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Sample records for solid tumors patients

  1. Anxiety, depression in patients receiving chemotherapy for solid tumors

    International Nuclear Information System (INIS)

    Mansoor, S.; Jehangir, S.

    2015-01-01

    To determine the frequency of anxiety and depression in patients undergoing chemotherapy for solid tumors using Hospital Anxiety Depression Scale (HADS). Study Design: Cross sectional descriptive study. Place and Duration of Study: Out-patient department of Armed Forces Institute of Mental Health, Rawalpindi from June 2011 to December 2011. Methodology: Consecutive non probability sampling technique was used to select patients of age (25-70 years), male or female, who had received atleast 03 cycles of chemotherapy for solid tumors. Those with history of prior psychiatric illness, current use of psychotropic medication or psychoactive substance use, and any major bereavement in past one year were excluded from the study. After taking informed consent, relevant socio- demographic data was collected and HADS was administered. HADS-A cut off score of 7 was taken as significant anxiety while a HADS-D cut off score of 7 was taken as significant depression. Results: The total number of participants was 209. The mean age of patients was 42.9 years, with 55.5% males and 44.5% females. Overall 33/209 (15.8%) patients had anxiety while 56/209 (26.8%) were found to have depression. There was a higher frequency of anxiety and depression in younger patients (less than age 40 years), females, patients who were single or divorced, and patients receiving chemotherapy for pancreatic carcinoma. Conclusion: Patients undergoing chemotherapy suffer from considerable levels of anxiety and depression, thus highlighting the need for specialized interventions. (author)

  2. Association between tumor-stroma ratio and prognosis in solid tumor patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Wu, Jiayuan; Liang, Caixia; Chen, Manyu; Su, Wenmei

    2016-10-18

    Tumor-related stroma plays an active role in tumor invasion and metastasis. The tumor-stroma ratio (TSR) in the pathologic specimen has drawn increasing attention from the field of predicting tumor prognosis. However, the prognostic value of TSR in solid tumors necessitates further elucidation. We conducted a meta-analysis on 14 studies with 4238 patients through a comprehensive electronic search on databases updated on May 2016 to explore the relationship between TSR and prognosis of solid tumors. The overall hazard ratio showed that rich stroma in tumor tissue was associated with poor overall survival (OS) (14 studies, 4238 patients) and disease-free survival (DFS) (9 studies, 2235 patients) of patients with solid tumors. The effect of low TSR on poor OS was observed among various cancer types, but not in the early stage of cervical caner. A significant relationship between low TSR and poor OS was also observed in the subgroup analyses based on study region, blinding status, and Newcastle-Ottawa Scale (NOS) score. Subgroup analyses indicated that cancer type, clinical stage, study region, blinding status, and NOS score did not affect the prognostic value of TSR for DFS. Moreover, low TSR was significantly correlated with the serious clinical stage, advanced depth of invasion, and positive lymph node metastasis. These findings indicate that a high proportion of stroma in cancer tissue is associated with poor clinical outcomes in cancer patients, and TSR may serve as an independent prognostic factor for solid tumors.

  3. Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases

    NARCIS (Netherlands)

    Raber-Durlacher, J. E.; Weijl, N. I.; Abu Saris, M.; de Koning, B.; Zwinderman, A. H.; Osanto, S.

    2000-01-01

    The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150 patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients were treated with chemotherapeutic regimens

  4. Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

    Science.gov (United States)

    Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

    2018-01-01

    The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  5. MRI after magnetic drug targeting in patients with advanced solid malignant tumors

    International Nuclear Information System (INIS)

    Lemke, A.-J.; Senfft von Pilsach, M.-I.; Felix, R.; Luebbe, A.; Bergemann, C.; Riess, H.

    2004-01-01

    The purpose of this study was to evaluate the ability of MRI to detect magnetic particle uptake into advanced solid malignant tumors and to document the extension of these tumors, carried out in the context of magnetic drug targeting. In a prospective phase I trial, 11 patients were examined with MRI before and after magnetic drug targeting. The sequence protocol included T1-WI and T2-WI in several planes, followed by quantitative and qualitative evaluation of the signal intensities and tumor extensions. In nine patients, a signal decrease was observed in the early follow-up (2-7 days after therapy) on the T2-weighted images; two patients did not show a signal change. The signal changes in T1-WI were less distinct. In late follow-up (4-6 weeks after therapy), signal within nine tumors reached their initially normal level on both T1-WI and T2-WI; two tumors showed a slight signal decrease on T2-WI and a slight signal increase on T1-WI. Within the surveillance period, tumor remission in 3 out of 11 patients was observed, and in 5 patients tumor growth had stopped. The remaining three patients showed significant tumor growth. There was no statistically significant correlation between signal change and response. MRI is a suitable method to detect magnetite particles, deposited at the tumor site via magnetic drug targeting. MRI is therefore eligible to control the success of MDT and to assess the tumor size after the end of therapy. (orig.)

  6. Evaluating the Needs of Patients Living With Solid Tumor Cancer: A Survey Design.

    Science.gov (United States)

    Schmidt, April L; Lorenz, Rebecca A; Buchanan, Paula M; McLaughlin, Laura

    2018-03-01

    To describe the unmet needs of adult patients living with solid tumor cancer. Survey design. Adult patients living with solid tumor cancer from two outpatient clinics were mailed the Sheffield Profile for Assessment and Referral to Care, a holistic screening questionnaire for assessing palliative care needs, and a demographics questionnaire. One hundred fifteen patients returned the instruments, corresponding to a 62% response rate. There were no significant differences by cancer type (breast, non-breast) or gender. However, Caucasians reported significantly more psychological issues, such as anxiety, than non-Caucasians ([ n = 101 (87.8%)] and [ n = 14 (12.2%)], respectively, p = .032). Older patients reported more concerns about loss of independence/activity ( p = .012) compared with younger age groups. Patients living with Stage III/IV cancer reported more distressed about independence/activity ( p = .034), family/social issues ( p = .007), and treatment side effects ( p = .027) than patients living with Stage I/II cancer. Patients living with solid tumor cancer have a myriad of unmet needs regardless of age, gender, cancer type, or cancer stage. There appears to be important differences by cancer stage. The Sheffield Profile for Assessment and Referral to Care questionnaire provides a holistic approach for nurses to identify unmet needs and concerns. Future research should explore the preferred methods of receiving support and information.

  7. Palliative Care Use Among Patients With Solid Cancer Tumors: A National Cancer Data Base Study.

    Science.gov (United States)

    Osagiede, Osayande; Colibaseanu, Dorin T; Spaulding, Aaron C; Frank, Ryan D; Merchea, Amit; Kelley, Scott R; Uitti, Ryan J; Ailawadhi, Sikander

    2018-01-01

    Palliative care has been increasingly recognized as an important part of cancer care but remains underutilized in patients with solid cancers. There is a current gap in knowledge regarding why palliative care is underutilized nationwide. To identify the factors associated with palliative care use among deceased patients with solid cancer tumors. Using the 2016 National Cancer Data Base, we identified deceased patients (2004-2013) with breast, colon, lung, melanoma, and prostate cancer. Data were described as percentages. Associations between palliative care use and patient, facility, and geographic characteristics were evaluated through multivariate logistic regression. A total of 1 840 111 patients were analyzed; 9.6% received palliative care. Palliative care use was higher in the following patient groups: survival >24 months (17% vs 2%), male (54% vs 46%), higher Charlson-Deyo comorbidity score (16% vs 8%), treatment at designated cancer programs (74% vs 71%), lung cancer (76% vs 28%), higher grade cancer (53% vs 24%), and stage IV cancer (59% vs 13%). Patients who lived in communities with a greater percentage of high school degrees had higher odds of receiving palliative care; Central and Pacific regions of the United States had lower odds of palliative care use than the East Coast. Patients with colon, melanoma, or prostate cancer had lower odds of palliative care than patients with breast cancer, whereas those with lung cancer had higher odds. Palliative care use in solid cancer tumors is variable, with a preference for patients with lung cancer, younger age, known insurance status, and higher educational level.

  8. Gene therapy for patients with advanced solid tumors

    DEFF Research Database (Denmark)

    Spanggaard, Iben; Dahlstroem, Karin; Laessoee, Line

    2017-01-01

    -computed tomography (PET-CT) scans. RESULTS: Seven patients were enrolled and treated at dose levels from 50 to 250 μg of plasmid AMEP, the study was terminated early due to cessation of plasmid production. Minimal systemic toxicity was observed and only transient mild pain was associated with the delivery......BACKGROUND: Gene electrotrotransfer describes the use of electric pulses to transfer DNA to cells. Particularly skeletal muscle has potential for systemic secretion of therapeutic proteins. Gene electrotransfer to muscle using the integrin inhibitor plasmid AMEP (Antiangiogenic MEtargidin Peptide...... of the electric pulses. MRI of the treated muscles revealed discrete intramuscular edema 24 h after treatment. The changes in the muscle tissue resolved within 2 weeks after treatment. Peak concentrations of plasmid AMEP was detected only in plasma within the first 24 hours after injection. Protein AMEP could...

  9. The prognostic role of controlling nutritional status scores in patients with solid tumors.

    Science.gov (United States)

    Liang, Ruo-Fei; Li, Jun-Hong; Li, Mao; Yang, Yuan; Liu, Yan-Hui

    2017-11-01

    We conducted a meta-analysis to investigate the association between preoperative controlling nutritional status (CONUT) scores in various solid tumors and clinical outcomes. Relevant studies published up to August 12, 2017 were identified using electronic databases, including PubMed, Embase, and Web of Science. The pooled hazard ratios (HR) and their corresponding 95% confidence intervals (CI) for overall survival (OS) and event-free survival (EFS) were calculated to explore the relationship between preoperative CONUT score and prognosis. In total, 674 patients with solid tumors from four published studies were included in this meta-analysis. The pooled HR for OS was 1.98 (95% CI, 1.34-2.91, p=0.001), indicating that patients with high CONUT scores had worse OS. The pooled HR for EFS was 1.98 (95% CI, 1.34-2.93, p=0.001), revealing that high CONUT scores were significantly associated with short EFS. Our data suggest that high preoperative CONUT scores indicate poor prognosis for patients with solid tumors. Further studies are needed to verify the significance of CONUT scores in clinical practice. Copyright © 2017. Published by Elsevier B.V.

  10. Strategy of diagnosis and treatment for pediatric solid tumor patients using FDG-PET

    International Nuclear Information System (INIS)

    Hosono, Ako; Watanabe, Atsuko; Tsuji, Naoko; Kawamoto, Hiroshi; Makimoto, Atsushi; Tateishi, Ukihide; Terauthi, Takashi

    2006-01-01

    Usefulness of FDG-PET (18F-deoxyglucose PET) was investigated in diagnosis and therapeutic planning of childhood and adolescence malignant solid tumors. Evidence was based on 46 patients (25 males) of ages 5-30 y, involving those with rhabdomyosarcoma (17 cases), Ewing's sarcoma (13), osteosarcoma (5), neuroblastoma (4), Wilms' tumor (2), germinoma (2), and each 1 case of ganglioblastoma, retinoblastoma and hepatoblastoma. In total, they underwent 104 FDG-PET examinations for diagnosis before and during treatment in authors' hospital in the period from January 2005 to February 2006. Evaluations were done with the standard uptake value (SUV, 1 x 1 cm ROI of abnormally high distribution area of radioactivity in the lesion/FDG dose/kg body wt.), by recurrence, by early detection of exacerbation and by follow up of residual tumors, of which typical image findings were herein presented. From the aspects of the present purposes, it was concluded that FDG-PET had advantages of high resolution, short imaging time, quantitative diagnosis (SUV) as well as the tumor detection, and had defects of difficulty of detection of tumors of <1 cm size, of distribution to normal or benign tissues and of difficulty of central nervous system (CNS) imaging. (T.I.)

  11. Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials

    OpenAIRE

    Kelly, K; Infante, JR; Taylor, MH; Patel, MR; Wong, DJ; Iannotti, N; Mehnert, JM; Loos, AH; Koch, H; Speit, I; Gulley, JL

    2018-01-01

    © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. BACKGROUND: Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. METHODS: Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patient...

  12. A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

    Science.gov (United States)

    Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

    2002-03-01

    To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being patients. An L1210 bioassay was used to determine bizelesin plasma levels. The terminal elimination half-life was 140 min at the recommended Phase II dose. The area under the concentration time curve increased in proportion to administered dose, and the clearance remained constant over the dose range studied. Correlation analysis demonstrated relationships between dose and area under the concentration with cycle 1 hematological parameters, including absolute neutrophil and leukocyte nadirs. Bizelesin administered every 4 weeks as an i.v. push is well tolerated with dose-limiting toxicity of neutropenia. The maximum-tolerated dose (and recommended Phase II dose) is 0.8 microg/m(2) administered once every 4 weeks.

  13. Effect of Itraconazole and Rifampin on the Pharmacokinetics of Olaparib in Patients With Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Dirix, Luc; Swaisland, Helen; Verheul, Henk M W

    2016-01-01

    ) and inducer (rifampin) to alter the pharmacokinetic (PK) profile of olaparib following single oral tablet doses. METHODS: Two Phase I, open-label, non-randomized trials were conducted in patients with advanced solid tumors. In Study 7, patients received olaparib alone and co-administered with itraconazole...... analysis following treatment with olaparib alone and olaparib plus itraconazole, respectively; in Study 8 (N = 22; 4 male, 18 female), all patients were evaluable. Co-administration of olaparib with itraconazole resulted in a statistically significant increase in the relative bioavailability of olaparib......: Cmax treatment ratio, 1.42 (90% CI, 1.33-1.52); mean AUC treatment ratio, 2.70 (90% CI, 2.44-2.97). Mean CL/F and Vz/F were reduced (8.16 vs 3.05 L/h and 192 vs 75.1 L), although mean t½ was unchanged (15.0 vs 15.6 hours). Co-administration of olaparib with rifampin resulted in a statistically...

  14. PNU-145156E, a novel angiogenesis inhibitor, in patients with solid tumors : A phase I and pharmacokinetic study

    NARCIS (Netherlands)

    Groen, HJM; de Vries, EGE; Wynendaele, W; van der Graaf, WTA; Lechuga, EFMJ; Poggesi, [No Value; Dirix, LY; van Oosterom, AT

    2001-01-01

    Our aim was to establish, in patients with solid tumors, the dose-limiting toxicity, maximum tolerated dose (MTD), and pharmacology of PNU-145156E, a new sulfonated distamycin A derivative that blocked circulating angiogenesis-promoting growth factors in animal studies and exhibited an antitumor

  15. First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors.

    Science.gov (United States)

    Stein, Mark N; Bertino, Joseph R; Kaufman, Howard L; Mayer, Tina; Moss, Rebecca; Silk, Ann; Chan, Nancy; Malhotra, Jyoti; Rodriguez, Lorna; Aisner, Joseph; Aiken, Robert D; Haffty, Bruce G; DiPaola, Robert S; Saunders, Tracie; Zloza, Andrew; Damare, Sherri; Beckett, Yasmeen; Yu, Bangning; Najmi, Saltanat; Gabel, Christian; Dickerson, Siobhan; Zheng, Ling; El-Deiry, Wafik S; Allen, Joshua E; Stogniew, Martin; Oster, Wolfgang; Mehnert, Janice M

    2017-08-01

    Purpose: ONC201 is a small-molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, pharmacokinetic, and pharmacodynamic information. Results: No grade >1 drug-related adverse events occurred, and the RP2D was defined as 625 mg. Pharmacokinetic analysis revealed a C max of 1.5 to 7.5 μg/mL (∼3.9-19.4 μmol/L), mean half-life of 11.3 hours, and mean AUC of 37.7 h·μg/L. Pharmacodynamic assays demonstrated induction of caspase-cleaved keratin 18 and prolactin as serum biomarkers of apoptosis and DRD2 antagonism, respectively. No objective responses by RECIST were achieved; however, radiographic regression of several individual metastatic lesions was observed along with prolonged stable disease (>9 cycles) in prostate and endometrial cancer patients. Conclusions: ONC201 is a selective DRD2 antagonist that is well tolerated, achieves micromolar plasma concentrations, and is biologically active in advanced cancer patients when orally administered at 625 mg every 3 weeks. Clin Cancer Res; 23(15); 4163-9. ©2017 AACR . ©2017 American Association for Cancer Research.

  16. Solid pseudopapillary pancreas tumors. Often neglected

    International Nuclear Information System (INIS)

    Herrmann, K.A.; Reiser, M.F.; Zech, C.J.; Helmberger, T.; Bruns, C.

    2008-01-01

    Solid pseudopapillary tumors of the pancreas (SPTP) are rare tumors of the pancreas with low malignancy potential and a very good prognostic outcome after surgery. They typically occur in young women or adolescents and consist of solid, cystic and cystic-hemorrhagic components. Imaging findings in these tumors are characteristic and include a fibrotic capsule with a clear delineation and exhibit solid and cystic-hemorrhagic signal and density characteristics. Calcifications may be present in the periphery of the tumor. The tumor capsule shows contrast enhancement, the solid components in the periphery enhance in the early phase and gradually and inhomogeneously in late phases. MRI is superior to CT and other imaging modalities for characterization of SPTP. Awareness and knowledge of this tumor entity with an excellent prognosis is crucial to guide the patient towards effective, predominantly organ-sparing surgical treatment. (orig.) [de

  17. Serum cross-linked n-telopeptides of type 1 collagen (NTx in patients with solid tumors

    Directory of Open Access Journals (Sweden)

    Fernando Jablonka

    Full Text Available CONTEXT AND OBJECTIVE: Cross-linked N-telopeptides of type I collagen (NTx increase in concentration in situations in which bone resorption is increased, such as osteoporosis and bone metastasis (BM. We aimed to evaluate the serum concentrations of NTx in a sample of patients with several types of solid tumors. DESIGN AND SETTING: Cross-sectional analytical study with a control group in a tertiary public hospital. METHODS: We performed the quantitative enzyme-linked immunosorbent assay (ELISA on serum NTx levels in 19 subjects without a history of cancer and 62 patients with various solid tumors who had been referred for a bone scan. Three experienced analysts read all bone scans. RESULTS: The serum NTx levels in patients with cancer and BM, with cancer but without BM and without cancer were 46.77 ± 2.58, 32.85 ± 2.05 and 22.32 ± 2.90 respectively (P < 0.0001. We did not find any significant correlations of serum NTx with age, gender, history of bone pain, tumor type and bone alkaline phosphatase levels. We found a significant correlation between serum NTx and alkaline phosphatase levels (R² = 0.08; P = 0.022. CONCLUSIONS: Serum NTx levels are significantly higher in patients with solid tumors and bone metastases than they are in patients without bone metastases and in normal controls.

  18. Therapy-associated Solid Tumors

    International Nuclear Information System (INIS)

    Travis, Lois B.

    2002-01-01

    As survival after a diagnosis of cancer improves, characterization of the late sequelae of treatment becomes critical. The development of second malignant neoplasms represents one of the most serious side effects of treatment with radiation and chemotherapy. Although secondary leukemia was the first reported carcinogenic effect resulting from cancer treatment, solid tumors now comprise the largest second tumor burden in some populations of survivors. It should be recognized, however, that solid cancers do not necessarily represent an adverse effect of therapy, but may also reflect the operation of shared etiologic factors, host determinants, gene-environment interactions, and other influences. Quantification of second cancer risk is important in terms of patient management, enabling clinicians to make informed decisions with regard to optimal treatment of the initial cancer, balancing efficacy against acute and chronic sequelae. This article focuses on selected highlights and recent developments in treatment-associated solid malignancies, with emphasis on radiotherapy and chemotherapy in adults, and summarizes areas for future research. Although cancer therapy represents a double-edged sword, it should always be recognized that it is advances in treatment that are largely responsible for the tremendous improvement in patient survival. Thus, the benefit derived from many cancer therapies far outweighs any risk of developing a second cancer

  19. Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors

    International Nuclear Information System (INIS)

    Rossi, Sabrina; Toschi, Luca; Castello, Angelo; Grizzi, Fabio; Mansi, Luigi; Lopci, Egesta

    2017-01-01

    The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging

  20. Clinical characteristics of patient selection and imaging predictors of outcome in solid tumors treated with checkpoint-inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, Sabrina; Toschi, Luca [Humanitas Clinical and Research Hospital, Medical Oncology, Rozzano (Italy); Castello, Angelo [Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano (Italy); Grizzi, Fabio [Humanitas Clinical and Research Hospital, Immunology and Inflammation, Rozzano (Italy); Mansi, Luigi [Seconda Universita di Napoli, Nuclear Medicine, Naples (Italy); Lopci, Egesta [Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano (Italy); Humanitas Cancer Center, Humanitas Clinical and Research Hospital, Nuclear Medicine, Rozzano, MI (Italy)

    2017-12-15

    The rapidly evolving knowledge on tumor immunology and the continuous implementation of immunotherapy in cancer have recently led to the FDA and EMA approval of several checkpoint inhibitors as immunotherapic agents in clinical practice. Anti-CTLA-4, anti-PD-1, and anti-PDL-1 antibodies are becoming standard of care in advanced melanoma, as well as in relapsed or metastatic lung and kidney cancer, demonstrating higher and longer response compared to standard chemotherapy. These encouraging results have fostered the evaluation of these antibodies either alone or in combination with other therapies in several dozen clinical trials for the treatment of multiple tumor types. However, not all patients respond to immune checkpoint inhibitors, hence, specific biomarkers are necessary to guide and monitor therapy. The utility of PD-L1 expression as a biomarker has varied in different clinical trials, but, to date, no consensus has been reached on whether PD-L1 expression is an ideal marker for response and patient selection; approximately 20-25% of patients will respond to immunotherapy with checkpoint inhibitors despite a negative PD-L1 staining. On the other hand, major issues concern the evaluation of objective response in patients treated with immunotherapy. Pure morphological criteria as commonly used in solid tumors (i.e. RECIST) are not sufficient because change in size is not an early and reliable marker of tumor response to biological therapies. Thus, the scientific community has required a continuous adaptation of immune-related response criteria (irRC) to overcome the problem. In this context, metabolic information and antibody-based imaging with positron emission tomography (PET) have been investigated, providing a powerful approach for an optimal stratification of patients at staging and during the evaluation of the response to therapy. In the present review we provide an overview on the clinical characteristics of patient selection when using imaging

  1. Safety, pharmacokinetics, and antitumor activity of AMG 386, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors.

    Science.gov (United States)

    Herbst, Roy S; Hong, David; Chap, Linnea; Kurzrock, Razelle; Jackson, Edward; Silverman, Jeffrey M; Rasmussen, Erik; Sun, Yu-Nien; Zhong, Don; Hwang, Yuying C; Evelhoch, Jeffrey L; Oliner, Jonathan D; Le, Ngocdiep; Rosen, Lee S

    2009-07-20

    PURPOSE AMG 386 is an investigational peptide-Fc fusion protein (ie, peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 with their receptor, Tie2. This first-in-human study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors. PATIENTS AND METHODS Patients in sequential cohorts received weekly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg. Results Thirty-two patients were enrolled on the study and received AMG 386. One occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden that was possibly related to AMG 386. The most common toxicities were fatigue and peripheral edema. Proteinuria (n = 11) was observed without clinical sequelae. Only four patients (12%) experienced treatment-related toxicities greater than grade 1. A maximum-tolerated dose was not reached. PK was dose-linear and the mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days. Serum AMG 386 levels appeared to reach steady-state after four weekly doses, and there was minimal accumulation. No anti-AMG 386 neutralizing antibodies were detected. Reductions in volume transfer constant (K(trans); measured by dynamic contrast-enhanced magnetic resonance imaging) were observed in 10 patients (13 lesions) 48 hours to 8 weeks after treatment. One patient with refractory ovarian cancer achieved a confirmed partial response (ie, 32.5% reduction by Response Evaluation Criteria in Solid Tumors) and withdrew from the study with a partial response after 156 weeks of treatment; four patients experienced stable disease for at least 16 weeks. CONCLUSION Weekly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor-axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this patient

  2. Whole-body MRI in comparison to skeletal scintigraphy for detection of skeletal metastases in patients with solid tumors

    International Nuclear Information System (INIS)

    Ghanem, N.; Altehoefer, C.; Winterer, J.; Schaefer, O.; Bley, T.A.; Langer, M.; Kelly, T.; Moser, E.

    2004-01-01

    The aim of this study was to compare the diagnostic efficacy of whole-body magnetic resonance imaging (WB-MRI) as a new and rapid examination technique with skeletal scintigraphy for detection of skeletal metastases from solid tumors. In 129 patients with solid malignant tumors, WB-MRI was performed for individual comparison with skeletal scintigraphy. Examinations were performed with the innovative AngioSURF trademark rolling table with integrated phased array surface coil and coronary TIRM sequences for different body regions. The results for WB-MRI and skeletal scintigraphy were concordant in 81% of the cases, whereby both procedures excluded skeletal metastases in 43%. WB-MRI and skeletal scintigraphy demonstrated skeletal metastases in 38% of the cases, whereby WB-MRI provided more comprehensive findings in 45%. In 12% of the cases, skeletal scintigraphy was superior to WB-MRI and in 19% the findings were discordant, whereby WB-MRI detected skeletal metastases in 15 cases which had not been found on skeletal scintigraphy. In nine cases, skeletal scintigraphy was positive when the WB-MRI was negative. In 60% of the cases, WB-MRI evidenced tumor-associated findings. WB-MRI represents a promising new staging technique for detection of skeletal metastases, which is more sensitive in many cases than skeletal scintigraphy in detecting and assessing the extent of skeletal metastases - and tumor-associated findings that are relevant for treatment strategy. (orig.) [de

  3. Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

    Science.gov (United States)

    2013-12-13

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

  4. Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Jappe Annette

    2011-01-01

    Full Text Available Abstract Background This phase I, randomized, multicenter, open-label study investigated the pharmacokinetics, safety, and efficacy of the oral mammalian target of rapamycin inhibitor everolimus in Chinese patients with advanced solid tumors. Methods A total of 24 patients with advanced breast cancer (n = 6, gastric cancer (n = 6, non-small cell lung cancer (n = 6, or renal cell carcinoma (n = 6 who were refractory to/unsuitable for standard therapy were randomized 1:1 to oral everolimus 5 or 10 mg/day. Primary end points were pharmacokinetic parameters and safety and tolerability. Pharmacokinetic 24-h profiles were measured on day 15; trough level was measured on days 2, 8, 15, 16, and 22. Tolerability was assessed continuously. This final analysis was performed after all patients had received 6 months of study drug or had discontinued. Results Everolimus was absorbed rapidly; median Tmax was 3 h (range, 1-4 and 2 h (range, 0.9-6 in the 5 and 10 mg/day groups, respectively. Pharmacokinetic parameters increased dose proportionally from the 5 and 10 mg/day doses. Steady-state levels were achieved by day 8 or earlier. The most common adverse events suspected to be related to everolimus therapy were increased blood glucose (16.7% and 41.7% and fatigue (16.7% and 33.3% in the everolimus 5 and 10 mg/day dose cohorts, respectively. Best tumor response was stable disease in 10 (83% and 6 (50% patients in the 5 and 10 mg/day groups, respectively. Conclusions Everolimus 5 or 10 mg/day was well tolerated in Chinese patients with advanced solid tumors. The observed safety and pharmacokinetic profile of everolimus from this study were consistent with previous studies. Trial registration Chinese Health Authorities 2008L09346

  5. The role of chemotherapy in the treatment of patients with brain metastases from solid tumors

    International Nuclear Information System (INIS)

    Walbert, T.; Gilbert, M.R.

    2009-01-01

    Brain metastases are the most frequent cancer in the central nervous system, being ten times more common than primary brain tumors. Patients generally have a poor outcome with a median survival of 4 months after diagnosis of the metastases. Therapeutic options include surgery, stereotactic, radiosurgery, whole-brain radiotherapy (WBRT), and chemotherapy. Patients with a limited number of brain metastases and well-controlled systemic cancer benefit from brain metastases-specific therapies, including surgery, radiosurgery, and conventional radiation. The role of chemotherapy for brain metastases remains limited. There is concern about drug delivery because of the blood-brain barrier. However, higher response rates are noted with initial therapies, suggesting that part of the poor response rate may be related to the late onset of brain metastases and the use of second- and third-line regimens. Recent studies have demonstrated objective responses with systemic therapy in a variety of cancer types, especially when combined with WBRT. Individual therapeutic strategies for central nervous system metastases must be chosen based on performance status, the extent of intracranial disease, and the chemosensitivity of the underlying tumor, as well as the control of the systemic cancer. In this article we review important prognostic factors and challenges in using chemotherapy. We specifically review recent advances in the treatment of brain metastases from breast and lung cancer as well as melanoma. Future treatment advances will require a multidisciplinary approach integrating surgical, radiation, and chemotherapeutic options to improve neurological function and quality of life, rather than just focusing on survival endpoints. (author)

  6. 17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

    Science.gov (United States)

    2013-01-24

    Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenstr

  7. Role of denosumab in the management of skeletal complications in patients with bone metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Stopeck AT

    2012-04-01

    Full Text Available Ursa Brown-Glaberman, Alison T StopeckUniversity of Arizona Cancer Center, Tucson, AZ, USAAbstract: Skeletal-related events (SREs including pain, fractures, and hypercalcemia are a major source of morbidity for cancer patients with bone metastases. The receptor activator of NF-κB ligand (RANKL is a key mediator of osteoclast formation and activity in normal bone physiology as well as cancer-induced bone resorption. The first commercially available drug that specifically targets and inhibits the RANKL pathway is denosumab, a fully human monoclonal antibody that binds and neutralizes RANKL, thereby inhibiting osteoclast function. In this review, we summarize the major studies leading to the US Food and Drug Administration-approval of denosumab for the prevention of SREs in patients with bone metastases from solid tumors. Further, we discuss the role of denosumab in the prevention and treatment of SREs and bone loss in cancer patients. As a monoclonal antibody, denosumab has several advantages over bisphosphonates, including improved efficacy, better tolerability, and the convenience of administration by subcutaneous injection. In addition, as denosumab has no known renal toxicity, it may be the preferred choice over bisphosphonates in patients with baseline renal insufficiency or receiving nephrotoxic therapies. However, other toxicities, including osteonecrosis of the jaw and hypocalcemia, appear to be class effects of agents that potently inhibit osteoclast activity and are associated with both denosumab and bisphosphonate use. The data presented highlight the differences associated with intravenous bisphosphonate and denosumab use as well as confirm the essential role bone-modifying agents play in maintaining the quality of life for patients with bone metastases.Keywords: denosumab, bone metastases, solid tumor, breast cancer, prostate cancer, skeletal related events, skeletal complications 

  8. Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma.

    Science.gov (United States)

    Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O'Dwyer, Peter J; Amaravadi, Ravi K

    2014-08-01

    The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted.

  9. Defining Survivorship Trajectories Across Patients With Solid Tumors: An Evidence-Based Approach.

    Science.gov (United States)

    Dood, Robert L; Zhao, Yang; Armbruster, Shannon D; Coleman, Robert L; Tworoger, Shelley; Sood, Anil K; Baggerly, Keith A

    2018-06-02

    Survivorship involves a multidisciplinary approach to surveillance and management of comorbidities and secondary cancers, overseen by oncologists, surgeons, and primary care physicians. Optimal timing and coordination of care, however, is unclear and often based on arbitrary 5-year cutoffs. To determine high- and low-risk periods for all tumor types that could define when survivorship care might best be overseen by oncologists and when to transition to primary care physicians. In this pan-cancer, longitudinal, observational study, excess mortality hazard, calculated as an annualized mortality risk above a baseline population, was plotted over time. The time this hazard took to stabilize defined a high-risk period. The percent morality elevation above age- and sex-matched controls in the latter low-risk period was reported as a mortality gap. The US population-based Surveillance, Epidemiology, and End Results database defined the cancer population, and the US Census life tables defined controls. Incident cases of patients with cancer were separated into tumor types based on International Classification of Diseases for Oncology definitions. Population-level data on incident cancer cases was compared with the general US population. Overall mortality and cause of death were reported on observed cancer cases. A total of 2 317 185 patients (median age, 63 years; 49.8% female) with 66 primary tumor types were evaluated. High-risk surveillance period durations ranged from less than 1 year (breast, prostate, lip, ocular, and parathyroid cancers) up to 19 years (unspecified gastrointestinal cancers). The annualized mortality gap, representing the excess mortality in the stable period, ranged from a median 0.26% to 9.33% excess annual mortality (thyroid and hypopharyngeal cancer populations, respectively). Cluster analysis produced 6 risk cluster groups: group 1, with median survival of 16.2 (5th to 95th percentile range [PR], 10.7-40.2) years and median high-risk period

  10. Phase I clinical, pharmacokinetic, and pharmacodynamic study of KOS-862 (Epothilone D) in patients with advanced solid tumors and lymphoma.

    Science.gov (United States)

    Konner, Jason; Grisham, Rachel N; Park, Jae; O'Connor, Owen A; Cropp, Gillian; Johnson, Robert; Hannah, Alison L; Hensley, Martee L; Sabbatini, Paul; Mironov, Svetlana; Miranov, Svetlana; Danishefsky, Samuel; Hyman, David; Spriggs, David R; Dupont, Jakob; Aghajanian, Carol

    2012-12-01

    To determine the maximum tolerated dose and safety of the epothilone, KOS-862, in patients with advanced solid tumors or lymphoma. Patients were treated weekly for 3 out of 4 weeks (Schedule A) or 2 out of 3 weeks (Schedule B) with KOS-862 (16-120 mg/m(2)). Pharmacokinetic (PK) sampling was performed during cycles 1 and 2; pharmacodynamic (PD) assessment for microtubule bundle formation (MTBF) was performed after the 1st dose, only at or above 100 mg/m(2). Thirty-two patients were enrolled, and twenty-nine completed ≥1 cycle of therapy. Dose limiting toxicity [DLT] was observed at 120 mg/m(2). PK data were linear from 16 to 100 mg/m(2), with proportional increases in mean C(max) and AUC(tot) as a function of dose. Full PK analysis (mean ± SD) at 100 mg/m(2) revealed the following: half-life (t (½)) = 9.1 ± 2.2 h; volume of distribution (V(z)) = 119 ± 41 L/m(2); clearance (CL) = 9.3 ± 3.2 L/h/m(2). MTBF (n = 9) was seen in 40% of PBMCs within 1 h and in 15% of PBMC at 24-hours post infusion at 100 mg/m(2). Tumor shrinkage (n = 2, lymphoma), stable disease >3 months (n = 5, renal, prostate, oropharynx, cholangiocarcinoma, and Hodgkin lymphoma), and tumor marker reductions (n = 1, colorectal cancer/CEA) were observed. KOS-862 was well tolerated with manageable toxicity, favorable PK profile, and the suggestion of clinical activity. The maximum tolerated dose was determined to be 100 mg/m(2) weekly 3-on/1-off. MTBF can be demonstrated in PBMCs of patients exposed to KOS-862.

  11. Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction

    Science.gov (United States)

    2014-02-21

    IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

  12. Safety and Clinical Activity of Pembrolizumab and Multisite Stereotactic Body Radiotherapy in Patients With Advanced Solid Tumors.

    Science.gov (United States)

    Luke, Jason J; Lemons, Jeffrey M; Karrison, Theodore G; Pitroda, Sean P; Melotek, James M; Zha, Yuanyuan; Al-Hallaq, Hania A; Arina, Ainhoa; Khodarev, Nikolai N; Janisch, Linda; Chang, Paul; Patel, Jyoti D; Fleming, Gini F; Moroney, John; Sharma, Manish R; White, Julia R; Ratain, Mark J; Gajewski, Thomas F; Weichselbaum, Ralph R; Chmura, Steven J

    2018-02-13

    Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1-treatment outcomes may be improved with lower disease burden. In this context, we conducted a phase I study to evaluate the safety of pembrolizumab with multisite SBRT in patients with metastatic solid tumors. Patients and Methods Patients progressing on standard treatment received SBRT to two to four metastases. Not all metastases were targeted, and metastases > 65 mL were partially irradiated. SBRT dosing varied by site and ranged from 30 to 50 Gy in three to five fractions with predefined dose de-escalation if excess dose-limiting toxicities were observed. Pembrolizumab was initiated within 7 days after completion of SBRT. Pre- and post-SBRT biopsy specimens were analyzed in a subset of patients to quantify interferon-γ-induced gene expression. Results A total of 79 patients were enrolled; three patients did not receive any treatment and three patients only received SBRT. Patients included in the analysis were treated with SBRT and at least one cycle of pembrolizumab. Most (94.5%) of patients received SBRT to two metastases. Median follow-up for toxicity was 5.5 months (interquartile range, 3.3 to 8.1 months). Six patients experienced dose-limiting toxicities with no radiation dose reductions. In the 68 patients with imaging follow-up, the overall objective response rate was 13.2%. Median overall survival was 9.6 months (95% CI, 6.5 months to undetermined) and median progression-free survival was 3.1 months (95% CI, 2.9 to 3.4 months). Expression of interferon-γ-associated genes from post-SBRT tumor biopsy specimens significantly correlated with nonirradiated tumor response. Conclusion Multisite SBRT followed by pembrolizumab was well tolerated with acceptable toxicity. Additional studies exploring the clinical benefit and predictive biomarkers of combined

  13. A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Ying G

    2013-01-01

    Full Text Available Zhongling Zhu,1,4 Zhengzi Qian,2,4 Zhao Yan,1,4 Cuicui Zhao,2,4 Huaqing Wang,2,4 Guoguang Ying3,41Department of Clinical Pharmacology, 2Department of Lymphoma, 3Laboratory of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China; 4Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of ChinaBackground: Ursolic acid is a promising anticancer agent. The current study aims to evaluate the single- and multiple-dose pharmacokinetics (PK as well as the safety of ursolic acid nanoliposomes (UANL in healthy volunteers and in patients with advanced solid tumors.Methods: Twenty-four healthy volunteers in the single-dose PK study were divided into three different groups, which received 37, 74, and 98 mg/m2 of UANL. Eight patients in the multiple-dose PK study were administered with 74 mg/m2 of UANL daily for 14 days. The UA plasma concentrations were determined using ultra-performance liquid chromatograph-tandem mass spectrometry.Results: The plasma concentration profiles of all subjects were characterized by a biexponential decline after infusion. The mean peak plasma concentration (Cmax increased linearly as a function of the dose (r = 0.999. The mean area under the plasma concentration-time curve (AUC from 0 to 16 hours also increased proportionally with dose escalation (r = 0.998. However, the clearance was constant over the specific dose interval. In the multiple-dose PK study, the trough and average concentrations remained low. The mean AUC, half-life, Cmax, time to Cmax, and the volume of distribution on the first day were similar to those on the last day. All subjects tolerated the treatments well. Most UANL-associated adverse events varied from mild to moderate.Conclusions: UANL exhibits relatively linear PK behavior with dose levels from 37 mg/m2 to 98 mg/m2. No drug accumulation was observed with repeated doses of UANL. The intravenous infusion of UANL was well

  14. First-in-Class, First-in-Human Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Patients With Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Abdul Razak, Albiruni R; Mau-Sørensen, Morten; Gabrail, Nashat Y

    2016-01-01

    PURPOSE: This trial evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of selinexor (KPT-330), a novel, oral small-molecule inhibitor of exportin 1 (XPO1/CRM1), and determined the recommended phase II dose. PATIENTS AND METHODS: In total, 189 patients with advanced solid tumors...

  15. A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors

    Science.gov (United States)

    Sanoff, Hanna K.; Davies, Janine M.; Walko, Christine; Irvin, William; Buie, Larry; Keller, Kimberly; Ivanova, Anastasia; Chiu, Wing-Keung; O'Neil, Bert H.; Stinchcombe, Thomas E.

    2010-01-01

    Summary Purpose Epidermal growth factor receptor (EGFR) inhibition may overcome chemotherapy resistance by inhibiting important anti-apoptotic signals that are constitutively activated by an overstimulated EGFR pathway. Methods This phase I dose escalation trial assessed the safety and efficacy of vinflunine, a novel vinca alkaloid microtubule inhibitor, with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with refractory solid tumors. Results Seventeen patients were treated, 10 with continuous erlotinib, and 7 with intermittent erlotinib. At dose level 1, vinflunine 280 mg/m2 IV day 1 and erlotinib 75 mg PO days 2–21 (“continuous erlotinib”) in 21 day cycles, two of four patients experienced DLTs. At dose level -1 (vinflunine 250 mg/m2 every 21 days and erlotinib 75 mg/day), two of six patients experienced DLTs. The study was amended to enroll to “intermittent erlotinib” dosing: vinflunine day 1 and erlotinib days 2–15 of a 21 day cycle. Two of seven experienced DLTs and the study was terminated. One patient with breast cancer had a partial response; three had stable disease ≥6 cycles. All were treated in the continuous erlotinib group. Conclusions Given the marked toxicity in our patient population, the combination of vinflunine and erlotinib cannot be recommended for further study with these dosing schemas. PMID:20387090

  16. Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

    International Nuclear Information System (INIS)

    Anthoney, D Alan; Miwa, Masanori; Twelves, Christopher; Evans, TRJ; Naik, Jay; MacPherson, Iain RJ; Crawford, Donna; Hartley, John M; Hartley, Janet A; Saito, Tomohisa; Abe, Masaichi; Jones, Keith

    2012-01-01

    A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m 2 . MTD was 10 mg/m 2 ; DLTs at 12 (2/4 patients) and 10 mg/m 2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhoea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and C max from 1–10 mg/m 2 . Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. TP300 had predictable hematologic toxicity, and diarrhoea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage. EU-CTR2006-001345-33

  17. Epidemiology and Outcomes of Bloodstream Infections in Patients With Solid Tumors in a Central American Population at Mexico Hospital, San Jose, Costa Rica

    Directory of Open Access Journals (Sweden)

    Jorge Calvo-Lon

    2017-12-01

    Full Text Available Purpose: Bloodstream infections (BSIs are an important cause of mortality in patients with solid tumors. We conducted a retrospective study to evaluate the epidemiologic profile and mortality of patients with solid tumors who have BSIs and were admitted to Mexico Hospital. This is the first study in Costa Rica and Central America describing the current epidemiologic situation. Methods: We analyzed the infectious disease database for BSIs in patients with solid tumors admitted to Mexico Hospital from January 2012 to December 2014. Epidemiology and mortality were obtained according to microorganism, antibiotic sensitivity, tumor type, and presence of central venous catheter (CVC. Descriptive statistics were used. Results: A total of 164 BSIs were recorded, the median age was 58 years, 103 patients (63% were males, and 128 cases of infection (78% were the result of gram-negative bacilli (GNB. Klebsiella pneumoniae (21%, Escherichia coli (21%, and Pseudomonas aeruginosa (15% were the most common microorganisms isolated. Gram-positive cocci (GPC were found in 36 patients, with the most frequent microorganisms being Staphylococcus aureus (10% and Staphyloccocus epidermidis (6%. With respect to tumor type, BSIs were more frequent in the GI tract (57% followed by head and neck (9% and genitourinary tract (8%. Regarding antibiotic susceptibility, only 17% (GNB expressed extended-spectrum beta-lactamase and 12% (GPC had methicillin resistance. Patients with CVCs (n = 59 were colonized mainly by GNB (78%. Overall the mortality rate at 30 days was about 30%. Conclusion: GNB are the most frequent cause of BSIs in solid tumors and in patients with CVCs. GI cancers had more BSIs than other sites. Mortality and antibiotic sensitivity remained stable and acceptable during this observational period in this Latin American population.

  18. Effect of veliparib (ABT-888) on cardiac repolarization in patients with advanced solid tumors : a randomized, placebo-controlled crossover study

    NARCIS (Netherlands)

    Munasinghe, Wijith; Stodtmann, Sven; Tolcher, Anthony; Calvo, Emiliano; Gordon, Michael; Jalving, Mathilde; de Vos-Geelen, Judith; Medina, Diane; Bergau, Dennis; Nuthalapati, Silpa; Hoffman, David; Shepherd, Stacie; Xiong, Hao

    2016-01-01

    Veliparib (ABT-888) is an orally bioavailable potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1 and PARP-2. This phase 1 study evaluated the effect of veliparib on corrected QT interval using Fridericia's formula (QTcF). Eligible patients with advanced solid tumors received single-dose oral

  19. Safety profile of avelumab in patients with advanced solid tumors: A pooled analysis of data from the phase 1 JAVELIN solid tumor and phase 2 JAVELIN Merkel 200 clinical trials.

