Doppler ultrasound. Results: The cumulative survival rate was 90% at 1 year, 74.8% at 3 years, 57.2% at 5 years, and 45.8% at 7 years without recurrence in a median period of 1148.5 days The survival was poorer in patients with HCC (47% at 3 years, 9.4% at 5 years, p < 0.0001) than without (89.2% at 3 years, 81.9% at 5 years, 67.5% at 7 years), in patients with Child B/C (57.7% at 3 years, 42.1% at 5 years, 28.1% at 7 years, p = 0.0016) than with Child A (91.8% at 3 years, 71.5% at 5 years, 62.1% at 7 years), and in patients with GP-R ≥ 1.0 (58.9% at 3 years, p = 0.0485) than with GP-R < 1.0 (76.3% at 3 years, 62% at 5 years, 49.6% at 7 years). Multivariate analysis identified the presence of HCC (hazard ratio, 12.486; 95% CI, 4.08-38.216; p < 0.0001), Child B/C (hazard ratio, 3.41; 95% CI, 1.594-7.15; p = 0.0051) and GP-R ≥ 1.0 (hazard ratio, 2.701; 95% CI, 1.07-6.15; p = 0.0221) as independent factors for poor prognosis. Conclusion: GP-R ≥ 1.0 on Doppler ultrasound before B-RTO may be a predictive indicator for poor prognosis in cirrhotic patients with FV after B-RTO, in addition to the presence of HCC and severe liver damage.

  12. Pre-treatment hemodynamic features involved with long-term survival of cirrhotic patients after embolization of gastric fundal varices

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Hitoshi, E-mail: maru-cib@umin.ac.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Okugawa, Hidehiro, E-mail: hideun@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Kobayashi, Satoshi, E-mail: kobakobakopa@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Yoshizumi, Hiroaki, E-mail: yossih04@yahoo.co.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan); Yokosuka, Osamu, E-mail: yokosukao@faculty.chiba-u.j [Department of Medicine and Clinical Oncology, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chuou-ku, Chiba, 260-8670 (Japan)

    2010-08-15

    Purpose: To clarify the pre-treatment hemodynamic features involved in the long-term survival of cirrhotic patients with gastric fundal varices (FV) after balloon-occluded retrograde transvenous obliteration (B-RTO). Materials and methods: Eighty-one cirrhotic patients with medium- or large-grade FV treated by B-RTO were enrolled in this retrospective study. Pre-treatment flow volume ratio between gastric vein and portal trunk (GP-R) was obtained by Doppler ultrasound. Results: The cumulative survival rate was 90% at 1 year, 74.8% at 3 years, 57.2% at 5 years, and 45.8% at 7 years without recurrence in a median period of 1148.5 days The survival was poorer in patients with HCC (47% at 3 years, 9.4% at 5 years, p < 0.0001) than without (89.2% at 3 years, 81.9% at 5 years, 67.5% at 7 years), in patients with Child B/C (57.7% at 3 years, 42.1% at 5 years, 28.1% at 7 years, p = 0.0016) than with Child A (91.8% at 3 years, 71.5% at 5 years, 62.1% at 7 years), and in patients with GP-R {>=} 1.0 (58.9% at 3 years, p = 0.0485) than with GP-R < 1.0 (76.3% at 3 years, 62% at 5 years, 49.6% at 7 years). Multivariate analysis identified the presence of HCC (hazard ratio, 12.486; 95% CI, 4.08-38.216; p < 0.0001), Child B/C (hazard ratio, 3.41; 95% CI, 1.594-7.15; p = 0.0051) and GP-R {>=} 1.0 (hazard ratio, 2.701; 95% CI, 1.07-6.15; p = 0.0221) as independent factors for poor prognosis. Conclusion: GP-R {>=} 1.0 on Doppler ultrasound before B-RTO may be a predictive indicator for poor prognosis in cirrhotic patients with FV after B-RTO, in addition to the presence of HCC and severe liver damage.

  13. Twist-1 Up-Regulation in Carcinoma Correlates to Poor Survival

    Directory of Open Access Journals (Sweden)

    Alimujiang Wushou

    2014-11-01

    Full Text Available Epithelial-to-mesenchymal transition (EMT facilitates tumor metastasis. Twist is a basic helix-loop-helix protein that modulates many target genes through E-box-responsive elements. There are two twist-like proteins, Twist-1 and Twist-2, sharing high structural homology in mammals. Twist-1 was found to be a key factor in the promotion of metastasis of cancer cells, and is known to induce EMT. Twist-1 participation in carcinoma progression and metastasis has been reported in a variety of tumors. However, controversy exists concerning the correlation between Twist-1 and prognostic value with respect to carcinoma. A systematic review and meta-analysis were performed to determine whether the expression of Twist-1 was associated with the prognosis of carcinoma patients. This analysis included 17 studies: four studies evaluated lung cancer, three evaluated head and neck cancer, two evaluated breast cancer, two evaluated esophageal cancer, two evaluated liver cancer and one each evaluated osteosarcoma, bladder, cervical and ovarian cancer. A total of 2006 patients were enrolled in these studies, and the median trial sample size was 118 patients. Twist-1 expression was associated with worse overall survival (OS at both 3 years (hazard ratio “HR” for death = 2.13, 95% CI = 1.86 to 2.45, p < 0.001 and 5 years (HR for death = 2.01, 95% CI = 1.76 to 2.29, p < 0.001. Expression of Twist-1 is associated with worse survival in carcinoma.

  14. Prediction of survival in patients with Stage IV kidney cancer

    Directory of Open Access Journals (Sweden)

    L. V. Mirilenko

    2015-01-01

    Full Text Available The efficiency of treatment was evaluated and the predictors of adjusted survival (AS were identified in patients with disseminated kidney cancer treated at the Republican Research and Practical Center for Oncology and Medical Radiology in 1999 to 2011 (A.E. Okeanov, P.I. Moiseev, L.F. Levin. Malignant tumors in Belarus, 2001–2012. Edited by O.G. Sukonko. Seven factors (regional lymph node metastases; distant bone metastases; a high-grade tumor; sarcomatous tumor differentiation; hemoglobin levels of < 125 g/l in women and < 150 g/l in men; an erythrocyte sedimentation rate of 40 mm/h; palliative surgery were found to have an independent, unfavorable impact on AS. A multidimensional model was built to define what risk group low (no more than 2 poor factors, moderate (3–4 poor factors, and high (more than 4 poor factors the patients with Stage IV kidney cancer belonged to. In these groups, the median survival was 34.7, 17.2, and 4.0 months and 3-year AS rates were 48.6, 24.6, and 3.2 %, respectively. 

  15. Computation of the chiral condensate using N{sub f}=2 and N{sub f}=2+1+1 dynamical flavors of twisted mass fermions

    Energy Technology Data Exchange (ETDEWEB)

    Cichy, K. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Poznan Univ. (Poland). Faculty of Physics; Garcia-Ramos, E. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Humboldt-Universitaet, Berlin (Germany); Jansen, K. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC; Shindler, A. [Forschungszentrum Juelich (Germany). IAS; Forschungszentrum Juelich (Germany). IKP; Forschungszentrum Juelich (Germany). JCHP; Collaboration: European Twisted Mass Collaboration

    2013-12-15

    We apply the spectral projector method, recently introduced by Giusti and Luescher, to compute the chiral condensate using N{sub f}=2 and N{sub f}=2+1+1 dynamical flavors of maximally twisted mass fermions. We present our results for several quark masses at three different lattice spacings which allows us to perform the chiral and continuum extrapolations. In addition we report our analysis on the O(a) improvement of the chiral condensate for twisted mass fermions. We also study the effect of the dynamical strange and charm quarks by comparing our results for N{sub f}=2 and N{sub f}=2+1+1 dynamical flavors.

  16. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

    DEFF Research Database (Denmark)

    Kolko, M; DeCoster, M A; de Turco, E B

    1996-01-01

    glutamate and sPLA2 from bee venom. sPLA2, at concentrations eliciting low neurotoxicity (acid into triacylglycerols. Free [3H]arachidonic acid accumulated at higher enzyme concentrations......, from Taipan snake venom. The NMDA receptor antagonist MK-801 blocked glutamate effects and partially inhibited sPLA2 OS2 but not sPLA2 from bee venom-induced arachidonic acid release. Thus, the synergy with glutamate and very low concentrations of exogenously added sPLA2 suggests a potential role......Secretory and cytosolic phospholipases A2 (sPLA2 and cPLA2) may contribute to the release of arachidonic acid and other bioactive lipids, which are modulators of synaptic function. In primary cortical neuron cultures, neurotoxic cell death and [3H]arachidonate metabolism was studied after adding...

  17. Impact of CyberKnife Radiosurgery on Overall Survival and Various Parameters of Patients with 1-3 versus ≥ 4 Brain Metastases.

    Science.gov (United States)

    Murovic, Judith; Ding, Victoria; Han, Summer S; Adler, John R; Chang, Steven D

    2017-10-24

    Introduction This study's objective is to compare the overall survivals (OSs) and various parameters of patients with 1-3 versus ≥ 4 brain metastases post-CyberKnife radiosurgery (CKRS) (Accuray, Sunnyvale, California) alone. Methods Charts of 150 patients, from 2009-2014, treated with only CKRS for brain metastases were reviewed retrospectively for overall survival (OS) and patient, tumor, and imaging characteristics. Parameters included demographics, Eastern Cooperative Oncology Group (ECOG) performance scores, number and control of extracranial disease (ECD) sites, cause of death (COD), histology, tumor volume (TV), and post-CKRS whole brain radiotherapy (WBRT). The imaging characteristics assessed were time of complete response (CR), partial response (PR), stable imaging or local failure (LF), and distal brain failure (DBF). Patients and their data were divided into those with 1-3 (group 1) versus ≥ 4 brain metastases (group 2). For each CR and LF patient, absolute neutrophil count (ANC), absolute lymphocyte count (ALC)), and ANC/ALC ratio (NLR) were obtained, when available, at the time of CKRS. Results Both group 1 and group 2 had a median OS of 13 months. The patient median age for the 115 group 1 patients versus the 35 group 2 patients was 62 versus 56 years. Group 1 had slightly more males and group 2, females. The predominant ECOG score for each group was 1 and the number of ECD sites was one and two, respectively. Uncontrolled ECD occurred in the majority of both group 1 and group 2 patients. The main COD was ECD in both groups. The prevalent tumor histology for groups 1 and 2 was non-small cell lung carcinoma. Median TVs were 1.08 cc versus 1.42 cc for groups 1 and 2, respectively. The majority of patients in both groups did not undergo post-CKRS WBRT. Imaging outcomes were LC (CR, PR, or stable imaging) in 93 (80.9%) and 26 (74.3%) group 1 and 2 patients, of whom 32 (27.8%) and six (17.1%) had CR; 38 (33.0%) and 18 (51.4%), PR and 23

  18. The preoperative HbA1c level is an independent prognostic factor for the postoperative survival after resection of non-small cell lung cancer in elderly patients.

    Science.gov (United States)

    Motoishi, Makoto; Sawai, Satoru; Hori, Tetsuo; Yamashita, Naoki

    2018-05-01

    The aim of this study was to investigate the influence of a history of diabetes mellitus (DM) and the glycated hemoglobin (HbA1c) level on the survival in patients who underwent complete resection for non-small cell lung cancer (NSCLC). Of the patients who underwent complete resection for NSCLC between 2007 and 2015, 468 were classified into DM (who were currently taking medication for DM) and no DM groups as well as into high HbA1c (≥ 6.5) and normal HbA1c (HbA1c group than in the high-HbA1c group (5-year survival rate: 84.7 versus 37.2%, respectively, p HbA1c level were found to be independent risk factors for the OS. We revealed that a high preoperative HbA1c level was associated with a poor OS in elderly patients who underwent complete resection for NSCLC. This suggests that it is necessary to achieve diabetic control prior to complete resection in NSCLC patients.

  19. Association of germline variation in CCNE1 and CDK2 with breast cancer risk, progression and survival among Chinese Han women.