    Science.gov (United States)

    Kelly, Karen; Infante, Jeffrey R; Taylor, Matthew H; Patel, Manish R; Wong, Deborah J; Iannotti, Nicholas; Mehnert, Janice M; Loos, Anja H; Koch, Helga; Speit, Isabell; Gulley, James L

    2018-05-01

    Antibodies targeting the programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint may cause adverse events (AEs) that are linked to the mechanism of action of this therapeutic class and unique from those observed with conventional chemotherapy. Patients with advanced solid tumors who were enrolled in the phase 1 JAVELIN Solid Tumor (1650 patients) and phase 2 JAVELIN Merkel 200 (88 patients) trials received avelumab, a human anti-PD-L1 IgG1 antibody at a dose of 10 mg/kg every 2 weeks. Treatment-related AEs (TRAEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). In post hoc analyses, immune-related AEs (irAEs) were identified via an expanded AE list and medical review, and infusion-related reactions (IRRs) occurring ≤2 days after infusion and symptoms occurring ≤1 day after infusion and resolving ≤2 days after onset were identified based on prespecified Medical Dictionary for Regulatory Activities (MedDRA) terms. Of the 1738 patients analyzed, grade ≥3 TRAEs occurred in 177 (10.2%); the most common were fatigue (17 patients; 1.0%) and IRR (10 patients; 0.6%). TRAEs led to discontinuation in 107 patients (6.2%) and death in 4 patients (0.2%). Grade ≥3 irAEs occurred in 39 patients (2.2%) and led to discontinuation in 34 patients (2.0%). IRRs or related symptoms occurred in 439 patients (25.3%; grade 3 in 0.5% [9 patients] and grade 4 in 0.2% [3 patients]). An IRR occurred at the time of first infusion in 79.5% of 439 patients who had an IRR, within the first 4 doses in 98.6% of 439 patients who had an IRR, and led to discontinuation in 35 patients (2.0%). Avelumab generally was found to be well tolerated and to have a manageable safety profile. A minority of patients experienced grade ≥3 TRAEs or irAEs, and discontinuation was uncommon. IRRs occurred mainly at the time of first infusion, and repeated events were infrequent. Cancer 2018;124:2010-7. © 2018 The Authors

  20. Importance of antiresorptive therapies for patients with bone metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Talreja DB

    2012-09-01

    Full Text Available Draupadi B TalrejaDepartment of Medicine, David Geffen School of Medicine at UCLA and Northridge Hospital Medical Center, Northridge, CA, USAAbstract: Patients with bone metastases are at risk of skeletal-related events such as pathologic fractures, spinal cord compression, the need for orthopedic surgery to bone, and palliative radiotherapy for severe bone pain. Antiresorptive therapies have demonstrated efficacy for reducing the risk of skeletal-related events and ameliorating bone pain. Despite the well documented clinical benefits of antiresorptive therapies, patient benefits can be limited or compromised by nonadherence with scheduled therapy. Potential reasons for poor compliance include lack of understanding of how antiresorptive therapies work, neglecting the importance of bone health in maintaining quality of life, and being unaware of the potentially debilitating effects of skeletal-related events caused by bone metastases. Indeed, patients may stop therapy after bone pain subsides or discontinue due to generally mild and usually manageable adverse events, leaving them at an increased risk of developing skeletal-related events. In addition, the cost of antiresorptive therapy can be a concern for many patients with cancer. Medical care for patients with cancer requires a coordinated effort between primary care physicians and oncologists. Patients' medical care teams can be leveraged to help educate them about the importance of adherence to antiresorptive therapy when cancer has metastasized to bone. Because primary care physicians generally have more contact with their patients than oncologists, they are in a unique position to understand patient perceptions and habits that may lead to noncompliance and to help educate patients about the benefits and risks of various antiresorptive therapies in the advanced cancer setting. Therefore, primary care physicians need to be aware of various mechanistic and clinical considerations regarding

  1. Importance of antiresorptive therapies for patients with bone metastases from solid tumors

    International Nuclear Information System (INIS)

    Talreja, Draupadi B

    2012-01-01

    Patients with bone metastases are at risk of skeletal-related events such as pathologic fractures, spinal cord compression, the need for orthopedic surgery to bone, and palliative radiotherapy for severe bone pain. Antiresorptive therapies have demonstrated efficacy for reducing the risk of skeletal-related events and ameliorating bone pain. Despite the well documented clinical benefits of antiresorptive therapies, patient benefits can be limited or compromised by nonadherence with scheduled therapy. Potential reasons for poor compliance include lack of understanding of how antiresorptive therapies work, neglecting the importance of bone health in maintaining quality of life, and being unaware of the potentially debilitating effects of skeletal-related events caused by bone metastases. Indeed, patients may stop therapy after bone pain subsides or discontinue due to generally mild and usually manageable adverse events, leaving them at an increased risk of developing skeletal-related events. In addition, the cost of antiresorptive therapy can be a concern for many patients with cancer. Medical care for patients with cancer requires a coordinated effort between primary care physicians and oncologists. Patients’ medical care teams can be leveraged to help educate them about the importance of adherence to antiresorptive therapy when cancer has metastasized to bone. Because primary care physicians generally have more contact with their patients than oncologists, they are in a unique position to understand patient perceptions and habits that may lead to noncompliance and to help educate patients about the benefits and risks of various antiresorptive therapies in the advanced cancer setting. Therefore, primary care physicians need to be aware of various mechanistic and clinical considerations regarding antiresorptive treatment options

  2. A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors.

    Science.gov (United States)

    Schelman, William R; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M; Ivy, Percy; Wilding, George; Traynor, Anne M

    2009-05-01

    To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine administered in combination with doxorubicin. Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m(2) and Triapine 25 mg/m(2). PK analysis was performed at various time-points before and after treatment. Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m(2), Triapine 45 mg/m(2)), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m(2)) with Triapine 45 mg/m(2). The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine were reduced to 45 and 25 mg/m(2), respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Pretreated patients with advanced malignancies can tolerate the combination of Triapine and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m(2) on day 1 and Triapine 25 mg/m(2) on days 1-4 of a 21-day cycle.

  3. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

    OpenAIRE

    Dirix, Luc Y.; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E.; Somer, Robert; Smakal, Martin; Emens, Leisha A.; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja

    2017-01-01

    Purpose Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. Methods In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 week...

  4. Disseminated intravascular coagulation in solid tumors

    International Nuclear Information System (INIS)

    Terzieff, V.; Alonso, I.; Vázquez, A.

    2004-01-01

    It is estimated that 20-25% of cases of disseminated intravascular coagulation (DIC) relate to an underlying neoplasia primarily hematologic. It is estimated that about 5% of patients with solid tumors have CID clinic, although the incidence of subclinical alterations is much higher. The CID is not limited to the activation of the coagulation cascade, which leads to bleeding micro thrombosis and consumption of coagulation factors. Solid tumors are frequently associated adenocarcinomas producers mucin (especially gastric), usually in the context of a disseminated disease. The mucin may act as a promoter of the cascade, but probably it is a multi-event. High levels of TNF to produced by the tumor mass and chemotherapy-induced cell lysis have Also linked. Although the bleeding is usually oriented diagnosis, the most frequent cause of death is thrombosis. There are no specific tests for diagnosis. Elevated levels of D-dimer and products oriented fibrinogen degradation diagnosis. No reduction fibrinogen and almost always, one thrombocytopenia consumption. Treatment is complex and there is no consensus on many points. To recover the lost factors for consumption, it is recommended to use fresh frozen plasma and / or washed red blood cells. the heparin anticoagulation low dose is indicated since the disease causal can not be controlled quickly, but should not be initiated if there thrombocytopenia 50.000.El under profuse bleeding can require the use of tranexamic acid or EACA. Acute DIC, the case of our patient, is rare and very serious

  5. Chromosomal differences between acute nonlymphocytic leukemia in patients with prior solid tumors and prior hematologic malignancies. A study of 14 cases with prior breast cancer

    International Nuclear Information System (INIS)

    Mamuris, Z.; Dumont, J.; Dutrillaux, B.; Aurias, A.

    1989-01-01

    A cytogenetic study of 14 patients with secondary acute nonlymphocytic leukemia (S-ANLL) with prior treatment for breast cancer is reported. The chromosomes recurrently involved in numerical or structural anomalies are chromosomes 7, 5, 17, and 11, in decreasing order of frequency. The distribution of the anomalies detected in this sample of patients is similar to that observed in published cases with prior breast or other solid tumors, though anomalies of chromosome 11 were not pointed out, but it significantly differs from that of the S-ANLL with prior hematologic malignancies. This difference is principally due to a higher involvement of chromosome 7 in patients with prior hematologic malignancies and of chromosomes 11 and 17 in patients with prior solid tumors. A genetic determinism involving abnormal recessive alleles located on chromosomes 5, 7, 11, and 17 uncovered by deletions of the normal homologs may be a cause of S-ANLL. The difference between patients with prior hematologic malignancies or solid tumors may be explained by different constitutional mutations of recessive genes in the two groups of patients

  6. Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

    Science.gov (United States)

    Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

    2012-04-01

    Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

  7. A Phase I study of intermittently dosed vorinostat in combination with bortezomib in patients with advanced solid tumors.

    Science.gov (United States)

    Deming, Dustin A; Ninan, Jacob; Bailey, Howard H; Kolesar, Jill M; Eickhoff, Jens; Reid, Joel M; Ames, Matthew M; McGovern, Renee M; Alberti, Dona; Marnocha, Rebecca; Espinoza-Delgado, Igor; Wright, John; Wilding, George; Schelman, William R

    2014-04-01

    Accumulating evidence shows evidence of efficacy with the combination of vorinostat and bortezomib in solid tumors. We previously examined a once-daily continuous dosing schedule of vorinostat in combination with bortezomib which was well tolerated in cycles 1 and 2; however, there was concern regarding the tolerability through multiple cycles. This study was conducted to evaluate an intermittent dosing schedule of vorinostat with bortezomib. Vorinostat was initially administered orally twice daily on days 1-14 with bortezomib IV on days 1, 4, 8, and 11 of a 21 day cycle. Two DLTs (elevated ALT and fatigue) were observed at dose level 1, thus the protocol was amended to administer vorinostat intermittently twice daily on days 1-4 and 8-11. 29 patients were enrolled; 13 men and 16 women. Common cancer types included sarcoma, pancreatic, colorectal, GIST, and breast. The most common Grade 3-4 toxicities at any dose level included thrombocytopenia, fatigue, increased ALT, elevated INR, and diarrhea. DLTs in the intermittent dosing scheduled included thrombocytopenia and fatigue. The Cmax and AUC for the intermittent dosing regimen were similar to those observed in the daily dosing. In this heavily pretreated population, stable disease was observed in patients with sarcoma, colorectal adenocarcinoma and GIST. The MTD was established at vorinostat 300 mg BID on days 1-4 and 8-11 and bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, and 11 of a 21 day cycle. Tolerability was not improved with the intermittent dosing schedule of vorinostat when compared to continuous dosing.

  8. Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis.

    Science.gov (United States)

    Wu, Jiayuan; Tan, Wenkai; Chen, Lin; Huang, Zhe; Mai, Shao

    2018-03-02

    C-reactive protein/albumin ratio (CAR) was originally used as a novel inflammation-based prognostic score in predicting outcomes in septic patients. Recently, more and more studies have reported the prognostic value of pretreatment CAR in solid tumors. However, the results remain controversial rather than conclusive. We conducted a meta-analysis based on 24 studies with 10203 patients to explore the relationship between CAR and survival outcomes in patients with solid tumors. The correlation between CAR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was applied to be the effect size estimate. The overall results showed that elevated CAR was associated with shorter overall survival (OS) (including 23 studies and 10067 patients) and poorer disease-free survival (DFS) (including 6 studies and 2904 patients). Significant associations between high CAR level and poor OS were also found in the subgroup analyses of study region, cancer type, primary treatment, clinical stage, cut-off selection, sample size, and cut-off value. Moreover, subgroup analyses demonstrated that study region, primary treatment, clinical stage, sample size, and cut-off value did not alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was correlated with certain phenotypes of tumor aggressiveness, such as poor histological grade, serious clinical stage, advanced tumor depth, positive lymph node metastasis, and positive distant metastasis. Together, our meta-analysis suggests that elevated level of serum CAR predicts worse survival and unfavorable clinical characteristics in cancer patients, and CAR may serve as an effective prognostic factor for solid tumors.

  9. A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors.

    Science.gov (United States)

    Lin, Jianqing; Gilbert, Jill; Rudek, Michelle A; Zwiebel, James A; Gore, Steve; Jiemjit, Anchalee; Zhao, Ming; Baker, Sharyn D; Ambinder, Richard F; Herman, James G; Donehower, Ross C; Carducci, Michael A

    2009-10-01

    This was a phase I trial to determine the minimal effective dose and optimal dose schedule for 5-azacytidine (5-AC) in combination with sodium phenylbutyrate in patients with refractory solid tumors. The pharmacokinetics, pharmacodynamics, and antineoplastic effects were also studied. Three dosing regimens were studied in 27 patients with advanced solid tumors, and toxicity was recorded. The pharmacokinetics of the combination of drugs was evaluated. Repeat tumor biopsies and peripheral blood mononuclear cells (PBMC) were analyzed to evaluate epigenetic changes in response to therapy. EBV titers were evaluated as a surrogate measure for gene re-expression of epigenetic modulation in PBMC. The three dose regimens of 5-AC and phenylbutyrate were generally well tolerated and safe. A total of 48 cycles was administrated to 27 patients. The most common toxicities were bone marrow suppression-related neutropenia and anemia, which were minor. The clinical response rate was disappointing for the combination of agents. One patient showed stable disease for 5 months whereas 26 patients showed progressive disease as the best tumor response. The administration of phenylbutyrate and 5-AC did not seem to alter the pharmacokinetics of either drug. Although there were individual cases of targeted DNA methyltransferase activity and histone H3/4 acetylation changes from paired biopsy or PBMC, no conclusive statement can be made based on these limited correlative studies. The combination of 5-AC and phenylbutyrate across three dose schedules was generally well tolerated and safe, yet lacked any real evidence for clinical benefit.

  10. High prevalence of malnutrition among patients with solid non-hematological tumors as found by using skinfold and circumference measurements

    Directory of Open Access Journals (Sweden)

    Adriana Garófolo

    Full Text Available CONTEXT AND OBJECTIVE: Malnutrition in cancer patients has many causes. Nutritional status is usually assessed from weight/height indices. These present limitations for the nutritional assessment of cancer patients: their weights include tumor mass, and lean mass changes are not reflected in weight/height indices. The objective was to evaluate differences between two anthropometric methods and compare deficits, in non-hematological tumor patients and hematological disease patients. DESIGN AND SETTING: Cross-sectional study at Instituto de Oncologia Pediátrica, Universidade Federal de São Paulo. METHODS: Children and adolescents were evaluated between March 1998 and January 2000. Traditional anthropometric measurements were obtained in the first month of treatment (induction therapy, by weight-for-height (W/H using z-scores index for children and body mass index (BMI for adolescents. Body composition evaluations consisted of specific anthropometric measurements: triceps skinfold thickness (TSFT, mid-upper arm circumference (MUAC and arm muscle circumference (AMC. Data were analyzed to compare nutritional assessment methods for diagnosing malnutrition prevalence. The chi-squared test was used for comparative analyses between tumor patients and hematological disease patients. RESULTS: Analysis was done on 127 patients with complete data. Higher percentages of deficits were found among tumor patients, by W/H z-scores or BMI and by MUAC and AMC. Higher percentages of deficits were shown by TSFT (40.2% and MUAC (35.4% than by W/H z-scores or BMI (18.9%. CONCLUSION: Non-hematological tumor patients presented higher malnutrition prevalence than did hematological disease patients. Body composition measurements by TSFT and MUAC detected more patients with malnutrition than did W/H or BMI.

  11. Advances in Cancer Immunotherapy in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Smitha Menon

    2016-11-01

    Full Text Available Immunotherapy is heralded as one of the most important advances in oncology. Until recently, only limited immunotherapeutic options were available in selected immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is an improved understanding that anti-tumor immunity is controlled by a delicate balance in the tumor microenvironment between immune stimulatory and immune inhibitory pathways. Either by blocking the inhibitory pathways or stimulating the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity can be enhanced leading to durable anti-tumor responses. Drugs which block the immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown tremendous promise in a wide spectrum of solid and hematological malignancies, significantly improving overall survival in newly diagnosed and heavily pretreated patients alike. Hence there is renewed enthusiasm in the field of immune oncology with current research focused on augmenting responses to checkpoint inhibitors by combination therapy as well as studies looking at other immune modulators and adoptive T cell therapy. In this article, we highlight the key clinical advances and concepts in immunotherapy with particular emphasis on checkpoint inhibition as well as the future direction in this field.

  12. CT differentiation of solid ovarian tumor and uterine subserosal leiomyoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Rae; Cho, Kyoung Sik [Asan Medical Center, Ulsan Univ. College of Medicine, Seoul (Korea, Republic of); Sohn, Chul Ho [Dongsan Medical Center, Keimyung Univ. College of Medicine, Taegu (Korea, Republic of); Ji, Eun Kyung [Bombit Hospital, Seoul (Korea, Republic of)

    1999-06-01

    On the basis of CT findings, to differentiate between solid ovarian tumor and uterine subserosal myoma. In eight surgically proven cases of solid ovarian tumor and in ten uterine subserosal myoma patients, contrast-enhanced CT images were obtained. Two genitourinary radiologists reviewed the findings with regard to degree of enhancement of the mass as compared with enhancement of uterine myometrium, thickening of round ligaments, visualization of normal ovaries, contour of the mass, and the presence of ascites in the pelvic cavity. Six of eight ovarian tumors but only two of ten uterine myomas were less enhanced than normal uterine myometrium (p<0.05). Pelvic ascites were seen in six of eight ovarian tumors, but in only one of ten uterine myomas (P<0.05). Three of 16 ovaries in ovarian tumor patients, but 12 of 20 ovaries in uterine myoma patients, were normal (p<0.05). Six of 16 round ligaments of the uterus in ovarian tumor patients, were thichened but 11 of 20 round ligaments in uterine myoma patients, were thickened (p>0.05). The contour of the mass was lobulated in two of eight ovarian tumor patients, but in five of ten uterine myoma patients (p>0.05). CT findings suggestive of solid ovarian tumor were less contrast enhancement of the mass than of normal uterine myometrium, pelvic ascites, and nonvisualization of normal ovary.

  13. Factors affecting the pharmacokinetics and pharmacodynamics of PEGylated liposomal irinotecan (IHL-305 in patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Wu H

    2015-02-01

    Full Text Available Huali Wu,1 Jeffrey R Infante,2 Vicki L Keedy,3 Suzanne F Jones,2 Emily Chan,3 Johanna C Bendell,2 Wooin Lee,4 Whitney P Kirschbrown,1 Beth A Zamboni,5 Satoshi Ikeda,6 Hiroshi Kodaira,6 Mace L Rothenberg,3 Howard A Burris III,2 William C Zamboni1,7–9 1UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 2Sarah Cannon Research Institute/Tennessee Oncology, PLLC, 3Vanderbilt University, Nashville, TN, 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 5Department of Mathematics, Carlow University, Pittsburgh, PA, USA; 6Yakult Honsha Co., Ltd., Medical Development Department, Tokyo, Japan; 7UNC Lineberger Comprehensive Cancer Center, 8UNC Institute for Pharmacogenomics and Individualized Therapy, 9Carolina Center for Cancer Nanotechology Excellence, University of North Carolina, Chapel Hill, NC, USA Abstract: IHL-305 is a PEGylated liposomal formulation of irinotecan (CPT-11. The objective of this study was to evaluate the factors associated with interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 in patients with advanced solid tumors. IHL-305 was administered intravenously once every 4 weeks as part of a Phase I study. Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed. Noncompartmental and compartmental pharmacokinetic analyses were conducted using pharmacokinetic data for sum total CPT-11. The pharmacokinetic variability of IHL-305 is associated with linear and nonlinear clearance. Patients whose age and body composition (ratio of total body weight to ideal body weight [TBW/IBW] were greater than the median age and TBW/IBW of the study had a 1.7-fold to 2.6-fold higher ratio of released CPT-11 area under the concentration versus time

  14. First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors

    DEFF Research Database (Denmark)

    Dienstmann, Rodrigo; Lassen, Ulrik; Cebon, Jonathan

    2016-01-01

    V600-mutated advanced solid tumors. PATIENTS AND METHODS: Patients received RG7256 orally over 8 dose levels from 200 mg once a day (QD) to 2400 mg twice a day (BID) (50-, 100- and 150-mg tablets) using a classic 3 + 3 dose escalation design. RESULTS: In total, 45 patients were enrolled; most (87...... %) had advanced melanoma (94 % BRAF V600E). RG7256 was rapidly absorbed, with limited accumulation and dose-proportional increase in exposure up to 1950 mg BID. The maximal tolerated dose (MTD) was not reached. The most common drug-related adverse events (AEs) were dyspepsia (20 %), dry skin (18 %), rash...

  15. Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors

    Directory of Open Access Journals (Sweden)

    Yongkun Sun

    2016-10-01

    Full Text Available Abstract Background Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. Methods Anlotinib (5–16 mg was orally administered in patients with solid tumor once a day on two schedules: (1 four consecutive weeks (4/0 or (2 2-week on/1-week off (2/1. Pharmacokinetic sampling was performed in all patients. Twenty-one patients were further enrolled in an expanded cohort study on the recommended dose and schedule. Preliminary tumor response was also assessed. Results On the 4/0 schedule, dose-limiting toxicity (DLT was grade 3 hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib had long elimination half-lives and significant accumulation during multiple oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum tolerated dose for the expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft tissue sarcoma were assessable for antitumor activity of anlotinib: 3 patients had partial response, 14 patients had stable disease including 12 tumor burden shrinkage, and 3 had disease progression. The main serious adverse effects were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation. Conclusions At the dose of 12 mg once daily at the 2/1 schedule, anlotinib displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential, justifying the conduct of further studies.

  16. Fanconi's anemia and clinical radiosensitivity. Report on two adult patients with locally advanced solid tumors treated by radiotherapy

    International Nuclear Information System (INIS)

    Bremer, M.; Karstens, J.H.; Schindler, D.; Gross, M.; Doerk, T.; Morlot, S.

    2003-01-01

    Background: Patients with Fanconi's anemia (FA) may exhibit an increased clinical radiosensitivity of various degree, although detailed clinical data are scarce. We report on two cases to underline the possible challenges in the radiotherapy of FA patients. Case Report and Results: Two 24- and 32-year-old male patients with FA were treated by definitive radiotherapy for locally advanced squamous cell head and neck cancers. In the first patient, long-term tumor control could be achieved after delivery of 67 Gy with a - in part - hyperfractionated split-course treatment regimen and, concurrently, one course of carboplatin followed by salvage neck dissection. Acute toxicity was marked, but no severe treatment-related late effects occurred. 5 years later, additional radiotherapy was administered due to a second (squamous cell carcinoma of the anus) and third (squamous cell carcinoma of the head and neck) primary, which the patient succumbed to. By contrast, the second patient experienced fatal acute hematologic toxicity after delivery of only 8 Gy of hyperfractionated radiotherapy. While the diagnosis FA could be based on flow cytometric analysis of a lymphocyte culture in the second patient, the diagnosis in the first patient had to be confirmed by hypersensitivity to mitomycin of a fibroblast cell line due to complete somatic lymphohematopoietic mosaicism. In this patient, phenotype complementation and molecular genetic analysis revealed a pathogenic mutation in the FANCA gene. The first patient has not been considered to have FA until he presented with his second tumor. Conclusion: FA has to be considered in patients presenting at young age with squamous cell carcinoma of the head and neck or anus. The diagnosis FA is of immediate importance for guiding the optimal choice of treatment. Radiotherapy or even radiochemotherapy seems to be feasible and effective in individual cases. (orig.)

  17. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study.

    Science.gov (United States)

    Dirix, Luc Y; Takacs, Istvan; Jerusalem, Guy; Nikolinakos, Petros; Arkenau, Hendrik-Tobias; Forero-Torres, Andres; Boccia, Ralph; Lippman, Marc E; Somer, Robert; Smakal, Martin; Emens, Leisha A; Hrinczenko, Borys; Edenfield, William; Gurtler, Jayne; von Heydebreck, Anja; Grote, Hans Juergen; Chin, Kevin; Hamilton, Erika P

    2018-02-01

    Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade ≥ 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC.

  18. Photodynamic therapy of solid tumors

    Science.gov (United States)

    Jori, Giulio

    Some porphyrin compounds, which are characterized by a relatively large degree of hydrophobicity (n-octanol/water partition coefficient above 8), are accumulated in greater amounts and retained for longer periods of time by neoplastic as compared with normal tissues. The affinity of these dyes for tumors is partially a consequence of their in vivo transport by low-density lipoproteins, which are preferentially endocytosized by hyperproliferating tissues in a receptor-mediated process. In general, at 24-48 h after the systematic administration of porphyrin doses in the range of 2.5 mg/kg body weight, the ratio of drug concentration between the neoplastic and the surrounding tissues is sufficiently large to guarantee a selective photoexcitation of the porphyrin. Toward this aim, the porphyrin-containing tumor tissues are irradiated with light wavelengths longer than 600 nm, since the transmittance of biological tissues is maximal in this spectral region. The electronically excited porphyrin transfers its excitation energy to oxygen, thus generating activated oxygen species (mainly, singlet oxygen): as a consequence, the photooxidative modification of subcellular targets (e.g. the plasma membrane and mitochondria) is readily obtained leading to an irreversible necrosis of the cell. With the most frequently used porphyrins for clinical phototherapy (including hematoporphyrin and its derivatives HpD and Photofrin II), one observes the preferential photosensitized destruction of endothelial cells, hence the vascular damage is a major process involved in the necrosis of tumors. The optimization of the phototherapy of tumors is presently pursued by the definition of clinical protocols tailored to the optical properties of specific neoplastic tissues as well as by the use of porphyrin analogs, such as chlorins and phthalocyanines, having an extinction coefficient in the red spectral region larger than that typical of hematoporphyrin and HpD.

  19. Radiotherapy of the most frequent solid tumors in childhood

    International Nuclear Information System (INIS)

    Pfeiffer, J.; Kamprad, F.

    1980-01-01

    During the past decade the prognosis of malignant tumors in childhood could be clearly improved, realized by combining surgery, radiation therapy and chemotherapy. Recommendations for the use of radiotherapy for the most frequent solid tumors in childhood are represented basing on the experience of the study groups 'Pediatric Hematology and Oncology' of the Society for Pediatrics of the GDR and 'Tumors in Childhood' of the Section of Children's Surgery of the GDR. Besides general problems which have to be taken into consideration in the treatment of infantile tumors the radiotherapeutical measures for Wilms' tumors, neuroblastomas, cerebral tumors, embryonal sarcomas of the soft parts and bone tumors are discussed. The necessary close cooperation of the attending branches is pointed out and both the regional centralization of patients' care and a superregional cooperation are required. (author)

  20. Solid-pseudo papillary tumor of the pancreas: Frantz's tumor

    International Nuclear Information System (INIS)

    Oliveira, Bruno Righi Rodrigues de; Moreira, Reni Cecilia Lopes; Campos, Marcelo Esteves Chaves

    2010-01-01

    The pseudo papillary solid tumor of the pancreas, also known as Frantz's tumor, is a rare disease, taking place in approximately 0.17% to 2.7% of non-endocrine tumors of the pancreas. Recently, the increase of its incidence has been noted with more than two-thirds of the total cases described in the last 10 years. A possible explanation is a greater knowledge of the disease and a greater uniformity of conceptualization in the last years. Generally, it affects young adult females. In most of the series, the tumor principally attacks the body and tail of the pancreas. The objective of the present report is to present the diagnostic and therapeutic option used in this rare pancreatic tumor of low-grade malignancy. (author)

  1. Profiling of tryptophan-related plasma indoles in patients with carcinoid tumors by automated, on-line, solid-phase extraction and HPLC with fluorescence detection.

    Science.gov (United States)

    Kema, I P; Meijer, W G; Meiborg, G; Ooms, B; Willemse, P H; de Vries, E G

    2001-10-01

    Profiling of the plasma indoles tryptophan, 5-hydroxytryptophan (5-HTP), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) is useful in the diagnosis and follow-up of patients with carcinoid tumors. We describe an automated method for the profiling of these indoles in protein-containing matrices as well as the plasma indole concentrations in healthy controls and patients with carcinoid tumors. Plasma, cerebrospinal fluid, and tissue homogenates were prepurified by automated on-line solid-phase extraction (SPE) in Hysphere Resin SH SPE cartridges containing strong hydrophobic polystyrene resin. Analytes were eluted from the SPE cartridge by column switching. Subsequent separation and detection were performed by reversed-phase HPLC combined with fluorometric detection in a total cycle time of 20 min. We obtained samples from 14 healthy controls and 17 patients with metastasized midgut carcinoid tumors for plasma indole analysis. In the patient group, urinary excretion of 5-HIAA and serotonin was compared with concentrations of plasma indoles. Within- and between-series CVs for indoles in platelet-rich plasma were 0.6-6.2% and 3.7-12%, respectively. Results for platelet-rich plasma serotonin compared favorably with those obtained by single-component analysis. Plasma 5-HIAA, but not 5-HTP was detectable in 8 of 17 patients with carcinoid tumors. In the patient group, platelet-rich plasma total tryptophan correlated negatively with platelet-rich plasma serotonin (P = 0.021; r = -0.56), urinary 5-HIAA (P = 0.003; r = -0.68), and urinary serotonin (P manual, single-component analyses.

  2. Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors.

    Science.gov (United States)

    Camacho, Luis H; Olson, Jon; Tong, William P; Young, Charles W; Spriggs, David R; Malkin, Mark G

    2007-04-01

    Phenylbutyrate (PBA), and its metabolite phenylacetate (PAA), induce growth inhibition and cellular differentiation in multiple tumor models. However, despite their potential anti-cancer properties, several pharmacodynamic aspects remain unknown. We conducted a dose escalating trial to evaluate twice-daily intravenous PBA infusions for two consecutive weeks (Monday through Friday) every month at five dose levels (60-360 mg/kg/day). Twenty-one patients with the following malignancies were treated: colon carcinoma 4, non-small cell lung carcinoma 4; anaplastic astrocytoma 3, glioblastoma multiforme 3, bladder carcinoma 2, sarcoma 2, and ovarian carcinoma, rectal hemangiopericytoma, and pancreatic carcinoma 1 each. Conversion of PBA to PAA and phenylacetylglutamine (PAG) was documented without catabolic saturation. Plasma content of PBA > or =1 mM was documented for only 3 h following each dose at the top two dosages. The therapy was well tolerated overall. Common adverse effects included grade 1 nausea/vomiting, fatigue, and lightheadedness. Dose limiting toxicities were short-term memory loss, sedation, confusion, nausea, and vomiting. Two patients with anaplastic astrocytoma and a patient with glioblastoma remained stable without tumor progression for 5, 7, and 4 months respectively. Administration of PBA in a twice-daily infusion schedule is safe. The maximum tolerated dose is 300 mg/kg/day. Study designs with more convenient treatment schedules and specific molecular correlates may help to further delineate the mechanism of action of this compound. Future studies evaluating PBA's ability to induce histone acetylation and cell differentiation alone or in combination with other anti-neoplastics are recommended.

  3. Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors.

    Science.gov (United States)

    Zhao, Qiong; Shentu, Jianzhong; Xu, Nong; Zhou, Jianya; Yang, Guangdie; Yao, Yinan; Tan, Fenlai; Liu, Dongyang; Wang, Yingxiang; Zhou, Jianying

    2011-08-01

    The goal of this study was to assess the safety and tolerability of icotinib hydrochloride (BPI-2009H), a new selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), and to explore its pharmacokinetics (PK) and clinical activity in patients with advanced solid tumors, mainly those with non-small-cell lung cancer (NSCLC) after the failure of the prior platinum-based chemotherapy. Different doses of oral icotinib were administered once every 8 h (Q8H) for a 28-continuous-day cycle until disease progression and or undue toxicity was observed. PK studies of subjects' blood were performed during cycle one (day 1 through 28). Patients aged ≥18 and ≤70 years with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 and adequate organ functions eligible for the study. Tumor responses were assessed by Response Evaluation Criteria in Solid Tumors (RECIST). K-ras and EGFR mutations in the extracted DNA of fourteen specimens were examined using PCR-based direct sequencing assay. Thirty-six patients were enrolled in the study. PK analysis demonstrated that the mean elimination half-life of icotinib was 6 h, and the T(max) was around 2 h. The steady-state concentration of icotinib administered at a dose of 125 mg once every 8 h (Q8H) was significantly higher than that achieved by a dose of 100mg Q8H. The most frequent treatment-related adverse events (TRAEs) were an acne-like (folliculitis) rash (16/36, 44.4%), diarrhea (8/36, 22.2%) and a decrease in white blood cells (4/36, 11.1%). The maximum-tolerated dose (MTD) was not reached. Among 33 patients with NSCLC, 7 patients exhibited a partial response, 7 showed stable disease at the 24 weeks. Among 14 patients undergoing DNA sequence for K-ras and EGFR mutations, 3 with K-ras mutation presented 2 stable disease (SD) and 1 partial response (PR), 5 with EGFR exon 19 or 21 mutation 2 PR and 3 SD within 4 weeks. Oral icotinib was generally well tolerated, with manageable and

  4. A phase I trial of sorafenib combined with cisplatin/etoposide or carboplatin/pemetrexed in refractory solid tumor patients.

    Science.gov (United States)

    Davies, Janine M; Dhruva, Nirav S; Walko, Christine M; Socinski, Mark A; Bernard, Stephen; Hayes, D Neil; Kim, William Y; Ivanova, Anastasia; Keller, Kimberly; Hilbun, Layla R; Chiu, Michael; Dees, E Claire; Stinchcombe, Thomas E

    2011-02-01

    Sorafenib has demonstrated single agent activity in non-small cell (NSCLC) and small cell lung cancer (SCLC). Carboplatin/pemetrexed (CbP) and cisplatin/etoposide (PE) are commonly used in the treatment of these diseases. A phase I trial escalating doses of sorafenib in combination with fixed doses of PE (Arm A) or CbP (Arm B) was performed using a 3-patient cohort design to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT); DLT were assessed in the first cycle. The trial was subsequently amended with closure of Arm B and to include Arm C with a reduced dose of carboplatin. Between 9/2007 and 9/2008, 20 pts were treated on the trial; median age 62 (range 42-73), male/female ratio 12/8, PS 0/1 ratio 6/14, and median number of prior therapies 2 (range 1-4). The most common tumor types were NSCLC and SCLC. On Arm A at dose level 0 (sorafenib 200 mg BID), 2 of 4 patients experienced DLT; 2 patients were enrolled at dose level -1 (sorafenib 200 mg QD) without DLT, but this arm was closed due to slow accrual. On Arm B, 2 of 3 patients experienced DLT at dose level 0 (sorafenib 200 mg BID). On Arm C at dose level 0 (sorafenib 200 mg BID), 1 of 6 patients experienced DLT, and at dose level +1 (sorafenib 400 mg BID) 2 of 5 patients experienced a DLT. The MTD of sorafenib was 200 mg BID continuously in combination with carboplatin (AUC of 5) and pemetrexed 500 mg/m² every 3 weeks. However, only 6 patients were treated at this dose level, and the results should be interpreted cautiously. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  5. Phase I safety, pharmacokinetic and pharmacodynamic evaluation of the vascular disrupting agent ombrabulin (AVE8062) in patients with advanced solid tumors.

    Science.gov (United States)

    Sessa, Cristiana; Lorusso, Patricia; Tolcher, Anthony; Farace, Françoise; Lassau, Nathalie; Delmonte, Angelo; Braghetti, Antonio; Bahleda, Rastislav; Cohen, Patrick; Hospitel, Marie; Veyrat-Follet, Christine; Soria, Jean-Charles

    2013-09-01

    The vascular disrupting agent ombrabulin rapidly reduces tumor blood flow and causes necrosis in vivo. A phase I dose-escalation study was designed to determine the recommended phase II dose (RP2D) of single-agent ombrabulin administered once every three weeks in patients with advanced solid malignancies. Ombrabulin (30-minute infusion) was escalated from 6 to 60 mg/m2, with RP2D cohort expansion. Safety, tumor response, pharmacokinetics, and pharmacodynamic biomarkers were evaluated. Eleven dose levels were evaluated in 105 patients. Two patients had dose-limiting toxicities in cycle 1 during escalation: grade 3 abdominal pain at 50 mg/m2, grade 3 tumor pain/grade 3 hypertension at 60 mg/m2, and the RP2D was 50 mg/m2 (39 patients). Common toxicities were headache, asthenia, abdominal pain, nausea, diarrhea, transient hypertension, anemia, and lymphopenia. No clinically significant QTc prolongations or left ventricular ejection fraction (LVEF) decreases occurred. Ombrabulin was rapidly converted to its active metabolite RPR258063 (half-life 17 minutes and 8.7 hours, respectively), both having dose-proportional exposure. Weak inhibition of CYP2C19-mediated metabolism occurred at the clinical doses used and there was no effect on CYP1A2 and CYP3A4. A patient with rectal cancer had a partial response and eight patients had stable disease lasting four months or more. Circulating endothelial cells (CEC), VEGF, and matrix metalloproteinase (MMP)-9 levels increased significantly six to 10 hours postinfusion in a subset of patients. The recommended schedule for single-agent ombrabulin is 50 mg/m2 every 3 weeks. CECs, VEGF, and MMP-9 are potential biomarkers of ombrabulin activity. ©2013 AACR.

  6. A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients with Advanced Solid Tumors and Lymphomas.

    Science.gov (United States)

    Infante, Jeffrey R; Cassier, Philippe A; Gerecitano, John F; Witteveen, Petronella O; Chugh, Rashmi; Ribrag, Vincent; Chakraborty, Abhijit; Matano, Alessandro; Dobson, Jason R; Crystal, Adam S; Parasuraman, Sudha; Shapiro, Geoffrey I

    2016-12-01

    Ribociclib (an oral, highly specific cyclin-dependent kinase 4/6 inhibitor) inhibits tumor growth in preclinical models with intact retinoblastoma protein (Rb + ). This first-in-human study investigated the MTD, recommended dose for expansion (RDE), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of ribociclib in patients with Rb + advanced solid tumors or lymphomas. Patients received escalating doses of ribociclib (3-weeks-on/1-week-off or continuous). Dose escalation was guided by a Bayesian Logistic Regression Model with overdose control principle. Among 132 patients, 125 received ribociclib 3-weeks-on/1-week-off and 7 were dosed continuously. Nine dose-limiting toxicities were observed among 70 MTD/RDE evaluable patients during cycle 1, most commonly neutropenia (n = 3) and thrombocytopenia (n = 2). The MTD and RDE were established as 900 and 600 mg/day 3-weeks-on/1-week-off, respectively. Common treatment-related adverse events were (all-grade; grade 3/4) neutropenia (46%; 27%), leukopenia (43%; 17%), fatigue (45%; 2%), and nausea (42%; 2%). Asymptomatic Fridericia's corrected QT prolongation was specific to doses ≥600 mg/day (9% of patients at 600 mg/day; 33% at doses >600 mg/day). Plasma exposure increases were slightly higher than dose proportional; mean half-life at the RDE was 32.6 hours. Reduced Ki67 was observed in paired skin and tumor biopsies, consistent with ribociclib-mediated antiproliferative activity. There were 3 partial responses and 43 patients achieved a best response of stable disease; 8 patients were progression-free for >6 months. Ribociclib demonstrated an acceptable safety profile, dose-dependent plasma exposure, and preliminary signs of clinical activity. Phase I-III studies of ribociclib are under way in various indications. Clin Cancer Res; 22(23); 5696-705. ©2016 AACR. ©2016 American Association for Cancer Research.

  7. Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors.

    Science.gov (United States)

    Gandhi, Leena; Bahleda, Rastislav; Tolaney, Sara M; Kwak, Eunice L; Cleary, James M; Pandya, Shuchi S; Hollebecque, Antoine; Abbas, Richat; Ananthakrishnan, Revathi; Berkenblit, Anna; Krygowski, Mizue; Liang, Yali; Turnbull, Kathleen W; Shapiro, Geoffrey I; Soria, Jean-Charles

    2014-01-10

    Human epidermal growth factor (HER) -mediated signaling is critical in many cancers, including subsets of breast and lung cancer. HER family members signal via the phosphatidylinositide 3-kinase (PI3K) -AKT/protein kinase B-mammalian target of rapamycin (mTOR) cascade; mTOR activation is critical for the expression of multiple contributors to tumor growth and invasion. On the basis of preclinical data suggesting synergy of HER2 inhibition and mTOR inhibition in breast and lung cancer models, we conducted a phase I combination study of neratinib, a small-molecule irreversible pan-HER tyrosine kinase inhibitor, and temsirolimus, an mTOR inhibitor, in patients with advanced solid tumors. This study enrolled patients to dosing combinations of neratinib and temsirolimus. The primary objective was to estimate the toxicity contour of the combination and establish recommended phase II doses. Sixty patients were treated on 12 of 16 possible dosing combinations. Diarrhea was the most common drug-related (93%) and dose-limiting toxicity (DLT), constituting four of 10 DLTs. Dose-limiting grade 3 metabolic abnormalities were also observed. Other frequent drug-related toxicities included nausea, stomatitis (both 53%), and anemia (48%). Two maximum-tolerated dose combinations were identified: 200 mg of neratinib/25 mg of temsirolimus and 160 mg of neratinib/50 mg of temsirolimus. Responses were noted in patients with HER2-amplified breast cancer resistant to trastuzumab, HER2-mutant non-small-cell lung cancer, and tumor types without identified mutations in the HER-PI3K-mTOR pathway. The combination of neratinib and temsirolimus was tolerable and demonstrated antitumor activity in multiple tumor types, warranting further evaluation.

  8. Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.

    Science.gov (United States)

    Rangwala, Reshma; Leone, Robert; Chang, Yunyoung C; Fecher, Leslie A; Schuchter, Lynn M; Kramer, Amy; Tan, Kay-See; Heitjan, Daniel F; Rodgers, Glenda; Gallagher, Maryann; Piao, Shengfu; Troxel, Andrea B; Evans, Tracey L; DeMichele, Angela M; Nathanson, Katherine L; O'Dwyer, Peter J; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; Amaravadi, Ravi K

    2014-08-01

    Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.

  9. Recurrence of Solid Pseudopapillary Tumor: A Rare Pancreatic Tumor

    Directory of Open Access Journals (Sweden)

    Chandra Punch

    2016-01-01

    Full Text Available Solid pseudopapillary tumor of the pancreas (SPTP is a rare disease of young females that does not usually recur after resection. Here we report a case of an elderly female with history of SPTP ten years ago who presented with anorexia and a palpable left lower quadrant abdominal mass. Imaging revealed metastatic disease and US-guided biopsy of the liver confirmed the diagnosis of SPTP. Due to her advanced age and comorbidities, she elected to undergo hospice care. The objective of this case report is to increase awareness of this tumor and its possibility of recurrence, necessitating further guidelines for follow-up.

  10. Phase I dose escalation study of KOS-1584, a novel epothilone, in patients with advanced solid tumors.

    Science.gov (United States)

    Lam, Elaine T; Goel, Sanjay; Schaaf, Larry J; Cropp, Gillian F; Hannah, Alison L; Zhou, Yiqing; McCracken, Barbara; Haley, Brandi I; Johnson, Robert G; Mani, Sridhar; Villalona-Calero, Miguel A

    2012-02-01

    First-in-man study of KOS-1584, a second generation epothilone. Patients with advanced solid malignancies received KOS-1584 every 3 weeks until disease progression. Using a modified Fibonacci dose escalation scheme, one patient was enrolled at each dose level until the first instance of grade 2 toxicity. Thereafter, a standard 3 + 3 design was utilized. Sixty-six patients in 14 cohorts were dosed from 0.8 to 48 mg/m(2). Diarrhea, arthralgias, and encephalopathy were dose-limiting toxicities (DLTs) at doses ≥36 mg/m(2). At the recommended phase II dose (RP2D), the most common adverse effects were peripheral neuropathy (low grade), fatigue, arthralgias/myalgias, and diarrhea (31, 6%). The incidence of neutropenia was low. The overall clearance, volume of distribution, and half-life of KOS-1584 were 11 ± 6.17 L/h/m(2), 327 ± 161 L/m(2), and 21.9 ± 8.75 h, respectively. The half-life for the seco-metabolite (KOS-1891) was 29.6 ± 13.8 h. KOS-1584 exhibited linear pharmacokinetics. A dose-dependent increase in microtubulin bundle formation was observed at doses ≥27 mg/m(2). Two patients achieved partial responses and 24 patients had stable disease (SD). The RP2D of KOS-1584 is 36 mg/m(2). The lack of severe neurologic toxicity, diarrhea, neutropenia, or hypersensitivity reactions; favorable pharmacokinetic profile; and early evidence of activity support further evaluation.

  11. NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Patrick J. Mansky

    2013-01-01

    Full Text Available Purpose. European Mistletoe (Viscum album L. extracts (mistletoe are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM and mistletoe in advanced solid cancers (ASC evaluated: (1 safety, toxicity, and maximum tolerated dose (MTD, (2 absolute neutrophil count (ANC recovery, (3 formation of mistletoe lectin antibodies (ML ab, (4 cytokine plasma concentrations, (5 clinical response, and (6 pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT were grade (G 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

  12. A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.

    Science.gov (United States)

    Wong, Kwok-K; Fracasso, Paula M; Bukowski, Ronald M; Lynch, Thomas J; Munster, Pamela N; Shapiro, Geoffrey I; Jänne, Pasi A; Eder, Joseph P; Naughton, Michael J; Ellis, Matthew J; Jones, Suzanne F; Mekhail, Tarek; Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine; Burris, Howard A

    2009-04-01

    The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >or=24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.

  13. Exposure and Tumor Fn14 Expression as Determinants of Pharmacodynamics of the Anti-TWEAK Monoclonal Antibody RG7212 in Patients with Fn14-Positive Solid Tumors

    DEFF Research Database (Denmark)

    Meulendijks, Didier; Lassen, Ulrik N; Siu, Lillian L

    2016-01-01

    PURPOSE: The TWEAK-Fn14 pathway represents a novel anticancer target that is being actively investigated. Understanding the relationship between pharmacokinetics of anti-TWEAK therapeutics and tumor pharmacodynamics is critical. We investigated exposure-response relationships of RG7212, an anti...... changes in tumor TWEAK-Fn14 signaling in paired pre- and posttreatment tumor biopsies. The objectives of the analysis were to define exposure-response relationships and the relationship between pretreatment tumor Fn14 expression and pharmacodynamic effect. Associations between changes in TWEAK-Fn14...... longer time on study was observed with high versus low RG7212 exposure. CONCLUSIONS: RG7212 reduced tumor TWEAK-Fn14 signaling in a systemic exposure-dependent manner. In addition to higher exposure, relatively high Fn14 expression might be required for pharmacodynamic effect of anti-TWEAK monoclonal...

  14. THE THYMIDINE KINASE-1(TK-1 AS A POTENTIAL TUMOR MARKER: SERUM LEVELS IN SERUM OF PATIENTS WITH SOLID AND SYSTEM MALIGNANCE NEOPLASMS

    Directory of Open Access Journals (Sweden)

    N. S. Sergeeva

    2017-01-01

    Full Text Available The review summarizes the results of studies of levels and/or activity in the blood serum of a metabolic marker thymidine kinase-1 (TK-1 of proliferating cells in patients with lymphoproliferative diseases (LPD and malignant neopasms (NM.Comparison of the data in the literature in some cases have been difficult due to the fundamentally different methods of detection the activity or concentration of TK-1, used by authors, even despite the presence of relatively high (but not absolute correlation between these parameters (maximum 0.8.Many clinical and laboratory studies have shown levels of correlation and/or TK-1 activity with clinical stages and different types of LPD and solid MN and can serve as a prognostic factor for overall and recurrence-free survival of patients. When solid MN shown that the activity of TK-1 accurately reflects the proliferative status of tumor.A comparison of the dynamics of TC-1 in the process of chemotherapy and its clinical efficacy, different authors have received fundamentally different results: in some cases the marker reduction was associated with treatment efficacy, and in part of publications they show that the clinically relevant effects of the treatment observed increase in the marker after the first chemotherapy.The entire set of received data demonstrates the relevance of the further development of the algorithm use of TK-1 in oncology practice.

  15. Radio-immunotherapy of solid tumors

    International Nuclear Information System (INIS)

    Chatal, J.F.; Faivre Chauvet, A.; Bardies, M.; Kraeber-Bodere, F.; Barbet, J.