    Directory of Open Access Journals (Sweden)

    Ji-Yuan Han

    Full Text Available BACKGROUND: Somatic alterations of cyclin-dependent kinase 2 (CDK2-cyclin E complex have been shown to contribute to breast cancer (BC development and progression. This study aimed to explore the effects of single nucleotide polymorphisms (SNPs in CDK2 and CCNE1 (a gene encoding G1/S specific cyclin E1 protein, formerly called cyclin E on BC risk, progression and survival in a Chinese Han population. METHODOLOGY/PRINCIPAL FINDINGS: We herein genotyped 6 haplotype-tagging SNPs (htSNPs of CCNE1 and 2 htSNPs of CDK2 in 1207 BC cases and 1207 age-matched controls among Chinese Han women, and then reconstructed haplotype blocks according to our genotyping data and linkage disequilibrium status of these htSNPs. For CCNE1, the minor allele homozygotes of three htSNPs were associated with BC risk (rs3218035: adjusted odds ratio [aOR] = 3.35, 95% confidence interval [CI] = 1.69-6.67; rs3218038: aOR = 1.81, 95% CI = 1.22-2.70; rs3218042: aOR = 2.64, 95% CI = 1.31-5.34, and these three loci showed a dose-dependent manner in increasing BC risk (P(trend = 0.0001. Moreover, the 5-SNP haplotype CCGTC, which carried none of minor alleles of the 3 at-risk SNPs, was associated with a favorable event-free survival (hazard ratio [HR] = 0.53, 95% CI = 0.32-0.90. Stratified analysis suggested that the minor-allele homozygote carriers of rs3218038 had a worse event-free survival among patients with aggressive tumours (in tumour size>2 cm group: HR = 2.06, 95% CI = 1.06-3.99; in positive lymph node metastasis group: HR = 2.41, 95% CI = 1.15-5.03; in stage II-IV group: HR = 2.03, 95% CI = 1.09-3.79. For CDK2, no significant association was found. CONCLUSIONS/SIGNIFICANCE: This study indicates that genetic variants in CCNE1 may contribute to BC risk and survival in Chinese Han population. They may become molecular markers for individual evaluation of BC susceptibility and prognosis. Nevertheless, further validation studies are needed.

  20. Ten-year survival of patients with oesophageal squamous cell ...

    African Journals Online (AJOL)

    patients with oesophageal SCC continues to be poor, with 5-year survival rates ranging from 26.2% to ... approach, and the cervico-thoraco-abdominal procedure. The .... abuse, a family history of any cancer, neo-adjuvant treatment, pathological ... Of the entire series, 72 patients (6.9%) underwent neo-adjuvant therapy, and.

  1. Distant metastases and synchronous second primary tumors in patients with newly diagnosed oropharyngeal and hypopharyngeal carcinomas: evaluation of 18F-FDG PET and extended-field multi-detector row CT

    International Nuclear Information System (INIS)

    Ng, Shu-Hang; Ko, Sheung-Fat; Chin, Shu-Chyn; Chan, Sheng-Chieh; Yen, Tzu-Chen; Liao, Chun-Ta; Huang, Shiang-Fu; Chang, Joseph Tung-Chieh; Lin, Chin-Yu.; Wang, Hung-Ming

    2008-01-01

    Patients with oropharyngeal or hypopharyngeal squamous cell carcinoma (SCC) have a high risk of having distant metastases or second primary tumors. We prospectively evaluate the clinical usefulness of 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG PET), extended-field multi-detector computed tomography (MDCT), and their side-by-side visual correlation for the detection of distant malignancies in these two tumors at presentation. A total of 160 patients with SCC of the oropharynx (n = 74) or hypopharynx (n=86) underwent 18 F-FDG PET and extended-field MDCT to detect distant metastases or second primary tumors. Suspected lesions were investigated by means of biopsy, clinical, or imaging follow-up. Twenty-six (16.3%) of our 160 patients were found to have distant malignancy. Diagnostic yields of 18 F-FDG PET and MDCT were 12.5% and 8.1%, respectively. The sensitivity of 18 F-FDG PET for detection of distant malignancies was 1.5-fold higher than that of MDCT (76.9% vs. 50.0%, P=0.039), while its specificity was slightly lower (94.0% vs. 97.8%, P=0.125). Side-by-side visual correlation of MDCT and 18 F-FDG PET improved the sensitivity and specificity up to 80.8% and 98.5%, respectively, leading to alteration of treatment in 13.1% of patients. A significant difference in survival rates between its positive and negative results was observed. 18 F-FDG PET and extended-field MDCT had acceptable diagnostic yields for detection of distant malignancies in untreated oropharyngeal and hypopharyngeal SCC. 18 F-FDG PET was 1.5-fold more sensitive than MDCT, but had more false-positive findings. Their visual correlation improved the diagnostic accuracy, treatment planning, and prognosis prediction. (orig.)

  2. Multicenter Phase 2 Study of Cisplatin and 5-Fluorouracil With Concurrent Radiation Therapy as an Organ Preservation Approach in Patients With Squamous Cell Carcinoma of the Cervical Esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Zenda, Sadamoto, E-mail: szenda@east.ncc.go.jp [Department of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Kojima, Takashi [Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba (Japan); Kato, Ken [Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo (Japan); Izumi, Sachiko [Department of Radiation Oncology, Tokyo Women' s Medical University, Tokyo (Japan); Ozawa, Taijiro [Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Aichi (Japan); Kiyota, Naomi [Department of Medical Oncology and Hematology, Kobe University Hospital, Hyogo (Japan); Katada, Chikatoshi [Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara (Japan); Tsushima, Takahiro [Department of Gastrointestinal Endoscopy and Oncology, Shizuoka Cancer Center Hospital, Shizuoka (Japan); Ito, Yoshinori [Division of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan); Akimoto, Tetsuo [Department of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Hasegawa, Yasuhisa [Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Aichi (Japan); Kanamaru, Miyuki [Department of Radiation Oncology, National Cancer Center Hospital East, Chiba (Japan); Daiko, Hiroyuki [Department of Surgery, National Cancer Center Hospital East, Chiba (Japan)