    2001-01-01

    A convincing efficacy of radio-immunotherapy of solid tumors has not been documented yet in clinical studies. Consequently, a methodological optimization is needed within the scope in increasing absorbed doses delivered to tumor targets by amplifying cumulative tumor activity and in the same time in reducing absorbed doses delivered normal organs. Multi-step pre-targeting techniques allow to approach these goals. The most developed technique is based on the high affinity for biotin. In a first step an anti-tumor antibody coupled to avidin or biodin is injected. In a second step, 24 hours later, the circulating residual immuno-conjugate is bound to a molecular complex and eliminated through the reticulo endothelial system of the liver ('chase'phase). A third step, a few hours later, consists in injecting biotin coupled to DOTA chelating agent and labeled with yttrium 90. This small molecule rapidly diffuses to tumor targets and binds to pre-localized immuno-conjugate. Another technique, designed and developed in France, is based on antigen-antibody affinity. In a first step an anti-tumor / anti-hapten bi-specific antibody is injected and, in a second step, a few days later, the small hapten molecule is radiolabeled with I-131 and injected. It diffuses rapidly to the tumor targets and binds to the anti-hapten arm of the pre-localized bi-specific antibody. An alternative way to increase radio-immunotherapy efficacy consists in combining this low-dose rate irradiation to radiosensitizing molecules within the scope of an additive or supra additive effect which has previously documented. (author)

  16. Targeted radionuclide therapy for solid tumors: An overview

    International Nuclear Information System (INIS)

    De Nardo, Sally J.; De Nardo, Gerald L.

    2006-01-01

    Although radioimmunotherapy (RIT) has been effective in non-Hodgkin's lymphoma (NHL) as a single agent, solid tumors have shown less clinically significant therapeutic response to RIT alone. The clinical impact of RIT or other forms of targeted radionuclide therapy for solid tumors depends on the development of a high therapeutic index (TI) for the tumor vs. normal tissue effect, and the implementation of RIT as part of synergistic combined modality therapy (CMRIT). Preclinical and clinical studies have provided a wealth of information, and new prototypes or paradigms have shed light on future possibilities in many instances. Evidence suggests that combination and sequencing of RIT in CMRIT appropriately can provide effective treatment for many solid tumors. Vascular targets provide RIT enhancement opportunities and nanoparticles may prove to be effective carriers for RIT combined with intracellular drug delivery or alternating magnetic frequency (AMF) induced thermal tumor necrosis. The sequence and timing of combined modality treatments will be of critical importance to achieve synergy for therapy while minimizing toxicity. Fortunately, the radionuclide used for RIT also provides a signal useful for nondestructive quantitation of the influence of sequence and timing of CMRIT on events in animals and patients. This can be readily accomplished clinically using quantitative high-resolution imaging (e.g., positron emission tomography [PET])

  17. A phase 1 study of KOS-862 (Epothilone D) co-administered with carboplatin (Paraplatin®) in patients with advanced solid tumors.

    Science.gov (United States)

    Monk, J Paul; Villalona-Calero, Miguel; Larkin, Joe; Otterson, Greg; Spriggs, David S; Hannah, Alison L; Cropp, Gillian F; Johnson, Robert G; Hensley, Martee L

    2012-08-01

    To determine the maximally tolerated dose (MTD) and pharmacokinetics of carboplatin plus KOS-862 (Epothilone D) a novel cytotoxic macrolide capable of causing mitotic arrest, in patients with advanced solid malignancies. Patients who have progressed on standard regimens were treated at four different levels of KOS-862(mg/m(2))/Carboplatin(AUC): 50/5,75/5, 75/6 and 100/6 in a "3 + 3" phase I study study design to determine MTD. Patients received KOS-862 on Days 1 and 8, and carboplatin on day 1, of 3-week cycles. Pharmacokinetics of KOS-862 and Carboplatin were studied. Twenty-seven patients enrolled in the study. At the top dose level, 2 out of the 9 patients experienced Dose Limiting Toxicity. (grade 3 peripheral motor neuropathy in both patients) Twenty-seven patients had sufficient plasma data points for pharmacokinetic analysis Both the parent drug, KOS-862, and the major inactive metabolite Seco-D KOS-862 (KOS-1965) were quantified in plasma. Kinetics of KOS-862 were the same as seen in monotherapy studies using the same route and time of administration. Two patients had tumor response after study treatment. Ten of 20 evaluable patients had stable disease after 2 cycles of study treatment. The MTD in the present study was KOS-862 100 mg/m(2) + carboplatin AUC = 6. The pharmacokinetics of KOS-862 were similar in this combination study to those seen in previous monotherapy studies using the same route and time of administration. We have described the MTD of this schedule. The neurotoxicity seen with this regimen should be considered prior to its administration in unselected populations.

  18. A retrospective study of treatment and prophylaxis of ifosfamide-induced hemorrhagic cystitis in pediatric and adolescent and young adult (AYA) patients with solid tumors.

    Science.gov (United States)

    Saito, Yoshimasa; Kumamoto, Tadashi; Makino, Yoshinori; Tamai, Ikumi; Ogawa, Chitose; Terakado, Hiroyuki

    2016-09-01

    Ifosfamide (IFO) is considered an essential drug for the treatment of pediatric, adolescent and young adult patients with solid tumors. Hemorrhagic cystitis (HC) is one of the dose-limiting toxicity of IFO. However, there are insufficient evidence for risk factor and supportive care of IFO-induced HC. In this retrospective study, patients (daily IFO dosage was 1.2-3.0 g/m(2). HC occurred in 14/425 IFO-based chemotherapy cycles (3.3%). The daily IFO dosages (mean ± SD) in patients with or without HC were 2.23 ± 0.58 g/m(2) and 1.85 ± 0.50 g/m(2), respectively (P = 0.006). Only one of the nine patients who developed IFO-induced HC had experienced this complication in a subsequent cycle of treatment. The incidence of IFO-induced HC may be associated with the dosage of IFO. When administering IFO higher than 2.0 g/m(2)/day, the volume of hydration, dosage of mesna and duration of mesna infusion should be increased to prevent HC. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors.

    Science.gov (United States)

    Molife, L Rhoda; Yan, Li; Vitfell-Rasmussen, Joanna; Zernhelt, Adriane M; Sullivan, Daniel M; Cassier, Philippe A; Chen, Eric; Biondo, Andrea; Tetteh, Ernestina; Siu, Lillian L; Patnaik, Amita; Papadopoulos, Kyriakos P; de Bono, Johann S; Tolcher, Anthony W; Minton, Susan

    2014-01-03

    Inhibition of AKT with MK-2206 has demonstrated synergism with anticancer agents. This phase 1 study assessed the MTD, DLTs, PK, and efficacy of MK-2206 in combination with cytotoxic and targeted therapies. Advanced solid tumor patients received oral MK-2206 45 or 60 mg (QOD) with either carboplatin (AUC 6.0) and paclitaxel 200 mg/m2 (arm 1), docetaxel 75 mg/m2 (arm 2), or erlotinib 100 or 150 mg daily (arm 3); alternative schedules of MK-2206 135-200 mg QW or 90-250 mg Q3W were also tested. MTD of MK-2206 (N = 72) was 45 mg QOD or 200 mg Q3W (arm 1); MAD was 200 mg Q3W (arm 2) and 135 mg QW (arm 3). DLTs included skin rash (arms 1, 3), febrile neutropenia (QOD, arms 1, 2), tinnitus (Q3W, arm 2), and stomatitis (QOD, arm 3). Common drug-related toxicities included fatigue (68%), nausea (49%), and rash (47%). Two patients with squamous cell carcinoma of the head and neck (arm 1; Q3W) demonstrated a complete and partial response (PR); additional PRs were observed in patients (1 each) with melanoma, endometrial, neuroendocrine prostate, NSCLC, and cervical cancers. Six patients had stable disease ≥6 months. MK-2206 plus carboplatin and paclitaxel, docetaxel, or erlotinib was well-tolerated, with early evidence of antitumor activity.

  20. Optimized multiparametric flow cytometric analysis of circulating endothelial cells and their subpopulations in peripheral blood of patients with solid tumors: a technical analysis.

    Science.gov (United States)

    Zhou, Fangbin; Zhou, Yaying; Yang, Ming; Wen, Jinli; Dong, Jun; Tan, Wenyong

    2018-01-01

    Circulating endothelial cells (CECs) and their subpopulations could be potential novel biomarkers for various malignancies. However, reliable enumerable methods are warranted to further improve their clinical utility. This study aimed to optimize a flow cytometric method (FCM) assay for CECs and subpopulations in peripheral blood for patients with solid cancers. An FCM assay was used to detect and identify CECs. A panel of 60 blood samples, including 44 metastatic cancer patients and 16 healthy controls, were used in this study. Some key issues of CEC enumeration, including sample material and anticoagulant selection, optimal titration of antibodies, lysis/wash procedures of blood sample preparation, conditions of sample storage, sufficient cell events to enhance the signal, fluorescence-minus-one controls instead of isotype controls to reduce background noise, optimal selection of cell surface markers, and evaluating the reproducibility of our method, were integrated and investigated. Wilcoxon and Mann-Whitney U tests were used to determine statistically significant differences. In this validation study, we refined a five-color FCM method to detect CECs and their subpopulations in peripheral blood of patients with solid tumors. Several key technical issues regarding preanalytical elements, FCM data acquisition, and analysis were addressed. Furthermore, we clinically validated the utility of our method. The baseline levels of mature CECs, endothelial progenitor cells, and activated CECs were higher in cancer patients than healthy subjects ( P technical issues found in previously published assays and validated the reproducibility and sensitivity of our proposed method. Future work is required to explore the potential of our optimized method in clinical oncologic applications.

  1. Repeatability of quantitative 18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis.

    Science.gov (United States)

    Kramer, G M; Liu, Y; de Langen, A J; Jansma, E P; Trigonis, I; Asselin, M-C; Jackson, A; Kenny, L; Aboagye, E O; Hoekstra, O S; Boellaard, R

    2018-06-01

    3'-deoxy-3'-[ 18 F]fluorothymidine ( 18 F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative 18 F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of 18 F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five 18 F-FLT repeatability cohorts in solid tumors. 18 F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUV max , SUV mean , SUV peak , proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all 18 F-FLT uptake metrics (R 2  ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUV peak (RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUV max  ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics. In multi-center studies

  2. Complications related to the use of an intraventricular access device for the treatment of leptomeningeal metastases from solid tumor: a single centre experience in 112 patients.

    Science.gov (United States)

    Zairi, Fahed; Le Rhun, Emilie; Bertrand, Nicolas; Boulanger, Thomas; Taillibert, Sophie; Aboukais, Rabih; Assaker, Richard; Chamberlain, Marc C

    2015-09-01

    Ventricular access devices (VAD) offer several advantages compared to intralumbar injections for the administration of intra-CSF agents in the treatment of leptomeningeal metastases (LM). However, there are few prospective studies reporting on complications with the use of VADs. All complications were prospectively collected that pertained to the implantation and use of a VAD in consecutive patients with solid tumor-related LM from June 2006 to December 2013. Clinical follow-up was every 2 weeks during the initial 2 months of treatment and then once monthly. Complete neuraxis MRI was performed at baseline and then every 2-3 months. A total of 112 patients (88 women) with a mean age of 51.1 years (range 26-73) were included. Primary cancers included breast (79 patients), lung (12) and melanoma (6). All patients were treated with intra-CSF liposomal cytarabine. 72 % of the patients received concomitant systemic and intra-CSF chemotherapy. The placement of the VAD was performed under local anesthesia in all cases. The mean operative time was 15 min and no perioperative complications were reported. The mean number of intraventricular injections per patient was 9.34 (range 1-47). A total of 11 complications in 11 patients were seen including 7 infections, 1 intracranial hemorrhage, 2 instances of symptomatic leukoencephalopathy and 1 catheter malpositioning. 8 complications required an operation and 1 complication was fatal. The use of a VAD is safe and may improve patients' comfort and compliance with LM-directed therapy.

  3. Akt Inhibitor MK2206 and Hydroxychloroquine in Treating Patients With Advanced Solid Tumors, Melanoma, Prostate or Kidney Cancer

    Science.gov (United States)

    2018-05-15

    Adult Solid Neoplasm; Hormone-Resistant Prostate Carcinoma; Recurrent Melanoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Prostate Cancer AJCC v7; Stage IV Renal Cell Cancer AJCC v7

  4. Characterization of cell suspensions from solid tumors

    International Nuclear Information System (INIS)

    Pallavicini, M.

    1985-01-01

    The desirable features of cells in suspension will necessarily be dependent upon the use for which the cells were prepared. Adequate cell yield or recovery is defined by the measurement to be performed. Retention of cellular morphology is important for microscopic identification of cell types in a heterogenous cell suspension, and may be used to determine whether the cells in suspension are representative of those in the tumor in situ. Different dispersal protocols may yield cells with different degrees of clonogenicity, as well as altered biochemical features, such as loss of cellular proteins, surface antigens, nucleotide pools, etc. The quality of the cell suspension can be judged by the degree of cell clumping and level of cellular debris, both of which impact on flow cytometric measurements and studies in which the number of cells be known accurately. Finally, if the data measured on the cells in suspension are to be extrapolated to phenomena occurring in the tumor in situ, it is desirable that the cells in suspension are representative of those in the solid tumor in vivo. This report compares characteristics of tumor cell suspensions obtained by different types of selected disaggregation methods. 33 refs., 2 figs., 4 tabs

  5. Quality-of-Life (QOL during Screening for Phase 1 Trial Studies in Patients with Advanced Solid Tumors and Its Impact on Risk for Serious Adverse Events

    Directory of Open Access Journals (Sweden)

    Sidra Anwar

    2017-06-01

    Full Text Available Background: Serious adverse events (SAEs and subject replacements occur frequently in phase 1 oncology clinical trials. Whether baseline quality-of-life (QOL or social support can predict risk for SAEs or subject replacement among these patients is not known. Methods: Between 2011–2013, 92 patients undergoing screening for enrollment into one of 22 phase 1 solid tumor clinical trials at Roswell Park Cancer Institute were included in this study. QOL Questionnaires (EORTC QLQ-C30 and FACT-G, Medical Outcomes Study Social Support Survey (MOSSSS, Charlson comorbidity scores (CCS and Royal Marsden scores (RMS were obtained at baseline. Frequency of dose limiting toxicities (DLTs, subject replacement and SAEs that occurred within the first 4 cycles of treatment were recorded. Fisher’s exact test and Mann-Whitney-Wilcoxon test were used to study the association between categorical and continuous variables, respectively. A linear transformation was used to standardize QOL scores. p-value ≤ 0.05 was considered statistically significant. Results: Baseline QOL, MOSSSS, CCS and RMS were not associated with subject replacement nor DLTs. Baseline EORTC QLQ-C30 scores were significantly lower among patients who encountered SAEs within the first 4 cycles (p = 0.04. Conclusions: Lower (worse EORTC QLQ-C30 score at baseline is associated with SAE occurrence during phase 1 oncology trials.

  6. Epoetin alfa 40000 U once weekly and intravenous iron supply in solid tumor patients: early increase of hemoglobin level during chemotherapy

    International Nuclear Information System (INIS)

    Lalle, M.; Antimi, M.; Pistillucci, G.; D'Aprile, M.

    2005-01-01

    The objective of this observational study was the early evaluation of the impact, a week after the first administration of epoetin alfa 40000 U once weekly and i.v. dose of 62.5 mg sodium ferric gluconate for seven days in improving hemoglobin levels in cancer patients affected by mild/moderate or severe anemia during chemotherapy. Twenty patients affected by solid tumors who received epoetin alfa 40000 U once weekly and daily i.v. sodium ferric gluconate for one week were evaluated: 90% of the patients showed hemoglobin increase, with a median level of hemoglobin increase of 0.73 g/L from baseline, and 50% of them showing a hemoglobin increase > 1 gr/L. The treatment was well tolerated and no adverse event was observed. The early increase of hemoglobin level from baseline is interesting and suggestive for the possibility of achieving an adequate hemoglobin level with a short-term treatment. It is still necessary to further explore the real need of iron supplementation to maintain adequate erythropoiesis prior and during epoetin therapy

  7. Potential of epigenetic therapies in the management of solid tumors

    International Nuclear Information System (INIS)

    Valdespino, Victor; Valdespino, Patricia M

    2015-01-01

    Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails

  8. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors

    NARCIS (Netherlands)

    de Weger, Vincent A; Goel, Sanjay; von Moos, Roger; Schellens, Jan H M; Mach, Nicholas; Tan, Eugene; Anand, Suraj; Scott, Jeffrey W; Lassen, Ulrik N

    PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS:

  9. A drug-drug interaction study to assess the effect of the CYP1A2 inhibitor fluvoxamine on the pharmacokinetics of dovitinib (TKI258) in patients with advanced solid tumors

    DEFF Research Database (Denmark)

    de Weger, Vincent A; Goel, Sanjay; von Moos, Roger

    2018-01-01

    PURPOSE: Dovitinib is an orally available multi tyrosine kinase inhibitor which inhibits VEGFR 1-3, FGFR 1-3, and PDGFR. This study was performed to investigate the potential drug-drug interaction of dovitinib with the CYP1A2 inhibitor fluvoxamine in patients with advanced solid tumors. METHODS: ...

  10. Immunoconjugates against solid tumors: mind the gap.

    Science.gov (United States)

    Ricart, A D

    2011-04-01

    The objective of immunoconjugate development is to combine the specificity of immunoglobulins with the efficacy of cytotoxic molecules. This therapeutic approach has been validated in hematologic malignancies; however, several obstacles to achieving efficacy in treating solid tumors have been identified. These include insufficient specificity of targets and poor antibody delivery, most specifically to the tumor core. Heterogeneous antigen expression, imperfect vascular supply, and elevated interstitial fluid pressure have been suggested as the factors responsible for the poor delivery of antibodies. Promising immunoconjugates are in development: immunoconjugates targeting the prostate-specific membrane antigen, trastuzumab-DM1, lorvotuzumab mertansine, and SS1P. Advances in cancer biology and antibody engineering may overcome some of the challenges. New small antibody formats, such as single-chain Fv, Fab, and diabodies, may improve penetration within tumor masses. Nevertheless, the cost of treatment might require justification in terms of demonstrable improvement in quality of life in addition to efficacy; further economic evaluation might be necessary before this approach can replace the current standards of care in clinical practice.

  11. Open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of intravenously administered CNF1010 (17-(allylamino)-17-demethoxygeldanamycin [17-AAG]) in patients with solid tumors.

    Science.gov (United States)

    Saif, M W; Erlichman, C; Dragovich, T; Mendelson, D; Toft, D; Burrows, F; Storgard, C; Von Hoff, D

    2013-05-01

    17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin that binds to and inhibits the Hsp90 family of molecular chaperones leading to the proteasomal degradation of client proteins critical in malignant cell proliferation and survival. We have undertaken a Phase 1 trial of CNF1010, an oil-in-water nanoemulsion of 17-AAG. Patients with advanced solid tumors and adequate organ functions received CNF1010 by 1-h intravenous (IV) infusion, twice a week, 3 out of 4 weeks. Doses were escalated sequentially in single-patient (6 and 12 mg/m(2)/day) and three-to-six-patient (≥25 mg/m(2)/day) cohorts according to a modified Fibonacci's schema. Plasma pharmacokinetic (PK) profiles and biomarkers, including Hsp70 in PBMCs, HER-2 extracellular domain, and IGFBP2 in plasma, were performed. Thirty-five patients were treated at doses ranging from 6 to 225 mg/m(2). A total of 10 DLTs in nine patients (2 events of fatigue, 83 and 175 mg/m(2); shock, abdominal pain, ALT increased, increased transaminases, and pain in extremity at 175 mg/m(2); extremity pain, atrial fibrillation, and metabolic encephalopathy at 225 mg/m(2)) were noted. The PK profile of 17-AAG after the first dose appeared to be linear up to 175 mg/m(2), with a dose-proportional increase in C max and AUC0-inf. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects of CNF1010 at doses >83 mg/m(2). The maximum tolerated dose was not formally established. Hsp70 induction in PBMCs and inhibition of serum HER-2 neu extracellular domain indicated biological effects. The CNF1010 clinical program is no longer being pursued due to the toxicity profile of the drug and the development of second-generation Hsp90 molecules.

  12. Optimized multiparametric flow cytometric analysis of circulating endothelial cells and their subpopulations in peripheral blood of patients with solid tumors: a technical analysis

    Directory of Open Access Journals (Sweden)

    Zhou F

    2018-03-01

    with solid tumors. Several key technical issues regarding preanalytical elements, FCM data acquisition, and analysis were addressed. Furthermore, we clinically validated the utility of our method. The baseline levels of mature CECs, endothelial progenitor cells, and activated CECs were higher in cancer patients than healthy subjects (P<0.01. However, there was no significant difference in resting CEC levels between healthy subjects and cancer patients (P=0.193.Conclusion: We integrated and comprehensively addressed significant technical issues found in previously published assays and validated the reproducibility and sensitivity of our proposed method. Future work is required to explore the potential of our optimized method in clinical oncologic applications. Keywords: circulating endothelial cells, CECs, CEC subpopulations, flow cytometry, methods

  13. Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors

    NARCIS (Netherlands)

    Kuenen, Bart C.; Rosen, Lee; Smit, Egbert F.; Parson, Mandy R. N.; Levi, Marcel; Ruijter, Rita; Huisman, Holger; Kedde, Marc A.; Noordhuis, Paul; van der Vijgh, Wim J. F.; Peters, Godefridus J.; Cropp, Gillian F.; Scigalla, Paul; Hoekman, Klaus; Pinedo, Herbert M.; Giaccone, Giuseppe

    2002-01-01

    Purpose: To investigate the feasibility and pharmacokinetics of the combination cisplatin, gemcitabine, and SU5416. Patients and Methods: Patients received cisplatin 80 mg/m(2) on day 1, gemcitabine 1,250 mg/m(2) on days 1 and 8, repeated every 3 weeks, and SU5416 (85 and 145 mg/m(2)) intravenously

  14. A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety.

    Directory of Open Access Journals (Sweden)

    Joseph J Grudzinski

    Full Text Available (131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK and safety profiles of (131I-CLR1404.Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on (127I-CLR1404 mass measurements. To evaluate renal clearance of (131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software.Single administrations of 370 MBq of (131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma (127I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t values were 72.2 ng/mL and 15753 ng • hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.Preliminary data suggest that (131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.ClinicalTrials.gov NCT00925275.

  15. Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane®) on three treatment schedules in patients with solid tumors

    Science.gov (United States)

    Stinchcombe, Thomas E.; Socinski, Mark A.; Walko, Christine M.; O’Neil, Bert H.; Collichio, Frances A.; Ivanova, Anastasia; Mu, Hua; Hawkins, Michael J.; Goldberg, Richard M.; Lindley, Celeste; Dees, E Claire

    2010-01-01

    Purpose Albumin-bound paclitaxel, ABI-007 (Abraxane ®), has a different toxicity profile than solvent-based paclitaxel, including a lower rate of severe neutropenia. The combination of ABI-007 and carboplatin may have significant activity in a variety of tumor types including non-small and small cell lung cancer, ovarian cancer, and breast cancer. The purpose of this study was to determine the maximum tolerated dose (MTD) of ABI-007, on three different schedules in combination with carboplatin. Methods Forty-one patients with solid tumors were enrolled, and received ABI-007 in combination with carboplatin AUC of 6 on day 1. Group A received ABI-007 at doses ranging from 220 to 340 mg/m2 on day 1 every 21 days; group B received ABI-007 at 100 or 125 mg/m2 on days 1, 8, and 15 every 28 days; and group C received ABI-007 125 or 150 mg/m2 on days 1 and 8 every 21 days. Dose-limiting toxicities were assessed after the first cycle. Doses were escalated in cohorts of three to six patients. Fifteen patients participated in a pharmacokinetic study investigating the effects of the sequence of infusion. ABI-007 was infused first followed by carboplatin in cycle 1, and vice versa in cycle 2. Results The MTD of ABI-007 in combination with carboplatin was 300, 100, and 125 mg/m2 in groups A, B, and C, respectively. Myelosuppression was the primary dose limiting toxicity. No unexpected or new toxicities were reported. Sequence of infusion did not affect either the pharmacokinetics of ABI-007 or the degree of neutropenia. Responses were seen in melanoma, lung, bladder, esophageal, pancreatic, breast cancer, and cancer of unknown primary. Conclusions The recommended dose for phase II studies of ABI-007 in combination with carboplatin (AUC of 6) is 300, 100, 125 mg/m2 for the schedules A, B, and C, respectively. The combination of ABI-007 and carboplatin is well tolerated and active in this heavily pretreated patient population. PMID:17285317

  16. A Phase I Study of Triapine® in Combination with Doxorubicin in Patients with Advanced Solid Tumors

    Science.gov (United States)

    Schelman, William R.; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M.; Ivy, Percy; Wilding, George; Traynor, Anne M.

    2011-01-01

    Purpose To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine® administered in combination with doxorubicin. Study Design Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine® IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m2 and Triapine® 25 mg/m2. PK analysis was performed at various time-points before and after treatment. Results Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m2, Triapine® 45 mg/m2), 2 patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional 3 patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m2) with Triapine® 45 mg/m2. The 2 patients enrolled on this level had 2 DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine® were reduced to 45 mg/m2 and 25 mg/m2, respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Conclusions Pretreated patients with advanced malignancies can tolerate the combination of Triapine® and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m2 on day 1 and Triapine® 25 mg/m2 on

  17. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer

    OpenAIRE

    Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

    2017-01-01

    SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260–570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety...

  18. Early sorafenib-induced toxicity is associated with drug exposure and UGTIA9 genetic polymorphism in patients with solid tumors: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Pascaline Boudou-Rouquette

    Full Text Available BACKGROUND: Identifying predictive biomarkers of drug response is of key importance to improve therapy management and drug selection in cancer therapy. To date, the influence of drug exposure and pharmacogenetic variants on sorafenib-induced toxicity remains poorly documented. The aim of this pharmacokinetic/pharmacodynamic (PK/PD study was to investigate the relationship between early toxicity and drug exposure or pharmacogenetic variants in unselected adult outpatients treated with single-agent sorafenib for advanced solid tumors. METHODS: Toxicity was recorded in 54 patients on days 15 and 30 after treatment initiation and sorafenib exposure was assessed in 51 patients. The influence of polymorphisms in CYP3A5, UGT1A9, ABCB1 and ABCG2 was examined in relation to sorafenib exposure and toxicity. Clinical characteristics, drug exposure and pharmacogenetic variants were tested univariately for association with toxicities. Candidate variables with p<0.1 were analyzed in a multivariate analysis. RESULTS: Gender was the sole parameter independently associated with sorafenib exposure (p = 0.0008. Multivariate analysis showed that increased cumulated sorafenib (AUC(cum was independently associated with any grade ≥ 3 toxicity (p = 0.037; UGT1A9 polymorphism (rs17868320 with grade ≥ 2 diarrhea (p = 0.015 and female gender with grade ≥ 2 hand-foot skin reaction (p = 0.018. Using ROC curve, the threshold AUC(cum value of 3,161 mg/L.h was associated with the highest risk to develop any grade ≥ 3 toxicity (p = 0.018. CONCLUSION: In this preliminary study, increased cumulated drug exposure and UGT1A9 polymorphism (rs17868320 identified patients at high risk for early sorafenib-induced severe toxicity. Further PK/PD studies on larger population are warranted to confirm these preliminary results.

  19. Recombinant Immunotoxin Therapy of Solid Tumors: Challenges and Strategies.

    Science.gov (United States)

    Shan, Liang; Liu, Yuanyi; Wang, Paul

    2013-01-01

    Immunotoxins are a group of protein-based therapeutics, basically comprising two functional moieties: one is the antibody or antibody Fv fragment that allows the immunotoxin to bind specifically to target cells; another is the plant or bacterial toxin that kills the cells upon internalization. Immunotoxins have several unique features which are superior to conventional chemotherapeutics, including high specificity, extraordinary potency, and no known drug resistance. Development of immunotoxins evolves with time and technology, but significant progress has been achieved in the past 20 years after introduction of recombinant DNA technique and generation of the first single-chain variable fragment of monoclonal antibodies. Since then, more than 1,000 recombinant immunotoxins have been generated against cancer. However, most success in immunotoxin therapy has been achieved against hematological malignancies, several issues persist to be significant barriers for effective therapy of human solid tumors. Further development of immunotoxins will largely focus on the improvement of penetration capability to solid tumor mass and elimination of immunogenicity occurred when given repeatedly to patients. Promising strategies may include construction of recombinant antibody fragments with higher binding affinity and stability, elimination of immunodominant T- and B-cell epitopes of toxins, modification of immunotoxins with macromolecules like poly(ethylene glycol) and liposomes, and generation of immunotoxins with humanized antibody fragments and human endogenous cytotoxic enzymes. In this paper, we briefly reviewed the evolution of immunotoxin development and then discussed the challenges of immunotoxin therapy for human solid tumors and the potential strategies we may seek to overcome the challenges.

  20. Is Whole Exome Sequencing an Ethically Disruptive Technology? Perspectives of Pediatric Oncologists and Parents of Pediatric Patients with Solid Tumors

    Science.gov (United States)

    McCullough, Laurence B.; Slashinski, Melody J.; McGuire, Amy L.; Street, Richard L.; Eng, Christine M.; Gibbs, Richard A.; Parsons, D. Williams; Plon, Sharon E.

    2016-01-01

    Background Some anticipate that physician and parents will be ill-prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive. Procedure As part of the Baylor Advancing Sequencing in Childhood Cancer Care (BASIC3) study, we conducted semi-structured interviews with 16 pediatric oncologists and 40 parents of pediatric patients with cancer prior to the return of sequencing results. We elicited expectations and attitudes concerning the impact of sequencing on clinical decision-making, clinical utility, and treatment expectations from both groups. Using accepted methods of qualitative research to analyze interview transcripts, we completed a thematic analysis to provide inductive insights into their views of sequencing. Results Our major findings reveal that neither pediatric oncologists nor parents anticipate sequencing to be an ethically disruptive technology, because they expect to be prepared to integrate sequencing results into their existing approaches to learning and using new clinical information for care. Pediatric oncologists do not expect sequencing results to be more complex than other diagnostic information and plan simply to incorporate these data into their evidence-based approach to clinical practice although they were concerned about impact on parents. For parents, there is an urgency to protect their chil's health and in this context they expect genomic information to better prepare them to participate in decisions about their chil's care. Conclusion Our data do not support concern that introducing genome sequencing into childhood cancer care will be ethically disruptive, i.e., leave physicians or parents ill-prepared or unprepared to make responsible decisions about patient care. PMID:26505993

  1. OS03.4 Gammaknife versus Linac based (EDGE) radiosurgery (SRS) for patients with limited brain metastases (BMS) from different solid tumor: a phase III randomized trial.

    Science.gov (United States)

    Scorsetti, M.; Navarria, P.; Ascolese, A.; Clerici, E.; Mancosu, P.; Picozzi, P.; Pecchioli, G.; Franzese, C.; Reggiori, G.; Tomatis, S.

    2017-01-01

    Abstract Introduction: Radiosurgery is an emerging terapeutich approach for the treatment of brain metastases (BMs), considering the effective local control obtained without neurological impairment. Different technological modalities have been used: Gammaknife, Cybernife, or Linac with comparable results and different incidence of symptomatic radionecrosis. To date no comparative randomized studies have been published on this matter. We draw this randomized phase III trial with the aim to evaluate incidence of symptomatic radionecrosis using gamma knife radiosurgery versus linac based (EDGE) radiosurgery. Local control (LC) rate and patients overall survival (OS) were assessed as well. Materials: Patients with limited BMs (up to 4) from different solid tumors, except SCLC or hematologic malignancies, were enrolled. Inclusion criteria were a histopatological diagnosis of malignant primary tumor, a KPS ≥70, RPA class I-II, and BMs with maximum diameter ≤3 cm and/or with a total tumor volume <30 cm3. The total dose prescribed was 24 Gy for BMs ≤ 20 mm or 4.2 cm3, and 20 Gy for BMs 21–30 mm or volume <14.1 cm3 as suggested by RTOG guidelines. Clinical outcome was evaluated by neurological examination and MRI at 2 months after SRS and then every 3 months. The radionecrosis was considered the presence of central hypodensity and peripheral enhancement on T1-weighted post-contrast imaging, with edema on T2-weighted sequences and a clear lack of perfusion without any nodular highly vascularized area within the contrast enhanced lesion on perfusion MRI. Local progression was defined as radiographic increase of the enhancing abnormality in the irradiated volume on serial MR imaging, and distant failure by the presence of new brain metastases or leptomeningeal enhancement outside the irradiated volume. Results: From October 2014 to December 2015, 101 consecutives patients of the expected 250, for 167 BMs treated, were evaluated. The most common primary

  2. Cross-immunity among allogeneic tumors of rats immunized with solid tumors

    International Nuclear Information System (INIS)

    Ogasawara, Masamichi

    1979-01-01

    Several experiments were done for the study of cross-immunity among allogeneic rat tumors by immunization using gamma-irradiated or non-irradiated solid tumors. Each group of rats which were immunized with gamma-irradiation solid tumor inocula from ascites tumor cell line of tetra-ploid Hirosaki sarcoma, Usubuchi sarcoma or AH 130, showed an apparent resistance against the intraperitoneal challenge with Hirosaki sarcoma. A similar resistance was demonstrated in the case of the challenge with Usubuchi sarcoma into rats immunized with non-irradiated methylcholanthrene (MCA)-induced tumors. In using solid MCA tumors as immunogen and Hirosaki sarcoma as challenge tumor, it was also demonstrated in 2 out of 3 groups immunized with non-irradiated tumors. In the experiment of trying to induce cross-immunity between 2 MCA tumors by immunization with irradiated solid tumor only, the inhibitory effect on the growth was observed in the early stage in the treated groups as compared with the control one. From the above results, it may be considered that the immunization with irradiated solid tumors fromas cites cell lines and non-irradiated solid MCA tumors induced strong cross-immunity in general, but that the immunization with only irradiated solid MCA tumors induced weak cross-immunity commonly. (author)

  3. Bone marrow transplantation in aplastic anemia, acute leukemia and solid tumors

    International Nuclear Information System (INIS)

    Champlin, R.; Feig, S.; Gale, R.P.

    1980-01-01

    Results of bone marrow transplantation for the treatment of aplastic anemia, acute leukemia and solid tumors in the first 141 patients treated between September 1973 and January 1980 are reviewed. Preparation for transplantation with total body irradiation is described. (Auth.)

  4. AKT Inhibition in Solid Tumors With AKT1 Mutations.

    Science.gov (United States)

    Hyman, David M; Smyth, Lillian M; Donoghue, Mark T A; Westin, Shannon N; Bedard, Philippe L; Dean, Emma J; Bando, Hideaki; El-Khoueiry, Anthony B; Pérez-Fidalgo, José A; Mita, Alain; Schellens, Jan H M; Chang, Matthew T; Reichel, Jonathan B; Bouvier, Nancy; Selcuklu, S Duygu; Soumerai, Tara E; Torrisi, Jean; Erinjeri, Joseph P; Ambrose, Helen; Barrett, J Carl; Dougherty, Brian; Foxley, Andrew; Lindemann, Justin P O; McEwen, Robert; Pass, Martin; Schiavon, Gaia; Berger, Michael F; Chandarlapaty, Sarat; Solit, David B; Banerji, Udai; Baselga, José; Taylor, Barry S

    2017-07-10

    Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST). Tumor biopsies and plasma cell-free DNA (cfDNA) were collected in the majority of patients to identify predictive biomarkers of response. Results In patients with AKT1 E17K-mutant tumors (n = 52) and a median of five lines of prior therapy, the median PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3 months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen receptor-positive breast, gynecologic, and other solid tumors, respectively. In an exploratory biomarker analysis, imbalance of the AKT1 E17K-mutant allele, most frequently caused by copy-neutral loss-of-heterozygosity targeting the wild-type allele, was associated with longer PFS (hazard ratio [HR], 0.41; P = .04), as was the presence of coincident PI3K pathway hotspot mutations (HR, 0.21; P = .045). Persistent declines in AKT1 E17K in cfDNA were associated with improved PFS (HR, 0.18; P = .004) and response ( P = .025). Responses were not restricted to patients with detectable AKT1 E17K in pretreatment cfDNA. The most common grade ≥ 3 adverse events were hyperglycemia (24%), diarrhea (17%), and rash (15.5%). Conclusion This study provides the first clinical data that AKT1 E17K is a therapeutic target in human cancer. The genomic context of the AKT1 E17K mutation further conditioned response to AZD5363.

  5. Prospective Clinical Study of Precision Oncology in Solid Tumors.

    Science.gov (United States)

    Sohal, Davendra P S; Rini, Brian I; Khorana, Alok A; Dreicer, Robert; Abraham, Jame; Procop, Gary W; Saunthararajah, Yogen; Pennell, Nathan A; Stevenson, James P; Pelley, Robert; Estfan, Bassam; Shepard, Dale; Funchain, Pauline; Elson, Paul; Adelstein, David J; Bolwell, Brian J

    2015-11-09

    Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent. Tumors were sequenced using FoundationOne (Cambridge, MA). Results were reviewed at the Cleveland Clinic Genomics Tumor Board. Outcomes included feasibility and clinical impact. Colorectal (25%), breast (18%), lung (13%), and pancreatobiliary (13%) cancers were the most common diagnoses. Median time from consent to result was 25 days (range = 3-140). Of 223 evaluable samples, 49% (n = 109) of patients were recommended a specific therapy, but only 11% (n = 24) received such therapy: 12 on clinical trials, nine off-label, three on-label. Lack of clinical trial access (n = 49) and clinical deterioration (n = 29) were the most common reasons for nonrecommendation/nonreceipt of genomics-driven therapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea Pession

    2011-06-01

    Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

  7. Profiling of tryptophan-related plasma indoles in patients with carcinoid tumors by automated, on-line, solid-phase extraction and HPLC with fluorescence detection

    NARCIS (Netherlands)

    Kema, IP; Meijer, WG; Meiborg, G; Ooms, B; Willemse, PHB; de Vries, EGE

    2001-01-01

    Background: Profiling of the plasma indoles tryptophan, 5-hydroxytryptophan (5-HTP), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) is useful in the diagnosis and follow-up of patients with carcinoid tumors. We describe an automated method for the profiling of these indoles in protein-containing

  8. [Desmoid tumors in three patients].

    Science.gov (United States)

    Mohos, E; Kovács, T; Brittig, F; Nagy, A

    2001-12-01

    Desmoids are rare tumors of the connective tissue. It develops about 1:1000 times more in patients with familial adenomatous polyposis (FAP, Gardner syndrome) compared to normal population. It has been shown in molecular genetic examinations, that different mutations of the APC gene are responsible for desmoid tumors in FAP. It means, that this disease is one of the extraintestinal manifestations of Gardner syndrome. This tumor has high recurrence rate and is growing rapidly, and as a result it is the second most common cause of death in FAP patients. That is why genetic examination for FAP patients is advised to decide if the patient has higher risk for desmoid formation. If the result of the genetic test is positive, it is advisable to try to slow the progression of polyposis with medical treatment, and so to delay the date of the colectomy because the surgical intervention--and connective tissue damage--can induce desmoid formation in these patients. At the same time it is reasonable to examine and regularly control patients with sporadic desmoid tumors searching for other manifestations of Gardner syndrome (colon, stomach and duodenum polyposis, tumor of papilla Vateri, retinopathy, etc.). Palliative surgery is not indicated in patients with inoperable intraabdominal desmoid tumors, because partial resections (R1, R2, debulking) result in further tumor progression. In these patients medical treatment (sulindac, tamoxifen), chemotherapy (doxorubicin, dacarbazin) and radiotherapy or combination of them can result tumor remission. We describe our three patients (an abdominal wall desmoid four years following Cesarean section; a desmoid tumor in the retroperitoneum and in the pelvis diagnosed three years after total colectomy; and a retroperitoneal and abdominal wall desmoid one year after total colectomy) and etiology, diagnosis and therapy of desmoid tumors are discussed.

  9. Intracranial tumors in pediatric patients; Intrakranielle Tumoren im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Reith, W. [Universitaetsklinikum Saarland, Homburg (Germany). Klinik fuer Diagnostische und Interventionelle Neuroradiologie; Hagen, T. [Radiologengemeinschaft, Augsburg (Germany)

    2007-06-15

    Every year, 400 children suffer from a brain tumor. These are the most frequent solid tumors in the pediatric patient. They represent a very heterogenic group of tumors with different clinical symptoms, pathology, therapy and prognosis. Imaging modalities such as CT and MRI are important for the diagnosis and follow-up after therapy. Brain tumors in children are responsible for 15-20% of all brain tumors. Tumors of the central nervous system are the second most common tumors after leukemia. Infra- and supratentorial tumors occur in equal number, however, there are differences in the age of occurrence: supratentorial tumors occur more often within the first 2-3 years of life, whereas infratentorial tumors reach there peak between 4 and 10 years. After the tenth year, infra- and supratentorial tumors occur with equal frequency. (orig.)

  10. Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Hamid R. Mirzaei

    2017-12-01

    Full Text Available Adoptive cellular immunotherapy (ACT employing engineered T lymphocytes expressing chimeric antigen receptors (CARs has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.

  11. Fanconi's anemia and clinical radiosensitivity. Report on two adult patients with locally advanced solid tumors treated by radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, M.; Karstens, J.H. [Hannover Medical School, Hannover (Germany). Dept. of Radiation Oncology; Schindler, D.; Gross, M. [Univ. Wuerzburg (Germany). Inst. of Human Genetics; Doerk, T. [Hannover Medical School, Hannover (Germany). Dept. of Obstetrics and Gynecology; Morlot, S. [Hannover Medical School, Hannover (Germany). Inst. of Human Genetics

    2003-11-01

    Background: Patients with Fanconi's anemia (FA) may exhibit an increased clinical radiosensitivity of various degree, although detailed clinical data are scarce. We report on two cases to underline the possible challenges in the radiotherapy of FA patients. Case Report and Results: Two 24- and 32-year-old male patients with FA were treated by definitive radiotherapy for locally advanced squamous cell head and neck cancers. In the first patient, long-term tumor control could be achieved after delivery of 67 Gy with a - in part - hyperfractionated split-course treatment regimen and, concurrently, one course of carboplatin followed by salvage neck dissection. Acute toxicity was marked, but no severe treatment-related late effects occurred. 5 years later, additional radiotherapy was administered due to a second (squamous cell carcinoma of the anus) and third (squamous cell carcinoma of the head and neck) primary, which the patient succumbed to. By contrast, the second patient experienced fatal acute hematologic toxicity after delivery of only 8 Gy of hyperfractionated radiotherapy. While the diagnosis FA could be based on flow cytometric analysis of a lymphocyte culture in the second patient, the diagnosis in the first patient had to be confirmed by hypersensitivity to mitomycin of a fibroblast cell line due to complete somatic lymphohematopoietic mosaicism. In this patient, phenotype complementation and molecular genetic analysis revealed a pathogenic mutation in the FANCA gene. The first patient has not been considered to have FA until he presented with his second tumor. Conclusion: FA has to be considered in patients presenting at young age with squamous cell carcinoma of the head and neck or anus. The diagnosis FA is of immediate importance for guiding the optimal choice of treatment. Radiotherapy or even radiochemotherapy seems to be feasible and effective in individual cases. (orig.)

  12. Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors.

    Science.gov (United States)

    Zhang, Bing-Lan; Qin, Di-Yuan; Mo, Ze-Ming; Li, Yi; Wei, Wei; Wang, Yong-Sheng; Wang, Wei; Wei, Yu-Quan

    2016-04-01

    Recent reports on the impressive efficacy of chimeric antigen receptor (CAR)-modified T cells against hematologic malignancies have inspired oncologists to extend these efforts for the treatment of solid tumors. Clinical trials of CAR-T-based cancer immunotherapy for solid tumors showed that the efficacies are not as remarkable as in the case of hematologic malignancies. There are several challenges that researchers must face when treating solid cancers with CAR-T cells, these include choosing an ideal target, promoting efficient trafficking and infiltration, overcoming the immunosuppressive microenvironment, and avoiding associated toxicity. In this review, we discuss the obstacles imposed by solid tumors on CAR-T cell-based immunotherapy and strategies adopted to improve the therapeutic potential of this approach. Continued investigations are necessary to improve therapeutic outcomes and decrease the adverse effects of CAR-T cell therapy in patients with solid malignancies in the future.

  13. Differentiation of Solid Renal Tumors with Multiparametric MR Imaging.

    Science.gov (United States)

    Lopes Vendrami, Camila; Parada Villavicencio, Carolina; DeJulio, Todd J; Chatterjee, Argha; Casalino, David D; Horowitz, Jeanne M; Oberlin, Daniel T; Yang, Guang-Yu; Nikolaidis, Paul; Miller, Frank H

    2017-01-01

    Characterization of renal tumors is critical to determine the best therapeutic approach and improve overall patient survival. Because of increased use of high-resolution cross-sectional imaging in clinical practice, renal masses are being discovered with increased frequency. As a result, accurate imaging characterization of these lesions is more important than ever. However, because of the wide array of imaging features encountered as well as overlapping characteristics, identifying reliable imaging criteria for differentiating malignant from benign renal masses remains a challenge. Multiparametric magnetic resonance (MR) imaging based on various anatomic and functional parameters has an important role and adds diagnostic value in detection and characterization of renal masses. MR imaging may allow distinction of benign solid renal masses from several renal cell carcinoma (RCC) subtypes, potentially suggest the histologic grade of a neoplasm, and play an important role in ensuring appropriate patient management to avoid unnecessary surgery or other interventions. It is also a useful noninvasive imaging tool for patients who undergo active surveillance of renal masses and for follow-up after treatment of a renal mass. The purpose of this article is to review the characteristic MR imaging features of RCC and common benign renal masses and propose a diagnostic imaging approach to evaluation of solid renal masses using multiparametric MR imaging. © RSNA, 2017.

  14. Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer.

    Science.gov (United States)

    Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

    2017-10-03

    SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m 2 ) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort ( N = 19; unselected population, including three patients with MET -amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m 2 . Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m 2 in the dose-expansion cohort, comprising patients with MET -amplified tumors ( N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m 2 has acceptable tolerability and modest

  15. Pregnancy following Radical Resection of Solid Pseudopapillary Tumor of the Pancreas

    Directory of Open Access Journals (Sweden)

    James M. O’Brien

    2014-01-01

    Full Text Available Solid pseudopapillary tumor of the pancreas is a rare tumor seen in predominately young women and carries a low malignant potential. We discuss a patient, who presented to our high risk clinic, with a clinical history of solid pseudopapillary tumor of the pancreas, predating her pregnancy. The patient had undergone previous surgery and imaging which had excluded recurrence of disease; however, increased attention was paid to the patient during her pregnancy secondary to elevated hormonal levels of progesterone, which any residual disease would have a heightened sensitivity to. In cases of pregnant patients with a history of pancreatic tumors, a multidisciplinary approach with maternal fetal medicine, medicine, and general surgery is appropriate and can result in a healthy mother and healthy term infant.