    2016-12-01

    Purpose: To clarify, in a multicenter, single-arm, phase 2 study (UMIN Clinical Trials Registry no. UMIN000001439), the clinical profile of chemoradiotherapy (CRT) for cervical esophageal cancer. Patients and Methods: Patients with operable cervical esophageal cancer, excluding candidates for endoscopic resection, were enrolled. Protocol treatment consisted of CRT and adjuvant chemotherapy (CT). First, patients received concurrent CRT with 5-fluorouracil (5-FU) plus cisplatin (CDDP). Chemotherapy consisted of 5-FU at 700 mg/m{sup 2} intravenous on days 1 to 4 and CDDP at 70 mg/m{sup 2} intravenous on day 1, repeated every 4 weeks for 2 cycles. Radiation therapy consisted of 60 Gy in 30 fractions. After completion of CRT, 2 additional cycles of CT with 5-FU (800 mg/m{sup 2}, days 1-5) and CDDP (80 mg/m{sup 2}, day 1) were repeated at a 4-week interval. The primary endpoint was 3-year overall survival. Results: Thirty patients were enrolled across 8 institutions in Japan, consisting of 26 men and 4 women with a median age of 64.5 years (range, 50-75 years). No grade 4 hematologic toxicity was seen in the CRT phase, and 1 grade 4 thrombocytopenia was seen in the CT phase. Grade 3 nonhematologic acute toxicities in the CRT phase were nausea (10%), mucositis (13.3%), and dysphagia (13.3%). No treatment-related death in either phase occurred. Overall complete response rate was 73%, and 3-year overall and laryngectomy-free survival were 66.5% and 52.5%, respectively. Regarding T4 disease, 3-year overall and laryngectomy-free survival were 58.3% and 38.5%, respectively. Conclusions: This study, the first prospective study for cervical esophageal cancer, showed that CRT has sufficient efficacy and safety for use as an alternative to surgery for these patients.

  3. Calculation of thermodynamic properties and transport coefficients of C5F10O-CO2 thermal plasmas

    Science.gov (United States)

    Li, Xingwen; Guo, Xiaoxue; Murphy, Anthony B.; Zhao, Hu; Wu, Jian; Guo, Ze

    2017-10-01

    The thermodynamic properties and transport coefficients of C5F10O-CO2 gas mixtures, which are being considered as substitutes for SF6 in circuit breaker applications, are calculated for the temperature range from 300 K to 30 000 K and the pressure range from 0.05 MPa to 1.6 MPa. Special attention is paid on investigating the evolution of thermophysical properties of C5F10O-CO2 mixtures with different mixing ratios and with different pressures; both the mixing ratio and pressure significantly affect the properties. This is explained mainly in terms of the changes in the temperatures at which the dissociation and ionization reactions take place. Comparisons of different thermophysical properties of C5F10O-CO2 mixtures with those of SF6 are also carried out. It is found that most of the thermophysical properties of the C5F10O-CO2 mixtures, such as thermal conductivity, viscosity, and electrical conductivity, become closer to those of SF6 as the C5F10O concentration increases. The composition and thermophysical properties of pure C5F10O in the temperature range from 300 K to 2000 K based on the decomposition pathway are also given. The calculation results provide a basis for further study of the insulation and arc-quenching capability of C5F10O-CO2 gas mixtures as substitutes for SF6.

  4. Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers.

    Science.gov (United States)

    Kurian, Allison W; Sigal, Bronislava M; Plevritis, Sylvia K

    2010-01-10

    Women with BRCA1/2 mutations inherit high risks of breast and ovarian cancer; options to reduce cancer mortality include prophylactic surgery or breast screening, but their efficacy has never been empirically compared. We used decision analysis to simulate risk-reducing strategies in BRCA1/2 mutation carriers and to compare resulting survival probability and causes of death. We developed a Monte Carlo model of breast screening with annual mammography plus magnetic resonance imaging (MRI) from ages 25 to 69 years, prophylactic mastectomy (PM) at various ages, and/or prophylactic oophorectomy (PO) at ages 40 or 50 years in 25-year-old BRCA1/2 mutation carriers. With no intervention, survival probability by age 70 is 53% for BRCA1 and 71% for BRCA2 mutation carriers. The most effective single intervention for BRCA1 mutation carriers is PO at age 40, yielding a 15% absolute survival gain; for BRCA2 mutation carriers, the most effective single intervention is PM, yielding a 7% survival gain if performed at age 40 years. The combination of PM and PO at age 40 improves survival more than any single intervention, yielding 24% survival gain for BRCA1 and 11% for BRCA2 mutation carriers. PM at age 25 instead of age 40 offers minimal incremental benefit (1% to 2%); substituting screening for PM yields a similarly minimal decrement in survival (2% to 3%). Although PM at age 25 plus PO at age 40 years maximizes survival probability, substituting mammography plus MRI screening for PM seems to offer comparable survival. These results may guide women with BRCA1/2 mutations in their choices between prophylactic surgery and breast screening.

  5. EFICIÊNCIA AGRONÔMICA DOS RIZÓBIOS SEMIA 6156, F 3 (4, F 2 (1, F2 - 2B, CPAC-B10 EM FEIJÃO DE PORCO

    Directory of Open Access Journals (Sweden)

    Thiago Santos de Paula Silva

    2015-07-01

    Full Text Available O objetivo foi validar e recomendar bactérias fixadoras de nitrogênio usadas em inoculantes comerciais na leguminosa Canavalia ensiformis. O trabalho foi conduzido durante os meses de novembro de 2013 a fevereiro 2014. O delineamento experimental foi o de blocos ao acaso com quatro repetições e com unidade experimental de 24 m2, o plantio realizado no espaçamento de 0,5 m entre sulcos, densidade de 10 sementes por metro linear, As estirpes de rizóbio avaliadas foram: SEMIA 6156, F 3 (4, F 2 (1, F2 - 2B, CPAC-B10. A primeira avaliação foi realizada aos 30 dias após a semeadura (DAS, para número e massa de nódulos frescos e secos, massa seca da parte aérea e raízes. A segunda avaliação foi realizada quando 50% das plantas estavam em florescimento, quantificando-se a massa seca das folhas e caules, massa seca total da parte aérea e análise total de macronutrientes em folhas e caule. A estirpe F 2 (1 pode realizar efetiva simbiose com as plantas de feijão de porco, promovendo ganhos no acúmulo de massa seca de parte aérea das plantas, sendo assim considerada agronomicamente eficiente e recomendada para uso em inoculantes comerciais.

  6. Synthesis, Properties and Stereochemistry of 2-Halo-1,2λ5-oxaphosphetanes

    Directory of Open Access Journals (Sweden)

    Anastasy O. Kolodiazhna

    2016-10-01

    Full Text Available Results of research into four-membered 2-halo-1,2λ5-oxaphosphetane phosphorus(V-heterocycles are presented. The preparation of 2-halo-1,2λ5-oxaphosphetanes by reaction of P-haloylides with carbonyl compounds is described. The mechanism of asynchronous [2+2]-сycloaddition of ylides to aldehydes was proposed on the base of low-temperature NMR investigations. 2-Halo-1,2λ5-oxaphosphetanes were isolated as individual compounds and their structures were confirmed by 1Н-, 13C-, 19F- and 31Р-NMR spectra. These compounds are convenient reagents for preparing of various organic and organophosphorus compounds hardly available by other methods. Chemical and physical properties of the 2-halo-1,2λ5-oxaphosphetanes are reviewed. The 2-chloro-1,2λ5-oxaphosphetanes, rearrange with formation of 2-chloroalkyl-phosphonates or convert into trans-phosphorylated alkenes depending on the substituents at the α-carbon atom. Prospective synthetic applications of 2-halo-1,2λ5-oxaphosphetanes are analyzed. The 2-halo-1,2λ5-oxaphosphetanes may be easily converted to various alkenylphosphonates: allyl- or vinylphosphonates, phosphorus ketenes, thioketenes, ketenimines.

  7. UK Renal Registry 15th annual report: Chapter 5 survival and causes of death of UK adult patients on renal replacement therapy in 2011: national and centre-specific analyses.

    Science.gov (United States)

    Steenkamp, Retha; Shaw, Catriona; Feest, Terry

    2013-01-01

    These analyses examine a) survival from the start of renal replacement therapy (RRT) based on the total incident UK RRT population reported to the UK Renal Registry, b) survival of prevalent patients. Changes in survival between 1997 and 2011 are also reported. Survival was calculated for both incident and prevalent patients on RRT and compared between the UK countries after adjustment for age. Survival of incident patients (starting RRT during 2010) was calculated both from the start of RRT and from 90 days after starting RRT, both with and without censoring at transplantation. Prevalent dialysis patients were censored at transplantation; this means that the patient is considered alive up to the point of transplantation, but the patient's status post-transplant is not considered. Both Kaplan-Meier and Cox adjusted models were used to calculate survival. Causes of death were analysed for both groups. The relative risk of death was calculated compared with the general UK population. The unadjusted 1 year after 90 day survival for patients starting RRT in 2010 was 87.3%, representing an increase from the previous year (86.6%). In incident patients aged 18-64 years, the unadjusted 1 year survival had risen from 86.0% in patients starting RRT in 1997 to 92.6% in patients starting RRT in 2010 and for those aged ≥65 it had increased from 63.9% to 77.0% over the same period. The age-adjusted one year survival (adjusted to age 60) of prevalent dialysis patients increased from 88.1% in the 2001 cohort to 89.8% in the 2010 cohort. Prevalent diabetic patient one year survival rose from 82.1% in the 2002 cohort to 84.7% in the 2010 cohort. The age-standardised mortality ratio for prevalent RRT patients compared with the general population was 18 for age group 30-34 and 2.5 at age 85+ years. In the prevalent RRT dialysis population, cardiovascular disease accounted for 22% of deaths, infection and treatment withdrawal 18% each and 25% were recorded as other causes of death

  8. Prognostic significance of signal transducer and activator of transcription 5 and 5b expression in Epstein-Barr virus-positive patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Diamantopoulos, Panagiotis T; Sofotasiou, Maria; Georgoussi, Zafiroula; Giannakopoulou, Nefeli; Papadopoulou, Vasiliki; Galanopoulos, Athanasios; Kontandreopoulou, Elina; Zervakis, Panagiotis; Pallaki, Paschalina; Kalala, Fani; Kyrtsonis, Marie-Christine; Dimitrakopoulou, Aglaia; Vassilakopoulos, Theodoros; Angelopoulou, Maria; Spanakis, Nikolaos; Viniou, Nora-Athina

    2016-09-01

    Signal transducer and activator of transcription (STAT) proteins have been intensively studied in hematologic malignancies, and the efficacy of agents against STATs in lymphomas is already under research. We investigated the expression of total STAT5 and STAT5b in peripheral blood samples of patients with chronic lymphocytic leukemia (CLL) in correlation with the presence of Epstein-Barr Virus (EBV) and its major oncoprotein (latent membrane protein 1, LMP1). The EBV load was measured in the peripheral blood by real-time PCR for the BXLF1 gene and the levels of LMP1 by PCR and ELISA. Western blotting was performed for total STAT5 and STAT5b in protein extracts. STAT5b was only expressed in patients (not in healthy subjects) and STAT5 but particularly STAT5b expression was correlated with the presence of the virus (77.3% vs. 51.2%, P = 0.006 for STAT5b) and to the expression of LMP1 (58.3% vs. 21.6%, P = 0.011 for STAT5b). Moreover, the expression of STAT5b and the presence of EBV and LMP1 were strongly negatively correlated with the overall survival of the patients (log-rank test P = 0.011, 0.015, 0.006, respectively). Double positive (for EBV and STAT5b) patients had the lowest overall survival (log-rank test P = 0.013). This is the first report of a survival disadvantage of EBV+ patients with CLL, and the first time that STAT5b expression is correlated with survival. The correlation of STAT5 expression with the presence of the virus, along with our survival correlations defines a subgroup of patients with CLL that may benefit from anti-STAT agents. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  9. Clinical significance of VEGFR-2 and {sup 18}F-FDG PET/CT SUVmax pretreatment score in predicting the long-term outcome of patients with locally advanced rectal cancer treated with neoadjuvant therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sole, Claudio V. [Hospital General Universitario Gregorio Maranon, Department of Oncology, Madrid (Spain); School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Institute for Sanitary Research, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Madrid (Spain); Calvo, Felipe A. [Hospital General Universitario Gregorio Maranon, Department of Oncology, Madrid (Spain); School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Institute for Sanitary Research, Madrid (Spain); Alvarez, Emilio; Peligros, Isabel [School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Department of Pathology, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Institute for Sanitary Research, Madrid (Spain); Garcia-Alfonso, Pilar [Hospital General Universitario Gregorio Maranon, Service of Medical Oncology, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Institute for Sanitary Research, Madrid (Spain); Ferrer, Carlos; Ochoa, Enrique [Hospital Provincial de Castellon, Institute of Oncology, Castellon de la Plana (Spain); Herranz, Rafael [Hospital General Universitario Gregorio Maranon, Service of Radiation Oncology, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Institute for Sanitary Research, Madrid (Spain); Carreras, Jose L. [School of Medicine Complutense University, Madrid (Spain); Hospital General Universitario Gregorio Maranon, Department of Radiology and Medical Physics, Madrid (Spain)