  16. Cancer stem cells in solid tumors: elusive or illusive?

    Directory of Open Access Journals (Sweden)

    Lehrach Hans R

    2010-05-01

    Full Text Available Abstract During the past years in vivo transplantation experiments and in vitro colony-forming assays indicated that tumors arise only from rare cells. These cells were shown to bear self-renewal capacities and the ability to recapitulate all cell types within an individual tumor. Due to their phenotypic resemblance to normal stem cells, the term "cancer stem cells" is used. However, some pieces of the puzzle are missing: (a a stringent definition of cancer stem cells in solid tumors (b specific markers that only target cells that meet the criteria for a cancer stem cell in a certain type of tumor. These missing parts started an ongoing debate about which is the best method to identify and characterize cancer stem cells, or even if their mere existence is just an artifact caused by the experimental procedures. Recent findings query the cancer stem cell hypothesis for solid tumors itself since it was shown in xenograft transplantation experiments that under appropriate conditions tumor-initiating cells are not rare. In this review we critically discuss the challenges and prospects of the currently used major methods to identify cancer stem cells. Further on, we reflect the present discussion about the existence of cancer stem cells in solid tumors as well as the amount and characteristics of tumor-initiating cells and finally provide new perspectives like the correlation of cancer stem cells and induced pluripotent cells.

  17. Four cases of solid pseudopapillary tumors of pancreas: Imaging findings and pathological correlations

    International Nuclear Information System (INIS)

    Vargas-Serrano, Blanca; Dominguez-Ferreras, Esther; Chinchon-Espino, David

    2006-01-01

    Objective: Solid pseudopapillary tumor of the pancreas (SPTP tumor) is a rare pancreatic neoplasm with low malignant potential, which usually affects female patients in the second or third decades of life. It is a non-functional, slow-growing neoplasm that very often reaches considerable size before the first symptoms appear. Symptomatology is frequently related to tumor size. Surgical excision is usually curative in most cases. Infrequently the tumor can appear in male patients or in aged women, which can make the diagnosis more difficult. Some patients develop liver metastases in the follow-up that can be resected. Our purpose is to review the radiological and pathological findings of SPTP with emphasis on these infrequent cases. Subjects and methods: The medical records and radiological findings of patients who underwent surgery for SPTP between 2000 and 2005 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resection and that a SPTP had been pathologically proved. Results: Four cases of solid pseudopapillary tumor of the pancreas were diagnosed and treated in our institution in the study period. Two of the patients, developed on follow-up liver metastases, and peritoneal, hepatic, and nodal metastases, respectively. Conclusion: Solid pseudopapillary tumors are well-encapsulated neoplasms that usually have a good prognosis after surgical excision. A malignant behavior is uncommon and in this case lymph node involvement, hepatic metastases and occasionally peritoneal invasion may also occur. Resection of liver metastases can prolong the long-term survival of the patients

  18. Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)

    Science.gov (United States)

    2018-05-15

    Advanced Malignant Solid Neoplasm; RB1 Positive; Recurrent Childhood Ependymoma; Recurrent Ewing Sarcoma; Recurrent Glioma; Recurrent Hepatoblastoma; Recurrent Kidney Wilms Tumor; Recurrent Langerhans Cell Histiocytosis; Recurrent Malignant Germ Cell Tumor; Recurrent Malignant Glioma; Recurrent Medulloblastoma; Recurrent Neuroblastoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Osteosarcoma; Recurrent Peripheral Primitive Neuroectodermal Tumor; Recurrent Rhabdoid Tumor; Recurrent Rhabdomyosarcoma; Recurrent Soft Tissue Sarcoma; Refractory Ependymoma; Refractory Ewing Sarcoma; Refractory Glioma; Refractory Hepatoblastoma; Refractory Langerhans Cell Histiocytosis; Refractory Malignant Germ Cell Tumor; Refractory Malignant Glioma; Refractory Medulloblastoma; Refractory Neuroblastoma; Refractory Non-Hodgkin Lymphoma; Refractory Osteosarcoma; Refractory Peripheral Primitive Neuroectodermal Tumor; Refractory Rhabdoid Tumor; Refractory Rhabdomyosarcoma; Refractory Soft Tissue Sarcoma

  19. Endoscopic ultrasound-guided radiofrequency ablation for management of benign solid pancreatic tumors.

    Science.gov (United States)

    Choi, Jun-Ho; Seo, Dong-Wan; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

    2018-05-04

     Radiofrequency ablation (RFA) has been increasingly employed in experimental and clinical settings for the management of pancreatic lesions. This study aimed to assess the safety and efficacy of endoscopic ultrasound (EUS)-guided RFA for benign solid pancreatic tumors.  In a single-center, prospective study, 10 patients with benign solid pancreatic tumors underwent EUS-RFA. After the RFA electrode had been inserted into the pancreatic mass, the radiofrequency generator was activated to deliver 50 W of ablation power.  Among the 10 patients, 16 sessions of EUS-RFA were successfully performed. Diagnoses included nonfunctioning neuroendocrine tumor (n = 7), solid pseudopapillary neoplasm (n = 2), and insulinoma (n = 1); the median largest diameter of the tumors was 20 mm (range 8 - 28 mm). During follow-up (median 13 months), radiologic complete response was achieved in seven patients. Two adverse events (12.4 %; 1 moderate and 1 mild) occurred.  EUS-RFA may be a safe and potentially effective treatment option in selected patients with benign solid pancreatic tumors. Multiple sessions may be required if there is a remnant tumor, and adverse events must be carefully monitored. © Georg Thieme Verlag KG Stuttgart · New York.

  20. A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors.

    Science.gov (United States)

    Shimizu, Toshio; Fukuoka, Kazuya; Takeda, Masayuki; Iwasa, Tutomu; Yoshida, Takeshi; Horobin, Joanna; Keegan, Mitchell; Vaickus, Lou; Chavan, Ajit; Padval, Mahesh; Nakagawa, Kazuhiko

    2016-05-01

    VS-6063 (also known as defactinib or PF-04554878) is a second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine kinase-2. This phase 1 study evaluated the safety and tolerability, pharmacokinetics, and clinical activity of VS-6063 in Japanese subjects with advanced solid tumor malignancies in a first-in-Asian study setting. VS-6063 was administered orally twice daily (b.i.d.) in 21-day cycles to cohorts of three subjects each with a standard 3 + 3 dose-escalation design until disease progression or unacceptable toxicity. Blood samples for pharmacokinetics were collected on Day 1 and 15. The assessments were performed using CTCAE v4.0 for adverse events (AEs), and the Response Evaluation Criteria In Solid Tumors, version v1.1 (RECIST v1.1) for tumor response. Nine patients were treated across three dose levels (200-600 mg BID). No dose-limiting toxicities were observed at any dose level. Most frequent treatment-related AEs were Grade 1/2 unconjugated hyperbilirubinemia, fatigue, decreased appetite, and diarrhea. Only one subject in the 200 mg BID cohort experienced reversible and transient Grade 3 unconjugated hyperbilirubinemia. PK analyses confirmed that the exposure at the recommended Phase 2 dose (RP2D) of 400 mg BID was comparable with exposures previously reported in non-Japanese subjects. Durable stable disease of approximately 24 weeks was confirmed in two subjects (malignant mesothelioma and rectal cancer). VS-6063 was well tolerated at all dose levels investigated in this first-in-Asian study. These data support the administration of VS-6063 to Japanese subjects at the RP2D in clinical trials involving solid tumor malignancies.

  1. To Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors

    Science.gov (United States)

    2018-04-23

    Neuroblastoma; Rhabdomyosarcoma; Ewing's Sarcoma; Ewing's Tumor; Sarcoma, Ewing's; Sarcomas, Epitheliod; Sarcoma, Soft Tissue; Sarcoma, Spindle Cell; Melanoma; Malignant Melanoma; Clinical Oncology; Oncology, Medical; Pediatrics, Osteosarcoma; Osteogenic Sarcoma; Osteosarcoma Tumor; Sarcoma, Osteogenic; Tumors; Cancer; Neoplasia; Neoplasm; Histiocytoma; Fibrosarcoma; Dermatofibrosarcoma

  2. Irinotecan for relapsed Wilms tumor in pediatric patients

    DEFF Research Database (Denmark)

    Hol, Janna A; van den Heuvel-Eibrink, Marry M; Graf, Norbert

    2018-01-01

    While irinotecan has been studied in various pediatric solid tumors, its potential role in Wilms tumor (WT) is less clear. We evaluated response and outcome of irinotecan-containing regimens in relapsed WT and compared our results to the available literature. Among 14 evaluable patients, one...

  3. Some epidemiological and clinical characteristics of solid malignant tumors in children from Las Tunas

    Directory of Open Access Journals (Sweden)

    Silvio Laffita Estévez

    2015-11-01

    Full Text Available Background: cancer has kept up as the second cause of death in Las Tunas pediatric population.Objective: to characterize clinical and epidemiological variables of the cases diagnosed with solid malignant tumors in children seen and treated in the onco-pediatric consultation of “Mártires de Las Tunas” Pediatric Hospital from 2010 to 2014.Methods: a descriptive and retrospective study was carried out in 62 patients with solid malignant tumors in the pediatric population of Las Tunas province, from January, 2010 to December, 2014. The variables considered were: presumptive diagnosis, age, family history of tumors, clinical signs of alarm related to the tumor at the moment of diagnosis and investigations to confirm the diagnosis.  Results: non-Hodgkin lymphoma was the most frequently diagnosed tumor, with a 19, 35% of the patients. The most affected age group was between 11 and 14 years old, with a 33, 87%. The 16, 13% of the patients had family history of solid malignant tumors. The most frequent form of presentation was the abdominal tumor, with 29, 03 %. Abdominal ultrasound and computerized axial tomography were the most used complementary diagnostic means, both in the 17, 74% of the patients. Biopsy was used to confirm the 96, 77% of the cases.Conclusions: the clinical and epidemiological variables were characterized in pediatric patients diagnosed with solid malignant tumors in Las Tunas. Children between 11 and 14 years old and family history of malignant tumors were the most significant findings.

  4. Phase I study of OM-174, a lipid A analogue, with assessment of immunological response, in patients with refractory solid tumors

    International Nuclear Information System (INIS)

    Isambert, Nicolas; Bardou, Marc; Fumoleau, Pierre; Paul, Catherine; Ferrand, Christophe; Zanetta, Sylvie; Bauer, Jacques; Ragot, Kevin; Lizard, Gérard; Jeannin, Jean-François

    2013-01-01

    Lipids A, the lipophilic partial structure of lipopolysaccharides, induce regression of several tumor types in animal models. Rather than exerting direct cytotoxic effect, these compounds trigger the immune system which in turn stimulates secretion of cytokines, and activates the inducible nitric oxide synthase, as well as immune cell infiltration of tumors. OM-174 is an analogue of lipid A with dual action on Toll-like receptors 2 and 4. In an experimental model of peritoneal carcinomatosis induced in BDIX rats by intraperitoneal injection of syngeneic PROb colon cancer cells, it induced a complete regression of tumors. The present phase I trial was conducted to determine the maximum tolerated dose, the recommended phase II dose and biological response associated with OM-174 administered as intravenous infusion. Patients received OM-174 twice weekly for a total of 5, 10 or 15 injections of either 600, 800 or 1000 μg/m 2 . Blood samples for pharmacokinetic analysis and cytokine dosages were collected. NK cells activity and Toll-like receptors 4 polymorphism analysis were also performed. Seventeen patients were included. The highest dose administered was 1000 μg/m 2 repeated in 15 injections. The most common toxicities were a chills, fever, nausea/vomiting, diarrhea, fatigue and headache. No patient experienced haematological side effects. As no dose limiting toxicity was observed, despite a grade 3 respiratory complication, the maximal tolerated dose and recommended dose were not established. Three patients exhibited disease stabilization with a mean duration of 4 months. Pharmacokinetic profile of OM-174 was characterized by a low distribution volume and clearance. Analysis of TLR 4 polymorphysm showed that most (16/17) patients carried the wild type alleles. A progressive increase in NK cell number and activity was observed only in patients receiving 1000 μg/m 2 of OM-174. A peak of IL-8 and IL-10 concentrations were observed after each OM-174 injection. Peaks

  5. Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers.

    Science.gov (United States)

    Yap, Timothy A; Yan, Li; Patnaik, Amita; Tunariu, Nina; Biondo, Andrea; Fearen, Ivy; Papadopoulos, Kyriakos P; Olmos, David; Baird, Richard; Delgado, Liliana; Tetteh, Ernestina; Beckman, Robert A; Lupinacci, Lisa; Riisnaes, Ruth; Decordova, Shaun; Heaton, Simon P; Swales, Karen; deSouza, Nandita M; Leach, Martin O; Garrett, Michelle D; Sullivan, Daniel M; de Bono, Johann S; Tolcher, Anthony W

    2014-11-15

    Multiple cancers harbor genetic aberrations that impact AKT signaling. MK-2206 is a potent pan-AKT inhibitor with a maximum tolerated dose (MTD) previously established at 60 mg on alternate days (QOD). Due to a long half-life (60-80 hours), a weekly (QW) MK-2206 schedule was pursued to compare intermittent QW and continuous QOD dosing. Patients with advanced cancers were enrolled in a QW dose-escalation phase I study to investigate the safety and pharmacokinetic-pharmacodynamic profiles of tumor and platelet-rich plasma (PRP). The QOD MTD of MK-2206 was also assessed in patients with ovarian and castration-resistant prostate cancers and patients with advanced cancers undergoing multiparametric functional magnetic resonance imaging (MRI) studies, including dynamic contrast-enhanced MRI, diffusion-weighted imaging, magnetic resonance spectroscopy, and intrinsic susceptibility-weighted MRI. A total of 71 patients were enrolled; 38 patients had 60 mg MK-2206 QOD, whereas 33 received MK-2206 at 90, 135, 150, 200, 250, and 300 mg QW. The QW MK-2206 MTD was established at 200 mg following dose-limiting rash at 250 and 300 mg. QW dosing appeared to be similarly tolerated to QOD, with toxicities including rash, gastrointestinal symptoms, fatigue, and hyperglycemia. Significant AKT pathway blockade was observed with both continuous QOD and intermittent QW dosing of MK-2206 in serially obtained tumor and PRP specimens. The functional imaging studies demonstrated that complex multiparametric MRI protocols may be effectively implemented in a phase I trial. Treatment with MK-2206 safely results in significant AKT pathway blockade in QOD and QW schedules. The intermittent dose of 200 mg QW is currently used in phase II MK-2206 monotherapy and combination studies (NCT00670488). ©2014 American Association for Cancer Research.

  6. Integrin α5β1, the Fibronectin Receptor, as a Pertinent Therapeutic Target in Solid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Schaffner, Florence; Ray, Anne Marie; Dontenwill, Monique, E-mail: monique.dontenwill@unistra.fr [UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Tumoral signaling and therapeutic targets, Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch (France)

    2013-01-15

    Integrins are transmembrane heterodimeric proteins sensing the cell microenvironment and modulating numerous signalling pathways. Changes in integrin expression between normal and tumoral cells support involvement of specific integrins in tumor progression and aggressiveness. This review highlights the current knowledge about α5β1 integrin, also called the fibronectin receptor, in solid tumors. We summarize data showing that α5β1 integrin is a pertinent therapeutic target expressed by tumoral neovessels and tumoral cells. Although mainly evaluated in preclinical models, α5β1 integrin merits interest in particular in colon, breast, ovarian, lung and brain tumors where its overexpression is associated with a poor prognosis for patients. Specific α5β1 integrin antagonists will be listed that may represent new potential therapeutic agents to fight defined subpopulations of particularly aggressive tumors.

  7. Chimeric antigen receptor T-cell therapy for solid tumors

    Directory of Open Access Journals (Sweden)

    Kheng Newick

    2016-01-01

    Full Text Available Chimeric antigen receptor (CAR T cells are engineered constructs composed of synthetic receptors that direct T cells to surface antigens for subsequent elimination. Many CAR constructs are also manufactured with elements that augment T-cell persistence and activity. To date, CAR T cells have demonstrated tremendous success in eradicating hematological malignancies (e.g., CD19 CARs in leukemias. This success is not yet extrapolated to solid tumors, and the reasons for this are being actively investigated. Here in this mini-review, we discuss some of the key hurdles encountered by CAR T cells in the solid tumor microenvironment.

  8. Molecular mechanisms for synergistic effect of proteasome inhibitors with platinum-based therapy in solid tumors.

    Science.gov (United States)

    Chao, Angel; Wang, Tzu-Hao

    2016-02-01

    The successful development of the proteasome inhibitor bortezomib as an anticancer drug has improved survival in patients with multiple myeloma. With the emergence of the newly US Food and Drug Administration-approved proteasome inhibitor carfilzomib, ongoing trials are investigating this compound and other proteasome inhibitors either alone or in combination with other chemotherapy drugs. However, in solid tumors, the efficacy of proteasome inhibitors has not lived up to expectations. Results regarding the potential clinical efficacy of bortezomib combined with other agents in the treatment of solid tumors are eagerly awaited. Recent identification of the molecular mechanisms (involving apoptosis and autophagy) by which bortezomib and cisplatin can overcome chemotherapy resistance and sensitize tumor cells to anticancer therapy can provide insights into the development of novel therapeutic strategies for patients with solid malignancies. Copyright © 2016. Published by Elsevier B.V.

  9. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    Science.gov (United States)

    2014-08-26

    ; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  11. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  12. Combination effect of cisplatin and radiation in murine solid tumors

    International Nuclear Information System (INIS)

    Egawa, Shin; Lee, Kan-ei; Ishibashi, Akira; Komiyama, Hiroki; Umezawa, Iwao.

    1986-01-01

    The combination effect of cisplatin and radiation was studied using the two different murine systems of sarcoma 180 and Ehrlich solid tumors. In sarcoma 180 solid tumor the minimal effective doses (MED) of cisplatin and radiation were 19.5 mg/kg and 10375 rad respectively whereas these doses did not show any effective antitumor activity practically. Administration of cisplatin with a doses of 9 mg/kg given 24 hours before radiation (1000 rad), however, showed synergistic antitumor activity. In Ehrlich solid tumor the MED of cisplatin and radiation were 13.8 mg/kg and 2892 rad respectively. Treatment with cisplatin, 3, 6 or 9 mg/kg, given 24 hours before radiation (1000 rad) showed also synergistic antitumor activity also. Sodium thiosulfate (STS) rescue was effective in reducing toxicity of cisplatin on combined use of the drug with radiation. Cell kinetics of sarcoma 180 solid tumor in vivo after the combined treatment was analyzed by computer aided flowcytometry. Accumulation of cells in the radiosensitive G 2 + M phase was observed 18 to 42 hours after a single intraperitoneal administration of 9 mg/kg of cisplatin. It is strongly suggested that this synchronization is one of the mechanisms of the synergism in the combination therapy. (author)

  13. Epigenetic changes in solid and hematopoietic tumors.

    Science.gov (United States)

    Toyota, Minoru; Issa, Jean-Pierre J

    2005-10-01

    There are three connected molecular mechanisms of epigenetic cellular memory in mammalian cells: DNA methylation, histone modifications, and RNA interference. The first two have now been firmly linked to neoplastic transformation. Hypermethylation of CpG-rich promoters triggers local histone code modifications resulting in a cellular camouflage mechanism that sequesters gene promoters away from transcription factors and results in stable silencing. This normally restricted mechanism is ubiquitously used in cancer to silence hundreds of genes, among which some critically contribute to the neoplastic phenotype. Virtually every pathway important to cancer formation is affected by this process. Methylation profiling of human cancers reveals tissue-specific epigenetic signatures, as well as tumor-specific signatures, reflecting in particular the presence of epigenetic instability in a subset of cancers affected by the CpG island methylator phenotype. Generally, methylation patterns can be traced to a tissue-specific, proliferation-dependent accumulation of aberrant promoter methylation in aging tissues, a process that can be accelerated by chronic inflammation and less well-defined mechanisms including, possibly, diet and genetic predisposition. The epigenetic machinery can also be altered in cancer by specific lesions in epigenetic effector genes, or by aberrant recruitment of these genes by mutant transcription factors and coactivators. Epigenetic patterns are proving clinically useful in human oncology via risk assessment, early detection, and prognostic classification. Pharmacologic manipulation of these patterns-epigenetic therapy-is also poised to change the way we treat cancer in the clinic.

  14. Development of cell-cycle checkpoint therapy for solid tumors.

    Science.gov (United States)

    Tamura, Kenji

    2015-12-01

    Cellular proliferation is tightly controlled by several cell-cycle checkpoint proteins. In cancer, the genes encoding these proteins are often disrupted and cause unrestrained cancer growth. The proteins are over-expressed in many malignancies; thus, they are potential targets for anti-cancer therapies. These proteins include cyclin-dependent kinase, checkpoint kinase, WEE1 kinase, aurora kinase and polo-like kinase. Cyclin-dependent kinase inhibitors are the most advanced cell-cycle checkpoint therapeutics available. For instance, palbociclib (PD0332991) is a first-in-class, oral, highly selective inhibitor of CDK4/6 and, in combination with letrozole (Phase II; PALOMA-1) or with fulvestrant (Phase III; PALOMA-3), it has significantly prolonged progression-free survival, in patients with metastatic estrogen receptor-positive, HER2-negative breast cancer, in comparison with that observed in patients using letrozole, or fulvestrant alone, respectively. In this review, we provide an overview of the current compounds available for cell-cycle checkpoint protein-directed therapy for solid tumors. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

    Directory of Open Access Journals (Sweden)

    Katerina T. Xenaki

    2017-10-01

    Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

  16. Value of apparent diffusion coefficients in patients with brain tumors

    International Nuclear Information System (INIS)

    De Luca, Silvina; Stoisa, Daniela; Mondello, Eduardo; Vietti, Julio; Casas, Gabriel; Florenzano, Nestor; Eyheremendy, Eduardo; Martinez Boero, Macarena

    2004-01-01

    Purpose: To determine the utility of ADC values for the diagnosis of encephalic tumors. Material and method: Forty patients with encephalic tumors histopathologically confirmed, have been studied by conventional MR, diffusion and ADC maps. The intensities were measured in the solid tumor portion and the normal white matter, ratios were obtained and correlated in 13 patients with their respective cellularity indexes. Results: Seventeen were glial tumors, with lower ADC values in cases of greater malignancy. In 12 patients the diagnosis was secondary lesions in which the lowest ADC values were obtained. This feature was shared by the epidermoid cyst. The hamartomas, neurinomas, oligodendrogliomas and ependymomas have shown intermediate ADC values. Conclusion: The ADC map is a complement of conventional MR which provides additional information for the diagnosis of encephalic tumors. Low ADC values correlated with high grade malignant tumors. (author)

  17. Secondary solid tumors following radiation in Hodgkin's disease: experience of the Institut Gustave-Roussy

    International Nuclear Information System (INIS)

    Cosset, J.M.; Henry-Amar, M.; Dietrich, P.Y.; Socie, G.; Girinsky, T.; Hayat, M.; Tubiana, M.

    1992-01-01

    From 1961 to 1984, in the Institut Gustave-Roussy, 893 patients have been treated in Hodgkin's disease. The authors study the solid tumors that they have observed after exclusive radiotherapy and chemo-radiotherapy in order to know the radiation effect in the birth of this type of cancer

  18. Antibody or Antibody Fragments : Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

    NARCIS (Netherlands)

    Xenaki, Katerina T; Oliveira, Sabrina; van Bergen En Henegouwen, Paul M P

    2017-01-01

    The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody-drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are

  19. Tumor lysis syndrome in a patient with metastatic colon cancer after treatment with oxaliplatin and 5-Fu

    Directory of Open Access Journals (Sweden)

    Ruo-Han Tseng

    2016-12-01

    Full Text Available Tumor lysis syndrome in solid tumors is a rare occurrence, with a poor prognosis. We present the case of a patient of recurrent colon cancer who received chemotherapy with FOLFOX regimen (lencovorin, fluorouracil, and oxaliplatin with subsequent tumor lysis. We present a recurrent rectal cancer patient suffered from tumor lysis syndrome after salvage FOLFOX regimen. After treat with CVVH with improved conscious status. In this case report, we had review the tumor lysis in solid tumor.

  20. New Chimeric Antigen Receptor Design for Solid Tumors

    Directory of Open Access Journals (Sweden)

    Yuedi Wang

    2017-12-01

    Full Text Available In recent years, chimeric antigen receptor (CAR T-cell therapy has become popular in immunotherapy, particularly after its tremendous success in the treatment of lineage-restricted hematologic cancers. However, the application of CAR T-cell therapy for solid tumors has not reached its full potential because of the lack of specific tumor antigens and inhibitory factors in suppressive tumor microenvironment (TME (e.g., programmed death ligand-1, myeloid-derived suppressor cells, and transforming growth factor-β. In this review, we include some limitations in CAR design, such as tumor heterogeneity, indefinite spatial distance between CAR T-cell and its target cell, and suppressive TME. We also summarize some new approaches to overcome these hurdles, including targeting neoantigens and/or multiple antigens at once and depleting some inhibitory factors.

  1. Solid and cystic pseudopapillary tumor of the pancreas: A case report

    Directory of Open Access Journals (Sweden)

    Milošević Bojan Z.

    2013-01-01

    Full Text Available Introduction. Solid and cystic pseudopapillary tumor of the pancreas is a rare tumor of the pancreas, for the first time described by Frantz et al. in 1959. The majority of patients are young females and most of them are asymptomatic. Case Outline. We report a case of 25-year old woman who was admitted to our institution with abdominal pain and a palpable mass in the left hypochondrial area. US and CT scan revealed a solid and cystic pseudopapillary tumor in the head of the pancreas. The patient was treated by Whipple procedure, modification Longmire-Traverso. There was no metastatic disease either in the liver or peritoneum. Histologically the tumor was diagnosed as a solid and cystic pseudopapillary tumor of the pancreas. Conclusion. The unclear pre-operative diagnoses, together with incidence of potential malignancy as well as good outcome with resection, suggest that all suspected cystic tumors of the pancreas should be resected. The exact diagnosis is based on histological findings. [Projekat Ministarstva nauke Republike Srbije, br. III41007 i br. III41010

  2. Turnover rate of hypoxic cells in solid tumors

    International Nuclear Information System (INIS)

    Ljungkvist, A.S.E.; Bussink, J.; Rijken, P.F.J.W.; Van Der Kogel, A.J.

    2003-01-01

    Most solid tumors contain hypoxic cells, and both the amount and duration of tumor hypoxia has been shown to influence the effect of radiation treatment negatively. It is important to understand the dynamic processes within the hypoxic cell population in non-treated tumors, and the effect of different treatment modalities on the kinetics of hypoxic cells to be able to design optimal combined modality treatments. The turnover rate of hypoxic cells was analyzed in three different solid tumor models with a double bio-reductive hypoxic marker assay with sequential injection of the two hypoxic markers. Previously it was shown that this assay could be used to detect both a decrease and an increase of tumor hypoxia in relation to the tumor vasculature with high spatial resolution. In this study the first hypoxic marker, pimonidazole, was administered at variable times relative to tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. The hypoxic cell turnover rate was calculated as the loss of pimonidazole positive cells relative to CCI-103F. The murine C38 line had the fastest hypoxic turnover rate of 60% /24h and the human xenograft line SCCNij3 had the slowest hypoxic turnover rate of 30% /24 h. The hypoxic turnover rate was most heterogeneous in the SCCNij3 line that even contained viable groups of cells that had been hypoxic for at least 5 days. The human xenograft line MEC82 fell in between with a hypoxic turnover rate of 50% /24 h. The hypoxic cell turnover was related to the potential tumor volume doubling time (Tpot) with a Tpot of 26h in C38 and 103h in SCCNij3. The dynamics of hypoxic cells, quantified with a double hypoxic marker method, showed large differences in hypoxic cell turnover rate and were related to Tpot

  3. In vitro anti-proliferative effect of interferon alpha in solid tumors: A potential predicative test

    International Nuclear Information System (INIS)

    Fuchsberger, N.; Kubes, M.; Kontsek, P.; Borecky, L.; Hornak, M.; Silvanova; Godal, A.; Svec, J.

    1993-01-01

    An in vitro test for the anti-proliferative effect of human leukocyte interferon (IFN-alpha) was performed in primary cultures of tumor cells obtained from 32 patients with either malignant melanoma (13), renal carcinoma (4) or bladder carcinoma (15). Our results demonstrated activity of IFN in all three groups of solid tumors. However, appreciable differences in sensitivity to anti-proliferative effect of IFN between individual tumors of the same type were found. The potential of this anti-proliferative test for prediction of treatment response in IFN-therapy is discussed. (author)

  4. A phase 1b study of humanized KS-interleukin-2 (huKS-IL2) immunocytokine with cyclophosphamide in patients with EpCAM-positive advanced solid tumors

    International Nuclear Information System (INIS)

    Connor, Joseph P; Henslee-Downey, Jean; Kramer, Daniel; Neugebauer, Roland; Stupp, Roger; Cristea, Mihaela C; Lewis, Nancy L; Lewis, Lionel D; Komarnitsky, Philip B; Mattiacci, Maria R; Felder, Mildred; Stewart, Sarah; Harter, Josephine

    2013-01-01

    Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent. Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m 2 on day 1), and escalating doses of huKS-IL2 (0.5–4.0 mg/m 2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated. Twenty-seven patients were treated for up to 6 cycles; 26 were evaluable for response. The MTD of huKS-IL2 in combination with 300 mg/m 2 cyclophosphamide was 3.0 mg/m 2 . At higher doses, myelosuppression was dose-limiting. Transient lymphopenia was the most common grade 3/4 adverse event (AE). Other significant AEs included hypotension, hypophosphatemia, and increase in serum creatinine. All patients recovered from these AEs. The huKS-IL2 exposure was dose-dependent, but not dose-proportional, accumulation was negligible, and elimination half-life and systemic clearance were independent of dose and time. Most patients had a transient immune response to huKS-IL2. Immunologic activity was observed at all doses. Ten patients (38%) had stable disease as best response, lasting for ≥ 4 cycles in 3 patients. The combination of huKS-IL2 with low-dose cyclophosphamide was well tolerated. Although no objective responses were observed, the combination showed evidence of immunologic activity and 3 patients showed stable disease for ≥ 4 cycles.

  5. Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors.

    Science.gov (United States)

    Mahalingam, Devalingam; Mita, Monica; Sarantopoulos, John; Wood, Leslie; Amaravadi, Ravi K; Davis, Lisa E; Mita, Alain C; Curiel, Tyler J; Espitia, Claudia M; Nawrocki, Steffan T; Giles, Francis J; Carew, Jennifer S

    2014-08-01

    We previously reported that inhibition of autophagy significantly augmented the anticancer activity of the histone deacetylase (HDAC) inhibitor vorinostat (VOR) through a cathepsin D-mediated mechanism. We thus conducted a first-in-human study to investigate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and VOR in patients with advanced solid tumors. Of 27 patients treated in the study, 24 were considered fully evaluable for study assessments and toxicity. Patients were treated orally with escalating doses of HCQ daily (QD) (d 2 to 21 of a 21-d cycle) in combination with 400 mg VOR QD (d one to 21). Treatment-related adverse events (AE) included grade 1 to 2 nausea, diarrhea, fatigue, weight loss, anemia, and elevated creatinine. Grade 3 fatigue and/or myelosuppression were observed in a minority of patients. Fatigue and gastrointestinal AE were dose-limiting toxicities. Six-hundred milligrams HCQ and 400 mg VOR was established as the maximum tolerated dose and recommended phase II regimen. One patient with renal cell carcinoma had a confirmed durable partial response and 2 patients with colorectal cancer had prolonged stable disease. The addition of HCQ did not significantly impact the PK profile of VOR. Treatment-related increases in the expression of CDKN1A and CTSD were more pronounced in tumor biopsies than peripheral blood mononuclear cells. Based on the safety and preliminary efficacy of this combination, additional clinical studies are currently being planned to further investigate autophagy inhibition as a new approach to increase the efficacy of HDAC inhibitors.

  6. First-in-Human Phase I Study of Single-agent Vanucizumab, A First-in-Class Bispecific Anti-Angiopoietin-2/Anti-VEGF-A Antibody, in Adult Patients with Advanced Solid Tumors.

    Science.gov (United States)

    Hidalgo, Manuel; Martinez-Garcia, Maria; Le Tourneau, Christophe; Massard, Christophe; Garralda, Elena; Boni, Valentina; Taus, Alvaro; Albanell, Joan; Sablin, Marie-Paule; Alt, Marie; Bahleda, Ratislav; Varga, Andrea; Boetsch, Christophe; Franjkovic, Izolda; Heil, Florian; Lahr, Angelika; Lechner, Katharina; Morel, Anthony; Nayak, Tapan; Rossomanno, Simona; Smart, Kevin; Stubenrauch, Kay; Krieter, Oliver

    2018-04-01

    Purpose: Vanucizumab is an investigational antiangiogenic, first-in-class, bispecific mAb targeting VEGF-A and angiopoietin-2 (Ang-2). This first-in-human study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of vanucizumab in adults with advanced solid tumors refractory to standard therapies. Experimental Design: Patients received escalating biweekly (3-30 mg/kg) or weekly (10-30 mg/kg) intravenous doses guided by a Bayesian logistic regression model with overdose control. Results: Forty-two patients were treated. One dose-limiting toxicity, a fatal pulmonary hemorrhage from a large centrally located mediastinal mass judged possibly related to vanucizumab, occurred with the 19 mg/kg biweekly dose. Arterial hypertension (59.5%), asthenia (42.9%), and headache (31%) were the most common toxicities. Seventeen (41%) patients experienced treatment-related grade ≥3 toxicities. Toxicity was generally higher with weekly than biweekly dosing. A MTD of vanucizumab was not reached in either schedule. Pharmacokinetics were dose-linear with an elimination half-life of 6-9 days. All patients had reduced plasma levels of free VEGF-A and Ang-2; most had reductions in K TRANS (measured by dynamic contrast-enhanced MRI). Two patients (renal cell and colon cancer) treated with 30 mg/kg achieved confirmed partial responses. Ten patients were without disease progression for ≥6 months. A flat-fixed 2,000 mg biweekly dose (phamacokinetically equivalent to 30 mg/kg biweekly) was recommended for further investigation. Conclusions: Biweekly vanucizumab had an acceptable safety and tolerability profile consistent with single-agent use of selective inhibitors of the VEGF-A and Ang/Tie2 pathway. Vanucizumab modulated its angiogenic targets, impacted tumor vascularity, and demonstrated encouraging antitumor activity in this heterogeneous population. Clin Cancer Res; 24(7); 1536-45. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Hypoxic cell turnover in different solid tumor lines

    International Nuclear Information System (INIS)

    Ljungkvist, Anna S.E.; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert J. van der

    2005-01-01

    Purpose: Most solid tumors contain hypoxic cells, and the amount of tumor hypoxia has been shown to have a negative impact on the outcome of radiotherapy. The efficacy of combined modality treatments depends both on the sequence and timing of the treatments. Hypoxic cell turnover in tumors may be important for optimal scheduling of combined modality treatments, especially when hypoxic cell targeting is involved. Methods and Materials: Previously we have shown that a double bioreductive hypoxic marker assay could be used to detect changes of tumor hypoxia in relation to the tumor vasculature after carbogen and hydralazine treatments. This assay was used in the current study to establish the turnover rate of hypoxic cells in three different tumor models. The first hypoxic marker, pimonidazole, was administered at variable times before tumor harvest, and the second hypoxic marker, CCI-103F, was injected at a fixed time before harvest. Hypoxic cell turnover was defined as loss of pimonidazole (first marker) relative to CCI-103F (second marker). Results: The half-life of hypoxic cell turnover was 17 h in the murine C38 colon carcinoma line, 23 h and 49 h in the human xenograft lines MEC82 and SCCNij3, respectively. Within 24 h, loss of pimonidazole-stained areas in C38 and MEC82 occurred concurrent with the appearance of pimonidazole positive cell debris in necrotic regions. In C38 and MEC82, most of the hypoxic cells had disappeared after 48 h, whereas in SCCNij3, viable cells that had been labeled with pimonidazole were still observed after 5 days. Conclusions: The present study demonstrates that the double hypoxia marker assay can be used to study changes in both the proportion of hypoxic tumor cells and their lifespan at the same time. The present study shows that large differences in hypoxic cell turnover rates may exist among tumor lines, with half-lives ranging from 17-49 h

  8. Clinicopathologic features and surgical outcome of solid pseudopapillary tumor of the pancreas: analysis of 17 cases

    Directory of Open Access Journals (Sweden)

    Wang Xiao-Guang

    2013-02-01

    Full Text Available Abstract Background We summarize our experience of the diagnosis, surgical treatment, and prognosis of solid pseudopapillary tumors (SPTs. Methods We carried out a retrospective study of clinical data from a series of 17 patients with SPT managed in two hospitals between October 2001 and November 2011. Results All of the 17 patients were female and the average age at diagnosis was 26.6 years (range 11 years to 55 years. The tumor was located in the body or tail in ten patients, the head in five patients, and the neck in two patients. The median tumor size was 5.5 cm (range 2 cm to 10 cm. All 17 patients had curative resections, including seven distal pancreatectomies, five local resections, four pancreaticoduodenectomies, and one central pancreatectomy. Two patients required concomitant splenic vein resection due to local tumor invasion. All patients were alive and disease-free at a median follow-up of 48.2 months (range 2 to 90 months. There were no significant associations between clinicopathologic factors and malignant potential of SPT. Ki-67 was detected in three patients with pancreatic parenchyma invasion. Conclusions The SPT is an infrequent tumor, typically affecting young women without notable symptoms. Surgical resection is justified even in the presence of local invasion or metastases, as patients demonstrate excellent long-term survival. Positive immunoreactivity for Ki-67 may predict the malignant potential of SPTs.

  9. Solid-pseudo papillary tumor of the pancreas: Frantz's tumor

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    Oliveira, Bruno Righi Rodrigues de; Moreira, Reni Cecilia Lopes; Campos, Marcelo Esteves Chaves [Instituto Mario Penna, Belo Horizonte, MG (Brazil)], e-mail: brunorighi@yahoo.com.br

    2010-07-01

    The pseudo papillary solid tumor of the pancreas, also known as Frantz's tumor, is a rare disease, taking place in approximately 0.17% to 2.7% of non-endocrine tumors of the pancreas. Recently, the increase of its incidence has been noted with more than two-thirds of the total cases described in the last 10 years. A possible explanation is a greater knowledge of the disease and a greater uniformity of conceptualization in the last years. Generally, it affects young adult females. In most of the series, the tumor principally attacks the body and tail of the pancreas. The objective of the present report is to present the diagnostic and therapeutic option used in this rare pancreatic tumor of low-grade malignancy. (author)

  10. Solid KHT tumor dispersal for flow cytometric cell kinetic analysis

    International Nuclear Information System (INIS)

    Pallavicini, M.G.; Folstad, L.J.; Dunbar, C.

    1981-01-01

    A bacterial neutral protease was used to disperse KHT solid tumors into single cell suspensions suitable for routine cell kinetic analysis by flow cytometry and for clonogenic cell survival. Neutral protease disaggregation under conditions which would be suitable for routine tumor dispersal was compared with a trypsin/DNase procedure. Cell yield, clonogenic cell survival, DNA distributions of untreated and drug-perturbed tumors, rates of radioactive precursor incorporation during the cell cycle, and preferential cell cycle phase-specific cell loss were investigated. Tumors dispersed with neutral protease yielded approximately four times more cells than those dispersed with trypsin/DNase and approximately a 1.5-fold higher plating efficiency in a semisolid agar system. Quantitative analysis of DNA distributions obtained from untreated and cytosine-arabinoside-perturbed tumors produced similar results with both dispersal procedures. The rates of incorporation of tritiated thymidine during the cell cycle were also similar with neutral protease and trypsin/DNase dispersal. Preferential phase-specific cell loss was not obseved with either technique. We find that neutral protease provides good single cell suspensions of the KHT tumor for cell survival measurements and for cell kinetic analysis of drug-induced perturbations by flow cytometry. In addition, the high cell yields facilitate electronic cell sorting where large numbers of cells are often required

  11. Targeting solid tumors with non-pathogenic obligate anaerobic bacteria.

    Science.gov (United States)

    Taniguchi, Shun'ichiro; Fujimori, Minoru; Sasaki, Takayuki; Tsutsui, Hiroko; Shimatani, Yuko; Seki, Keiichi; Amano, Jun

    2010-09-01

    Molecular-targeting drugs with fewer severe adverse effects are attracting great attention as the next wave of cancer treatment. There exist, however, populations of cancer cells resistant to these drugs that stem from the instability of tumor cells and/or the existence of cancer stem cells, and thus specific toxicity is required to destroy them. If such selectivity is not available, these targets may be sought out not by the cancer cell types themselves, but rather in their adjacent cancer microenvironments by means of hypoxia, low pH, and so on. The anaerobic conditions present in malignant tumor tissues have previously been regarded as a source of resistance in cancer cells against conventional therapy. However, there now appears to be a way to make use of these limiting factors as a selective target. In this review, we will refer to several trials, including our own, to direct attention to the utilizable anaerobic conditions present in malignant tumor tissues and the use of bacteria as carriers to target them. Specifically, we have been developing a method to attack solid cancers using the non-pathogenic obligate anaerobic bacterium Bifidobacterium longum as a vehicle to selectively recognize and target the anaerobic conditions in solid cancer tissues. We will also discuss the existence of low oxygen pressure in tumor masses in spite of generally enhanced angiogenesis, overview current cancer therapies, especially the history and present situation of bacterial utility to treat solid tumors, and discuss the rationality and future possibilities of this novel mode of cancer treatment. © 2010 Japanese Cancer Association.

  12. Solid pancreatic pseudopapillary tumor managed laparoscopically: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    D. Cuccurullo

    Full Text Available Background: Solid pancreatic pseudopapillary tumors are a rare neoplasms, about 1–3% of all pancreatic neoplasms. This cancer mainly affects women between the third and fourth decade of life.They are not well known; the molecular origins represent a low degree of malignancy, in which the complete resection is curative. We report our experience with a case report of SPT in a young man. Presentation of case: Thirty-six years old male patient with a mass about 10 cm in the pancreatic tail and splenic ilum. After following CT and MR, the patient was subjected to surgery. Histophatological result was solid tumor pseudopapillary of pancreas with no pathological lymph nodes. Discussion and conclusion: Solid pseudopapillary neoplasm shows histological characteristic solid and pseudopapillary proliferation. Immunohistochemistry detects, among the causes of tumor development, a correlation between the Beta-catenin mutations, alteration of the E-cadherin. In the most cases, therapy is surgical treatment with laparoscopic. Keywords: Pancreatic pseudopapillary neoplasm, Pancreatic tumor, Laparoscopic surgery

  13. First-in-human study of pbi-05204, an oleander-derived inhibitor of akt, fgf-2, nf-κΒ and p70s6k, in patients with advanced solid tumors.

    Science.gov (United States)

    Hong, D S; Henary, H; Falchook, G S; Naing, A; Fu, S; Moulder, S; Wheler, J J; Tsimberidou, A; Durand, J B; Khan, R; Yang, P; Johansen, M; Newman, R A; Kurzrock, R

    2014-12-01

    PBI-05204, a Nerium oleander extract (NOE) containing the cardiac glycoside oleandrin, inhibits the α-3 subunit of Na-K ATPase, as well as FGF-2 export, Akt and p70S6K, hence attenuating mTOR activity. This first-in-human study determined the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of PBI-05204 in patients with advanced cancer. Methods Forty-six patients received PBI-05204 by mouth for 21 of 28 days (3 + 3 trial design). Dose was escalated 100% using an accelerated titration design until grade 2 toxicity was observed. Plasma PK and mTOR effector (p70S6K and pS6) protein expressions were evaluated. Results Dose-limiting toxicities (grade 3 proteinuria, fatigue) were observed at dose level 8 (0.3383 mg/kg/day). Common possible drug-related adverse were fatigue (26 patients, 56.5%), nausea (19 patients, 41.3%) and diarrhea (15 patients, 32.6 %). Electrocardiogram monitoring revealed grade 1 atrioventricular block (N = 10 patients) and grade 2 supraventricular tachycardia (N = 1). The MTD was DL7 (0.2255 mg/kg) where no toxicity of grade ≥ 3 was observed in seven patients treated. Seven patients (15%) had stable disease > 4 months. Mean peak oleandrin concentrations up to 2 ng/mL were achieved, with area under the curves 6.6 to 25.5 μg/L*hr and a half-life range of 5-13 h. There was an average 10% and 35% reduction in the phosphorylation of Akt and pS6 in PBMC samples in 36 and 32 patients, respectively, tested between predose and 21 days of treatment. Conclusions PBI-05204 was well tolerated in heavily pretreated patients with advanced solid tumors. The recommended Phase II dose is 0.2255 mg/kg/day.

  14. L-Asparaginase delivered by Salmonella typhimurium suppresses solid tumors

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    Kwangsoo Kim

    Full Text Available Bacteria can be engineered to deliver anticancer proteins to tumors via a controlled expression system that maximizes the concentration of the therapeutic agent in the tumor. L-asparaginase (L-ASNase, which primarily converts asparagine to aspartate, is an anticancer protein used to treat acute lymphoblastic leukemia. In this study, Salmonellae were engineered to express L-ASNase selectively within tumor tissues using the inducible araBAD promoter system of Escherichia coli. Antitumor efficacy of the engineered bacteria was demonstrated in vivo in solid malignancies. This result demonstrates the merit of bacteria as cancer drug delivery vehicles to administer cancer-starving proteins such as L-ASNase to be effective selectively within the microenvironment of cancer tissue.

  15. Photoirradiation system for solid tumors in photodynamic therapy

    International Nuclear Information System (INIS)

    Pacheco, L.; Stolik, S.; Rosa, J.M. de la

    2012-01-01

    Photodynamic therapy (PDT) is a clinical procedure which induces cell death for destroying cancerous tissues mostly. This is accomplished by photochemical reaction produced by the combined action of three elements: photo sensitizer, light and oxygen. One aspect of the development of PDT is focused on the treatment of solid and deep tumors, where a set of delivering-light probes are placed into the tumor mass. However, this technique still has several challenges, for although certain parameters involved in the procedure may be adjusted, the complex geometry and non-homogeneity of a tumor difficult to establish the appropriate treatment planning. This paper addresses an overview of interstitial PDT and presents our proposal of photo irradiation system. (Author)

  16. Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Hamidreza Namazi

    2016-01-01

    Full Text Available Cancer is a class of diseases characterized by out-of-control cells’ growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments.

  17. Targeted drug delivery and penetration into solid tumors.

    Science.gov (United States)

    Corti, Angelo; Pastorino, Fabio; Curnis, Flavio; Arap, Wadih; Ponzoni, Mirco; Pasqualini, Renata

    2012-09-01

    Delivery and penetration of chemotherapeutic drugs into tumors are limited by a number of factors related to abnormal vasculature and altered stroma composition in neoplastic tissues. Coupling of chemotherapeutic drugs with tumor vasculature-homing peptides or administration of drugs in combination with biological agents that affect the integrity of the endothelial lining of tumor vasculature is an appealing strategy to improve drug delivery to tumor cells. Promising approaches to achieve this goal are based on the use of Asn-Gly-Arg (NGR)-containing peptides as ligands for drug delivery and of NGR-TNF, a peptide-tumor necrosis factor-α fusion protein that selectively alters drug penetration barriers and that is currently tested in a randomized Phase III trial in patients with malignant pleural mesothelioma. © 2011 Wiley Periodicals, Inc.

  18. Solid tumors are poroelastic solids with a chemo-mechanical feedback on growth.

    Science.gov (United States)

    Ambrosi, D; Pezzuto, S; Riccobelli, D; Stylianopoulos, T; Ciarletta, P

    2017-12-01

    The experimental evidence that a feedback exists between growth and stress in tumors poses challenging questions. First, the rheological properties (the "constitutive equations") of aggregates of malignant cells are still a matter of debate. Secondly, the feedback law (the "growth law") that relates stress and mitotic-apoptotic rate is far to be identified. We address these questions on the basis of a theoretical analysis of in vitro and in vivo experiments that involve the growth of tumor spheroids. We show that solid tumors exhibit several mechanical features of a poroelastic material, where the cellular component behaves like an elastic solid. When the solid component of the spheroid is loaded at the boundary, the cellular aggregate grows up to an asymptotic volume that depends on the exerted compression. Residual stress shows up when solid tumors are radially cut, highlighting a peculiar tensional pattern. By a novel numerical approach we correlate the measured opening angle and the underlying residual stress in a sphere. The features of the mechanobiological system can be explained in terms of a feedback of mechanics on the cell proliferation rate as modulated by the availability of nutrient, that is radially damped by the balance between diffusion and consumption. The volumetric growth profiles and the pattern of residual stress can be theoretically reproduced assuming a dependence of the target stress on the concentration of nutrient which is specific of the malignant tissue.

  19. Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors

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    Griffiths Gary L

    2009-06-01

    Full Text Available Abstract Background The existence of large pores in the blood-tumor barrier (BTB of malignant solid tumor microvasculature makes the blood-tumor barrier more permeable to macromolecules than the endothelial barrier of most normal tissue microvasculature. The BTB of malignant solid tumors growing outside the brain, in peripheral tissues, is more permeable than that of similar tumors growing inside the brain. This has been previously attributed to the larger anatomic sizes of the pores within the BTB of peripheral tumors. Since in the physiological state in vivo a fibrous glycocalyx layer coats the pores of the BTB, it is possible that the effective physiologic pore size in the BTB of brain tumors and peripheral tumors is similar. If this were the case, then the higher permeability of the BTB of peripheral tumor would be attributable to the presence of a greater number of pores in the BTB of peripheral tumors. In this study, we probed in vivo the upper limit of pore size in the BTB of rodent malignant gliomas grown inside the brain, the orthotopic site, as well as outside the brain in temporalis skeletal muscle, the ectopic site. Methods Generation 5 (G5 through generation 8 (G8 polyamidoamine dendrimers were labeled with gadolinium (Gd-diethyltriaminepentaacetic acid, an anionic MRI contrast agent. The respective Gd-dendrimer generations were visualized in vitro by scanning transmission electron microscopy. Following intravenous infusion of the respective Gd-dendrimer generations (Gd-G5, N = 6; Gd-G6, N = 6; Gd-G7, N = 5; Gd-G8, N = 5 the blood and tumor tissue pharmacokinetics of the Gd-dendrimer generations were visualized in vivo over 600 to 700 minutes by dynamic contrast-enhanced MRI. One additional animal was imaged in each Gd-dendrimer generation group for 175 minutes under continuous anesthesia for the creation of voxel-by-voxel Gd concentration maps. Results The estimated diameters of Gd-G7 dendrimers were 11 ± 1 nm and those of Gd-G8

  20. Outcome for children with metastatic solid tumors over the last four decades.

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    Stephanie M Perkins

    Full Text Available Outcomes for pediatric solid tumors have significantly improved over the last 30 years. However, much of this improvement is due to improved outcome for patients with localized disease. Here we evaluate overall survival (OS for pediatric patients with metastatic disease over the last 40 years.The United States Surveillance, Epidemiology, and End Results (SEER database was used to conduct this study. Patients diagnosed between 0 and 18 years of age with metastatic Ewings sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma or Wilms tumor were included in the analysis.3,009 patients diagnosed between 1973-2010 met inclusion criteria for analysis. OS at 10 years for patients diagnosed between 1973-1979, 1980-1989, 1990-1999 and 2000-2010 was 28.3%, 37.2%, 44.7% and 49.3%, respectively (p<0.001. For patients diagnosed between 2000-2010, 10-year OS for patients with Ewing sarcoma, neuroblastoma, osteosarcoma, rhabdomyosarcoma and Wilms tumor was 30.6%, 54.4%, 29.3%, 27.5%, and 76.6%, respectively, as compared to 13.8%, 25.1%, 13.6%, 17.9% and 57.1%, respectively, for patients diagnosed between 1973-1979. OS for neuroblastoma significantly increased with each decade. For patients with osteosarcoma and Ewing sarcoma, there was no improvement in OS over the last two decades. There was no improvement in outcome for patients with rhabdomyosarcoma or Wilms tumor over the last 30 years.OS for pediatric patients with metastatic solid tumors has significantly improved since the 1970s. However, outcome has changed little for some malignancies in the last 20-30 years. These data underscore the importance of continued collaboration and studies to improve outcome for these patients.

  1. A phase i study of the cyclin-dependent kinase 4/6 inhibitor ribociclib (LEE011) in patients with advanced solid tumors and lymphomas

    NARCIS (Netherlands)

    Infante, Jeffrey R.; Cassier, Philippe A.; Gerecitano, John F.; Witteveen, Petronella O.; Chugh, Rashmi; Ribrag, Vincent; Chakraborty, Abhijit; Matano, Alessandro; Dobson, Jason R.; Crystal, Adam S.; Parasuraman, Sudha; Shapiro, Geoffrey I.

    2016-01-01

    Purpose: Ribociclib (an oral, highly specific cyclin-dependent kinase 4/6 inhibitor) inhibits tumor growth in preclinical models with intact retinoblastoma protein (Rb+). This first-in-human study investigated the MTD, recommended dose for expansion (RDE), safety, preliminary activity,

  2. A phase I and pharmacokinetic study of a powder-filled capsule formulation of oral irinotecan (CPT-11) given daily for 5 days every 3 weeks in patients with advanced solid tumors.

    Science.gov (United States)

    Pitot, Henry C; Adjei, Alex A; Reid, Joel M; Sloan, Jeff A; Atherton, Pamela J; Rubin, Joseph; Alberts, Steven R; Duncan, Barbara A; Denis, Louis; Schaaf, Larry J; Yin, Donghua; Sharma, Amarnath; McGovren, Patrick; Miller, Langdon L; Erlichman, Charles

    2006-08-01

    Intravenous (i.v.) irinotecan is a cytotoxic topoisomerase I inhibitor with broad clinical activity in metastatic colorectal cancer and other tumors. The development of an oral formulation of irinotecan could enhance convenience and lessen the expense of palliative irinotecan delivery. This phase I study evaluated the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of irinotecan given as a powder-filled capsule (PFC) daily for 5 days every 3 weeks. Patients with advanced solid tumors received escalating doses of oral irinotecan daily for 5 days every 3 weeks. Plasma samples were collected following the first and fifth doses of irinotecan during Cycle 1 to determine the PK of irinotecan and its major circulating metabolites: SN-38, SN-38G, and APC. 20 patients (median age 61.5 years, range 40-75; M/F 12/8; ECOG PS 0=5, 1=11, 2=4) received oral irinotecan at dose levels of 30 (n=3), 40 (n=3), 50 (n=6), and 60 (n=8) mg/m(2)/day. Of the eight patients enrolled at 60 mg/m(2), three patients experienced DLT (> or = grade 3) consisting of nausea (three patients), vomiting (three patients), diarrhea (two patients), and febrile neutropenia (two patients) for which all the three patients required hospitalization. Treatment of six patients at the 50-mg/m(2) dose level resulted in no DLT. Other toxicities observed include abdominal pain, alopecia, anorexia, and asthenia. After oral administration, irinotecan was rapidly absorbed into systemic circulation and converted to the active metabolite SN-38. Increasing dose levels resulted in a dose-dependent increase in mean exposure parameters (Cmax and AUC) of irinotecan and metabolites. Systemic exposure parameters (Cmax and AUC(0-24)) of irinotecan and SN-38 were comparable between days 1 and 5. The extent of conversion from irinotecan to SN-38 was approximately threefold higher after the oral administration compared to that previously observed after i.v. administration. The exposure

  3. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  4. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial.

    Science.gov (United States)

    Gulley, James L; Rajan, Arun; Spigel, David R; Iannotti, Nicholas; Chandler, Jason; Wong, Deborah J L; Leach, Joseph; Edenfield, W Jeff; Wang, Ding; Grote, Hans Juergen; Heydebreck, Anja von; Chin, Kevin; Cuillerot, Jean-Marie; Kelly, Karen

    2017-05-01

    Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA. Eligible patients had confirmed stage IIIB or IV NSCLC with squamous or non-squamous histology, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), tumour biopsy or archival sample for biomarker assessment, and Eastern Cooperative Oncology Group performance status 0 or 1, among other criteria. Patient selection was not based on PD-L1 expression or expression of other biomarkers, including EGFR or KRAS mutation or ALK translocation status. Patients received infusional avelumab monotherapy 10 mg/kg every 2 weeks until disease progression or toxicity. The primary objective was to assess safety and tolerability. This trial is registered with ClinicalTrials.gov, number NCT01772004; enrolment in this cohort is closed and the trial is ongoing. Between Sept 10, 2013, and June 24, 2014, 184 patients were enrolled and initiated treatment with avelumab. Median follow-up duration was 8·8 months (IQR 7·2-11·9). The most common treatment-related adverse events of any grade were fatigue (46 [25%] of 184 patients), infusion-related reaction (38 [21%]), and nausea (23 [13%]). Grade 3 or worse treatment-related adverse events occurred in 23 (13%) of 184 patients; the most common (occurring in more than two patients) were infusion-related reaction (four [2%] patients) and

  5. Obtaining S values for rectangular--solid tumors inside rectangular--solid host organs

    International Nuclear Information System (INIS)

    Stinchcomb, T.G.; Durham, J.S.; Fisher, D.R.

    1991-01-01

    A method is described for obtaining S values between a tumor and its host organ for use with the MIRD formalism. It applies the point-source specific absorbed fractions for an infinite water medium, tabulated by Berger, to a rectangular solid of arbitrary dimensions which contains a rectangular tumor of arbitrary dimensions. Contributions from pairs of source and target volume elements are summed for the S values between the tumor and itself, between the remaining healthy host organ and itself, and between the tumor and the remaining healthy host organ, with the reciprocity theorem assumed for the last. This method labeled MTUMOR, is interfaced with the widely used MIRDOSE program which incorporates the MIRD formalism. An example is calculated

  6. Recent advances of bispecific antibodies in solid tumors

    Directory of Open Access Journals (Sweden)

    Shengnan Yu

    2017-09-01

    Full Text Available Abstract Cancer immunotherapy is the most exciting advancement in cancer therapy. Similar to immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T, bispecific antibody (BsAb is attracting more and more attention as a novel strategy of antitumor immunotherapy. BsAb not only offers an effective linkage between therapeutics (e.g., immune effector cells, radionuclides and targets (e.g., tumor cells but also simultaneously blocks two different oncogenic mediators. In recent decades, a variety of BsAb formats have been generated. According to the structure of Fc domain, BsAb can be classified into two types: IgG-like format and Fc-free format. Among these formats, bispecific T cell engagers (BiTEs and triomabs are commonly investigated. BsAb has achieved an exciting breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. In this review, we focus on the preclinical experiments and clinical studies of epithelial cell adhesion molecule (EpCAM, human epidermal growth factor receptor (HER family, carcinoembryonic antigen (CEA, and prostate-specific membrane antigen (PSMA related BsAbs in solid tumors, as well as discuss the challenges and corresponding approaches in clinical application.

  7. Differentiation between benign and malignant solid pseudopapillary tumor of the pancreas by MDCT

    International Nuclear Information System (INIS)

    Yin, Qihua; Wang, Mingliang; Wang, Chengsheng; Wu, Zhiyuan; Yuan, Fei; Chen, Kun; Tang, Yonghua; Zhao, Xuesong; Miao, Fei

    2012-01-01

    Purpose: The purpose of this study was to determine if characteristic features on computed tomographic and (or) magnetic resonance imaging can differentiate benign and malignant solid pseudopapillary neoplasms (SPN). Materials and methods: A total of 82 pathologically diagnosed SPN patients were included. CT and MRI were reviewed by 3 radiologists. Each tumor was analyzed through the clinical and imaging features. Results: The highest occurrence of malignant SPN was observed in the group of patients (11–19 years old) followed by the group of patients (50–65 years old). When the tumor was located in the tail and the size was equal or larger than 6.0 cm, the positive and predictive value, the predictive value, sensitivity and specificity for a malignant SPN were 61.5%, 100%, 100% and 78.6%, respectively. Presence of complete encapsulation was more frequent in benign SPNs, but focal discontinuity in the malignant SPNs. Amorphous or scattered calcifications, all near-solid tumors and presence of upstream pancreatic ductal was found in the benign SPNs. Conclusion: A focal discontinuity of the capsule, large tumor size (>6.0 cm) and a pancreatic tail location may suggest malignancy of SPN. In contrast, tumors with amorphous or scattered calcifications, and all near-solid tumors may be indicative of benignancy. Age (less than 20 or more than 50 years old) is a possible risk factor of SPN. In comparison to other pancreatic neoplasms, such as ductal adenocarcinoma, a complete/incomplete pseudo-capsule, without upstream pancreatic duct dilatation and lymph nodes metastasis, and the presence of internal calcification and hemorrhage are more likely SPN.

  8. Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

    Science.gov (United States)

    Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

    2016-02-01

    Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

  9. Monoclonal antibodies and Fc fragments for treating solid tumors

    Directory of Open Access Journals (Sweden)

    Eisenbeis AM

    2012-01-01

    Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

  10. Echinococcus cysticus of the liver - sonographic pattern suggestive of solid tumor

    International Nuclear Information System (INIS)

    Grosser, G.; Hauenstein, K.H.; Henke, W.

    1985-01-01

    In a patient with Hodgkin's disease, an intrahepatic echodense mass was diagnosed incidentally by ultrasonography. The sonographic pattern suggested a solid tumor. Despite negative or borderline serology, computed tomography establised the diagnosis of echinococcus cysticus by documentation of one ''daughter'' cyst; this diagnosis was confirmed by surgery. The criteria of echinococcus cysticus in modern imaging methods like sonography and computed tomography are summarized and the diagnostic value of various procedures including diagnostic procedure in seronegative cases are discussed. (orig.) [de

  11. Chimeric antigen receptor T cell (CAR-T) immunotherapy for solid tumors: lessons learned and strategies for moving forward.

    Science.gov (United States)

    Li, Jian; Li, Wenwen; Huang, Kejia; Zhang, Yang; Kupfer, Gary; Zhao, Qi

    2018-02-13

    Recently, the US Food and Drug Administration (FDA) approved the first chimeric antigen receptor T cell (CAR-T) therapy for the treatment CD19-positive B cell acute lymphoblastic leukemia. While CAR-T has achieved remarkable success in the treatment of hematopoietic malignancies, whether it can benefit solid tumor patients to the same extent is still uncertain. Even though hundreds of clinical trials are undergoing exploring a variety of tumor-associated antigens (TAA), no such antigen with comparable properties like CD19 has yet been identified regarding solid tumors CAR-T immunotherapy. Inefficient T cell trafficking, immunosuppressive tumor microenvironment, suboptimal antigen recognition specificity, and lack of safety control are currently considered as the main obstacles in solid tumor CAR-T therapy. Here, we reviewed the solid tumor CAR-T clinical trials, emphasizing the studies with published results. We further discussed the challenges that CAR-T is facing for solid tumor treatment and proposed potential strategies to improve the efficacy of CAR-T as promising immunotherapy.

  12. Applications of lipid nanocarriers for solid tumors therapy: literature review

    International Nuclear Information System (INIS)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury; Taveira, Eliseu Jose Fleury

    2012-01-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed R database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  13. Impact of a walking intervention on cardiorespiratory fitness, self-reported physical function, and pain in patients undergoing treatment for solid tumors.

    Science.gov (United States)

    Griffith, Kathleen; Wenzel, Jennifer; Shang, JingJing; Thompson, Carol; Stewart, Kerry; Mock, Victoria

    2009-10-15

    Cancer treatment is associated with decline in measured and self-reported physical function and increased pain. In the current study, the authors evaluated the impact of a walking intervention on these outcomes during chemotherapy/radiation. Patients with breast, prostate, and other cancers (N=126) were randomized to a home-based walking intervention (exercise) or usual care (control). Exercise dose during the intervention was assessed using a 5-item Physical Activity Questionnaire. Outcome measures were cardiorespiratory fitness, expressed as peak oxygen uptake (VO2) measured during treadmill testing (n=85) or estimated by 12-minute walk (n=27), and self-reported physical function, role limitations, and pain derived from Medical Outcomes Study Short Form 36. Linear regression was used to evaluate pre-to-post intervention change outcomes between groups. The mean (standard deviation) age of the patients was 60.2 (10.6) years. Diagnoses included prostate (55.6%) and breast (32.5%) cancer. Treatment included external beam radiotherapy (52.3%) and chemotherapy (34.9%). Exercise patients reported worsening Medical Outcomes Study physical function role limitations by the end of cancer treatment (P=.037). Younger age was associated with improved Medical Outcomes Study physical function (P=.048). In all patients, increased exercise dose was associated with decreased Medical Outcomes Study pain (P=.046), regardless of diagnosis. The percent change of VO2 between prostate and nonprostate cancer patients when adjusted for baseline VO2 and Physical Activity Questionnaire values was 17.45% (P=.008), with better VO2 maintenance in the prostate group. Exercise during cancer treatment improves cardiorespiratory fitness and self-reported physical function in prostate cancer patients and in younger patients, regardless of diagnosis, and may attenuate loss of those capacities in patients undergoing chemotherapy. Exercise also reduces the pain experience. Copyright (c) 2009 American

  14. Solid and papillary epithelial tumor of the pancreas

    International Nuclear Information System (INIS)

    Vega, Alejandro de la; Eyheremendy, Eduardo; Mondello, Eduardo; Florenzano, Nestor

    2001-01-01

    We report a case of a teenage female patient who presented upper abdominal pain and bilious vomiting. Laboratory analysis, abdominal ultrasound and contrast enhanced CT was performed. On the bases of these results she underwent a corporocaudal pancreatectomy. Pathology studied with immunohistochemical test, showed a solid and papillary epithelial neoplasm of the pancreas, which is an unusual disease. (author)

  15. Brain tumors in patients primarly treated psychiatrically

    Directory of Open Access Journals (Sweden)

    Ignjatović-Ristić Dragana

    2011-01-01

    Full Text Available Introduction. Psychiatric symptoms are not rare manifestations of brain tumors. Brain tumors presented by symptoms of raised intracranial pressure, focal neurological signs, or convulsions are usually first seen by the neurologist or less frequently by the neurosurgeon in routine diagnostic procedures. On the other hand, when psychiatric symptoms are the first manifestation in “neurologically silent” brain tumors, the patients are sent to the psychiatrist for the treatment of psychiatric symptoms and brain tumors are left misdiagnosed for a long period of time. Case Report. We presented three patients with the diagnosed brain tumor where psychiatrist had been the first specialist to be consulted. In all three cases neurological examination was generally unremarkable with no focal signs or features of raised intracranial pressure. CT scan demonstrated right insular tumor in a female patient with obsessive-compulsive disorder (OCD; right parietal temporal tumor in a patient with delusions and depression and left frontal tumor in a patient with history of alcohol dependency. Conclusion. Psychiatric symptoms/disorders in patients with brain tumors are not specific enough and can have the same clinical presentation as the genuine psychiatric disorder. Therefore, we emphasize the consideration of neuroimaging in patients with abrupt beginning of psychiatric symptoms, in those with a change in mental status, or when headaches suddenly appear or in cases of treatment resistant psychiatric disorders regardless the lack of neurological symptoms.

  16. A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors.

    Science.gov (United States)

    Hudis, Clifford; Swanton, Charles; Janjigian, Yelena Y; Lee, Ray; Sutherland, Stephanie; Lehman, Robert; Chandarlapaty, Sarat; Hamilton, Nicola; Gajria, Devika; Knowles, James; Shah, Jigna; Shannon, Keith; Tetteh, Ernestina; Sullivan, Daniel M; Moreno, Carolina; Yan, Li; Han, Hyo Sook

    2013-11-19

    Trastuzumab is effective in human epidermal growth factor receptor 2 (HER2)-over-expressing breast and gastric cancers. However, patients may develop resistance through downstream signaling via the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. This phase 1 trial was conducted to determine the safety and tolerability of the investigational AKT inhibitor MK-2206, to prepare for future studies to determine whether the combination with trastuzumab could inhibit compensatory signaling. Patients with HER2+ treatment-refractory breast and gastroesophageal cancer were enrolled. Treatment consisted of standard doses of intravenous trastuzumab and escalating dose levels of oral MK-2206 using either an every-other-day (45 mg and 60 mg QOD) or once-weekly (135 mg and 200 mg QW) schedule. A total of 34 patients with HER2+ disease were enrolled; 31 received study-drug. The maximum tolerated dose (MTD) for MK-2206 in combination with trastuzumab was 60 mg for the QOD schedule and 135 mg for the QW schedule, although a true MTD was not established due to early termination of the trial. The most common treatment-emergent toxicities included fatigue, hyperglycemia, and dermatologic rash, consistent with prior experience; one death unrelated to treatment was reported. There was one complete response in a patient with metastatic breast cancer, one patient achieved a partial response, and 5 patients had stable disease for at least 4 months, despite progression on multiple prior trastuzumab- and lapatinib-based therapies. Results also indicate that trastuzumab does not affect the pharmacokinetics of MK-2206. Results suggest the AKT inhibitor MK-2206 can be safely combined with trastuzumab, and is associated with clinical activity, supporting further investigation. ClinicalTrials.gov; identifier: NCT00963547.

  17. Evaluation of malignant solid tumor in childhood with FDG-PET

    International Nuclear Information System (INIS)

    Ishida, Amane; Goto, Hiroaki; Kuroki, Fumiko

    2006-01-01

    Usefulness of FDG-PET (18F-deoxyglucose PET) was examined in evaluation of diagnosis and therapeutic efficacy of childhood malignant solid tumors. Subjects were 32 patients (16 males) of the median age of 7 y (1 - 27 y), involving those with neuroblastoma (9 cases), hepatoblastoma (4), chronic granulomatous disorder (4) and others (each ≤2). They underwent 75 FDG-PET examinations for diagnosis before and during treatment in authors' hospital in the period from May 2001 to December 2003. Standard uptake value (SUV), 1 x 1 cm region of interest (ROI) of abnormally high distribution area of radioactivity in the lesion/FDG dose/kg body wt., was used for evaluation: SUV>1.5 was defined positive. In neuroblastoma, FDG was found to be highly distributed and kinetics of SUV, to be useful for evaluation of therapeutic efficacy and early metastasis detection. In some cases of hepatoblastoma, the therapeutic effectiveness and recurrence were not satisfactorily evaluative. The distribution of FDG was not satisfactory in Wilms' tumor relative to other tumors. The PET was thought to be useful, despite their small case number examined, for those evaluations of Ewing's tumor, dysgerminoma and Langerhans cell histiocytosis. Thus FDG-PET was found useful for detection, evaluation of therapeutic efficacy and early metastasis detection of pediatric malignant solid tumors. (T.I.)

  18. Comparison of F-18-FDG PET/CT findings between pancreatic solid pseudopapillary tumor and pancreatic ductal adenocarcinoma

    International Nuclear Information System (INIS)

    Kim, Yong-il; Kim, Seok-ki; Paeng, Jin Chul; Lee, Ho-Young

    2014-01-01

    Objective: Pancreatic solid pseudopapillary tumor (SPT) is a rare benign tumor. Little data are available on positron emission tomographic/computed tomographic (PET/CT) characteristics of this tumor. Therefore, we analyzed the metabolic characteristics of SPT using F-18-FDG PET/CT and compared the results with those of pancreatic ductal adenocarcinoma. Methods: We retrospectively reviewed the records of 11 SPT patients and 46 patients with ductal adenocarcinoma. Ten SPT patients had primary tumors and 1 patient had metastatic SPT. Maximum standardized uptake value (max SUV), mean SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background ratio (TBR) were evaluated. Mann–Whitney U test between pancreatic SPT and ductal adenocarcinoma was performed. In addition, age, gender and tumor size-adjusted analysis of covariance (ANCOVA) was done between pancreatic SPT and ductal adenocarcinoma. Results: Compared with pancreatic ductal adenocarcinomas, SPTs had significantly higher tumor size-adjusted MTV and TLG. MTV and TLG values were significantly correlated with T-stage of the SPTs. In 1 SPT patient, metastases in the liver and mesentery were revealed by intense uptake of FDG on F-18-FDG PET/CT, and after PET/CT had suggested the presence of pancreatic SPT. Conclusion: We recommend that SPT be considered when a solid pancreatic mass with increased FDG metabolism is encountered on PET/CT. F-18-FDG PET/CT may be useful in detecting subtle metastases of SPT

  19. Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity

    DEFF Research Database (Denmark)

    Meulendijks, Didier; Jacob, Wolfgang; Voest, Emile E

    2017-01-01

    Purpose: This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.......Experimental Design: The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively. In both parts, patients received lumretuzumab doses from 400 to 2,000 mg plus cetuximab or erlotinib according to standard posology......) in the cetuximab part and two DLTs in the erlotinib part were reported. The most frequent adverse events were gastrointestinal and skin toxicities, which were manageable. The objective response rate (ORR) was 6.1% in the cetuximab part and 4.2% in the erlotinib part. In the sqNSCLC extension cohort...

  20. Solid tumors after chemotherapy or surgery for testicular nonseminoma: a population-based study.

    Science.gov (United States)

    Fung, Chunkit; Fossa, Sophie D; Milano, Michael T; Oldenburg, Jan; Travis, Lois B

    2013-10-20

    Increased risks of solid tumors after older radiotherapy strategies for testicular cancer (TC) are well established. Few population-based studies, however, focus on solid cancer risk among survivors of TC managed with nonradiotherapy approaches. We quantified the site-specific risk of solid cancers among testicular nonseminoma patients treated in the modern era of cisplatin-based chemotherapy, without radiotherapy. Standardized incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2008) and treated initially with either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy. Patients accrued 116,073 person-years of follow-up. Two hundred ten second solid cancers were observed. No increased risk followed surgery alone (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers) occurred after chemotherapy. Increased risks of solid cancers after chemotherapy were observed in most follow-up periods (median latency, 12.5 years), including more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33); significantly increased three- to seven-fold risks occurred for cancers of the kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to 7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78). To our knowledge, this is the first large population-based series reporting significantly increased risks of solid cancers among patients with testicular nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent analytic studies should focus on the evaluation of dose-response relationships, types of solid cancers, latency patterns, and interactions with other possible factors, including genetic susceptibility.

  1. Phase I dose-escalation study of vinflunine hard capsules administered twice a day for 2 consecutive days every week in patients with advanced/metastatic solid tumors.

    Science.gov (United States)

    Calvo, E; Vermorken, J B; Hiret, S; Rodon, J; Cortes, J; Senellart, H; Van den Brande, J; Dyck, J; Pétain, A; Ferre, P; Bennouna, J

    2012-06-01

    Vinflunine is a new microtubule inhibitor of the vinca-alkaloid family. It is marketed in transitional cell carcinoma of urothelial tract as a 20 min infusion given every 3 weeks in Europe. In this phase I study, vinflunine was administered to patients with advanced malignancies as hard capsules given twice a day on days 1-2 every week, with 3 weeks cycles. Serial blood samples were collected during the first cycle for pharmacokinetic investigations. Thirty-six patients (pts) were treated at 6 dose levels 150 (3 pts), 190 (3 pts), 230 (8 pts), 300 mg/day (6 pts) and then 250 (3 pts) and 270 mg/day (13 pts). The Maximal Tolerated Dose (MTD) was reached at 300 mg/day where 2 patients out of 6 experienced a dose limiting toxicity (febrile neutropenia with diarrhea). The lower dose level of 270 mg/day was the recommended dose (RD), the toxicity profile being mainly anaemia, neutropenia, fatigue and constipation. The pharmacokinetic analysis demonstrated the adequacy of the flat-fixed dosing regimen, as no correlation between clearance of vinflunine and body surface area was evidenced. Blood concentrations and exposure increased with dose, and a pharmacokinetic accumulation was observed, which is consistent with the terminal half-life of the compounds. The inter-individual exposure variability at the RD was 35%. Repeated weekly administration of oral vinflunine is feasible and exhibits a moderate inter-individual PK variability. The MTD was achieved at 300 mg/day given for 2 consecutive days. According to the protocol rules, the RD was established at 270 mg/day.

  2. Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors

    Science.gov (United States)

    2018-05-15

    Ewing's Sarcoma; Osteosarcoma; Astrocytoma; Atypical Teratoid/Rhabdoid Tumor; Ependymoma; Germ Cell Tumor; Glioma; Medulloblastoma; Rhabdoid Tumor; Retinoblastoma; Clear Cell Sarcoma; Renal Cell Carcinoma; Wilms Tumor; Hepatoblastoma; Neuroblastoma; Rhabdomyosarcoma

  3. Is Whole-Exome Sequencing an Ethically Disruptive Technology? Perspectives of Pediatric Oncologists and Parents of Pediatric Patients With Solid Tumors.

    Science.gov (United States)

    McCullough, Laurence B; Slashinski, Melody J; McGuire, Amy L; Street, Richard L; Eng, Christine M; Gibbs, Richard A; Parsons, D William; Plon, Sharon E

    2016-03-01

    It has been anticipated that physician and parents will be ill prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive. As a part of the Baylor Advancing Sequencing in Childhood Cancer Care study, we conducted semistructured interviews with 16 pediatric oncologists and 40 parents of pediatric patients with cancer prior to the return of sequencing results. We elicited expectations and attitudes concerning the impact of sequencing on clinical decision making, clinical utility, and treatment expectations from both groups. Using accepted methods of qualitative research to analyze interview transcripts, we completed a thematic analysis to provide inductive insights into their views of sequencing. Our major findings reveal that neither pediatric oncologists nor parents anticipate sequencing to be an ethically disruptive technology, because they expect to be prepared to integrate sequencing results into their existing approaches to learning and using new clinical information for care. Pediatric oncologists do not expect sequencing results to be more complex than other diagnostic information and plan simply to incorporate these data into their evidence-based approach to clinical practice, although they were concerned about impact on parents. For parents, there is an urgency to protect their child's health and in this context they expect genomic information to better prepare them to participate in decisions about their child's care. Our data do not support the concern that introducing genome sequencing into childhood cancer care will be ethically disruptive, that is, leave physicians or parents ill prepared or unprepared to make responsible decisions about patient care. © 2015 Wiley Periodicals, Inc.

  4. Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial.

    Science.gov (United States)

    Pramanik, Raja; Agarwala, Sandeep; Gupta, Yogendra Kumar; Thulkar, Sanjay; Vishnubhatla, Sreenivas; Batra, Atul; Dhawan, Deepa; Bakhshi, Sameer

    2017-09-01

    Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than

  5. The Use of Linezolid in Children with Malignant Solid Tumors

    Directory of Open Access Journals (Sweden)

    H.I. Klymniuk

    2015-09-01

    Full Text Available In recent decades, in the treatment of cancer there has been achieved a significant success not only by the introduction of cancer treatment protocol, but mostly due to the planned combination concomitant treatment of infectious complications. The need for antimicrobial agents against resistant Gram-positive bacteria, such as methicillin-resistant staphylococci, penicillin-resistant pneumococci, vancomycin-resistant enterococci, has significantly increased. In the department of pediatric oncology of the National cancer institute (Kyiv, linezolid preparations were used in children with infection of soft tissues and bones, febrile neutropenia and for the treatment of severe cases of sepsis. Experience of Linelid® use in the department of pediatric oncology of the National cancer institute indicates its effectiveness, safety and good tolerance in children with malignant solid tumors.

  6. Recent advances in the design of drug-loaded polymeric implants for the treatment of solid tumors.

    Science.gov (United States)

    Wadee, Ameena; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Penny, Clement; Ndesendo, Valence M K; Kumar, Pradeep; Murphy, Caragh S

    2011-10-01

    The effective treatment of solid tumors continues to be a great challenge to clinicians, despite the development of novel drugs. In order to improve the clinical efficacy of existing chemotherapeutic agents, researchers have considered the possibility of site-specific solid tumor treatment. The greatest advantage of localized delivery is the significantly fewer side effects experienced by patients. Recently, in situ forming implants have attracted considerable interest. These polymeric systems are injected as solutions into tumor sites and the injected solution forms an implant as a result of local environmental stimuli and hence removes the need for surgical implantation. This review summarizes the attempts that have been made to date in the development of polymeric implants for the treatment of solid tumors. Both in situ forming implants and preformed implants, fabricated using natural and synthetic polymers, are described. In addition, the peri- or intra-tumoral delivery of chemotherapeutic agents based on implants inserted surgically into the affected region is also discussed along with a short coverage of implants having an undesirable initial burst release effect. Although these implants have been shown to improve the treatment of various solid tumors, the ideal implant that is able to deliver high doses of chemotherapeutics to the tumor site, over prolonged periods with relatively few side effects on normal tissue, is yet to be formulated.

  7. Clinical significance of serum thymosin α1 assay in tumor patients

    International Nuclear Information System (INIS)

    Wang Jiamin; Lv Ming'en; Zhao Xiaojuan; Gao Weiqiang; Bai Xia; Wang Zhaoyue

    2003-01-01

    Objective: To investigate the clinical significance of thymosin α1(Tα1) measurement in evaluating clinical status of patients with solid malignant tumors. Methods: Tα1 levels in serum of 50 normal adults, 20 patients with benign tumors and 63 patients with malignant tumors were measured by enzyme linked immunosorbent assay (ELISA). The association of Tα1 level with tumor invasion, metastasis and its alteration after different treatment in patients with malignant tumors were also studied. Results: The serum Tα1 level was 0.69±0.35 μg/L in normal adults, 0.96±0.37 μg/L in patients with benign tumors and 1.46±0.90 μg/L in patients with malignant tumors. In comparison it was both increased between patients with benign and malignant tumors and the normal adults (P<0.01 and P<0.001). And its increasing extent in malignant tumors was much greater than that in benign tumors (P<0.05). The serum Tα1 level in patients with malignant tumors was correlated with tumor invasion, metastasis and different treatment intervention. Conclusions: Our findings suggest that the serum Tα1 level be increased in tumor patients, and that it may be used as a new tumor marker in clinic

  8. Radiotherapy of patients with germ cell tumor

    International Nuclear Information System (INIS)

    Inomata, Taisuke; Maeda, Tomoho; Yoshida, Shoji; Ogawa, Yasuhiro; Hamada, Fumio; Imajo, Yoshinari; Gose, Kyuhei; Fujiwara, Kiyoshi.

    1986-01-01

    Twenty-one patients with germ cell tumor who received radiotherapy were discussed. There were eight patients with germinoma, two patients with malignant teratoma, three patients with pineocytoma (out of category of germ cell tumor today) and eight unverified patients. Irradiated dose was mostly from 50 Gy to 60 Gy and local irradiation was performed after whole brain irradiation in many cases. The effect of radiotherapy was not so good in patients with malignant teratoma. On the contrary, it was relatively good in patients with germinoma and five out of eight patients are alive with no symptoms of recurrence. Six out of eight unverified patients are also alive. Among them, several patients with germinoma are considered to be included. Germinoma occupies many cases of germ cell tumor and has a good response to radiotherapy. Against spinal cord metastasis and late recurrence, additional therapy, such as chemotherapy, seems to be useful to improve cure ratio. (author)

  9. Autoantibody signature differentiates Wilms tumor patients from neuroblastoma patients.

    Directory of Open Access Journals (Sweden)

    Jana Schmitt

    Full Text Available Several studies report autoantibody signatures in cancer. The majority of these studies analyzed adult tumors and compared the seroreactivity pattern of tumor patients with the pattern in healthy controls. Here, we compared the autoimmune response in patients with neuroblastoma and patients with Wilms tumor representing two different childhood tumors. We were able to differentiate untreated neuroblastoma patients from untreated Wilms tumor patients with an accuracy of 86.8%, a sensitivity of 87.0% and a specificity of 86.7%. The separation of treated neuroblastoma patients from treated Wilms tumor patients' yielded comparable results with an accuracy of 83.8%. We furthermore identified the antigens that contribute most to the differentiation between both tumor types. The analysis of these antigens revealed that neuroblastoma was considerably more immunogenic than Wilms tumor. The reported antigens have not been found to be relevant for comparative analyses between other tumors and controls. In summary, neuroblastoma appears as a highly immunogenic tumor as demonstrated by the extended number of antigens that separate this tumor from Wilms tumor.

  10. Ultrasonic enhancement of drug penetration in solid tumors

    Directory of Open Access Journals (Sweden)

    Chun-yen eLai

    2013-08-01

    Full Text Available Increasing the penetration of drugs within solid tumors can be accomplished through multiple ultrasound-mediated mechanisms. The application of ultrasound can directly change the structure or physiology of tissues or can induce changes in a drug or vehicle in order to enhance delivery and efficacy. With each ultrasonic pulse, a fraction of the energy in the propagating wave is absorbed by tissue and results in local heating. When ultrasound is applied to achieve mild hyperthermia, the thermal effects are associated with an increase in perfusion or the release of a drug from a temperature-sensitive vehicle. Higher ultrasound intensities locally ablate tissue and result in increased drug accumulation surrounding the ablated region of interest. Further, the mechanical displacement induced by the ultrasound pulse can result in the nucleation, growth and collapse of gas bubbles. As a result of such cavitation, the permeability of a vessel wall or cell membrane can be increased. Finally, the radiation pressure of the propagating pulse can translate particles or tissues. In this perspective, we will review recent progress in ultrasound-mediated tumor delivery and the opportunities for clinical translation.

  11. Solid pseudopapillary tumors of the pancreas: 27 cases from a single institution

    Directory of Open Access Journals (Sweden)

    ZHOU Haiyang

    2013-01-01

    Full Text Available ObjectiveTo summarize the clinicopathologic features and treatment outcomes of solid pseudopapillary tumors (SPTs of the pancreas. MethodsTwenty-seven cases of SPT of the pancreas admitted for treatment to the Peking University Cancer Hospital between September 2008 and September 2012 were retrospectively analyzed. ResultsThe majority of the pancreatic SPT patients were young adults (median age: 29 years old and females (85.2%. All 27 patients were treated with surgical resection using pancreaticoduodenectomy (n=4, duodenum preserving pancreatic tumor resection (n=6, middle pancreatectomy (n=5, distal pancreatectomy (n=5, or distal pancreatectomy plus splenectomy (n=7. The minimum tumor diameter was 1.5 cm, the maximum diameter was 12.0 cm, and the average diameter was 5.4 cm. Twelve patients developed pancreatic leakage and pyrexia following the operation. One patient suffered splenic artery hemorrhage. All 27 patients survived and completed follow-up. Only one patient developed recurrence, which was treated by a second surgical resection, and all other patients showed no clinical signs of recurrence or metastasis. ConclusionSPT of the pancreas has uncertain malignant potential with good prognosis. Radical resection with preservation of the surrounding tissues is an effective and safe treatment for SPT.

  12. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors.

    Science.gov (United States)

    Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Sheehan, Christine E; Vallabhajosula, Shankar; Goldsmith, Stanley J; Ross, Jeffrey S; Bander, Neil H

    2007-02-10

    Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response. Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received 111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of 111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues. Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by 111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment. Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.

  13. Factors associated with abandonment of therapy by children diagnosed with solid tumors in Peru.

    Science.gov (United States)

    Vasquez, Liliana; Diaz, Rosdali; Chavez, Sharon; Tarrillo, Fanny; Maza, Ivan; Hernandez, Eddy; Oscanoa, Monica; García, Juan; Geronimo, Jenny; Rossell, Nuria

    2018-06-01

    Abandonment of treatment is a major cause of treatment failure and poor survival in children with cancer in low- and middle-income countries. The incidence of treatment abandonment in Peru has not been reported. The aim of this study was to examine the prevalence of and factors associated with treatment abandonment by pediatric patients with solid tumors in Peru. We retrospectively reviewed the sociodemographic and clinical data of children referred between January 2012 and December 2014 to the two main tertiary centers for childhood cancer in Peru. The definition of treatment abandonment followed the International Society of Paediatric Oncology, Paediatric Oncology in Developing Countries, Abandonment of Treatment recommendation. Data from 1135 children diagnosed with malignant solid tumors were analyzed, of which 209 (18.4%) abandoned treatment. Bivariate logistic regression analysis showed significantly higher abandonment rates in children living outside the capital city, Lima (forest; odds ratio [OR] 3.25; P < 0.001), those living in a rural setting (OR 3.44; P < 0.001), and those whose parent(s) lacked formal employment (OR 4.39; P = 0.001). According to cancer diagnosis, children with retinoblastoma were more likely to abandon treatment compared to children with other solid tumors (OR 1.79; P = 0.02). In multivariate regression analyses, rural origin (OR 2.02; P = 0.001) and lack of formal parental employment (OR 2.88; P = 0.001) were independently predictive of abandonment. Treatment abandonment prevalence of solid tumors in Peru is high and closely related to sociodemographical factors. Treatment outcomes could be substantially improved by strategies that help prevent abandonment of therapy based on these results. © 2018 Wiley Periodicals, Inc.

  14. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor.

    Science.gov (United States)

    Boissonnas, Alexandre; Fetler, Luc; Zeelenberg, Ingrid S; Hugues, Stéphanie; Amigorena, Sebastian

    2007-02-19

    Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8(+) cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration.

  15. Antibody-Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review.

    Science.gov (United States)

    Lambert, John M; Morris, Charles Q

    2017-05-01

    Attaching a cytotoxic "payload" to an antibody to form an antibody-drug conjugate (ADC) provides a mechanism for selective delivery of the cytotoxic agent to cancer cells via the specific binding of the antibody to cancer-selective cell surface molecules. The first ADC to receive marketing authorization was gemtuzumab ozogamicin, which comprises an anti-CD33 antibody conjugated to a highly potent DNA-targeting antibiotic, calicheamicin, approved in 2000 for treating acute myeloid leukemia. It was withdrawn from the US market in 2010 following an unsuccessful confirmatory trial. The development of two classes of highly potent microtubule-disrupting agents, maytansinoids and auristatins, as payloads for ADCs resulted in approval of brentuximab vedotin in 2011 for treating Hodgkin lymphoma and anaplastic large cell lymphoma, and approval of ado-trastuzumab emtansine in 2013 for treating HER2-positive breast cancer. Their success stimulated much research into the ADC approach, with >60 ADCs currently in clinical evaluation, mostly targeting solid tumors. Five ADCs have advanced into pivotal clinical trials for treating various solid tumors-platinum-resistant ovarian cancer, mesothelioma, triple-negative breast cancer, glioblastoma, and small cell lung cancer. The level of target expression is a key parameter in predicting the likelihood of patient benefit for all these ADCs, as well as for the approved compound, ado-trastuzumab emtansine. The development of a patient selection strategy linked to target expression on the tumor is thus critically important for identifying the population appropriate for receiving treatment.

  16. Drug delivery to solid tumors: the predictive value of the multicellular tumor spheroid model for nanomedicine screening

    Directory of Open Access Journals (Sweden)

    Millard M

    2017-10-01

    Full Text Available Marie Millard,1,2 Ilya Yakavets,1–3 Vladimir Zorin,3,4 Aigul Kulmukhamedova,1,2,5 Sophie Marchal,1,2 Lina Bezdetnaya1,2 1Centre de Recherche en Automatique de Nancy, Centre National de la Recherche Scientifique UMR 7039, Université de Lorraine, 2Research Department, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France; 3Laboratory of Biophysics and Biotechnology, 4International Sakharov Environmental Institute, Belarusian State University, Minsk, Belarus; 5Department of Radiology, Medical Company Sunkar, Almaty, Kazakhstan Abstract: The increasing number of publications on the subject shows that nanomedicine is an attractive field for investigations aiming to considerably improve anticancer chemotherapy. Based on selective tumor targeting while sparing healthy tissue, carrier-mediated drug delivery has been expected to provide significant benefits to patients. However, despite reduced systemic toxicity, most nanodrugs approved for clinical use have been less effective than previously anticipated. The gap between experimental results and clinical outcomes demonstrates the necessity to perform comprehensive drug screening by using powerful preclinical models. In this context, in vitro three-dimensional models can provide key information on drug behavior inside the tumor tissue. The multicellular tumor spheroid (MCTS model closely mimics a small avascular tumor with the presence of proliferative cells surrounding quiescent cells and a necrotic core. Oxygen, pH and nutrient gradients are similar to those of solid tumor. Furthermore, extracellular matrix (ECM components and stromal cells can be embedded in the most sophisticated spheroid design. All these elements together with the physicochemical properties of nanoparticles (NPs play a key role in drug transport, and therefore, the MCTS model is appropriate to assess the ability of NP to penetrate the tumor tissue. This review presents recent developments in MCTS models for a

  17. Targeting the PD-1 pathway in pediatric solid tumors and brain tumors

    Directory of Open Access Journals (Sweden)

    Wagner LM

    2017-04-01

    Full Text Available Lars M Wagner,1 Val R Adams2 1Division of Pediatric Hematology/Oncology, 2Department of Pharmacy Practice and Science, University of Kentucky, Lexington, KY, USA Abstract: While remarkable advances have been made in the treatment of pediatric leukemia over the past decades, new therapies are needed for children with advanced solid tumors and high-grade brain tumors who fail standard chemotherapy regimens. Immunotherapy with immune checkpoint inhibitors acting through the programmed cell death-1 (PD-1 pathway has shown efficacy in some chemotherapy-resistant adult cancers, generating interest that these agents may also be helpful to treat certain refractory pediatric malignancies. In this manuscript we review current strategies for targeting the PD-1 pathway, highlighting putative biomarkers and the rationale for investigation of these drugs to treat common pediatric tumors such as sarcoma, neuroblastoma, and high-grade glioma. We summarize the completed and ongoing clinical trial data available, and suggest potential applications for further study. Keywords: PD-1, nivolumab, pembrolizumab, pediatric, sarcoma, neuroblastoma, glioma

  18. Using a 3-d model system to screen for drugs effective on solid tumors

    OpenAIRE

    Fayad, Walid

    2011-01-01

    There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

  19. Echinococcus cysticus of the liver - sonographic pattern suggestive of solid tumor

    Energy Technology Data Exchange (ETDEWEB)

    Grosser, G.; Hauenstein, K.H.; Henke, W.