    2013-10-15

    Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR), and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumor progression and are important targets for cancer drugs. {sup 18}F-FDG maximum standardized uptake value (SUVmax) is a marker of tumor metabolic activity. The purpose of this study was to measure SUVmax combined with VEGFR-2, EGFR and COX-2 proteins in pretreatment tumor biopsies from patients with locally advanced rectal cancer receiving intensive neoadjuvant treatment and to correlate the findings with clinical outcome. VEGFR-2, EGFR and COX-2 were measured using the immunoreactive score (IRS). SUVmax (median 8.4) was quantified in tumors with molecular overexpression (IRS {>=}3 + SUVmax {>=} 8.4 indicating active tumors; SUVmax <8.4 indicating inactive tumors). The Cox proportional hazards model was used to explore associations between tumor markers, disease-free survival (DFS) and overall survival (OS). The study group comprised 38 patients with a median follow-up of 69.3 months (range 4.5 - 92 months). Multivariate analysis showed that active tumors (overexpressing VEGFR-2, high SUVmax) were associated with worse DFS (HR 4.73, 95 % CI 1.18 - 22.17; p = 0.04) and OS (HR 4.28, 95 % CI 1.04 - 20.12; p = 0.05). Active tumors overexpressing VEGFR-2 are associated with a worse overall outcome in patients with rectal cancer treated with induction chemotherapy followed by pelvic chemoradiation and surgery. The optimal diagnostic cut-off level for this novel biomarker association should be investigated. Evaluation in a clinical trial is required to determine whether selected patients could benefit from a VEGFR-targeting drug. (orig.)

  10. Stereotactic radiosurgery improves the survival in patients with solitary brain metastasis: a reasonable alternative to surgery

    International Nuclear Information System (INIS)

    Kwan, H. Cho; Hall, Walter A.; Lee, Andrew K.; Gerbi, Bruce J.; Higgins, Patrick D.; Nussbaum, Eric S.; Chung, K.K. Lee; Bohen, Marva; Clark, H. Brent

    1996-01-01

    Purpose: To evaluate the efficacy of stereotactic radiosurgery (SRS) in patients with solitary brain metastasis from extracranial primary cancer and to compare the outcome with that of external whole brain irradiation with or without surgical resection. Materials and Methods: Between September 1970 and November, 1995, 231 patients with solitary brain metastasis were treated at the Department of Radiation Oncology, University of Minnesota Hospital. One hundred twenty six patients (56%) were treated with external whole brain irradiation (WBI) only (Group 1), seventy three (32%) underwent surgical resection prior to WBI (Group 2) and thirty two (14%) underwent stereotactic radiosurgery (SRS) with WBI (Group 3). Lung (38%) was the most common site of primary cancer, followed by breast (15%), unknown primary (12%), gastro-intestinal tract (10%), skin (malignant melanoma: 9%), kidney (renal cell carcinoma: 8%) and others (9%). The median dose to the whole brain was 3750 cGy in 15 fractions (ranges from 2000 cGy to 5000 cGy). The median radiosurgical dose of 17.5 Gy (range, 12-40 Gy) was delivered to the 40%-90% isodose line encompassing the target. Eighteen patients were treated with SRS for recurrent or persistent disease following WBI and 14 patients received SRS as a boost in conjunction with WBI. Actuarial survival was calculated from the date of treatment according to the Kaplan-Meier method and statistical significance was assessed with the log-rank test. Results: The actuarial median survivals were 3.8 months for Group 1 (ranges from 1 to 84 months), 10.5 months for Group 2 (ranges from 1 to 125 months) and 9.8 months for Group 3 (ranges from 1 to 36 months). The survivals at one and two years were 19% and 6% for Group 1, 47% and 19% for Group 2, and 44% and 21% for Group 3, respectively. The survival advantage of Groups 2 or 3 over Group 1 was statistically significant (p < 0.0001 by log-rank test). There was no survival advantage of surgery (Group 2) over SRS

  11. Dwarf Elliptical Galaxies in the M81 Group: The Structure and Stellar Populations of BK5N and F8D1

    OpenAIRE

    Caldwell, Nelson; Armandroff, Taft E.; Da Costa, G. S.; Seitzer, Patrick

    1997-01-01

    We have obtained HST WFPC2 images through the F555W and F814W filters of two M81 group dE's: BK5N and a new system, designated F8D1. The resulting color-magnitude diagrams show the upper two magnitudes of the red giant branch. Surface brightness and total magnitude measurements indicate that BK5N and F8D1 have similar central surface brightness (24.5 and 25.4 mag/arcsec^2 in V, respectively), but F8D1's larger length scale results in it being 3 magnitudes more luminous than BK5N. BK5N lies on...

  12. Secretory Phospholipase A2-IIA and Cardiovascular Disease

    DEFF Research Database (Denmark)

    Holmes, Michael V; Simon, Tabassome; Exeter, Holly J

    2013-01-01

    This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.......This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease....