    1985-09-01

    In a patient with Hodgkin's disease, an intrahepatic echodense mass was diagnosed incidentally by ultrasonography. The sonographic pattern suggested a solid tumor. Despite negative or borderline serology, computed tomography establised the diagnosis of echinococcus cysticus by documentation of one ''daughter'' cyst; this diagnosis was confirmed by surgery. The criteria of echinococcus cysticus in modern imaging methods like sonography and computed tomography are summarized and the diagnostic value of various procedures including diagnostic procedure in seronegative cases are discussed.

  20. Tumor size and prognosis in patients with Wilms tumor

    Directory of Open Access Journals (Sweden)

    Valentina Oliveira Provenzi

    2015-03-01

    Full Text Available OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ and before preoperative chemotherapy (TVBPQ with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015 and histologic types of risk (p=0.008. It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037. When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013, i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable.

  1. Tenascin-W is a better cancer biomarker than tenascin-C for most human solid tumors

    Directory of Open Access Journals (Sweden)

    Brellier Florence

    2012-09-01

    Full Text Available Abstract Background Tenascins are large glycoproteins found in the extracellular matrix of many embryonic and adult tissues. Tenascin-C is a well-studied biomarker known for its high overexpression in the stroma of most solid cancers. Tenascin-W, the least studied member of the family, is highly expressed in the stroma of colon and breast tumors and in gliomas, but not in the corresponding normal tissues. Other solid tumors have not been analyzed. The present study was undertaken to determine whether tenascin-W could serve as a cancer-specific extracellular matrix protein in a broad range of solid tumors. Methods We analyzed the expression of tenascin-W and tenascin-C by immunoblotting and by immunohistochemistry on multiple frozen tissue microarrays of carcinomas of the pancreas, kidney and lung as well as melanomas and compared them to healthy tissues. Results From all healthy adult organs tested, only liver and spleen showed detectable levels of tenascin-W, suggesting that tenascin-W is absent from most human adult organs under normal, non-pathological conditions. In contrast, tenascin-W was detectable in the majority of melanomas and their metastases, as well as in pancreas, kidney, and lung carcinomas. Comparing lung tumor samples and matching control tissues for each patient revealed a clear overexpression of tenascin-W in tumor tissues. Although the number of samples examined is too small to draw statistically significant conclusions, there seems to be a tendency for increased tenascin-W expression in higher grade tumors. Interestingly, in most tumor types, tenascin-W is also expressed in close proximity to blood vessels, as shown by CD31 co-staining of the samples. Conclusions The present study extends the tumor biomarker potential of tenascin-W to a broad range of solid tumors and shows its accessibility from the blood stream for potential therapeutic strategies.

  2. BRAF mutation testing in solid tumors: a methodological comparison.

    Science.gov (United States)

    Weyant, Grace W; Wisotzkey, Jeffrey D; Benko, Floyd A; Donaldson, Keri J

    2014-09-01

    Solid tumor genotyping has become standard of care for the characterization of proto-oncogene mutational status, which has traditionally been accomplished with Sanger sequencing. However, companion diagnostic assays and comparable laboratory-developed tests are becoming increasingly popular, such as the cobas 4800 BRAF V600 Mutation Test and the INFINITI KRAS-BRAF assay, respectively. This study evaluates and validates the analytical performance of the INFINITI KRAS-BRAF assay and compares concordance of BRAF status with two reference assays, the cobas test and Sanger sequencing. DNA extraction from FFPE tissue specimens was performed followed by multiplex PCR amplification and fluorescent label incorporation using allele-specific primer extension. Hybridization to a microarray, signal detection, and analysis were then performed. The limits of detection were determined by testing dilutions of mutant BRAF alleles within wild-type background DNA, and accuracy was calculated based on these results. The INFINITI KRAS-BRAF assay produced 100% concordance with the cobas test and Sanger sequencing and had sensitivity equivalent to the cobas assay. The INFINITI assay is repeatable with at least 95% accuracy in the detection of mutant and wild-type BRAF alleles. These results confirm that the INFINITI KRAS-BRAF assay is comparable to traditional sequencing and the Food and Drug Administration-approved companion diagnostic assay for the detection of BRAF mutations. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  3. Phenylalanine-coupled solid lipid nanoparticles for brain tumor targeting

    Energy Technology Data Exchange (ETDEWEB)

    Kharya, Parul; Jain, Ashish; Gulbake, Arvind; Shilpi, Satish; Jain, Ankit; Hurkat, Pooja [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India); Majumdar, Subrata [Bose Institute, Division of Molecular Medicine (India); Jain, Sanjay K., E-mail: drskjainin@yahoo.com [Dr. Hari Singh Gour University, Pharmaceutical Research Projects Laboratory, Department of Pharmaceutical Sciences (India)

    2013-11-15

    The purpose of this study is to investigate the targeting potential of amino acid (phenylalanine)-coupled solid lipid nanoparticles (SLN) loaded with ionically complexed doxorubicin HCl (Dox). Ionic complexation was used to enhance the loading efficiency and release characteristics of water soluble form of Dox. l-Type amino acid transporters (LAT1) are highly expressed on blood brain barrier as well as on many brain cancer cells, thus targeting LAT1 using phenylalanine improved anticancer activity of prepared nanocarrier. The phenylalanine-coupled SLN were characterized by fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, particle size, zeta potential, entrapment efficiency and in vitro release. The particle size of the resulting SLN was found to be in the range of 163.3 ± 5.2 to 113.0 ± 2.6 nm, with a slightly negative surface charge. In ex vivo study on C6 glioma cell lines, the cellular cytotoxicity of the SLN was highly increased when coupled with phenylalanine. In addition, stealthing sheath of PEG present on the surface of the SLN enhanced the cellular uptake of the SLN on C6 glioma cell line. Results of biodistribution and fluorescence studies clearly revealed that phenylalanine-coupled SLN could deliver high amount of drug into the brain tumor cells and showed the brain-targeting potential.

  4. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

    2015-01-01

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10 −9 ), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10 −3 ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection

  5. Somatic Genetic Variation in Solid Pseudopapillary Tumor of the Pancreas by Whole Exome Sequencing

    Directory of Open Access Journals (Sweden)

    Meng Guo

    2017-01-01

    Full Text Available Solid pseudopapillary tumor of the pancreas (SPT is a rare pancreatic disease with a unique clinical manifestation. Although CTNNB1 gene mutations had been universally reported, genetic variation profiles of SPT are largely unidentified. We conducted whole exome sequencing in nine SPT patients to probe the SPT-specific insertions and deletions (indels and single nucleotide polymorphisms (SNPs. In total, 54 SNPs and 41 indels of prominent variations were demonstrated through parallel exome sequencing. We detected that CTNNB1 mutations presented throughout all patients studied (100%, and a higher count of SNPs was particularly detected in patients with older age, larger tumor, and metastatic disease. By aggregating 95 detected variation events and viewing the interconnections among each of the genes with variations, CTNNB1 was identified as the core portion in the network, which might collaborate with other events such as variations of USP9X, EP400, HTT, MED12, and PKD1 to regulate tumorigenesis. Pathway analysis showed that the events involved in other cancers had the potential to influence the progression of the SNPs count. Our study revealed an insight into the variation of the gene encoding region underlying solid-pseudopapillary neoplasm tumorigenesis. The detection of these variations might partly reflect the potential molecular mechanism.

  6. Pneumothorax as a complication of combination antiangiogenic therapy in children and young adults with refractory/recurrent solid tumors.

    Science.gov (United States)

    Interiano, Rodrigo B; McCarville, M Beth; Wu, Jianrong; Davidoff, Andrew M; Sandoval, John; Navid, Fariba

    2015-09-01

    Antiangiogenic agents show significant antitumor activity against various tumor types. In a study evaluating the combination of sorafenib, bevacizumab, and low-dose cyclophosphamide in children with solid tumors, an unexpectedly high incidence of pneumothorax was observed. We evaluated patient characteristics and risk factors for the development of pneumothorax in patients receiving this therapy. Demographics, clinical course, and radiographic data of 44 patients treated with sorafenib, bevacizumab and cyclophosphamide were reviewed. Risk factors associated with the development of pneumothorax were analyzed. Pneumothorax likely related to study therapy developed in 11 of 44 (25%) patients of whom 33 had pulmonary abnormalities. Median age of patients was 14.7 years (range, 1.08-24.5). Histologies associated with pneumothorax included rhabdoid tumor, synovial sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and renal cell carcinoma. Cavitation of pulmonary nodules in response to therapy was associated with pneumothorax development (Ppneumothorax was 5.7 weeks (range, 2.4-31). The development of cavitary pulmonary nodules in response to therapy is a risk factor for pneumothorax. As pneumothorax is a potentially life-threatening complication of antiangiogenic therapy in children with solid tumors, its risk needs to be evaluated when considering this therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Anemia, tumor hypoxemia, and the cancer patient

    International Nuclear Information System (INIS)

    Varlotto, John; Stevenson, Mary Ann

    2005-01-01

    Purpose: To review the impact of anemia/tumor hypoxemia on the quality of life and survival in cancer patients, and to assess the problems associated with the correction of this difficulty. Methods: MEDLINE searches were performed to find relevant literature regarding anemia and/or tumor hypoxia in cancer patients. Articles were evaluated in order to assess the epidemiology, adverse patient effects, anemia correction guidelines, and mechanisms of hypoxia-induced cancer cell growth and/or therapeutic resistance. Past and current clinical studies of radiosensitization via tumor oxygenation/hypoxic cell sensitization were reviewed. All clinical studies using multi-variate analysis were analyzed to show whether or not anemia and/or tumor hypoxemia affected tumor control and patient survival. Articles dealing with the correction of anemia via transfusion and/or erythropoietin were reviewed in order to show the impact of the rectification on the quality of life and survival of cancer patients. Results: Approximately 40-64% of patients presenting for cancer therapy are anemic. The rate of anemia rises with the use of chemotherapy, radiotherapy, and hormonal therapy for prostate cancer. Anemia is associated with reductions both in quality of life and survival. Tumor hypoxemia has been hypothesized to lead to tumor growth and resistance to therapy because it leads to angiogenesis, genetic mutations, resistance to apoptosis, and a resistance to free radicals from chemotherapy and radiotherapy. Nineteen clinical studies of anemia and eight clinical studies of tumor hypoxemia were found that used multi-variate analysis to determine the effect of these conditions on the local control and/or survival of cancer patients. Despite differing definitions of anemia and hypoxemia, all studies have shown a correlation between low hemoglobin levels and/or higher amounts of tumor hypoxia with poorer prognosis. Radiosensitization through improvements in tumor oxygenation/hypoxic cell

  8. CAR-T cells: the long and winding road to solid tumors.

    Science.gov (United States)

    D'Aloia, Maria Michela; Zizzari, Ilaria Grazia; Sacchetti, Benedetto; Pierelli, Luca; Alimandi, Maurizio

    2018-02-15

    Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles.

  9. Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor

    International Nuclear Information System (INIS)

    Monzen, Hajime; Griffin, R.J.; Williams, B.W.; Amamo, Morikazu; Ando, Satoshi; Hasegawa, Takeo

    2004-01-01

    Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy. We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging (MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H and E) staining. Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an intraperitoneal (i.p.) injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days. The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor. (author)

  10. CBT-501 Study for Select Advanced or Relapsed/Recurrent Solid Tumors

    Science.gov (United States)

    2018-02-07

    Solid Tumor; Advanced Cancer; ColoRectal Cancer; Endometrial Cancer; Gastric Cancer; Hepatocellular Cancer; Nonsmall Cell Lung Cancer; Mesothelioma; Ovarian Cancer; Renal Cancer; Nasopharyngeal Cancer; Esophageal Cancer; Gastroesophageal Junction Adenocarcinoma

  11. Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

    Science.gov (United States)

    Riaz, Muhammad Kashif; Riaz, Muhammad Adil; Zhang, Xue; Lin, Congcong; Wong, Ka Hong; Chen, Xiaoyu; Lu, Aiping

    2018-01-01

    Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed. PMID:29315231

  12. Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review

    Directory of Open Access Journals (Sweden)

    Muhammad Kashif Riaz

    2018-01-01

    Full Text Available Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.

  13. Nutritional status changes in children with malignant solid tumor before and after chemotherapy

    OpenAIRE

    Boris Januar; Sri S Nasar; Rulina Suradi; Maria Abdulsalam

    2016-01-01

    Background Although aggressive multimodal treatment programs in childhood cancer have significantly increased survival rates, the morbidity caused by protein energy malnutrition related to therapy is still high. Objective To describe nutritional status changes in children with malignant solid tumors after 21 days of chemotherapy. Methods A descriptive prospective study with pre- and post-test design in children with malignant solid tumors was conducted in the Departmen...

  14. Angiogenesis and anti-angiogenesis: Perspectives for the treatment of solid tumors

    NARCIS (Netherlands)

    Hinsbergh, V.W.M. van; Collen, A.; Koolwijk, P.

    1999-01-01

    Angiogenesis is the formation of new blood vessels from preexisting ones. Many solid tumors depend on an extensive newly formed vascular network to become nourished and to expand. Tumor cells induce the formation of an extensive but aberrant vascular network by the secretion of angiogenic factors. A

  15. Approaches to drug resistance in solid tumors : with emphasis on lung cancer

    NARCIS (Netherlands)

    Bakker, Marleen

    2005-01-01

    De novo or acquired resistance of tumor cells to anticancer agents remains a major problem for the therapeutic efficacy of chemotherapeutic drugs. Most solid tumors are intrinsically insensitive or acquire resistance after initial response to chemotherapy. Different mechanisms seem to play a role in

  16. Utility of {sup 18}F-fluoroestradiol ({sup 18}F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Frank I. [National Cancer Institute, NIH, Cancer Imaging Program, Bethesda, MD (United States); National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Gonzalez, E.M.; Kurdziel, K.A.; Ton, A.; Turkbey, B.; Choyke, P.L.; Lindenberg, M.L. [National Cancer Institute, Molecular Imaging Program, Bethesda, MD (United States); Kummar, S.; Do, K.; Collins, J.M.; Doroshow, J.H. [National Cancer Institute, Division of Cancer Treatment and Diagnosis and Center for Cancer Research, Bethesda, MD (United States); Shih, J. [National Cancer Institute, NIH, Biometric Research Program, Bethesda, MD (United States); Adler, S. [Leidos Biomedical Research, Inc., Clinical Research Directorate/Clinical Monitoring Research Program, Frederick, MD (United States); Jacobs, P.M. [National Cancer Institute, NIH, Cancer Imaging Program, Bethesda, MD (United States); Bhattacharyya, S. [Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States); Chen, A.P. [National Cancer Institute, Early Clinical Trials Development Program, DCTD, Bethesda, MD (United States)

    2017-03-15

    Z-endoxifen is the most potent of the metabolites of tamoxifen, and has the potential to be more effective than tamoxifen because it bypasses potential drug resistance mechanisms attributable to patient variability in the expression of the hepatic microsomal enzyme CYP2D6. {sup 18}F-FES is a positron emission tomography (PET) imaging agent which selectively binds to estrogen receptor alpha (ER-α) and has been used for non-invasive in vivo assessment of ER activity in tumors. This study utilizes {sup 18}F-FES PET imaging as a pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen. Fifteen patients were recruited from a parent therapeutic trial of Z-endoxifen and underwent imaging with {sup 18}F-FES PET at baseline. Eight had positive lesions on the baseline scan and underwent follow-up imaging with {sup 18}F-FES 1-5 days post administration of Z-endoxifen. Statistically significant changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the baseline and follow-up scans as early as 1 day post drug administration. F-FES PET imaging could serve as a pharmacodynamic biomarker for patients treated with ER-directed therapy. (orig.)

  17. Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

    Science.gov (United States)

    Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

    2015-10-13

    Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

  18. Diagnosis and treatment of solid pseudopapillary tumor of the pancreas: experience of one single institution from Turkey

    Science.gov (United States)

    2013-01-01

    Background Solid pseudopapillary neoplasia (SPN) of the pancreas is an extremely rare epithelial tumor of low malignant potential. SPN accounts for less than 1% to 2% of exocrine pancreatic tumors. The aim of this study is to report our experience with SPN of the pancreas. It includes a summary of the current literature to provide a reference for the management of this rare clinical entity. Methods A retrospective analysis was performed of all patients diagnosed and treated for SPN in our hospital over the past 15 years (1998 to 2013). A database of the characteristics of these patients was developed, including age, gender, tumor location and size, treatment, and histopathological and immunohistochemical features. Results During this time period, 255 patients with pancreatic malignancy (which does not include ampulla vateri, distal choledocal and duodenal tumor) were admitted to our department, only 10 of whom were diagnosed as having SPN (2.5%). Nine patients were women (90%) and one patient was a man (10%). Their median age was 38.8 years (range 18 to 71). The most common symptoms were abdominal pain and dullness. Seven patients (70%) presented with abdominal pain or abdominal dullness and three patient (30%) were asymptomatic with the diagnosis made by an incidental finding on routine examination. Abdominal computed tomography and/or magnetic resonance imaging showed the typical features of solid pseudopapillary neoplasm in six (60%) of the patients. Four patients underwent distal pancreatectomy with splenectomy, one patient underwent a total mass excision, and one patient underwent total pancreatic resection. Two required extended distal pancreatectomy with splenectomy. Two underwent spleen-preserving distal pancreatectomy. Conclusions SPN is a rare neoplasm that primarily affects young women. The prognosis is favorable even in the presence of distant metastasis. Although surgical resection is generally curative, a close follow-up is advised in order to

  19. Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

    Science.gov (United States)

    Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

    2018-05-01

    The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions. © AlphaMed Press 2018.

  20. Pattern of malignant solid tumors and lymphomas in children in the east delta of Egypt: A five-year study.

    Science.gov (United States)

    Hesham, Mervat; Atfy, Mervat; Hassan, Tamer; Abdo, Mohamed; Morsy, Saed; El Malky, Mohamed; Latif, Dalia Abdel

    2014-11-01

    Worldwide, the incidence and mortality rates of childhood cancers differ. The study of incidence patterns and survival rates in childhood malignancies is important in aiding in the planning of treatment centers and in obtaining further information with regard to the etiology. Few studies have investigated the survival in cases of childhood solid tumors in Egypt. The aim of the current study was to evaluate the patterns, frequency and outcome of solid tumors and lymphomas in children admitted to and followed up at the Pediatric Oncology Department of Zagazig University Hospital (Zagazig, Egypt) over a duration of 5 years (January 2004 to December 2008). A retrospective study was conducted, which included 155 children with solid tumors and lymphomas. The medical records were reviewed and the relevant data collected, in particular, those concerning demographic, clinical, histopathological, laboratory and imaging data as well as the treatment plans and outcomes. The mean age of patients was 5.6±3.04 years at diagnosis. The patients comprised 94 males and 61 females. Non-Hodgkin lymphoma (NHL) was the most common tumor type, followed by neuroblastoma (31.0 and 29.0%, respectively). When patients were stratified in terms of age (<5, ≥5 but <10, and ≥10 years), the <5-years-of-age group exhibited the greatest number of patients. Fever, pallor and pain were the most frequent initial clinical presentations among the patients and stage II was the most common stage (39.1%) followed by stage IV, III and I (35.0, 20.3 and 5.6% respectively). The overall 5-year survival rate in the study group was 66.7%. The survival rate was significantly higher in patients with Wilm's tumor and Hodgkin lymphoma, followed by NHL (92.0, 88.0 and 72.0%, respectively; P<0.001), while the mortality rate was significantly higher in patients with neuroblastoma (P<0.001). In conclusion, NHL and neuroblastoma were the most common tumors; the survival rates were higher in patients with Wilm's tumor

  1. Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities.

    Science.gov (United States)

    Xia, An-Liang; Wang, Xiao-Chen; Lu, Yi-Jun; Lu, Xiao-Jie; Sun, Beicheng

    2017-10-27

    Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have been shown to have unprecedented efficacy in B cell malignancies, most notably in B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate using anti-CD19 CAR-T cells. However, CAR T-cell therapy for solid tumors currently is faced with numerous challenges such as physical barriers, the immunosuppressive tumor microenvironment and the specificity and safety. The clinical results in solid tumors have been much less encouraging, with multiple cases of toxicity and a lack of therapeutic response. In this review, we will discuss the current stats and challenges of CAR-T cell therapy for solid tumors, and propose possibl e solutions and future perspectives.

  2. Challenges and prospects of chimeric antigen receptor T cell therapy in solid tumors.

    Science.gov (United States)

    Jindal, Vishal; Arora, Ena; Gupta, Sorab

    2018-05-05

    Chimeric antigen receptor (CAR) T cell therapy is a novel and innovative immunotherapy. CAR-T cells are genetically engineered T cells, carrying MHC independent specific antigen receptor and co-stimulatory molecule which can activate an immune response to a cancer specific antigen. This therapy showed great results in hematological malignancies but were unable to prove their worth in solid tumors. Likely reasons for their failure are lack of antigens, poor trafficking, and hostile tumor microenvironment. Excessive amount of research is going on to improve the efficacy of CAR T cell therapy in solid tumors. In this article, we will discuss the challenges faced in improving the outcome of CAR T cell therapy in solid tumors and various strategies adopted to curb them.

  3. New Strategies for the Treatment of Solid Tumors with CAR-T Cells.

    Science.gov (United States)

    Zhang, Hao; Ye, Zhen-Long; Yuan, Zhen-Gang; Luo, Zheng-Qiang; Jin, Hua-Jun; Qian, Qi-Jun

    2016-01-01

    Recent years, we have witnessed significant progresses in both basic and clinical studies regarding novel therapeutic strategies with genetically engineered T cells. Modification with chimeric antigen receptors (CARs) endows T cells with tumor specific cytotoxicity and thus induce anti-tumor immunity against malignancies. However, targeting solid tumors is more challenging than targeting B-cell malignancies with CAR-T cells because of the histopathological structure features, specific antigens shortage and strong immunosuppressive environment of solid tumors. Meanwhile, the on-target/off-tumor toxicity caused by relative expression of target on normal tissues is another issue that should be reckoned. Optimization of the design of CAR vectors, exploration of new targets, addition of safe switches and combination with other treatments bring new vitality to the CAR-T cell based immunotherapy against solid tumors. In this review, we focus on the major obstacles limiting the application of CAR-T cell therapy toward solid tumors and summarize the measures to refine this new cancer therapeutic modality.

  4. Cytogenetics of solid tumors Revisión de tema Citogenética de tumores sólidos

    Directory of Open Access Journals (Sweden)

    José Luis Ramírez Castro

    2002-02-01

    Full Text Available Cytogenetic analysis of tumors has provided valuable information on the biology of cancer. It has been established that more than half of solid tumors show chromosomal anomalies; therefore, cytogenetic analysis is of great usefulness for diagnostic and prognostic purposes. Identification of recurrent chromosomal anomalies in numerous tumors has been considered as an indicador of clinical importance. Cytogenetic studies in tissue tumors have revealed near 100,000 clonal chromosome abnormalities belonging to more that 30,000 human neoplasms. However, due to technical difficulties in cell cultures, only one third of solid tumors have been cytogenetically characterized. Conventional cytogenetics has been very useful for molecular characterization of new oncogenes and tumor-suppressor genes involved in human tumorigenesis. In this review, some important issues related with tumors of chromosomal etiology, the diverse types of chromosomal anomalies with their frequencies, modern diagnostic techniques as well as their impact on the diagnosis and prognosis of cancer are presented. EL análisis citogenético de tumores ha proporcionado valiosa información sobre la biología del cáncer. Se ha establecido que más de la mitad de los tumores sólidos presentan alteraciones cromosómicas; por lo tanto, el análisis citogenético es de gran utilidad para el diagnóstico y el pronóstico. La identificación de cambios cromosómicos específicos recurrentes en numerosos tumores se considera un indicador de importancia clínica. Los estudios en este campo han revelado cerca de 100.000 alteraciones cromosómicas en más de 30.000 neoplasias humanas. Sin embargo, los tumores sólidos son los menos caracterizados citogenéticamente, sólo una tercera parte del total de ellos, debido a problemas técnicos en los cultivos celulares. La citogenética convencional ha sido muy útil para la posterior caracterización molecular de nuevos oncogenes y genes supresores de

  5. Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    A. Silvani

    2013-01-01

    Full Text Available Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC and liposomal antitumor agents (liposomal AraC. Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

  6. Uptake of labelled tallysomycin by solid Ehrlich ascites tumors in mice

    International Nuclear Information System (INIS)

    Liniecki, J.; Rembelska, M.; Koniarek, B.

    1983-01-01

    Tumor and normal tissue uptake of 51 Cr- or 57 Co-labelled bleomycin (BLEO) and tallysomycin (TLM) was compared in female solid Ehrlich ascites tumor mice of Swiss strain. The complexes were administered intraperitoneally: 30-50 μg of each complex with an activity of 40-120 μCi. Activity distribution factors (ADF) and tumor/non-tumor ratios for blood, bone, skeletal muscles, kidneys and liver were determined. The ratios were generally higher for complexes labelled with 57 Co than for the 51 Cr-labelled ones; bleomycin appears equivalent or superior to tallysomycin. (orig.) [de

  7. BRAFV600 mutations in solid tumors, other than metastatic melanoma and papillary thyroid cancer, or multiple myeloma: a screening study

    Directory of Open Access Journals (Sweden)

    Cohn AL

    2017-02-01

    Full Text Available Allen L Cohn,1 Bann-Mo Day,2 Sarang Abhyankar,3 Edward McKenna,2 Todd Riehl,4 Igor Puzanov5 1Medical Research, Rocky Mountain Cancer Centers, Denver, CO, 2US Medical Affairs, 3Global Safety and Risk Management, 4Product Development Oncology, Genentech, Inc., South San Francisco, CA, 5Melanoma Section, Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Background: Mutations in the BRAF gene have been implicated in several human cancers. The objective of this screening study was to identify patients with solid tumors (other than metastatic melanoma or papillary thyroid cancer or multiple myeloma harboring activating BRAFV600 mutations for enrollment in a vemurafenib clinical study.Methods: Formalin-fixed, paraffin-embedded tumor samples were collected and sent to a central laboratory to identify activating BRAFV600 mutations by bidirectional direct Sanger sequencing.Results: Overall incidence of BRAFV600E mutation in evaluable patients (n=548 was 3% (95% confidence interval [CI], 1.7–4.7: 11% in colorectal tumors (n=75, 6% in biliary tract tumors (n=16, 3% in non-small cell lung cancers (n=71, 2% in other types of solid tumors (n=180, and 3% in multiple myeloma (n=31. There were no BRAFV600 mutations in this cohort of patients with ovarian tumors (n=68, breast cancer (n=86, or prostate cancer (n=21.Conclusion: This multicenter, national screening study confirms previously reported incidences of BRAFV600 mutations from single-center studies. Patients identified with BRAFV600 mutations were potentially eligible for enrollment in the VE-BASKET study. Keywords: genetic testing, proto-oncogene proteins B-raf, PLX4032

  8. Impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. Introduction of a multiinstitutional research project

    International Nuclear Information System (INIS)

    Zips, D.; Petersen, C.; Adam, M.; Molls, M.; Philbrook, C.; Flentje, M.; Haase, A.; Schmitt, P.; Mueller-Klieser, W.; Thews, O.; Walenta, S.; Baumann, M.

    2004-01-01

    Background: recent developments in imaging technology and tumor biology have led to new techniques to detect hypoxia and related alterations of the metabolic microenvironment in tumors. However, whether these new methods can predict radiobiological hypoxia and outcome after fractionated radiotherapy still awaits experimental evaluation. Material and methods: the present article will introduce a multiinstitutional research project addressing the impact of hypoxia and the metabolic microenvironment on radiotherapy of solid tumors. The four laboratories involved are situated at the universities of Dresden, Mainz, Munich and Wuerzburg, Germany. Results: the joint scientific project started to collect data obtained on a set of ten different human tumor xenografts growing in nude mice by applying various imaging techniques to detect tumor hypoxia and related parameters of the metabolic microenvironment. These techniques include magnetic resonance imaging and spectroscopy, metabolic mapping with quantitative bioluminescence and single-photon imaging, histological multiparameter analysis of biochemical hypoxia, perfusion and vasculature, and immunohistochemistry of factors related to angiogenesis, invasion and metastasis. To evaluate the different methods, baseline functional radiobiological data including radiobiological hypoxic fraction and outcome after fractionated irradiation will be determined. Conclusion: besides increasing our understanding of tumor biology, the project will focus on new, clinically applicable strategies for microenvironment profiling and will help to identify those patients that might benefit from targeted interventions to improve tumor oxygenation. (orig.)

  9. Nanobody-based cancer therapy of solid tumors

    NARCIS (Netherlands)

    Kijanka, Marta|info:eu-repo/dai/nl/328212792; Dorresteijn, Bram|info:eu-repo/dai/nl/31401635X; Oliveira, Sabrina; van Bergen en Henegouwen, Paul M P|info:eu-repo/dai/nl/071919481

    The development of tumor-targeted therapies using monoclonal antibodies has been successful during the last 30 years. Nevertheless, the efficacy of antibody-based therapy is still limited and further improvements are eagerly awaited. One of the promising novel developments that may overcome the

  10. Bacteria-mediated in vivo delivery of quantum dots into solid tumor

    International Nuclear Information System (INIS)

    Liu, Ying; Zhou, Mei; Luo, Dan; Wang, Lijun; Hong, Yuankai; Yang, Yepeng; Sha, Yinlin

    2012-01-01

    Highlights: ► New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. ► Bifidobacterium bifidum delivery system has intrinsic biocompatibility. ► The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

  11. Bacteria-mediated in vivo delivery of quantum dots into solid tumor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ying [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Zhou, Mei [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Luo, Dan; Wang, Lijun; Hong, Yuankai [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Yang, Yepeng, E-mail: yangyepeng@bjmu.edu.cn [Dept. of Radiation Medicine, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Sha, Yinlin, E-mail: shyl@hsc.pku.edu.cn [Single-molecule and Nanobiology Lab., Dept. of Biophysics, School of Basic Medical Sciences, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China); Biomed-X Center, Peking University, Peking University, No. 38 Xue Yuan Road, Beijing 100091 (China)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer New approach using the probiotic Bifidobacterium bifidum as a vehicle to deliver QDs into the deep tissue of solid tumors in vivo was achieved. Black-Right-Pointing-Pointer Bifidobacterium bifidum delivery system has intrinsic biocompatibility. Black-Right-Pointing-Pointer The targeting efficacy was improved by folic acids. -- Abstract: Semiconductor nanocrystals, so-called quantum dots (QDs), promise potential application in bioimaging and diagnosis in vitro and in vivo owing to their high-quality photoluminescence and excellent photostability as well as size-tunable spectra. Here, we describe a biocompatible, comparatively safe bacteria-based system that can deliver QDs specifically into solid tumor of living animals. In our strategy, anaerobic bacterium Bifidobacterium bifidum (B. bifidum) that colonizes selectively in hypoxic regions of animal body was successfully used as a vehicle to load with QDs and transported into the deep tissue of solid tumors. The internalization of lipid-encapsuled QDs into B. bifidum was conveniently carried by electroporation. To improve the efficacy and specificity of tumor targeting, the QDs-carrying bacterium surface was further conjugated with folic acids (FAs) that can bind to the folic acid receptor overexpressed tumor cells. This new approach opens a pathway for delivering different types of functional cargos such as nanoparticles and drugs into solid tumor of live animals for imaging, diagnosis and therapy.

  12. Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors.

    Science.gov (United States)

    Yu, Man; Lee, Carol; Wang, Marina; Tannock, Ian F

    2015-10-01

    Cellular causes of resistance and limited drug distribution within solid tumors limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells mediate autophagy, which facilitates survival of stressed cells, and may contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in acidic endosomes, thereby diverting drugs from their target DNA and decreasing penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal pH, with potential to improve drug efficacy and distribution in solid tumors. We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin. To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models. Lansoprazole showed concentration-dependent effects to raise endosomal pH and to inhibit endosomal sequestration of doxorubicin in cultured tumor cells. Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of doxorubicin and enhanced its penetration through multilayered cell cultures. In solid tumors, lansoprazole improved the distribution of doxorubicin but also increased expression of biomarkers of drug activity throughout the tumor. Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone. Together, lansoprazole enhances the therapeutic effects of doxorubicin both by improving its distribution and increasing its activity in solid tumors. Use of PPIs to improve drug distribution and to inhibit autophagy represents a promising strategy to enhance the effectiveness of anticancer drugs in solid tumors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  13. Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors.

    Science.gov (United States)

    Ham, Stephanie L; Joshi, Ramila; Luker, Gary D; Tavana, Hossein

    2016-11-01

    Solid tumors develop as 3D tissue constructs. As tumors grow larger, spatial gradients of nutrients and oxygen and inadequate diffusive supply to cells distant from vasculature develops. Hypoxia initiates signaling and transcriptional alterations to promote survival of cancer cells and generation of cancer stem cells (CSCs) that have self-renewal and tumor-initiation capabilities. Both hypoxia and CSCs are associated with resistance to therapies and tumor relapse. This study demonstrates that 3D cancer cell models, known as tumor spheroids, generated with a polymeric aqueous two-phase system (ATPS) technology capture these important biological processes. Similar to solid tumors, spheroids of triple negative breast cancer cells deposit major extracellular matrix proteins. The molecular analysis establishes presence of hypoxic cells in the core region and expression of CSC gene and protein markers including CD24, CD133, and Nanog. Importantly, these spheroids resist treatment with chemotherapy drugs. A combination treatment approach using a hypoxia-activated prodrug, TH-302, and a chemotherapy drug, doxorubicin, successfully targets drug resistant spheroids. This study demonstrates that ATPS spheroids recapitulate important biological and functional properties of solid tumors and provide a unique model for studies in cancer research. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

    Science.gov (United States)

    de Paula Silva, Neimar; de Souza Reis, Rejane; Garcia Cunha, Rafael; Pinto Oliveira, Júlio Fernando; Santos, Marceli de Oliveira; Pombo-de-Oliveira, Maria S; de Camargo, Beatriz

    2016-01-01

    Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics. A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS) or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma). Children aged birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS) was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01)). Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma. This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

  15. Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps☆

    OpenAIRE

    Beatty, Gregory L.; O’Hara, Mark

    2016-01-01

    Chimeric antigen receptor (CAR) T cell therapy has shown promise in CD19 expressing hematologic malignancies, but how to translate this success to solid malignancies remains elusive. Effective translation of CAR T cells to solid tumors will require an understanding of potential therapeutic barriers, including factors that regulate CAR T cells expansion, persistence, trafficking, and fate within tumors. Herein, we describe the current state of CAR T cells in solid tumors; define key barriers t...

  16. Model construction of nursing service satisfaction in hospitalized tumor patients.

    Science.gov (United States)

    Chen, Yongyi; Liu, Jingshi; Xiao, Shuiyuan; Liu, Xiangyu; Tang, Xinhui; Zhou, Yujuan

    2014-01-01

    This study aims to construct a satisfaction model on nursing service in hospitalized tumor patients. Using questionnaires, data about hospitalized tumor patients' expectation, quality perception and satisfaction of hospital nursing service were obtained. A satisfaction model of nursing service in hospitalized tumor patients was established through empirical study and by structural equation method. This model was suitable for tumor specialized hospital, with reliability and validity. Patient satisfaction was significantly affected by quality perception and patient expectation. Patient satisfaction and patient loyalty was also affected by disease pressure. Hospital brand was positively correlated with patient satisfaction and patient loyalty, negatively correlated with patient complaint. Patient satisfaction was positively correlated with patient loyalty, patient complaints, and quality perception, and negatively correlated with disease pressure and patient expectation. The satisfaction model on nursing service in hospitalized tumor patients fits well. By this model, the quality of hospital nursing care may be improved.

  17. Analysis of the value of imaging in diagnosing pancreatic solid-pseudopapillary tumor

    International Nuclear Information System (INIS)

    Sun Canhui; Li Ziping; Meng Quanfei; Feng Shiting; Fan Miao; Peng Zhenpeng

    2007-01-01

    Objective: To describe the imaging features of solid-pseudopapillary tumor of the pancreas(SPTP) and evaluate the value of imaging in diagnosing SPTP. Methods: The imaging appearances in seven cases of SPTP confirmed by surgery and pathology were analyzed retrospectively. The un-enhanced and biphasic enhanced CT scanning were per- formed on all seven cases, including gastrointestinal barium meal series on three cases, endoscopic ultrasonography (EUS) on three cases, and MRI on one case. Results All tumors presented well-encapsulated heterogeneous soft tissue mass with varying degrees of solid and cystic components. Barium meal examination showed displaced gastrointestinal wall due to the tumoral compression. EUS demonstrated hyper-echoic mass with scattered small anechoic areas within the tumor. The tumor capsules were hyper-echoic. On un-enhanced CT, the mass appeared hypo-dense with mixed solid and cystic portions in six cases, and with predominantly cystic portion in one case. Calcification appeared in two cases. On biphasic enhanced CT, the mass showed peripheral and heterogeneous enhancement. Three tumors showed marked enhancement, and four tumors showed mild enhancement. Multiple small vessels within the tumor revealed on the arterial phase scanning in one case. The tumor capsules showed discontinuous enhancement in three cases. On T 1 WI, the mass appeared heterogeneous and predominantly isodense. On T 2 WI, the mass appeared heterogeneous and predominantly hyper-dense. The tumor capsule was hypo-dense on T 1 WI and T 2 WI. The mild dilatation of the biliary tract and pancreatic duct was revealed in two cases, respectively. Conclusion: Both CT and MRI can describe characteristic features of SPTP well, and should be used as the main diagnostic methods for SPTP before operation. (authors)

  18. Albumin-bound paclitaxel in solid tumors: clinical development and future directions.

    Science.gov (United States)

    Kundranda, Madappa N; Niu, Jiaxin

    2015-01-01

    Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel's indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice.

  19. Solid pseudopapillary tumor of pancreas with sickle cell trait: A rare case report

    Directory of Open Access Journals (Sweden)

    Harish S Permi

    2013-01-01

    Full Text Available Solid pseudopapillary tumor of pancreas is a rare pancreatic neoplasm affecting young women, has low malignant potential and amenable for surgical excision with good long-term survival. Sickle cell trait is benign condition, which involves one normal beta-globin chain and one HbS chain. Although it is a benign condition, individuals are prone to have rare complications that may predispose to death under certain circumstances. We report a rare coexistence of solid pseudopapillary tumor of pancreas with sickle cell trait in an 18-year-old female who underwent distal pancreatectomy with splenectomy. Histopathological examination and haemoglobin electrophoresis confirmed the diagnosis.

  20. Targeting Mitochondrial Function to Treat Quiescent Tumor Cells in Solid Tumors

    Directory of Open Access Journals (Sweden)

    Xiaonan Zhang

    2015-11-01

    Full Text Available The disorganized nature of tumor vasculature results in the generation of microenvironments characterized by nutrient starvation, hypoxia and accumulation of acidic metabolites. Tumor cell populations in such areas are often slowly proliferating and thus refractory to chemotherapeutical drugs that are dependent on an active cell cycle. There is an urgent need for alternative therapeutic interventions that circumvent growth dependency. The screening of drug libraries using multicellular tumor spheroids (MCTS or glucose-starved tumor cells has led to the identification of several compounds with promising therapeutic potential and that display activity on quiescent tumor cells. Interestingly, a common theme of these drug screens is the recurrent identification of agents that affect mitochondrial function. Such data suggest that, contrary to the classical Warburg view, tumor cells in nutritionally-compromised microenvironments are dependent on mitochondrial function for energy metabolism and survival. These findings suggest that mitochondria may represent an “Achilles heel” for the survival of slowly-proliferating tumor cells and suggest strategies for the development of therapy to target these cell populations.

  1. Subcutaneous administration of ketoprofen delays Ehrlich solid tumor growth in mice

    Directory of Open Access Journals (Sweden)

    C.M. Souza

    2014-10-01

    Full Text Available Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID has proven to exert anti-inflammatory, anti-proliferative and anti-angiogenic activities in both neoplastic and non-neoplastic conditions. We investigated the effects of this compound on tumor development in Swiss mice previously inoculated with Ehrlich tumor cells. To carry out this study the solid tumor was obtained from cells of the ascites fluid of Ehrlich tumor re-suspended in physiological saline to give 2.5x106 cells in 0.05mL. After tumor inoculation, the animals were separated into two groups (n = 10. The animals treated with ketoprofen 0.1µg/100µL/animal were injected intraperitoneally at intervals of 24h for 10 consecutive days. Animals from the control group received saline. At the end of the experiment the mice were killed and the tumor removed. We analyzed tumor growth, histomorphological and immunohistochemical characteristics for CDC47 (cellular proliferation marker and for CD31 (blood vessel marker. Animals treated with the ketoprofen 0.1µg/100µL/animal showed lower tumor growth. The treatment did not significantly influence the size of the areas of cancer, inflammation, necrosis and hemorrhage. Moreover, lower rates of tumor cell proliferation were observed in animals treated with ketoprofen compared with the untreated control group. The participation of ketoprofen in controlling tumor malignant cell proliferation would open prospects for its use in clinical and antineoplasic therapy.

  2. Circulating tumor cells in melanoma patients.

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    Gary A Clawson

    Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

  3. Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

    Science.gov (United States)

    Roy Chaudhuri, Tista

    An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

  4. Targeting the epidermal growth factor receptor in solid tumor malignancies

    DEFF Research Database (Denmark)

    Nedergaard, Mette K; Hedegaard, Chris J; Poulsen, Hans S

    2012-01-01

    been proposed as valid targets in many cancer therapy settings. Different strategies have been developed in order to either inhibit EGFR/EGFRvIII activity or to ablate EGFR/EGFRvIII-positive tumor cells. Drugs that inhibit these receptors include monoclonal antibodies (mAbs) that bind...... to the extracellular part of EGFR, blocking the binding sites for the EGFR ligands, and intracellular tyrosine kinase inhibitors (TKIs) that block the ATP binding site of the tyrosine kinase domain. Besides an EGFRvIII-targeted vaccine, conjugated anti-EGFR mAbs have been used in different settings to deliver lethal...... agents to the EGFR/EGFRvIII-positive cells; among these are radio-labelled mAbs and immunotoxins. This article reviews the current status and efficacy of EGFR/EGFRvIII-targeted therapies....

  5. Dynamic density functional theory of solid tumor growth: Preliminary models

    Directory of Open Access Journals (Sweden)

    Arnaud Chauviere

    2012-03-01

    Full Text Available Cancer is a disease that can be seen as a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT extended, for the first time, to the dynamics of living tissues by accounting for cell density correlations, different cell types, phenotypes and cell birth/death processes, in order to provide a biophysically consistent description of processes across the scales. We present an application of this approach to tumor growth.

  6. Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman

    Directory of Open Access Journals (Sweden)

    Valentin Lestelle

    2015-10-01

    Full Text Available We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

  7. Solid Pseudopapillary Tumor of the Pancreas: One Case with a Metastatic Evolution in a Caucasian Woman.

    Science.gov (United States)

    Lestelle, Valentin; de Coster, Claire; Sarran, Anthony; Poizat, Flora; Delpero, Jean-Robert; Raoul, Jean-Luc

    2015-01-01

    We report the case of a Caucasian woman, operated on for a solid pseudopapillary tumor of the pancreas in 2009, who recurred 4 years later with multiple liver metastases requiring liver resection. This disease is infrequent, particularly among the Caucasian population, and metastatic evolution is very rare.

  8. Biochemical parameters of bone metabolism in bone metastases of solid tumors (Review)

    NARCIS (Netherlands)

    Meijer, Wilhelmus; van der Veer, E; Willemse, P H

    1998-01-01

    The role of biochemical markers of bone metabolism in the diagnosis and monitoring of bone metastases in solid tumors is reviewed. Emphasis is on the recently developed markers, which may provide a more accurate quantitation of bone metabolism. In metastatic bone disease, bone formation and

  9. Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.

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    Dickson K Kirui

    Full Text Available BACKGROUND: Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs. We also determined the optimal time window at which maximal accumulation occur. RESULTS: In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm(2 amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion. CONCLUSIONS: Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy.

  10. An overview of viral oncology in Italy - report from the Pavia meeting on solid tumors

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    Perfetti Vittorio

    2012-09-01

    Full Text Available Abstract This is a report on some of the research activities currently ongoing in Italy as outlined at the “Viruses and solid tumors” meeting jointly organized by the Oncology Sections of IRCCS Policlinico “San Matteo” (Pavia and IRCCS National Cancer Institute (Aviano, held in Pavia, Italy, on October 2011. Experts from the various disciplines involved in the study of the complex relationships between solid tumors and viruses met to discuss recent developments in the field and to report their personal contributions to the specified topics. Secondary end point was to establish a multidisciplinary work group specifically devoted to solid tumors and infectious agents, aimed to identify areas of common interest, promoting and establishing collaborative projects and programs, and to coordinate clinical and research activities. The group, which will be named IVOG (Italian Viral Oncology Group, will operate under the patronage of the various scientific societies of interest.

  11. Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy.

    Science.gov (United States)

    Jin, Rong; Guo, Xuelian; Dong, Lingli; Xie, Enyuan; Cao, Aoneng

    2017-10-01

    A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH 2 ) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH 2 . These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Cancer stem cells in solid tumors: is 'evading apoptosis' a hallmark of cancer?