  13. SU-F-R-04: Radiomics for Survival Prediction in Glioblastoma (GBM)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H; Molitoris, J; Bhooshan, N; Choi, W; Lu, W; Mehta, M; D’Souza, W [University of Maryland School of Medicine, Baltimore, MD (United States); Tan, S [Huazhong University of Science & Technology, Wuhan (China); Giacomelli, I; Scartoni, D [University of Florence, Florence (Italy); Gzell, C [Northern Sydney Cancer Centre, Sydney (Australia)

    2016-06-15

    Purpose: To develop a quantitative radiomics approach for survival prediction of glioblastoma (GBM) patients treated with chemoradiotherapy (CRT). Methods: 28 GBM patients who received CRT at our institution were retrospectively studied. 255 radiomic features were extracted from 3 gadolinium-enhanced T1 weighted MRIs for 2 regions of interest (ROIs) (the surgical cavity and its surrounding enhancement rim). The 3 MRIs were at pre-treatment, 1-month and 3-month post-CRT. The imaging features comprehensively quantified the intensity, spatial variation (texture), geometric property and their spatial-temporal changes for the 2 ROIs. 3 demographics features (age, race, gender) and 12 clinical parameters (KPS, extent of resection, whether concurrent temozolomide was adjusted/stopped and radiotherapy related information) were also included. 4 Machine learning models (logistic regression (LR), support vector machine (SVM), decision tree (DT), neural network (NN)) were applied to predict overall survival (OS) and progression-free survival (PFS). The number of cases and percentage of cases predicted correctly were collected and AUC (area under the receiver operating characteristic (ROC) curve) were determined after leave-one-out cross-validation. Results: From univariate analysis, 27 features (1 demographic, 1 clinical and 25 imaging) were statistically significant (p<0.05) for both OS and PFS. Two sets of features (each contained 24 features) were algorithmically selected from all features to predict OS and PFS. High prediction accuracy of OS was achieved by using NN (96%, 27 of 28 cases were correctly predicted, AUC = 0.99), LR (93%, 26 of 28 cases were correctly predicted, AUC = 0.95) and SVM (93%, 26 of 28 cases were correctly predicted, AUC = 0.90). When predicting PFS, NN obtained the highest prediction accuracy (89%, 25 of 28 cases were correctly predicted, AUC = 0.92). Conclusion: Radiomics approach combined with patients’ demographics and clinical parameters can

  14. Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET.

    Science.gov (United States)

    Vaidyanathan, Ganesan; McDougald, Darryl; Choi, Jaeyeon; Koumarianou, Eftychia; Weitzel, Douglas; Osada, Takuya; Lyerly, H Kim; Zalutsky, Michael R

    2016-06-01

    The human growth factor receptor type 2 (HER2) is overexpressed in breast as well as other types of cancer. Immuno-PET, a noninvasive imaging procedure that could assess HER2 status in both primary and metastatic lesions simultaneously, could be a valuable tool for optimizing application of HER2-targeted therapies in individual patients. Herein, we have evaluated the tumor-targeting potential of the 5F7 anti-HER2 Nanobody (single-domain antibody fragment; ∼13 kDa) after (18)F labeling by 2 methods. The 5F7 Nanobody was labeled with (18)F using the novel residualizing label N-succinimidyl 3-((4-(4-(18)F-fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ((18)F-SFBTMGMB; (18)F-RL-I) and also via the most commonly used (18)F protein-labeling prosthetic agent N-succinimidyl 3-(18)F-fluorobenzoate ((18)F-SFB). For comparison, 5F7 Nanobody was also labeled using the residualizing radioiodination agent N-succinimidyl 4-guanidinomethyl-3-(125)I-iodobenzoate ((125)I-SGMIB). Paired-label ((18)F/(125)I) internalization assays and biodistribution studies were performed on HER2-expressing BT474M1 breast carcinoma cells and in mice with BT474M1 subcutaneous xenografts, respectively. Small-animal PET/CT imaging of 5F7 Nanobody labeled using (18)F-RL-I also was performed. Internalization assays indicated that intracellularly retained radioactivity for (18)F-RL-I-5F7 was similar to that for coincubated (125)I-SGMIB-5F7, whereas that for (18)F-SFB-5F7 was lower than coincubated (125)I-SGMIB-5F7 and decreased with time. BT474M1 tumor uptake of (18)F-RL-I-5F7 was 28.97 ± 3.88 percentage injected dose per gram of tissue (%ID/g) at 1 h and 36.28 ± 14.10 %ID/g at 2 h, reduced by more than 90% on blocking with trastuzumab, indicating HER2 specificity of uptake, and was also 26%-28% higher (P < 0.05) than that of (18)F-SFB-5F7. At 2 h, the tumor-to-blood ratio for (18)F-RL-I-5F7 (47.4 ± 13.1) was significantly higher (P < 0.05) than for (18)F-SFB-5F7 (25.4 ± 10

  15. Marital status and survival of patients with oral cavity squamous cell carcinoma: a population-based study.

    Science.gov (United States)

    Shi, Xiao; Zhang, Ting-Ting; Hu, Wei-Ping; Ji, Qing-Hai

    2017-04-25

    The relationship between marital status and oral cavity squamous cell carcinoma (OCSCC) survival has not been explored. The objective of our study was to evaluate the impact of marital status on OCSCC survival and investigate the potential mechanisms. Married patients had better 5-year cancer-specific survival (CSS) (66.7% vs 54.9%) and 5-year overall survival (OS) (56.0% vs 41.1%). In multivariate Cox regression models, unmarried patients also showed higher mortality risk for both CSS (Hazard Ratio [HR]: 1.260, 95% confidence interval (CI): 1.187-1.339, P married patients were more likely to be diagnosed at earlier stage (P Married patients still demonstrated better prognosis in the 1:1 matched group analysis (CSS: 62.9% vs 60.8%, OS: 52.3% vs 46.5%). 11022 eligible OCSCC patients were identified from Surveillance, Epidemiology, and End Results (SEER) database, including 5902 married and 5120 unmarried individuals. Kaplan-Meier analysis, Log-rank test and Cox proportional hazards regression model were used to analyze survival and mortality risk. Influence of marital status on stage, age at diagnosis and selection of treatment was determined by binomial and multinomial logistic regression. Propensity score matching method was adopted to perform a 1:1 matched cohort. Marriage has an independently protective effect on OCSCC survival. Earlier diagnosis and more sufficient treatment are possible explanations. Besides, even after 1:1 matching, survival advantage of married group still exists, indicating that spousal support from other aspects may also play an important role.

  16. Survival benefit of anti-HER2 therapy after whole-brain radiotherapy in HER2-positive breast cancer patients with brain metastasis.

    Science.gov (United States)

    Zhang, Qian; Chen, Jian; Yu, Xiaoli; Cai, Gang; Yang, Zhaozhi; Cao, Lu; Hu, Chaosu; Guo, Xiaomao; Sun, Jing; Chen, Jiayi

    2016-09-01

    We aimed to assess the survival benefit of epidermal growth factor receptor 2 (HER2)-positive breast cancer patients with brain metastasis (BM) after whole-brain radiotherapy (WBRT) in combination with systemic treatments, especially anti-HER2 therapy. This retrospective study analyzed the overall survival (OS) of 60 HER2-positive breast cancer patients with BM after WBRT in combination with systemic treatments. Among them, 42 patients received chemotherapy while 18 patients did not receive after WBRT. With regard to anti-HER2 therapy, after WBRT, 17 patients received anti-HER2 treatment without prior adjuvant trastuzumab-based therapy, 7 patients received anti-HER2 treatment with prior adjuvant trastuzumab-based therapy, and 36 patients did not receive further anti-HER2 treatment. All patients were followed up regularly until January 23, 2013. The median OS of patients with BM was 12 months. Patients who received anti-HER2 therapy and chemotherapy after WBRT had significantly better survival compared with patients who did not receive further treatment. Patients who received anti-HER2 treatment after WBRT but did not receive adjuvant trastuzumab-based therapy for early breast cancer had better OS, followed by patients who received anti-HER2 agent both in adjuvant treatment and after WBRT and patients who did not receive anti-HER2 treatment. Multivariate analysis showed that Karnofsky Performance Status, control of extracranial metastases, chemotherapy after WBRT, and anti-HER2 therapy combined with WBRT were all independent predictors for OS. Both chemotherapy and anti-HER2 therapy after WBRT could improve OS. Moreover, patients without prior exposure to adjuvant anti-HER2 treatment may have survival benefit superior to those of patients with prior exposure.

  17. Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-year Disease-free Survival and Toxicity Observations

    Directory of Open Access Journals (Sweden)

    Donald Blake Fuller

    2014-11-01

    Full Text Available PURPOSEProstate stereotactic body radiotherapy (SBRT may substantially recapitulate the dose distribution of high-dose-rate (HDR brachytherapy, representing an externally delivered Virtual HDR treatment method. Herein we present 5-year outcomes from a cohort of consecutively treated Virtual HDR SBRT prostate cancer patients.METHODSSeventy-nine patients were treated from 2006 - 2009, 40 low-risk and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in 4 fractions. The planning target volume (PTV included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered > 95% of the PTV (V100 >= 95%, with a minimum 150% PTV dose escalation to create HDR-like PTV dose distribution.RESULTSMedian pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70% but only 3 of them subsequently relapsed, Biochemical-relapse-free survival was 100% and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98% and 92% by Phoenix definition. Local relapse did not occur, distant metastasis-free survival was 100% and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10% and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0% and 1%, respectively, with no grade 3 or higher toxicity. Of patients potent pre-SBRT, 65% remained so at 5 years.CONCLUSIONSVirtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.

  18. Superconductivity in REO0.5F0.5BiS2 with high-entropy-alloy-type blocking layers

    Science.gov (United States)

    Sogabe, Ryota; Goto, Yosuke; Mizuguchi, Yoshikazu

    2018-05-01

    We synthesized new REO0.5F0.5BiS2 (RE: rare earth) superconductors with high-entropy-alloy-type (HEA-type) REO blocking layers. The lattice constant a systematically changed in the HEA-type samples with the RE concentration and the RE ionic radius. A sharp superconducting transition was observed in the resistivity measurements for all the HEA-type samples, and the transition temperature of the HEA-type samples was higher than that of typical REO0.5F0.5BiS2. The sharp superconducting transition and the enhanced superconducting properties of the HEA-type samples may indicate the effectiveness of the HEA states of the REO blocking layers in the REO0.5F0.5BiS2 system.

  19. Impact of Renal Failure on Survival of African Patients with Cirrhosis

    Directory of Open Access Journals (Sweden)

    Attia K

    2008-01-01

    Full Text Available To assess the effect of renal failure on the survival of black African patients with cirrhosis, we studied 132 (82 males, 50 females cirrhotic black African patients with mean age of 47.5 ±14.4 years and mean follow-up period of 373 ± 194 days. The edema and ascitis were the main reasons for admission to hospital. Renal failure was present in 30 (22.7% patients, and it was positively correlated to the severity of the stage of the liver disease, and associated with severe hyponatremia. Survival at 1 year was 60.1% and 37.6% in the absence or presence of renal failure, respectively (p< 0.001. The stage of the liver disease was significantly inversely corre-lated with survival, which was further diminished in the presence of renal failure:23.7% versus 12.5% for Child-Pugh-Turcote (CPT A-B in the absence or presence of renal failure, respectively (p= 0.67, 30.2% versus 81.8% for CPT C in the absence or the presence of renal failure respectively (p< 0.001. Hyponatremia has also appeared detrimental to survival, since mortality was 38.4% versus 81.8% in the absence or the presence of hyponatremia respectively (p< 0.001. By multivariate analysis, renal failure, CPT stage C, and hyponatremia independently significantly correlated to mortality in patients with cirrhosis. We conclude that renal failure is frequently associated with decompensated cirrhosis. The presence of renal failure in this setting often results in high mortality. Renal failure that occurs in the setting of a severe liver disease and hyponatremia may be part of hepatorenal syndrome.

  20. Complications and 2-year valve survival following Ahmed valve implantation during the first 2 years of life.

    Science.gov (United States)

    Almobarak, F; Al-Mobarak, F; Khan, A O

    2009-06-01

    To report complications and 2-year valve survival following Ahmed valve implantation during the first 2 years of life. Retrospective institutional case series. Forty-two eyes of 36 patients with Ahmed valve implantation (without prior drainage device surgery) during the first 2 years of life and 2 years' postsurgical follow-up were identified. Most eyes had primary congenital glaucoma (28/42, 66.7%), aphakic glaucoma (5/42, 11.9%) or Peters anomaly (5/42, 11.9%). All but three eyes had prior ocular surgery. Surgery was at a mean age of 11.83 months (m) (SD 5.63). The most common significant postoperative complications were tube malpositioning requiring intervention (11/42, 26.2%), endophthalmitis (3/42, 7.1%; one with tube exposure) and retinal detachment (3/42, 7.1%). Thirty-six eyes (85.8%) required resumption of antiglaucoma medications to maintain intraocular pressure (IOP) valve survival (IOPendophthalmitis and retinal detachment are known potential complications following any incisional surgery for advanced buphthalmos; however, tube exposure is a unique potential problem following aqueous shunt implantation that can lead to intraocular infection. Cumulative valve survival 2 years following implantation was 63.3%.