    Science.gov (United States)

    Enderling, Heiko; Hahnfeldt, Philip

    2011-08-01

    Conventional wisdom has long held that once a cancer cell has developed it will inevitably progress to clinical disease. Updating this paradigm, it has more recently become apparent that the tumor interacts with its microenvironment and that some environmental bottlenecks, such as the angiogenic switch, must be overcome for the tumor to progress. In parallel, attraction has been drawn to the concept that there is a minority population of cells - the cancer stem cells - bestowed with the exclusive ability to self-renew and regenerate the tumor. With therapeutic targeting issues at stake, much attention has shifted to the identification of cancer stem cells, the thinking being that the remaining non-stem population, already fated to die, will play a negligible role in tumor development. In fact, the newly appreciated importance of intercellular interactions in cancer development also extends in a unique and unexpected way to interactions between the stem and non-stem compartments of the tumor. Here we discuss recent findings drawn from a hybrid mathematical-cellular automaton model that simulates growth of a heterogeneous solid tumor comprised of cancer stem cells and non-stem cancer cells. The model shows how the introduction of cell fate heterogeneity paradoxically influences the tumor growth dynamic in response to apoptosis, to reveal yet another bottleneck to tumor progression potentially exploitable for disease control. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Use of magnetic resonance imaging to detect neoplastic meningitis: Limited use in leukemia and lymphoma but convincing results in solid tumors

    International Nuclear Information System (INIS)

    Pauls, Sandra; Fischer, Ann-Cathrin; Brambs, Hans-Jürgen; Fetscher, Sebastian; Höche, Wolfram; Bommer, Martin

    2012-01-01

    Background: An early diagnosis of meningitis is important to improve patients’ survival. Data about a direct comparison of cerebrospinal fluid cytology (CSF-cytology) and MRI are very limited. Therefore, the aim of this study was to compare these two diagnostic modalities in diagnosing meningitis in patients with hematopoietic and solid malignancies. Methods: In 68 patients suspicious for neoplastic meningitis, cytology and MRI (1.5 T) was performed. The meningeal, pial or intraparenchymal hyperintense signal or contrast enhancement was correlated to the final CNS diagnosis and to cytology. Results: 44 patients (64.7%) had neoplastic meningitis, 21 patients (30.9%) had non-neoplastic meningitis. The sensitivity to diagnose meningeal disease was 49.2% for MRI and 95.4% for cytology (p < 0.001). In patients with neoplastic meningitis, sensitivity was 45.5% for MRI and 93.2% for cytology (p < 0.001). In patients with infectious meningitis, sensitivity was 57.1% for MRI and 100% for cytology (p = 0.0013). In patients with solid tumors, the sensitivity was 84.6% for both diagnostic methods. The sensitivity for MRI was low in patients with leukemia (20.0%) and lymphoma (37.5%). The positive predictive value (PPV) for MRI to differentiate infectious from neoplastic meningitis was high in patients with infectious meningitis (75.0%), in patients with lymphoma (83.3%), and in patients with solid tumors (72.7%). Ppv was low in patients with leukemia (33.3%). Conclusion: Diagnostic value of MRI for diagnosing meningitis is especially limited in patients with hematopoietic malignancies. MRI better detected leptomeningeal involvement caused by solid tumors than by leukemia or lymphoma. The ppv to specify neoplastic meningitis depends on tumor subtype.

  14. Improving Care in Pediatric Neuro-oncology Patients: An Overview of the Unique Needs of Children With Brain Tumors.

    Science.gov (United States)

    Fischer, Cheryl; Petriccione, Mary; Donzelli, Maria; Pottenger, Elaine

    2016-03-01

    Brain tumors represent the most common solid tumors in childhood, accounting for almost 25% of all childhood cancer, second only to leukemia. Pediatric central nervous system tumors encompass a wide variety of diagnoses, from benign to malignant. Any brain tumor can be associated with significant morbidity, even when low grade, and mortality from pediatric central nervous system tumors is disproportionately high compared to other childhood malignancies. Management of children with central nervous system tumors requires knowledge of the unique aspects of care associated with this particular patient population, beyond general oncology care. Pediatric brain tumor patients have unique needs during treatment, as cancer survivors, and at end of life. A multidisciplinary team approach, including advanced practice nurses with a specialty in neuro-oncology, allows for better supportive care. Knowledge of the unique aspects of care for children with brain tumors, and the appropriate interventions required, allows for improved quality of life. © The Author(s) 2015.

  15. Whole-body magnetic resonance imaging for detection of skeletal metastases in children and young people with primary solid tumors - systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Smets, A.M.; Deurloo, E.E.; Slager, T.J.E.; Stoker, J.; Bipat, S. [Academic Medical Center (AMC), Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands)

    2018-02-15

    Many solid neoplasms have a propensity for osteomedullary metastases of which detection is important for staging and subsequent treatment. Whole-body magnetic resonance imaging (WB-MRI) has been shown to accurately detect osteomedullary metastases in adults, but these findings cannot be unconditionally extrapolated to staging of children with malignant solid tumors. To conduct a literature review on the sensitivity of WB-MRI for detecting skeletal metastases in children with solid tumors. Searches in MEDLINE and EMBASE databases up to 15 May 2017 were performed to identify studies on the diagnostic value of WB-MRI. Inclusion criteria were children and adolescents (age <21 years) with a primary solid tumor who were evaluated for skeletal metastases by WB-MRI and compared to any type of reference standard. The number of included patients had to be at least five and data on true positives, true negatives, false-positives and false-negatives had to be extractable. Five studies including 132 patients (96 patients with solid tumors) were eligible. Patient groups and used reference tests were heterogeneous, producing unclear or high risk of bias. Sensitivity of WB-MRI ranged between 82% and 100%. The positive predictive value of WB-MRI was variable among the studies and influenced by the used reference standard. Although WB-MRI may seem a promising radiation-free technique for the detection of skeletal metastases in children with solid tumors, published studies are small and too heterogeneous to provide conclusive evidence that WB-MRI can be an alternative to currently used imaging techniques. (orig.)

  16. Whole-body magnetic resonance imaging for detection of skeletal metastases in children and young people with primary solid tumors - systematic review

    International Nuclear Information System (INIS)

    Smets, A.M.; Deurloo, E.E.; Slager, T.J.E.; Stoker, J.; Bipat, S.

    2018-01-01

    Many solid neoplasms have a propensity for osteomedullary metastases of which detection is important for staging and subsequent treatment. Whole-body magnetic resonance imaging (WB-MRI) has been shown to accurately detect osteomedullary metastases in adults, but these findings cannot be unconditionally extrapolated to staging of children with malignant solid tumors. To conduct a literature review on the sensitivity of WB-MRI for detecting skeletal metastases in children with solid tumors. Searches in MEDLINE and EMBASE databases up to 15 May 2017 were performed to identify studies on the diagnostic value of WB-MRI. Inclusion criteria were children and adolescents (age <21 years) with a primary solid tumor who were evaluated for skeletal metastases by WB-MRI and compared to any type of reference standard. The number of included patients had to be at least five and data on true positives, true negatives, false-positives and false-negatives had to be extractable. Five studies including 132 patients (96 patients with solid tumors) were eligible. Patient groups and used reference tests were heterogeneous, producing unclear or high risk of bias. Sensitivity of WB-MRI ranged between 82% and 100%. The positive predictive value of WB-MRI was variable among the studies and influenced by the used reference standard. Although WB-MRI may seem a promising radiation-free technique for the detection of skeletal metastases in children with solid tumors, published studies are small and too heterogeneous to provide conclusive evidence that WB-MRI can be an alternative to currently used imaging techniques. (orig.)

  17. Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

    Directory of Open Access Journals (Sweden)

    Neimar de Paula Silva

    Full Text Available Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics.A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma. Children aged <6 years were selected. Adjustments were made for potential confounders. Odds ratios (OR with 95% confidence intervals (CI were computed by unconditional logistic regression analysis using SPSS.Males, high maternal education level, and birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01. Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma.This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

  18. Investigation of particle accumulation, chemosensitivity and thermosensitivity for effective solid tumor therapy using thermosensitive liposomes and hyperthermia

    NARCIS (Netherlands)

    W.J.M. Lokerse (Wouter); M. Bolkestein (Michiel); T.L.M. ten Hagen (Timo); M. de Jong (Marcel); A.M.M. Eggermont (Alexander); Grüll, H. (Holger); G.A. Koning (Gerben)

    2016-01-01

    textabstractDoxorubicin (Dox) loaded thermosensitive liposomes (TSLs) have shown promising results for hyperthermia-induced local drug delivery to solid tumors. Typically, the tumor is heated to hyperthermic temperatures (41-42 °C), which induced intravascular drug release from TSLs within the tumor

  19. Detection of tumor-specific cytotoxic drug activity in vitro using the fluorometric microculture cytotoxicity assay and primary cultures of tumor cells from patients.

    Science.gov (United States)

    Nygren, P; Fridborg, H; Csoka, K; Sundström, C; de la Torre, M; Kristensen, J; Bergh, J; Hagberg, H; Glimelius, B; Rastad, J

    1994-03-01

    The semi-automated fluorometric microculture cytotoxicity assay (FMCA), based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) by viable cells, was employed for cytotoxic drug sensitivity testing of tumor cells from patients with hematological or solid tumors. In total, 390 samples from 20 diagnoses were tested with up to 12 standard cytotoxic drugs. The technical success rate for different tumor types ranged from 67 to 95%. Fluorescence was linearly related to cell number but variably steep depending on tumor type. Samples from most solid tumors thus showed higher signal-to-noise ratios than hematological samples. A wide spectrum of in vitro drug activity was obtained, with acute leukemias and non-Hodgkin's lymphomas being sensitive to almost all tested drugs, whereas renal and adrenocortical carcinomas were essentially totally resistant. Between these extremes were samples of breast and ovarian carcinomas and sarcomas. When in vitro response was compared with known clinical response patterns, a good correspondence was observed. The results indicate that the FMCA is a rapid and efficient method for in vitro measurement of tumor-specific drug activity both in hematological and in solid tumors. The assay may be suitable for new drug development and direction of phase-2 trials to suitable patients.

  20. Blocking Blood Flow to Solid Tumors by Destabilizing Tubulin: An Approach to Targeting Tumor Growth.

    Science.gov (United States)

    Pérez-Pérez, María-Jesús; Priego, Eva-María; Bueno, Oskía; Martins, Maria Solange; Canela, María-Dolores; Liekens, Sandra

    2016-10-13

    The unique characteristics of the tumor vasculature offer the possibility to selectively target tumor growth and vascularization using tubulin-destabilizing agents. Evidence accumulated with combretastatin A-4 (CA-4) and its prodrug CA-4P support the therapeutic value of compounds sharing this mechanism of action. However, the chemical instability and poor solubility of CA-4 demand alternative compounds that are able to surmount these limitations. This Perspective illustrates the different classes of compounds that behave similar to CA-4, analyzes their binding mode to αβ-tubulin according to recently available structural complexes, and includes described approaches to improve their delivery. In addition, dissecting the mechanism of action of CA-4 and analogues allows a closer insight into the advantages and drawbacks associated with these tubulin-destabilizing agents that behave as vascular disrupting agents (VDAs).

  1. A case of pancreatic neuroendocrine tumor in a patient with neurofibromatosis-1

    Directory of Open Access Journals (Sweden)

    Nishi Takeshi

    2012-07-01

    Full Text Available Abstract Patients with neurofibromatosis-1 (NF-1 sometime develop neuroendocrine tumors (NET. Although these NETs usually occur in the duodenum or peri-ampullary region, they occasionally grow in the pancreas (PNET. A 62-year-old man with NF-1 had mild liver dysfunction and was admitted to our hospital for further examination. An abdominal contrast-enhanced computed tomography scan demonstrated a 30-mm tumor in the head of the pancreas. The scan showed an invasion of the tumor into the duodenum, and biopsy under an endoscopic ultrasonography indicated that the tumor was a NET. A subtotal stomach-preserving pancreaticoduodenectomy was performed. Macroscopically, the pancreatic tumor was white and elastic hard. Microscopically, tumor cells were composed of ribbons, cords, and solid nests with an acinus-like structure. The tumor was diagnosed as NET G2 according to the WHO classification (2010. The product of theNF-1 gene, i.e., neurofibromin, was weakly positive in the tumor cells, suggesting that the tumor was induced by a mutation in the NF-1 gene. This is the seventh case of PNET arising in NF-1 patients worldwide.

  2. CT of abdominal tumor

    International Nuclear Information System (INIS)

    Endo, Satoshi; Yamada, Kenji; Ito, Masatoshi; Ito, Hisao; Yamaura, Harutsugu

    1981-01-01

    CT findings in 33 patients who had an abdominal tumor were evaluated. CT revealed a tumor in 31 cases. The organ from which the tumor originated was correctly diagnosed in 18 patients. Whether the tumor was solid or cystic was correctly predicted in 28 patients. The diagnosis malignant or benign nature of tumor was correct, incorrect and impossible, in 23, 3, and five patiens, respectively. (Kondo, M.)

  3. Absolute and Functional Iron Deficiency Anemia among Different Tumors in Cancer Patients in South Part of Iran, 2014

    Science.gov (United States)

    Hashemi, Seyed Mehdi; Mashhadi, Mohammad Ali; Mohammadi, Mehdi; Ebrahimi, Maryam; Allahyari, Abolghasem

    2017-01-01

    Background: Anemia is a common problem in cancer patients. This study aimed to investigate the frequency rate of absolute and functional iron deficiency anemia among different tumors and its distribution in different stages of cancer in solid tumors. Materials and Methods: This study was performed on 597 patients with cancer referred to Ali-Ebne-Abitaleb Hospital in Zahedan. Laboratory tests included serum iron, transferrin saturation, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and complete blood count (CBC). The malignancy type and stages were recorded. Data were analysed using SPSS statistics software (Ver.19). Results: Four hundred and fifty-seven patients (76.5 %) diagnosed with solid tumors and 140 (23.5%) suffered from hematologic malignancies. Among patients with solid tumors, functional iron deficiency had the highest rate (300 patients had anemia and 243 (53.2%) of whom were functionally iron deficient), but in hematologic malignancies most of patients had not iron deficiency (66 patients had not iron deficiency against 12 patients had absolute iron deficiency and 62 patients had functional iron deficiency anemia) (P-value=0.021). No significant differences were observed among the various stages of cancers in terms of degrees of iron deficiency (P>0.05). Conclusion: The results of the study showed that solid tumors had a higher rate of absolute and functional iron deficiency anemia, compared to hematologic malignancies. But there was no difference between the different stages of the disease. PMID:28989585

  4. A quantitative theory of solid tumor growth, metabolic rate and vascularization.

    Directory of Open Access Journals (Sweden)

    Alexander B Herman

    Full Text Available The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed.

  5. MR imaging of diffuse bone marrow replacement in pediatric patients with solid malignancies

    International Nuclear Information System (INIS)

    Ruzal-Shapiro, C.; Berdon, W.E.; Cohen, M.D.; Abramson, S.J.

    1990-01-01

    This paper demonstrates that the MR imaging finding of dark T1/bright T2, associated with diffuse bone marrow tumor infiltration in leukemia, also occurs in solid tumors. The clinical course and results on plain radiographs, bone scans, and marrow aspiration were reviewed in two patients with solid tumors and two with leukemia whose MR studies showed a pattern of diffuse bone marrow T2 hypointensity and T2 hyperintensity. One case was followed serially through treatment. There were two cases of ALL, one neuroblastoma, and one rhabdomyosarcoma. Plain radiographs and bone scans showed metaphyseal changes with normal epiphyses and diaphyses. On MR images, flip-flop or reversal of the expected signal characteristics of fatty marrow was seen diffusely in the metaphyses, epiphyses, and diaphyses. All patients had positive bone marrow aspirates

  6. Solid and Cystic Tumor (SCT of the Pancreas in an Adult Man

    Directory of Open Access Journals (Sweden)

    K. Ohiwa

    1997-01-01

    Full Text Available Solid and cystic tumor (SCT of the pancreas predominantly Occurs in women, and the occurrence in men is extremely rare. We experienced a male case of SCT. A 38-year-old man was admitted with the complaint of upper abdominal pain. CT scan showed the presence of a mass in the head of the pancreas. The mass was composed of high density areas and low density areas. Ultrasonograms revealed the mass being composed of high echoic areas and low echoic areas. The mass .was hypovascular on angiography. SCT was suspected and pancreaticoduodenectomy was performed. The cut surface of the tumor showed mainly cystic degenerative areas containing dark red hemorrhagic materials. Microscopically, there were solid areas in the periphery and pseudopapillary areas in the center. No metastasis was found in the removed lymph nodes. The tumor cells were not stained by Grimelius' silver stain. The tumor cells were positive for alpha-l-antitrypsin (AAT and neuron-specific enolase (NSE. Pancreatic hormones such as insulin, glucagon, and somatostatin were all negative. Electron micrograph showed that tumor cells were rich in mitochondria. Zymogen granules and neurosecretory granules were not detected. Estrogen receptor (ER and progesterone receptor (PR were both negative.

  7. Characterization of a switchable chimeric antigen receptor platform in a pre-clinical solid tumor model.

    Science.gov (United States)

    Pishali Bejestani, Elham; Cartellieri, Marc; Bergmann, Ralf; Ehninger, Armin; Loff, Simon; Kramer, Michael; Spehr, Johannes; Dietrich, Antje; Feldmann, Anja; Albert, Susann; Wermke, Martin; Baumann, Michael; Krause, Mechthild; Bornhäuser, Martin; Ehninger, Gerhard; Bachmann, Michael; von Bonin, Malte

    2017-01-01

    The universal modular chimeric antigen receptor (UniCAR) platform redirects CAR-T cells using a separated, soluble targeting module with a short half-life. This segregation allows precise controllability and flexibility. Herein we show that the UniCAR platform can be used to efficiently target solid cancers in vitro and in vivo using a pre-clinical prostate cancer model which overexpresses prostate stem cell antigen (PSCA). Short-term administration of the targeting module to tumor bearing immunocompromised mice engrafted with human UniCAR-T cells significantly delayed tumor growth and prolonged survival of recipient mice both in a low and high tumor burden model. In addition, we analyzed phenotypic and functional changes of cancer cells and UniCAR-T cells in association with the administration of the targeting module to reveal potential immunoevasive mechanisms. Most notably, UniCAR-T cell activation induced upregulation of immune-inhibitory molecules such as programmed death ligands. In conclusion, this work illustrates that the UniCAR platform mediates potent anti-tumor activity in a relevant in vitro and in vivo solid tumor model.

  8. Multiphoton fluorescence lifetime imaging of chemotherapy distribution in solid tumors

    Science.gov (United States)

    Carlson, Marjorie; Watson, Adrienne L.; Anderson, Leah; Largaespada, David A.; Provenzano, Paolo P.

    2017-11-01

    Doxorubicin is a commonly used chemotherapeutic employed to treat multiple human cancers, including numerous sarcomas and carcinomas. Furthermore, doxorubicin possesses strong fluorescent properties that make it an ideal reagent for modeling drug delivery by examining its distribution in cells and tissues. However, while doxorubicin fluorescence and lifetime have been imaged in live tissue, its behavior in archival samples that frequently result from drug and treatment studies in human and animal patients, and murine models of human cancer, has to date been largely unexplored. Here, we demonstrate imaging of doxorubicin intensity and lifetimes in archival formalin-fixed paraffin-embedded sections from mouse models of human cancer with multiphoton excitation and multiphoton fluorescence lifetime imaging microscopy (FLIM). Multiphoton excitation imaging reveals robust doxorubicin emission in tissue sections and captures spatial heterogeneity in cells and tissues. However, quantifying the amount of doxorubicin signal in distinct cell compartments, particularly the nucleus, often remains challenging due to strong signals in multiple compartments. The addition of FLIM analysis to display the spatial distribution of excited state lifetimes clearly distinguishes between signals in distinct compartments such as the cell nuclei versus cytoplasm and allows for quantification of doxorubicin signal in each compartment. Furthermore, we observed a shift in lifetime values in the nuclei of transformed cells versus nontransformed cells, suggesting a possible diagnostic role for doxorubicin lifetime imaging to distinguish normal versus transformed cells. Thus, data here demonstrate that multiphoton FLIM is a highly sensitive platform for imaging doxorubicin distribution in normal and diseased archival tissues.

  9. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

    LENUS (Irish Health Repository)

    Shrotriya, Shiva

    2015-01-01

    A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence.

  10. Evaluation of esophageal peristalsis in patients with esophageal tumors. Initial experience with cine MR imaging

    International Nuclear Information System (INIS)

    Koyama, Takashi; Kobayashi, Ari; Hiraga, Akira; Umeoka, Shigeaki; Saga, Tsuneo; Watanabe, Go; Tamai, Ken; Shimada, Yutaka; Togashi, Kaori

    2005-01-01

    We evaluated esophageal peristalsis in patients with esophageal tumors by cine MR using steady-state free precession (SSFP) sequence and correlated the alteration of the esophageal peristalsis with clinical symptoms and tumor stages. Thirteen patients with pathologically proven esophageal tumors, including 12 esophageal cancers and one submucosal leiomyoma, underwent cine MRI using true fast imaging with steady precession (trueFISP) sequence, which is one SSFP sequence, after contrast-enhanced MR scanning for clinical purposes. A total of 120 serial images were obtained within 60 s through the plane along the long axis of the esophagus while patients chewed gum. The serial trueFISP images were evaluated for the presence, frequency, speed of progression, and passage of peristalsis through the tumor. The data from cine MRI were compared with clinical symptoms and tumor stages. Peristalsis was clearly identified in all patients. Seven patients with complete interruption of peristalsis had dysphagia; one with partially impaired peristalsis could intake solid foods with discomfort; and two with partially impaired peristalsis and three with preserved peristalsis remained asymptomatic. Patients with complete or partial interruption of peristalsis had Stage T3 or T4 esophageal cancer. In conclusion, trueFISP cine MR imaging enables direct visualization of esophageal peristalsis in relation to esophageal tumors. Complete interruption of peristalsis causes dysphagia, whereas partial interruption of and preserved peristalsis usually do not cause digestive problems. Interruption of peristalsis may indicate impaired muscle function caused by invasion of advanced esophageal cancers. (author)

  11. Solid renal tumor severity in von Hippel Lindau disease is related to germline deletion length and location.

    Science.gov (United States)

    Maranchie, Jodi K; Afonso, Anoushka; Albert, Paul S; Kalyandrug, Sivaram; Phillips, John L; Zhou, Shubo; Peterson, James; Ghadimi, Bijan M; Hurley, Katheen; Riss, Joseph; Vasselli, James R; Ried, Thomas; Zbar, Berton; Choyke, Peter; Walther, McClellan M; Klausner, Richard D; Linehan, W Marston

    2004-01-01

    von Hippel Lindau disease (VHL) is an autosomal dominant familial cancer syndrome linked to alteration of the VHL tumor suppressor gene. Affected patients are predisposed to develop pheochromocytomas and cystic and solid tumors of the kidney, CNS, pancreas, retina, and epididymis. However, organ involvement varies considerably among families and has been shown to correlate with the underlying germline alteration. Clinically, we observed a paradoxically lower prevalence of renal cell carcinoma (RCC) in patients with complete germline deletion of VHL. To determine if a relationship existed between the type of VHL deletion and disease, we retrospectively evaluated 123 patients from 55 families with large germline VHL deletions, including 42 intragenic partial deletions and 13 complete VHL deletions, by history and radiographic imaging. Each individual and family was scored for cystic or solid involvement of CNS, pancreas, and kidney, and for pheochromocytoma. Germline deletions were mapped using a combination of fluorescent in situ hybridization (FISH) and quantitative Southern and Southern blot analysis. An age-adjusted comparison demonstrated a higher prevalence of RCC in patients with partial germline VHL deletions relative to complete deletions (48.9 vs. 22.6%, p=0.007). This striking phenotypic dichotomy was not seen for cystic renal lesions or for CNS (p=0.22), pancreas (p=0.72), or pheochromocytoma (p=0.34). Deletion mapping revealed that development of RCC had an even greater correlation with retention of HSPC300 (C3orf10), located within the 30-kb region of chromosome 3p, immediately telomeric to VHL (52.3 vs. 18.9%, p <0.001), suggesting the presence of a neighboring gene or genes critical to the development and maintenance of RCC. Careful correlation of genotypic data with objective phenotypic measures will provide further insight into the mechanisms of tumor formation. Copyright 2003 Wiley-Liss, Inc.

  12. Eosinophilia in routine blood samples as a biomarker for solid tumor development

    DEFF Research Database (Denmark)

    Andersen, Christen Bertel L; Siersma, V.D.; Hasselbalch, H.C.

    2014-01-01

    eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design. MATERIAL AND METHODS: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing...... was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers. CONCLUSION: We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize...... that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution....

  13. Monitoring the effect of belinostat in solid tumors by H4 acetylation

    DEFF Research Database (Denmark)

    Marquard, L.; Petersen, K.D.; Persson, M.

    2008-01-01

    after treatment with HDAC inhibitors, and could thus be used as a marker for monitoring cellular response to HDAC inhibitor treatment. Here we describe the utility of a newly described monoclonal antibody against acetylated H4 for immunohistochemistry on paraffin-embedded fine needle biopsies from nude...... acetylation in fine needle biopsies using the T25 antibody may prove useful in monitoring HDAC inhibitor efficacy in clinical trials involving humans with solid tumors Udgivelsesdato: 2008/5...

  14. Polymodification. Short-term hyperglycemia and local hyperthermia in hypoxiradiotherapy of transplantable solid tumors

    International Nuclear Information System (INIS)

    Kozin, S.V.; Krimker, V.M.; Yarmonenko, S.P.

    1984-01-01

    Application possibilities of hyperglycemia and local hyperthermia in combination with hypoxiradiotherapy of solid tumors, have been evaluated. The experiments conducted have shown the great possibilities of combined use of radiation, hyperglycemia, hyperthermia, for selective affection of tumours, and application of gaseous hypoxia during irradiation - for simultaneous principal protection of normal tissues. Interaction of all the agents will undoubtedly require a versatile study to develop the optimum regimes of action

  15. Anti-m antibody in solid tumors-two case reports.

    Science.gov (United States)

    Soni, Shiv Kumar; Goyal, Hari; Sood, S K; Setia, Rasika

    2014-09-01

    Anti-M antibodies are usually of IgM, appear as cold agglutinins and are clinically insignificant. We are reporting two cases of anti-M in cases of solid tumors where the anti-M caused discrepancy in blood grouping, reacted in coombs phase of crossmatching. Anti-M in first case showed dosage effect. These antibodies can be clinical significant when detected in coombs phase, making M antigen negative coombs compatible unit transfusion imperative.

  16. Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

    Science.gov (United States)

    Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

    2003-07-15

    Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

  17. Tumor-infiltrating lymphocytes (TILs) from patients with glioma

    DEFF Research Database (Denmark)

    Liu, Zhenjiang; Meng, Qingda; Bartek, Jiri

    2017-01-01

    Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21...

  18. Recommendations for standardized diagnostics, treatment and following care in tumor diseases. Geriatric patient with tumor disease

    International Nuclear Information System (INIS)

    Hagmueller, E.; Neises, M.; Queisser, W.; Richter, H.; Schneider, G.

    2001-01-01

    The recommendations for the treatment of geriatric patients with tumor disease, presented in the paper, cover: surgery; chemotherapy; radiotherapy and immunotherapy. Radiotherapy is recommended for skin tumors, pain treatment in the bone metastases (40 - 50 Gy), system diseases (with reduction of the usual size of the irradiated area), small size tumors etc. It is considered as an appropriate method (excluding wide fields) for geriatric outpatients

  19. Lysis of fresh human solid tumors by autologous lymphocytes activated in vitro with lectins

    International Nuclear Information System (INIS)

    Mazumder, A.; Grimm, E.A.; Zhang, H.Z.; Rosenberg, S.A.

    1982-01-01

    Human peripheral blood lymphocytes (PBL), obtained from patients with a variety of cancers, were incubated in vitro with phytohemagglutinin, concanavalin A, and crude or lectin-free T-cell growth factors. The lectin-activated PBL of nine patients were capable of lysing fresh autologous tumor during a 4-hr 51Cr release assay. Multiple metastases from the same patient were equivalently lysed by these activated autologous PBL. No lysis of fresh PBL or lectin-induced lymphoblast cell targets was seen, although tumor, PBL, and lymphoblast cells were shown to be equally lysable using allosensitized cells. The activated cells could be expanded without loss of cytotoxicity in crude or lectin-free T-cell growth factors. The generation of cells lytic to fresh autologous tumor was dependent on the presence of adherent cells, although the lytic cell itself was not adherent. Proliferation was not involved in the induction of lytic cells since equal lysis was induced in irradiated and nonirradiated lymphocytes. Lectin was not required in the lytic assay, and the addition of alpha-methyl-D-mannoside to concanavalin A-activated lymphoid cells did not increase the lysis of fresh tumor cells. Activation by lectin for 3 days appears to be an efficient and convenient method for generating human cells lytic to fresh autologous tumor. These lytic cells may be of value for studies of the cell-mediated lysis of human tumor and possibly for tumor immunotherapy as well

  20. Induction of oncogene addiction shift to NF-κB by camptothecin in solid tumor cells

    International Nuclear Information System (INIS)

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto; Tsuruo, Takashi; Umezawa, Kazuo; Higashihara, Masaaki; Watanabe, Toshiki; Horie, Ryouichi

    2009-01-01

    The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-κB activity driven by IκB kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-κB during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-κB inhibitors.

  1. Induction of oncogene addiction shift to NF-{kappa}B by camptothecin in solid tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Togano, Tomiteru; Sasaki, Masataka; Watanabe, Mariko; Nakashima, Makoto [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Tsuruo, Takashi [Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-10-6 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Umezawa, Kazuo [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-0061 (Japan); Higashihara, Masaaki [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Watanabe, Toshiki [Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Horie, Ryouichi, E-mail: rhorie@med.kitasato-u.ac.jp [Department of Hematology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan)

    2009-12-04

    The biological basis of the resistance of solid tumor cells to chemotherapy is not well understood. While addressing this problem, we found that gastric cancer cell line St-4/CPT, lung cancer cell line A549/CPT, and colon cancer cell line HT-29/CPT, all of which are resistant to camptothecin (CPT), showed strong and constitutive nuclear factor (NF)-{kappa}B activity driven by I{kappa}B kinase compared with their parental cell lines St-4, A549, and HT-29. A new NF-{kappa}B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), reduced viability and induced apoptosis in St-4/CPT, A549/CPT, and HT-29/CPT cell lines, while their parental cell lines were resistant to DHMEQ. The results in this study present an example of the shift in signals that support the survival of solid tumor cells to NF-{kappa}B during the acquisition of resistance to CPT. The results also indicate that solid tumor cells that become resistant to chemotherapy may be more easily treated by NF-{kappa}B inhibitors.

  2. The combined effect of interferon synthesis inductors, radiosensitizing and antitumoral agents on solid tumors

    International Nuclear Information System (INIS)

    Leonidze, D.L.

    1987-01-01

    In experiments with mice bearing solid sarcoma 37 a study was conducted on the combined effect of radiation and inductors of endogenous inerferon synthesis (IEIS), together with hyperthermia or together with an alkylating and carbomoilating agent, dimethinur. The effect was estimated by the tumor growth coefficient and by the number of animals with the regressed tumors. Poly I; polyC was not shiown to influence the efficiency of hyperthermia combined with radiation with radiation; dextransulphate and tiloron increased the radiosensitizing effect of hyperthermia. Dimethinur aggravated the effect of radiation, but with IEIS used together with dimethynur and radiation, the response of the tumor increased insignificantly as compared to the effect of IEIS together with radiation

  3. Targeting doxorubicin encapsulated in stealth liposomes to solid tumors by non thermal diode laser.

    Science.gov (United States)

    Ghannam, Magdy M; El Gebaly, Reem; Fadel, Maha

    2016-04-05

    The use of liposomes as drug delivery systems is the most promising technique for targeting drug especially for anticancer therapy. In this study sterically stabilized liposomes was prepared from DPPC/Cholesterol/PEG-PE encapsulated doxorubicin. The effect of lyophilization on liposomal stability and hence expiration date were studied. Moreover, the effect of diode laser on the drug released from liposomesin vitro and in vivo in mice carrying implanted solid tumor were also studied. The results indicated that lyophilization of the prepared liposomes encapsulating doxorubicin led to marked stability when stored at 5 °C and it is possible to use the re-hydrated lyophilized liposomes within 12 days post reconstitution. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells is a promising method in cancer therapy. We can conclude that lyophilization of the liposomes encapsulating doxorubicin lead to marked stability for the liposomes when stored at 5 °C. Moreover, the use of low energy diode laser for targeting anticancer drug to the tumor cells through the use of photosensitive sterically stabilized liposomes loaded with doxorubicin is a promising method. It proved to be applicable and successful for treatment of Ehrlich solid tumors implanted in mice and eliminated toxic side effects of doxorubicin.

  4. Effect of Arrabidaea chica extracts on the Ehrlich solid tumor development

    Directory of Open Access Journals (Sweden)

    Ana Flávia C. Ribeiro

    2012-04-01

    Full Text Available The aim of this study was to investigate the effect of Arrabidaea chica (Humb. & Bonpl. B. Verl., Bignoniaceae, extracts on Ehrlich solid tumor development in Swiss mice. Leaves of A. chica were extracted with two distinct solvents, ethanol and water. The phytochemical analysis of the extracts indicated different classes of secondary metabolites like as anthocyanidins, flavonoids, tannins and saponins. Ethanol (EE and aqueous (AE extracts at 30 mg/kg reduced the development of Ehrlich solid tumor after ten days of oral treatment. The EE group presented increase in neutrophil count, α1 and β globulin values, and decrease of α2 globulin values. Furthermore, EE reduced the percentage of CD4+ T cells in blood but did not alter the percentage of inflammatory mononuclear cells associated with tumor suggesting a direct action of EE on tumor cells. Reduced tumor development observed in AE group was accompanied by a lower percentage of CD4+ T lymphocytes in blood. At the tumor microenvironment, this treatment decreased the percentage of CD3+ T cells, especially due to a reduction of CD8+ T subpopulation and NK cells. The antitumor activity presented by the AE is possibly related to an anti-inflammatory activity. None of the extracts produced toxic effects in animals. In conclusion, the ethanol and aqueous extracts of A. chica have immunomodulatory and antitumor activities attributed to the presence of flavonoids, such as kaempferol. These effects appear to be related to different mechanisms of action for each extract. This study demonstrates the potential of A. chica as an antitumor agent confirming its use in traditional popular medicine.

  5. Strategies for enhancing adoptive T-cell immunotherapy against solid tumors using engineered cytokine signaling and other modalities.

    Science.gov (United States)

    Shum, Thomas; Kruse, Robert L; Rooney, Cliona M

    2018-05-04

    Cancer therapy has been transformed by the demonstration that tumor-specific T-cells can eliminate tumor cells in a clinical setting with minimal long-term toxicity. However, significant success in the treatment of leukemia and lymphoma with T-cells using native receptors or redirected with chimeric antigen receptors (CARs) has not been recapitulated in the treatment of solid tumors. This lack of success is likely related to the paucity of costimulatory and cytokine signaling available in solid tumors, in addition to a range of inhibitory mechanisms. Areas covered: We summarize the latest developments in engineered T-cell immunotherapy, describe the limitations of these approaches in treating solid tumors, and finally highlight several strategies that may be useful in mediating solid tumor responses in the future, while also ensuring safety of engineered cells. Expert opinion: CAR-T therapies require further engineering to achieve their potential against solid tumors. Facilitating cytokine signaling in CAR T-cells appears to be essential in achieving better responses. However, the engineering of T-cells with potentially unchecked proliferation and potency raises the question of whether the simultaneous combination of enhancements will prove safe, necessitating continued advancements in regulating CAR-T activity at the tumor site and methods to safely switch off these engineered cells.

  6. Autoclaved Tumor Bone for Skeletal Reconstruction in Paediatric Patients: A Low Cost Alternative in Developing Countries

    Directory of Open Access Journals (Sweden)

    Masood Umer

    2013-01-01

    Full Text Available We reviewed in this series forty patients of pediatric age who underwent resection for malignant tumors of musculoskeletal system followed by biological reconstruction. Our surgical procedure for reconstruction included (1 wide en bloc resection of the tumor; (2 curettage of tumor from the resected bone; (3 autoclaving for 8 minutes (4 bone grafting from the fibula (both vascularized and nonvascularized fibular grafts used; (5 reimplantation of the autoclaved bone into the host bone defect and fixation with plates. Functional evaluation was done using MSTS scoring system. At final followup of at least 18 months (mean 29.2 months, 31 patients had recovered without any complications. Thirty-eight patients successfully achieved a solid bony union between the graft and recipient bone. Three patients had surgical site infection. They were managed with wound debridement and flap coverage of the defect. Local recurrence and nonunion occurred in two patients each. One patient underwent disarticulation at hip due to extensive local disease and one died of metastasis. For patients with non-union, revision procedure with bone graft and compression plates was successfully used. The use of autoclaved tumor grafts provides a limb salvage option that is inexpensive and independent of external resources and is a viable option for musculoskeletal tumor management in developing countries.

  7. Bilateral carotid body tumor resection in a female patient

    Directory of Open Access Journals (Sweden)

    Alfred Burgess

    Full Text Available Introduction: Carotid body tumors also called carotid paragangliomas are rare neuroendocrine neoplasms derived from neural crest cells, approximately 3% of all paragangliomas occur in the head and neck area (Xiao and She, 2015; although they represent 65% of the head and neck paragangliomas (Georgiadis et al., 2008. Presentation of case: We present the therapeutic management of a 65-year-old woman with bilateral carotid body tumors. The patient presented to medical clinic for unrelated signs and symptoms of weight loss, dyspepsia, and epigastric pain. Physical examination showed bilateral non-tender neck masses for which imaging studies were ordered resulting in the diagnosis of bilateral carotid tumor. Surgical resection was staged with one week of distance between each tumor resection. Discussion: Carotid Body Tumors can arise from the paraganglia located within the adventitia of the medial aspect of the carotid bifurcation.Resection is the only curative treatment. Carotid body tumors resection represents a special challenge due to potential neurovascular complications. Conclusions: Surgical resection of carotid body tumors represents a special challenge to the surgeon because of the complex anatomical location of the tumor, including close relationship with the cranial nerves, involvement of the carotid vessels and large vascularization of the tumor. With the advance of diagnosis and improvement in surgical techniques as well as the understanding of biological behavior of tumors, surgical treatment has become a safer alternative for treating these tumors. Keywords: Carotid body tumor, Bilateral, Paraganglioma, Resection

  8. Laparoscopic vs open distal pancreatectomy for solid pseudopapillary tumor of the pancreas

    Science.gov (United States)

    Zhang, Ren-Chao; Yan, Jia-Fei; Xu, Xiao-Wu; Chen, Ke; Ajoodhea, Harsha; Mou, Yi-Ping

    2013-01-01

    AIM: To compare short- and long-term outcomes of laparoscopic vs open distal pancreatectomy for solid pseudopapillary tumor (SPT) of the pancreas. METHODS: This retrospective study included 28 patients who underwent distal pancreatectomy for SPT of the pancreas between 1998 and 2012. The patients were divided into two groups based on the surgical approach: the laparoscopic surgery group and the open surgery group. The patients’ demographic data, operative results, pathological reports, hospital courses, morbidity and mortality, and follow-up data were compared between the two groups. RESULTS: Fifteen patients with SPT of the pancreas underwent laparoscopic distal pancreatectomy (LDP), and 13 underwent open distal pancreatectomy (ODP). Baseline characteristics were similar between the two groups except for a female predominance in the LDP group (100.0% vs 69.2%, P = 0.035). Mortality, morbidity (33.3% vs 38.5%, P = 1.000), pancreatic fistula rates (26.7% vs 30.8%, P = 0.728), and reoperation rates (0.0% vs 7.7%, P = 0.464) were similar in the two groups. There were no significant differences in the operating time (171 min vs 178 min, P = 0.755) between the two groups. The intraoperative blood loss (149 mL vs 580 mL, P = 0.002), transfusion requirement (6.7% vs 46.2%, P = 0.029), first flatus time (1.9 d vs 3.5 d, P = 0.000), diet start time (2.3 d vs 4.9 d, P = 0.000), and postoperative hospital stay (8.1 d vs 12.8 d, P = 0.029) were significantly less in the LDP group than in the ODP group. All patients had negative surgical margins at final pathology. There were no significant differences in number of lymph nodes harvested (4.6 vs 6.4, P = 0.549) between the two groups. The median follow-up was 33 (3-100) mo for the LDP group and 45 (17-127) mo for the ODP group. All patients were alive with one recurrence. CONCLUSION: LDP for SPT has short-term benefits compared with ODP. Long-term outcomes of LDP are similar to those of ODP. PMID:24115826

  9. Molecular imaging using Cu-ATSM and FDG in solid canine tumors

    DEFF Research Database (Denmark)

    Hansen, Anders Elias

    . Identification of hypoxic tumor and intratumoral hypoxic regions therefore hold the potential to serve as a basis for individualized treatment protocols, including image guided radiation therapy. The current PhD project was undertaken to study tumor hypoxia in cancer bearing dogs, with the aims of 1) identifying...... glycolysis and blood perfu- sion. 3) To compare tumor uptake of 64 Cu-ATSM and [ 18 F]fluoro-D-glucose ( 18 FDG) (glycolytic activity) to pimonidazole (immunological hypoxia marker) immunohistochemistry. 4) To investigate 18 FDG PET as a diagnostic modality in canine cancer patients. The thesis contains...

  10. Chimeric antigen receptor T cells: a novel therapy for solid tumors

    Directory of Open Access Journals (Sweden)

    Shengnan Yu

    2017-03-01

    Full Text Available Abstract The chimeric antigen receptor T (CAR-T cell therapy is a newly developed adoptive antitumor treatment. Theoretically, CAR-T cells can specifically localize and eliminate tumor cells by interacting with the tumor-associated antigens (TAAs expressing on tumor cell surface. Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. CAR-T cell therapy has achieved gratifying breakthrough in hematological malignancies and promising outcome in solid tumor as showed in various clinical trials. The third generation of CAR-T demonstrates increased antitumor cytotoxicity and persistence through modification of CAR structure. In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2, and mesothelin (MSLN, as well as the challenges for CAR-T cell therapy.

  11. Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

    International Nuclear Information System (INIS)

    Bonde, Anne-Katrine; Tischler, Verena; Kumar, Sushil; Soltermann, Alex; Schwendener, Reto A

    2012-01-01

    Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC). Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Data presented here identify a novel role for macrophages in EMT

  12. Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors.

    Directory of Open Access Journals (Sweden)

    Danika Lindsay

    2016-08-01

    Full Text Available Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the

  13. Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

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    Hamid R Molavian

    Full Text Available Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997 provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2 are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2 and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.

  14. Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

    Science.gov (United States)

    Stachler, Matthew; Jia, Yonghui; Sharaf, Nematullah; Wade, Jacqueline; Longtine, Janina; Garcia, Elizabeth; Sholl, Lynette M

    2015-01-01

    Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas.

  15. Magnetic resonance spectroscopy in patients with cerebral glial tumors

    International Nuclear Information System (INIS)

    Ugarte Moreno, Dayana; Ugarte Suarez, Jose Carlos; Pinnera Moliner, Jesus; Gonzalez, Jose Jordan

    2013-01-01

    The incidence of the intracranial primitive tumors is about 1 to 12 cases for 100 000 inhabitants per year. The most frequent tumors are gliomas that include tumors like astrocytomas benign and malignant. We studied twenty nine patients who were sent to Medical Surgical Research Center to make a magnetic resonance with spectroscopy, in a period of 18 months. The histological result was obtained by biopsy or autopsy

  16. Diagnostic Modalities for FGF23-Producing Tumors in Patients with Tumor-Induced Osteomalacia

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    Seiji Fukumoto

    2014-06-01

    Full Text Available Fibroblast growth factor 23 (FGF23 is a hormone that is produced by osteocytes and regulates phosphate and vitamin D metabolism through binding to the Klotho-FGF receptor complex. Excessive actions of FGF23 cause several kinds of hypophosphatemic rickets/osteomalacia. Tumor-induced rickets/osteomalacia (TIO is a paraneoplastic syndrome caused by overproduction of FGF23 from the responsible tumors. Because TIO is cured by complete resection of the causative tumors, it is of great clinical importance to locate these tumors. Several imaging methods including skeletal survey by magnetic resonance imaging and octreotide scintigraphy have been used to identify the tumors that cause TIO. However, none of these imaging studies indicate that the detected tumors are actually producing FGF23. Recently, systemic venous sampling was conducted for locating FGF23-producing tumor in suspected patients with TIO and demonstrated that this test might be beneficial to a subset of patient. Further studies with more patients are necessary to establish the clinical utility of venous sampling in patients with TIO.

  17. Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort.

    Science.gov (United States)

    Chi, Kwan-Hwa; Ko, Hui-Ling; Yang, Kai-Lin; Lee, Cheng-Yen; Chi, Mau-Shin; Kao, Shang-Jyh

    2015-06-30

    Autophagy is an important oncotarget that can be modulated during anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa) treatment and then inhibiting it using hydroxychloroquine (HCQ) could synergistically improve therapy outcome in cancer patients. It is still unclear whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug resistance. Twenty-five stage IV cancer patients were identified. They had no clinical response to first-line metronomic chemotherapy; the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4 lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma patients. Chemotherapy was administered for a total of 137 months. The median duration of chemotherapy cycles per patient was 4 months (95% confidence interval, 3-7 months). The overall response rate to this treatment was of 40%, with an 84% disease control rate. The most frequent and clinically significant toxicities were myelotoxicities. Grade ≥3 leucopenia occurred in 6 patients (24%), grade ≥3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them developed febrile neutropenia. Non-hematologic toxicities were fatigue (total 32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and grade V liver toxicity from hepatitis B reactivation (1 patient). Our results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a promising oncotarget and warrants further investigation in phase II studies.

  18. Tumor segmentation of whole-body magnetic resonance imaging in neurofibromatosis type 1 patients: tumor burden correlates

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    Heffler, Michael A.; Xi, Yin; Chhabra, Avneesh [University of Texas Southwestern Medical Center, Department of Radiology, Dallas, TX (United States); Le, Lu Q. [University of Texas Southwestern Medical Center, Department of Dermatology, Dallas, TX (United States)

    2017-01-15

    Segmentation of whole-body MRI (WBMRI) to assess the feasibility, quantitate the total tumor volume (tumor burden) in patients with neurofibromatosis type 1 (NF1) and examine associations with demographic, disease-related and anthropomorphic features. A consecutive series of patients with NF1 underwent WBMRI and were reviewed for tumors. Tumors were segmented using a semiautomated software-based tool. Tumors were classified as superficial or deep and discrete or plexiform. Segmentation times were recorded. Segmentation yielded the quantity and tumor burden of superficial, internal and plexiform tumors. Correlations between segmentation data and demographic, disease-related and anthropomorphic features were examined. Fifteen patients were evaluated (42.3 ± 13.6 years, 10 female, 5 male). Segmentation times were a median of 30 min and yielded 2,328 tumors (1,582 superficial, 746 internal and 23 plexiform). One tumor was malignant. Tumor counts ranged from 14 to 397. Tumor burden ranged from 6.95 cm3 to 571 cm3. Individual tumor volume ranged from 0.0120 cm3 to 298 cm3. Significant correlation was found between the total volume of superficial tumors and height (ρ = 0.5966, p < 0.02). Male patients had higher overall tumor burdens (p < 0.05) and higher superficial tumor burden (p < 0.03). Patients with negative family history had more tumors (p < 0.05). Segmentation of WBMRI in patients with NF1 is feasible and elucidates meaningful relationships among disease phenotype, anthropomorphic and demographic features. (orig.)

  19. Tumor segmentation of whole-body magnetic resonance imaging in neurofibromatosis type 1 patients: tumor burden correlates

    International Nuclear Information System (INIS)

    Heffler, Michael A.; Xi, Yin; Chhabra, Avneesh; Le, Lu Q.

    2017-01-01

    Segmentation of whole-body MRI (WBMRI) to assess the feasibility, quantitate the total tumor volume (tumor burden) in patients with neurofibromatosis type 1 (NF1) and examine associations with demographic, disease-related and anthropomorphic features. A consecutive series of patients with NF1 underwent WBMRI and were reviewed for tumors. Tumors were segmented using a semiautomated software-based tool. Tumors were classified as superficial or deep and discrete or plexiform. Segmentation times were recorded. Segmentation yielded the quantity and tumor burden of superficial, internal and plexiform tumors. Correlations between segmentation data and demographic, disease-related and anthropomorphic features were examined. Fifteen patients were evaluated (42.3 ± 13.6 years, 10 female, 5 male). Segmentation times were a median of 30 min and yielded 2,328 tumors (1,582 superficial, 746 internal and 23 plexiform). One tumor was malignant. Tumor counts ranged from 14 to 397. Tumor burden ranged from 6.95 cm3 to 571 cm3. Individual tumor volume ranged from 0.0120 cm3 to 298 cm3. Significant correlation was found between the total volume of superficial tumors and height (ρ = 0.5966, p < 0.02). Male patients had higher overall tumor burdens (p < 0.05) and higher superficial tumor burden (p < 0.03). Patients with negative family history had more tumors (p < 0.05). Segmentation of WBMRI in patients with NF1 is feasible and elucidates meaningful relationships among disease phenotype, anthropomorphic and demographic features. (orig.)

  20. Seizure prognosis of patients with low-grade tumors.

    Science.gov (United States)

    Kahlenberg, Cynthia A; Fadul, Camilo E; Roberts, David W; Thadani, Vijay M; Bujarski, Krzysztof A; Scott, Rod C; Jobst, Barbara C

    2012-09-01

    Seizures frequently impact the quality of life of patients with low grade tumors. Management is often based on best clinical judgment. We examined factors that correlate with seizure outcome to optimize seizure management. Patients with supratentorial low-grade tumors evaluated at a single institution were retrospectively reviewed. Using multiple regression analysis the patient characteristics and treatments were correlated with seizure outcome using Engel's classification. Of the 73 patients with low grade tumors and median follow up of 3.8 years (range 1-20 years), 54 (74%) patients had a seizure ever and 46 (63%) had at least one seizure before tumor surgery. The only factor significantly associated with pre-surgical seizures was tumor histology. Of the 54 patients with seizures ever, 25 (46.3%) had a class I outcome at last follow up. There was no difference in seizure outcome between grade II gliomas (astrocytoma grade II, oligodendroglioma grade II, mixed oligo-astrocytoma grade II) and other pathologies (pilocytic astrocytoma, ependymomas, DNET, gangliocytoma and ganglioglioma). Once seizures were established seizure prognosis was similar between different pathologies. Chemotherapy (p=0.03) and radiation therapy (p=0.02) had a positive effect on seizure outcome. No other parameter including significant tumor growth during the follow up period predicted seizure outcome. Only three patients developed new-onset seizures after tumor surgery that were non-perioperative. Anticonvulsant medication was tapered in 14 patients with seizures and 10 had no further seizures. Five patients underwent additional epilepsy surgery with a class I outcome in four. Two patients received a vagal nerve stimulator with >50% seizure reduction. Seizures at presentation are the most important factor associated with continued seizures after tumor surgery. Pathology does not influence seizure outcome. Use of long term prophylactic anticonvulsants is unwarranted. Chemotherapy and

  1. Smart thermosensitive liposomes for effective solid tumor therapy and in vivo imaging.

    Directory of Open Access Journals (Sweden)

    Kevin Affram

    Full Text Available In numerous studies, liposomes have been used to deliver anticancer drugs such as doxorubicin to local heat-triggered tumor. Here, we investigate: (i the ability of thermosensitive liposomal nanoparticle (TSLnp as a delivery system to deliver poorly membrane-permeable anticancer drug, gemcitabine (Gem to solid pancreatic tumor with the aid of local mild hyperthermia and, (ii the possibility of using gadolinium (Magnevist® loaded-TSLnps (Gd-TSLnps to increase magnetic resonance imaging (MRI contrast in solid tumor. In this study, we developed and tested gemcitabine-loaded thermosensitive liposomal nanoparticles (Gem-TSLnps and gadolinium-loaded thermosensitive liposomal nanoparticles (Gd-TSLnps both in in-vitro and in-vivo. The TSLnps exhibited temperature-dependent release of Gem, at 40-42°C, 65% of Gem was released within 10 min, whereas < 23% Gem leakage occurred at 37°C after a period of 2 h. The pharmacokinetic parameters and tissue distribution of both Gem-TSLnps and Gd-TSLnps were significantly greater compared with free Gem and Gd, while Gem-TSLnps plasma clearance was reduced by 17-fold and that of Gd-TSLpns was decreased by 2-fold. Area under the plasma concentration time curve (AUC of Gem-TSLnps (35.17± 0.04 μghr/mL was significantly higher than that of free Gem (2.09 ± 0.01 μghr/mL whereas, AUC of Gd-TSLnps was higher than free Gd by 3.9 fold high. TSLnps showed significant Gem accumulation in heated tumor relative to free Gem. Similar trend of increased Gd-TSLnps accumulation was observed in non-heated tumor compared to that of free Gd; however, no significant difference in MRI contrast enhancement between free Gd and Gd-TSLnps ex-vivo tumor images was observed. Despite Gem-TSLnps dose being half of free Gem dose, antitumor efficacy of Gem-TSLnps was comparable to that of free Gem(Gem-TSLnps 10 mg Gem/kg compared with free Gem 20 mg/kg. Overall, the findings suggest that TSLnps may be used to improve Gem delivery and enhance

  2. Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies.

    Science.gov (United States)

    Wu, Jiayuan; Hu, Liren; Chen, Manyu; Cao, Wenjun; Chen, Haicong; He, Taiping

    2016-01-01

    The expression of pyruvate kinase M2 (PKM2) has been linked to tumor formation and invasion. Specifically, the relationship between high PKM2 expression and prognosis has been evaluated in solid tumors of digestive system. However, the prognostic value of PKM2 remains controversial. A literature search of PubMed, Embase, and Cochrane databases was conducted until October 2015. The end point focused on overall survival (OS). The pooled hazard ratio (HR) or odds ratio and the 95% confidence intervals were calculated to correlate PKM2 overexpression with OS and clinicopathological characteristics by employing fixed- or random-effects models, depending on the heterogeneity of the included studies. We identified 18 cohorts in 16 studies involving 2,812 patients for this meta-analysis. Overall, the combined HR for OS in all tumor types was 1.74 (1.44-2.11; Pdigestive system, thereby suggesting that PKM2 might be an indicator of poor prognosis in digestive system cancers.

  3. Solid pseudopapillary neoplasm of the pancreas in pediatric patients: A case report and institutional case series

    Directory of Open Access Journals (Sweden)

    Justin B. Mahida

    2015-04-01

    Full Text Available Solid pseudopapillary neoplasm (SPN of the pancreas is a rare tumor presenting in adolescent and young adult females. A previously healthy 13 year-old female presented to our institution with abdominal pain and emesis. Imaging revealed a pancreatic cystic mass. Endoscopic ultrasound (EUS with fine needle biopsy suggested SPN. Pathologic evaluation following resection revealed immunohistochemical (IHC staining positive for β-catenin and α-1-antitrypsin despite extensive necrosis. We discuss this patient as well as our institutional series of SPN of the pancreas, describing the evaluation, management, and histopathology of this rare tumor.

  4. A novel gene therapy-based approach that selectively targets hypoxic regions within solid tumors

    International Nuclear Information System (INIS)

    Dougherty, S.T.; Dougherty, G.J.; Davis, P.D.

    2003-01-01

    There is compelling evidence that malignant cells present within the hypoxic regions that are commonly found within solid tumors contribute significantly to local recurrence following radiation therapy. We describe now a novel strategy designed to target such cells that exploits the differential production within hypoxic regions of the pro-angiogenic cytokine vascular endothelial cell growth factor (VEGF). Specifically, we have generated cDNA constructs that encode two distinct chimeric cell surface proteins that incorporate, respectively, the extracellular domains of the VEGF receptors Flk-1 or Flt-1, fused in frame to the membrane spanning and cytoplasmic domains of the pro-apoptotic protein Fas. Both chimeric proteins (Flk/Fas and Flt/Fas) appear stable and can be readily detected on the surface of transfected cells by Western blot and/or FACS analysis. Importantly, tumor cells expressing the chimeric proteins were rapidly killed in a dose-dependent fashion upon the addition of exogenous recombinant VEGF. Adenoviral vectors encoding Flk/Fas have been generated and shown to induce tumor cells to undergo apoptosis upon transfer to hypoxic conditions in vitro. This activity is dependent upon the endogenous production of VEGF. Studies are currently underway to test the ability of adenoviral Flk/Fas (Ad.Flk/Fas) to reduce tumor recurrence in vivo when used as an adjuvant therapy in conjunction with clinically relevant doses of ionizing radiation

  5. Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea eGras Navarro

    2015-04-01

    Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

  6. Multiple primary tumors in patients with uterine cancer

    International Nuclear Information System (INIS)

    Velikova, N.; Parvanova, V.; Dimitrova, N.

    2013-01-01

    Full text: Introduction: The aging population and improved medical care lead to increased likelihood for patients experienced a tumor to develop at least one more in the course of his life. The aim of the study was to analyze the clinical and biological characteristics and survival of patients with primary tumor multiplicity in which a tumor is cancer of the uterine body. Materials and Methods: For the period 1997-2007, in the department of radiotherapy were treated 191 women with carcinoma of the uterine body (in a group of moderate and high risk) with invasion of the myometrium more than one third. Patients ranged in age from 36 to 77 (average age 59.9) and were followed until 31.03.2013 with an average follow-up period 126 months. Postoperatively, all were carried intravaginal brachytherapy with high dose rate 3x5 Gy once a week, followed by percutaneous radiotherapy 22x2 Gy daily to the area of the pelvic lymph nodes. Data to diagnose combined tumors were obtained from the National Cancer Registry. Survival analysis was made by the method of Kaplan - Meier with Lograng test. Results: In 26 (13.6 %) of the analyzed patients a tumor multiplicity is find in 22 (84,6%) tumors are two in 3 (11.5 %)- three , and in 1 (3.8%) - four . A detailed analysis of 14 (53.8%) patients whose cancer of the uterine body is the first tumor and is followed by another. The distribution of the tumor according to the second location is: breast cancer 5 (35.7%) skin malignant melanoma without 4 (28.5%) of the column 3 (21.4 %) of stomach 1 (7.1%) , MALT lymphoma, 1 (7.1% ) . Evaluate and compare the 5 - and 10-year overall survival of patients whose cancer of the uterine body only, and those who are diagnosed with a malignant tumor following - in those without a second tumor is 85.3% and 81.4 %, and in the presence of such a - 78, 6% and 69.3% respectively. Conclusion: The matched tumors are the most common among the so-called hormone dependent cancers such as breast cancer, uterine

  7. 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

  8. Tumoral calcinosis, calciphylaxis, hyperparathyroidism and tuberculosis in a dialysis patient

    Directory of Open Access Journals (Sweden)

    Khawla Kammoun

    2011-01-01

    Full Text Available Tumoral calcinosis and calciphylaxis are uncommon but severe complications in ure-mic patients. They occur generally after long-term hemodialysis (HD treatment explained by ad-vanced secondary hyperparathyroidism and longstanding high calcium phosphorus product (Ca × P. Other factors such granulomatous diseases may worsen the calcium phosphate homeostasis alterations. We report a young male patient treated by HD for 6 years who developed tuberculosis in addition to tumoral calcinosis and calciphylaxis.

  9. Onconase-induced changes in radiation response and physiological parameters in solid tumors

    International Nuclear Information System (INIS)

    Lee, I.; Shui, C.; Shogen, K.; Mikulski, S.M.; Nunno, M.; Wallner, P.E.

    1996-01-01

    Purpose: Onconase (ONC), previously known as P-30 protein, is a novel basic amphibian protein isolated from eggs of the leopard frog. The original study conducted by Darzynkiewicz et al. (Cell Tissue Kinetics, 1988) demonstrated that ONC shows anti-proliferative and cytotoxic activities against several tumor cell lines in vitro. Since then, to our knowledge, no studies regarding the inhibitory effect of ONC in solid tumor models were performed. ONC is also known to inhibit cell-cycle progression from the radiation-sensitive G 1 phase to the radiation-resistant S phase. Thus, we examined the effect of ONC as a potential radiation sensitizer. The radiation response and physiological parameters were evaluated in C3H mice and/or nude mice bearing various (murine and/or human) tumor models. Materials and Method: First, we examined the effect of ONC on the cellular proliferative, as well as the clonogenic, response of various cell lines (i.e., H4IIE rat hepatoma, AsPC-1 human pancreas adenocarcinoma, DU145 human prostate carcinoma, LS174T human colon adenocarcinoma, A549 human lung carcinoma, MCaIV murine adenocarcinoma, FSaII murine fibrosarcoma, and CCL-209 bovine artery pulmonary endothelial cells) by using the MTT and clonogenic cell survival assays. Second, we determined the enhancement of radiation response before, during, and after treatment with ONC in several cell lines. Third, we determined whether ONC can inhibit the growth of solid tumors in vivo (i.e., FSaII and MCaIV in C3H mice, LS174T in nude mice). Fourth, we examined whether minocycline, an antiangiogenic agent, could amplify the tumoricidal efficacy of ONC in solid tumors. To test our hypothesis: if ONC could eradicate the outgrowth of tumor cells in confined spaces, it could lower the elevated pressure in solid tumors, we measured tumor interstitial fluid pressure (TIFP) using the wick-in-needle method, and systemic pressure using the right carotid artery cannulation method after treatment with ONC

  10. Contrast Dose and Radiation Dose Reduction in Abdominal Enhanced Computerized Tomography Scans with Single-phase Dual-energy Spectral Computerized Tomography Mode for Children with Solid Tumors

    OpenAIRE

    Tong Yu; Jun Gao; Zhi-Min Liu; Qi-Feng Zhang; Yong Liu; Ling Jiang; Yun Peng

    2017-01-01

    Background: Contrast dose and radiation dose reduction in computerized tomography (CT) scan for adult has been explored successfully, but there have been few studies on the application of low-concentration contrast in pediatric abdominal CT examinations. This was a feasibility study on the use of dual-energy spectral imaging and adaptive statistical iterative reconstruction (ASiR) for the reduction of radiation dose and iodine contrast dose in pediatric abdominal CT patients with solid tumors...

  11. Effect of fluid friction on interstitial fluid flow coupled with blood flow through solid tumor microvascular network.

    Science.gov (United States)

    Sefidgar, Mostafa; Soltani, M; Raahemifar, Kaamran; Bazmara, Hossein

    2015-01-01

    A solid tumor is investigated as porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multiscale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. The mathematical method involves processes such as blood flow through vessels and solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model predicts.

  12. Anti-infective Vaccination Strategies in Patients with Hematologic Malignancies or Solid Tumors - Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

    Science.gov (United States)

    Rieger, C T; Liss, B; Mellinghoff, S; Buchheidt, D; Cornely, O A; Egerer, G; Heinz, W J; Hentrich, M; Maschmeyer, G; Mayer, K; Sandherr, M; Silling, G; Ullmann, A; Vehreschild, M J G T; von Lilienfeld-Toal, M; Wolf, H H; Lehners, N

    2018-04-24

    Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.

  13. Oestrogen receptors in tumors of breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Levin, J; Kay, G; Da Fonseca, M [University of the Witwatersrand, Johannesburg (South Africa). Department of Nuclear Medicine; Lange, M [University of the Witwatersrand, Johannesburg (South Africa). Dept. of Surgery; De Moor, N G [University of the Witwatersrand, Johannesburg (South Africa). Department of Radiation Therapy; Savage, N [University of the Witwatersrand, Johannesburg (South Africa). Department of Physiological Chemistry

    1978-04-15

    Oestrogen receptors were measured in the cytoplasmic fraction of tumors from patients with breast cancer. Receptors were detected in 48% of patients, and 52% showed no receptors. A follow-up study of a small group of patients on hormone therapy is reported.

  14. Antibacterial activity of probiotics in bladder tumor patients

    Directory of Open Access Journals (Sweden)

    Molchanov R.N.

    2014-09-01

    Full Text Available The chronic urinary tract infection (UTI is a risk factor that worsens a natural course of bladder tumors. Using of probiotics, possessing antagonistic influence on pathogenic microflora and immunocorrection effect, for preventive maintenance and treat¬ment of a chronic UTI in bladder tumor patients is an actual and perspective direction. The goal of the research was studying antimicrobial and anti-inflammatory effect of a single bladder instillation of either lactobacilli or aerococci in bladder tumor patients. In the preoperative period a single bladder instillation with either lactobacterin or a-bacterin preparation to 35 bladder tumor patients was done. Bacteriuria, leucocyturia, lactobacilli and aerococci count in urine were measured before and in 1, 3, 6 and 24 hours after instillation. Decrease in bacteriuria level in both groups of patients was revealed. Lactobacilli and aerococci count in urine gradually decreased up to complete elimination in 24 hours (in 1 patient who received lactobacterin (12,5 % and in 9 patients who received a-bacterin. (40,9 %. Leucocyturia study did not show statistically confidence dynamics throughout the observation period in both groups. Thus, bladder instillation with lactobacterin or a-bacterin leads to suppression of uropathogenic microflora in bladder tumor patients; in the majority of patients spontaneous elimination of lactobacilli and aerococci occurs within 24 hours.

  15. Magnetite nanoparticles inhibit tumor growth and upregulate the expression of p53/p16 in Ehrlich solid carcinoma bearing mice.

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    Heba Bassiony

    Full Text Available BACKGROUND: Magnetite nanoparticles (MNPs have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues. METHOD: MNPs coated with ascorbic acid (size: 25.0±5.0 nm were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT or intraperitoneally (IP. Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry. RESULTS: Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group. CONCLUSION: MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.

  16. Glycemic Variation in Tumor Patients with Total Parenteral Nutrition

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    Jin-Cheng Yang

    2015-01-01

    Full Text Available Background: Hyperglycemia is associated with poor clinical outcomes and mortality in several patients. However, studies evaluating hyperglycemia variation in tumor patients receiving total parenteral nutrition (TPN are scarce. The aim of this study was to assess the relationship between glycemia and tumor kinds with TPN by monitoring glycemic variation in tumor patients. Methods: This retrospective clinical trial selected 312 patients with various cancer types, whose unique nutrition treatment was TPN during the monitoring period. All patients had blood glucose (BG values assessed at least six times daily during the TPN infusion. The glycemic variation before and after TPN was set as the indicator to evaluate the factors influencing BG. Results: The clinical trial lasted 7.5 ± 3.0 days adjusted for age, gender, family cancer history and blood types. There were six cancer types: Hepatic carcinoma (HC, 21.8%, rectal carcinoma (17.3%, colon carcinoma (CC, 14.7%, gastric carcinoma (29.8%, pancreatic carcinoma (11.5%, and duodenal carcinoma (DC, 4.8%. The patients were divided into diabetes and nondiabetes groups. No statistical differences in TPN glucose content between diabetes and nondiabetes groups were found; however, the tumor types affected by BG values were obvious. With increasing BG values, DC, HC and CC were more represented than other tumor types in this sequence in diabetic individuals, as well as in the nondiabetic group. BG was inclined to be more easily influenced in the nondiabetes group. Other factors did not impact BG values, including gender, body mass index, and TPN infusion duration time. Conclusions: When tumor patients are treated with TPN, BG levels should be monitored according to different types of tumors, besides differentiating diabetes or nondiabetes patients. Special BG control is needed for DC, HC and CC in both diabetic and nondiabetic patients. If BG overtly increases, positive measurements are needed to control BG

  17. Imaging of solid tumor using near-infrared emitting purple bacteria

    International Nuclear Information System (INIS)

    Moon, Sung Min; Min, Jung Joon; Kim, Sun A; Choy, Hyon E.; Bom, Hee Seung

    2005-01-01

    Rhodobacter sphaeroides 2.4.1 is α-3 purple nonsulfur eubacterium with an extensive metabolism. Under anaerobic conditions, it is able to grow by photosynthesis, respiration and fermentation. When grown photosynthetically, it uses wavelengths of light in the near-infrared and contains a reaction center that is the peripheral light-harvesting (LH2) complex. These molecules absorb and emit near-infrared light. Using this near-infrared fluorescent bacterial we investigated its targeting capacity of solid tumor in small animals. R. sphaeroides 2.4.1 strains were cultured in sistrons minimal medium A (SIS) at 32 C. Xenograft tumor model has been established by subcutaneous injection of CT26 mouse colon cancer cell line. 1X10 8 Rhodobacter sphaeroides cells suspended in 100 ul of PBS were injected via tail vein with 1-cc insulin syringe into tumor bearing mouse. In vivo fluorescence imaging has been done after 20 min to 30 days of purple bacteria using indocyanine (ICG) emission filter (Em=810∼835 nm). Near-infrared imaging signal from Rhodobacter sphaeroides was initially detected at liver for 3 days but at the necrotic region of tumor mass thereafter. Total photon flux measured 5.5X10 8 (p/s/cm 2 /sr) at Day 1. Also it was increased to 7.8X10 8 (p/s/cm 2 /sr) at 12 day. One of important characteristic is that the signal appeared only at central necrosis area. It has been monitored for 36 day. We successfully imaged cancer with near-infrared fluorescence bacteria. Our result indicate that near-infrared fluorescence purple bacteria are able to be used to monitor bacterial trafficking in living tumor models

  18. The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors

    International Nuclear Information System (INIS)

    Lee, Carol M; Tannock, Ian F

    2010-01-01

    Poor distribution of some anticancer drugs in solid tumors may limit their anti-tumor activity. Here we used immunohistochemistry to quantify the distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab in relation to blood vessels and to regions of hypoxia in human tumor xenografts. The antibodies were injected into mice implanted with human epidermoid carcinoma A431 or human breast carcinoma MDA-MB-231 transfected with ERBB2 (231-H2N) that express high levels of ErbB1 and ErbB2 respectively, or wild-type MDA-MB-231, which expresses intermediate levels of ErbB1 and low levels of ErbB2. The distribution of cetuximab in A431 xenografts and trastuzumab in 231-H2N xenografts was time and dose dependent. At early intervals after injection of 1 mg cetuximab into A431 xenografts, the concentration of cetuximab decreased with increasing distance from blood vessels, but became more uniformly distributed at later times; there remained however limited distribution and binding in hypoxic regions of tumors. Injection of lower doses of cetuximab led to heterogeneous distributions. Similar results were observed with trastuzumab in 231-H2N xenografts. In MDA-MB-231 xenografts, which express lower levels of ErbB1, homogeneity of distribution of cetuximab was achieved more rapidly. Cetuximab and trastuzumab distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic regions of tumors

  19. Pituitary tumors in patients with MEN1 syndrome

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    Luis V. Syro

    2012-01-01

    Full Text Available We briefly review the characteristics of pituitary tumors associated with multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 is an autosomal-dominant disorder most commonly characterized by tumors of the pituitary, parathyroid, endocrine-gastrointestinal tract, and pancreas. A MEDLINE search for all available publications regarding multiple endocrine neoplasia type 1 and pituitary adenomas was undertaken. The prevalence of pituitary tumors in multiple endocrine neoplasia type 1 may vary from 10% to 60% depending on the studied series, and such tumors may occur as the first clinical manifestation of multiple endocrine neoplasia type 1 in 25% of sporadic and 10% of familial cases. Patients were younger and the time between initial and subsequent multiple endocrine neoplasia type 1 endocrine lesions was significantly longer when pituitary disease was the initial manifestation of multiple endocrine neoplasia type 1. Tumors were larger and more invasive and clinical manifestations related to the size of the pituitary adenoma were significantly more frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Normalization of pituitary hypersecretion was much less frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Pituitary tumors in patients with multiple endocrine neoplasia type 1 syndrome tend to be larger, invasive and more symptomatic, and they tend to occur in younger patients when they are the initial presentation of multiple endocrine neoplasia type 1.

  20. Volumetric response classification in metastatic solid tumors on MSCT: Initial results in a whole-body setting

    International Nuclear Information System (INIS)

    Wulff, A.M.; Fabel, M.; Freitag-Wolf, S.; Tepper, M.; Knabe, H.M.; Schäfer, J.P.; Jansen, O.; Bolte, H.

    2013-01-01

    Purpose: To examine technical parameters of measurement accuracy and differences in tumor response classification using RECIST 1.1 and volumetric assessment in three common metastasis types (lung nodules, liver lesions, lymph node metastasis) simultaneously. Materials and methods: 56 consecutive patients (32 female) aged 41–82 years with a wide range of metastatic solid tumors were examined with MSCT for baseline and follow up. Images were evaluated by three experienced radiologists using manual measurements and semi-automatic lesion segmentation. Institutional ethics review was obtained and all patients gave written informed consent. Data analysis comprised interobserver variability operationalized as coefficient of variation and categorical response classification according to RECIST 1.1 for both manual and volumetric measures. Continuous data were assessed for statistical significance with Wilcoxon signed-rank test and categorical data with Fleiss kappa. Results: Interobserver variability was 6.3% (IQR 4.6%) for manual and 4.1% (IQR 4.4%) for volumetrically obtained sum of relevant diameters (p < 0.05, corrected). 4–8 patients’ response to therapy was classified differently across observers by using volumetry compared to standard manual measurements. Fleiss kappa revealed no significant difference in categorical agreement of response classification between manual (0.7558) and volumetric (0.7623) measurements. Conclusion: Under standard RECIST thresholds there was no advantage of volumetric compared to manual response evaluation. However volumetric assessment yielded significantly lower interobserver variability. This may allow narrower thresholds for volumetric response classification in the future

  1. Volumetric response classification in metastatic solid tumors on MSCT: Initial results in a whole-body setting

    Energy Technology Data Exchange (ETDEWEB)

    Wulff, A.M., E-mail: a.wulff@rad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Fabel, M. [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Freitag-Wolf, S., E-mail: freitag@medinfo.uni-kiel.de [Institut für Medizinische Informatik und Statistik, Brunswiker Str. 10, 24105 Kiel (Germany); Tepper, M., E-mail: m.tepper@rad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Knabe, H.M., E-mail: h.knabe@rad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Schäfer, J.P., E-mail: jp.schaefer@rad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Jansen, O., E-mail: o.jansen@neurorad.uni-kiel.de [Klinik für Diagnostische Radiologie, Arnold-Heller-Straße 3, Haus 23, 24105 Kiel (Germany); Bolte, H., E-mail: hendrik.bolte@ukmuenster.de [Klinik für Nuklearmedizin, Albert-Schweitzer-Campus 1, Gebäude A1, 48149 Münster (Germany)

    2013-10-01

    Purpose: To examine technical parameters of measurement accuracy and differences in tumor response classification using RECIST 1.1 and volumetric assessment in three common metastasis types (lung nodules, liver lesions, lymph node metastasis) simultaneously. Materials and methods: 56 consecutive patients (32 female) aged 41–82 years with a wide range of metastatic solid tumors were examined with MSCT for baseline and follow up. Images were evaluated by three experienced radiologists using manual measurements and semi-automatic lesion segmentation. Institutional ethics review was obtained and all patients gave written informed consent. Data analysis comprised interobserver variability operationalized as coefficient of variation and categorical response classification according to RECIST 1.1 for both manual and volumetric measures. Continuous data were assessed for statistical significance with Wilcoxon signed-rank test and categorical data with Fleiss kappa. Results: Interobserver variability was 6.3% (IQR 4.6%) for manual and 4.1% (IQR 4.4%) for volumetrically obtained sum of relevant diameters (p < 0.05, corrected). 4–8 patients’ response to therapy was classified differently across observers by using volumetry compared to standard manual measurements. Fleiss kappa revealed no significant difference in categorical agreement of response classification between manual (0.7558) and volumetric (0.7623) measurements. Conclusion: Under standard RECIST thresholds there was no advantage of volumetric compared to manual response evaluation. However volumetric assessment yielded significantly lower interobserver variability. This may allow narrower thresholds for volumetric response classification in the future.

  2. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

    Science.gov (United States)

    Shrotriya, Shiva; Walsh, Declan; Bennani-Baiti, Nabila; Thomas, Shirley; Lorton, Cliona

    2015-01-01

    A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence. MeSH (Medical Subject Heading) terms were used to search multiple electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, EBM-Cochrane). Two independent reviewers selected research papers. We also included a quality Assessment (QA) score. Reports with QA scores <50% were excluded. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) methodology was utilized for this review (S1 PRISMA Checklist). 271 articles were identified for final review. There were 45% prospective studies and 52% retrospective. 264 had intermediate QA score (≥50% but <80%); Seven were adequate (80% -100%); A high CRP was predictive of prognosis in 90% (245/271) of studies-80% of the 245 studies by multivariate analysis, 20% by univariate analysis. Many (52%) of the articles were about gastrointestinal malignancies (GI) or kidney malignancies. A high CRP was prognostic in 90% (127 of 141) of the reports in those groups of tumors. CRP was also prognostic in most reports in other solid tumors primary sites. A high CRP was associated with higher mortality in 90% of reports in people with solid tumors primary sites. This was particularly notable in GI malignancies and kidney malignancies. In other solid tumors (lung, pancreas, hepatocellular cancer, and bladder) an elevated CRP also predicted prognosis. In addition there is also evidence to support the use of CRP to help decide treatment response and identify tumor recurrence. Better designed large scale studies should be conducted to examine these issues more comprehensively.

  3. De novo appearance of primitive neuroectodermal tumor in a patient with systemic lupus erythematosus and moyamoya disease.

    Science.gov (United States)

    Park, D J; Kim, T J; Lee, H J; Lee, K E; Lee, S J; Seo, S R; Yoon, W; Moon, K S; Lee, K W; Lee, S S; Park, Y W

    2010-07-01

    Primitive neuroectodermal tumor is a rare brain tumor composed of undifferentiated or poorly differentiated neuroepithelial cells with a high malignant potential that usually occurs in children, and which is only occasionally encountered in adults. A 19-year-old female with systemic lupus erythematosus presented with right hemiparesis and a headache of 10 days duration. Brain magnetic resonance imaging showed a large solid mass with necrotic portions in the left frontoparietal lobe. Primitive neuroectodermal tumor was confirmed by a neuronavigator-guided brain biopsy. This is the first case report of primitive neuroectodermal tumor associated with systemic lupus erythematosus and moyamoya disease. This case demonstrates that brain tumors, such as primitive neuroectodermal tumor, should be included in the differential diagnosis of neurological manifestations in children and adolescent patients with systemic lupus erythematosus.

  4. Colorectal cancer patient-derived xenografted tumors maintain characteristic features of the original tumors.

    Science.gov (United States)

    Cho, Yong Beom; Hong, Hye Kyung; Choi, Yoon-La; Oh, Ensel; Joo, Kyeung Min; Jin, Juyoun; Nam, Do-Hyun; Ko, Young-Hyeh; Lee, Woo Yong

    2014-04-01

    Despite significant improvements in colon cancer outcomes over the past few decades, preclinical development of more effective therapeutic strategies is still limited by the availability of clinically relevant animal models. To meet those clinical unmet needs, we generated a well-characterized in vivo preclinical platform for colorectal cancer using fresh surgical samples. Primary and metastatic colorectal tumor tissues (1-2 mm(3)) that originate from surgery were implanted into the subcutaneous space of nude mice and serially passaged in vivo. Mutation status, hematoxylin and eosin staining, short tandem repeat profiling, and array comparative genomic hybridization were used to validate the similarity of molecular characteristics between the patient tumors and tumors obtained from xenografts. From surgical specimens of 143 patients, 97 xenograft models were obtained in immunodeficient mice (establish rate = 67%). Thirty-nine xenograft models were serially expanded further in mice with a mean time to reach a size of 1000-1500 mm(3) of 90 ± 20 d. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. Molecular analysis showed that genetic mutations, genomic alterations, and gene expression patterns of each patient tumor were also well conserved in the corresponding xenograft tumor. Xenograft animal models derived from fresh surgical sample maintained the key characteristic features of the original tumors, suggesting that this in vivo platform can be useful for preclinical development of novel therapeutic approaches to colorectal cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Intelligence Deficits in Chinese Patients with Brain Tumor: The Impact of Tumor Resection

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    Chao Shen

    2013-01-01

    Full Text Available Background. Intelligence is much important for brain tumor patients after their operation, while the reports about surgical related intelligence deficits are not frequent. It is not only theoretically important but also meaningful for clinical practice. Methods. Wechsler Adult Intelligence Scale was employed to evaluate the intelligence of 103 patients with intracranial tumor and to compare the intelligence quotient (IQ, verbal IQ (VIQ, and performance IQ (PIQ between the intracerebral and extracerebral subgroups. Results. Although preoperative intelligence deficits appeared in all subgroups, IQ, VIQ, and PIQ were not found to have any significant difference between the intracerebral and extracerebral subgroups, but with VIQ lower than PIQ in all the subgroups. An immediate postoperative follow-up demonstrated a decline of IQ and PIQ in the extracerebral subgroup, but an improvement of VIQ in the right intracerebral subgroup. Pituitary adenoma resection exerted no effect on intelligence. In addition, age, years of education, and tumor size were found to play important roles. Conclusions. Brain tumors will impair IQ, VIQ, and PIQ. The extracerebral tumor resection can deteriorate IQ and PIQ. However, right intracerebral tumor resection is beneficial to VIQ, and transsphenoidal pituitary adenoma resection performs no effect on intelligence.

  6. Bone scintigraphic patterns in patients of tumor induced osteomalacia

    International Nuclear Information System (INIS)

    Sood, Ashwani; Agarwal, Kanhaiyalal; Shukla, Jaya; Goel, Reema; Dhir, Varun; Bhattacharya, Anish; Rai Mittal, Bhagwant

    2013-01-01

    Tumor induced osteomalacia (TIO) or oncogenic osteomalacia is a rare condition associated with small tumor that secretes one of the phosphaturic hormones, i.e., fibroblast growth factor 23, resulting in abnormal phosphate metabolism. Patients may present with non-specific symptoms leading to delay in the diagnosis. Extensive skeletal involvement is frequently seen due to delay in the diagnosis and treatment. The small sized tumor and unexpected location make the identification of tumor difficult even after diagnosis of osteogenic osteomalacia. The bone scan done for the skeletal involvement may show the presence of metabolic features and the scan findings are a sensitive indicator of metabolic bone disorders. We present the bone scan findings in three patients diagnosed to have TIO

  7. Visual findings as primary manifestations in patients with intracranial tumors

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    Nazife Sefi-Yurdakul

    2015-08-01

    Full Text Available AIM:To evaluate the visual findings as primary manifestations in patients with intracranial tumors.METHODS:The medical charts of the patients with intracranial tumors who initially admitted to the Neuro-ophthalmology and Strabismus Department with ocular complaints between August 1999 and December 2012 were reviewed retrospectively. The detailed clinical history and the findings of neuro-ophthalmologic examination were recorded. Ocular symptoms and signs, the types and locations of intracranial tumors, and the duration of symptoms before the diagnosis were evaluated.RESULTS:The mean age of 11 women (61.1% and 7 men (38.9% was 42.2±11.0 (range 20-66y at the time of intracranial tumor diagnosis. Initial symptoms were transient visual obscurations, visual loss or visual field defect in 16 cases (88.9%, and diplopia in 2 cases (11.1%. Neuro-ophthalmologic examination revealed normal optic discs in both eyes of 6 patients (33.3%, paleness, atrophy or edema of optic disc in 12 patients (66.7%, and sixth cranial nerve palsy in 2 patients (11.1%. Visual acuity ranged between normal vision and loss of light perception. Cranial imaging demonstrated craniopharyngioma (n=1, plasmacytoma (n=1, meningioma (n=6; olfactory groove and tuberculum sellae, pontocerebellar angle, anterior cranial fossa, frontal vertex, suprasellar region, and pituitary macroadenoma (n=10. The mean duration between the onset of visual disturbances and the diagnosis of intracranial tumor was 9.8±18mo (range 3d-6y.CONCLUSION:The ophthalmologist is frequently the first physician to encounter a patient with clinical manifestations of intracranial tumors that may cause neurological and ocular complications. Neuro-ophthalmologic findings should be carefully evaluated to avoid a delay in the diagnosis of intracranial tumors.

  8. Visual findings as primary manifestations in patients with intracranial tumors

    Institute of Scientific and Technical Information of China (English)

    Nazife; Sefi-Yurdakul

    2015-01-01

    · AIM: To evaluate the visual findings as primary manifestations in patients with intracranial tumors.·METHODS: The medical charts of the patients with intracranial tumors who initially admitted to the Neuro-ophthalmology and Strabismus Department with ocular complaints between August 1999 and December 2012 were reviewed retrospectively. The detailed clinical history and the findings of neuro-ophthalmologic examination were recorded. Ocular symptoms and signs,the types and locations of intracranial tumors, and the duration of symptoms before the diagnosis were evaluated.·RESULTS: The mean age of 11 women(61.1%) and 7men(38.9%) was 42.2±11.0(range 20-66y) at the time of intracranial tumor diagnosis. Initial symptoms were transient visual obscurations, visual loss or visual field defect in 16 cases(88.9%), and diplopia in 2 cases(11.1%). Neuro-ophthalmologic examination revealed normal optic discs in both eyes of 6 patients(33.3%),paleness, atrophy or edema of optic disc in 12 patients(66.7%), and sixth cranial nerve palsy in 2 patients(11.1%). Visual acuity ranged between normal vision and loss of light perception. Cranial imaging demonstrated craniopharyngioma(n =1), plasmacytoma(n =1),meningioma(n =6; olfactory groove and tuberculum sellae, pontocerebellar angle, anterior cranial fossa,frontal vertex, suprasellar region), and pituitary macroadenoma(n =10). The mean duration between the onset of visual disturbances and the diagnosis of intracranial tumor was 9.8±18mo(range 3d-6y).·CONCLUSION: The ophthalmologist is frequently the first physician to encounter a patient with clinical manifestations of intracranial tumors that may cause neurological and ocular complications. Neuro-ophthalmologic findings should be carefully evaluated to avoid a delay in the diagnosis of intracranial tumors.

  9. PET/CT evaluation of response to chemotherapy in non-small cell lung cancer: PET response criteria in solid tumors (PERCIST) versus response evaluation criteria in solid tumors (RECIST).

    Science.gov (United States)

    Ding, Qiyong; Cheng, Xu; Yang, Lu; Zhang, Qingbo; Chen, Jianwei; Li, Tiannv; Shi, Haibin

    2014-06-01

    (18)F-FDG PET/CT is increasingly used in evaluation of treatment response for patients with non-small cell lung cancer (NSCLC). There is a need for an accurate criterion to evaluate the effect and predict the prognosis. The aim of this study is to evaluate therapeutic response in NSCLC with comparing PET response criteria in solid tumors (PERCIST) to response evaluation criteria in solid tumors (RECIST) criteria on PET/CT. Forty-four NSCLC patients who received chemotherapy but no surgery were studied. Chemotherapeutic responses were evaluated using (18)F-FDG PET and CT according to the RECIST and PERCIST methodologies. PET/CT scans were obtained before chemotherapy and after 2 or 4-6 cycles' chemotherapy. The percentage changes of tumor longest diameters and standardized uptake value (SUV) (corrected for lean body mass, SUL) before and after treatment were compared using paired t-test. The response was categorized into 4 levels according to RECIST and PERCIST: CR (CMR) =1, PR (PMR) =2, SD (SMD) =3, PD (PMD) =4. Pearson chi-square test was used to compare the proportion of four levels in RECIST and PERCIST. Finally the relationship between progression-free survival (PFS) and clinicopathologic parameters (such as TNM staging, percentage changes in diameters and SUL, RECIST and PERCIST results etc.) were evaluated using univariate and multivariate Cox proportional hazards regression method. The difference of percentage changes between diameters and SUL was not significant using paired t-test (t=-1.69, P=0.098). However the difference was statistically significant in the 40 cases without increasing SUL (t=-3.31, P=0.002). The difference of evaluation results between RECIST and PERCIST was not significant by chi-square test (χ(2)=5.008, P=0.171). If RECIST evaluation excluded the new lesions which could not be found or identified on CT images the difference between RECIST and PERCIST was significant (χ(2)=11.759, P=0.007). Reduction rate of SULpeak (%), RECIST and

  10. Bone marrow transplantation in the patients with malignant tumor. Studies on supralethal total body irradiation

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    Tatsuno, Ikuro; Saito, Yasuo

    1984-11-01

    Based on evidence gained from ten patients of allogeneic bone marrow transplantation (BMT) and eight patients of autologous BMT, recent knowledge on literatures of BMT and total body irradiation (TBI) is summarized. Interstitial pneumonia after BMT has a strong correlation with TBI. Low dose-rate and fractionation of TBI are seemed to reduce the lung injury, thereby reducing the incidence of nonleukemia deaths. BMT is applied to not only acute leukemia, malignant lymphoma and solid tumors but also to chronic leukemia. It is emphasized that several of the important prognostic factors are within the control of the transplantation team.

  11. Solid tumor models for the assessment of different treatment modalities. XIV. The evaluation of host and tumor response to cyclophosphamide and radiation

    International Nuclear Information System (INIS)

    Looney, W.B.; Hopkins, H.A.; MacLeod, M.S.; Ritenour, E.R.

    1979-01-01

    The effect of increasing doses of cyclophosphamide (50 to 250 mg/kg) on the time of occurrence of maximal and minimal tumor growth rates, tumor volume reduction, and linear doubling times (LDT) on the solid tumor model H-4-II-E has been determined. Tumor response to cyclophosphamide was classified as class I, tumor regression; class II, pseudo-regression; and class III, slow-down. The overall treatment efficiency (OTE) has been used to assess the magnitude of tumor volume changes after treatment. The maximum OTE occurred after 150 mg/kg of cyclophosphamide. Increasing the dose to 200 and 250 mg/kg of cyclophosphamide resulted in a decrease in OTE. Similar parameters were utilized to measure the effectiveness of increasing doses of local tumor radiation (750, 1500, 2000, 2500, 3000 and 3500R). The major increase in OTE occurs when the radiation dose is increased from 750R to 2000R. Increasing the dose further to 3500R results in smaller incremental increases in the OTE. Results of the study indicate that increasing the cyclophosphamide dose beyond a certain level (i.e., 150 mg/kg) increases mortality and morbidity without concomitant therapeutic benefit. The effects of increasing the dose of local tumor radiation on life span have given results which suggest that increasing the total radiation dose beyond a certain limit is less effective in increasing life span

  12. Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial.

    Science.gov (United States)

    Heery, Christopher R; O'Sullivan-Coyne, Geraldine; Madan, Ravi A; Cordes, Lisa; Rajan, Arun; Rauckhorst, Myrna; Lamping, Elizabeth; Oyelakin, Israel; Marté, Jennifer L; Lepone, Lauren M; Donahue, Renee N; Grenga, Italia; Cuillerot, Jean-Marie; Neuteboom, Berend; Heydebreck, Anja von; Chin, Kevin; Schlom, Jeffrey; Gulley, James L

    2017-05-01

    Avelumab (MSB0010718C) is a human IgG1 monoclonal antibody that binds to PD-L1, inhibiting its binding to PD-1, which inactivates T cells. We aimed to establish the safety and pharmacokinetics of avelumab in patients with solid tumours while assessing biological correlatives for future development. This open-label, single-centre, phase 1a, dose-escalation trial (part of the JAVELIN Solid Tumor trial) assessed four doses of avelumab (1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg), with dose-level cohort expansions to provide additional safety, pharmacokinetics, and target occupancy data. This study used a standard 3 + 3 cohort design and assigned patients sequentially at trial entry according to the 3 + 3 dose-escalation algorithm and depending on the number of dose-limiting toxicities during the first 3-week assessment period (the primary endpoint). Patient eligibility criteria included age 18 years or older, Eastern Cooperative Oncology Group performance status 0-1, metastatic or locally advanced previously treated solid tumours, and adequate end-organ function. Avelumab was given as a 1-h intravenous infusion every 2 weeks. Patients in the dose-limiting toxicity analysis set were assessed for the primary endpoint of dose-limiting toxicity, and all patients enrolled in the dose-escalation part were assessed for the secondary endpoints of safety (treatment-emergent and treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0), pharmacokinetic and pharmacodynamic profiles (immunological effects), best overall response by Response Evaluation Criteria, and antidrug antibody formation. The population for the pharmacokinetic analysis included a subset of patients with rich pharmacokinetic samples from two selected disease-specific expansion cohorts at the same study site who had serum samples obtained at multiple early timepoints. This trial is registered with ClinicalTrials.gov, number NCT

  13. Brain Tumor Database, a free relational database for collection and analysis of brain tumor patient information.

    Science.gov (United States)

    Bergamino, Maurizio; Hamilton, David J; Castelletti, Lara; Barletta, Laura; Castellan, Lucio

    2015-03-01

    In this study, we describe the development and utilization of a relational database designed to manage the clinical and radiological data of patients with brain tumors. The Brain Tumor Database was implemented using MySQL v.5.0, while the graphical user interface was created using PHP and HTML, thus making it easily accessible through a web browser. This web-based approach allows for multiple institutions to potentially access the database. The BT Database can record brain tumor patient information (e.g. clinical features, anatomical attributes, and radiological characteristics) and be used for clinical and research purposes. Analytic tools to automatically generate statistics and different plots are provided. The BT Database is a free and powerful user-friendly tool with a wide range of possible clinical and research applications in neurology and neurosurgery. The BT Database graphical user interface source code and manual are freely available at http://tumorsdatabase.altervista.org. © The Author(s) 2013.

  14. Mutational analysis of circulating tumor cells from colorectal cancer patients and correlation with primary tumor tissue.

    Directory of Open Access Journals (Sweden)

    Anna Lyberopoulou

    Full Text Available Circulating tumor cells (CTCs provide a non-invasive accessible source of tumor material from patients with cancer. The cellular heterogeneity within CTC populations is of great clinical importance regarding the increasing number of adjuvant treatment options for patients with metastatic carcinomas, in order to eliminate residual disease. Moreover, the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies than simple CTCs counting. In the present study we investigated the feasibility to detect KRAS, BRAF, CD133 and Plastin3 (PLS3 mutations in an enriched CTCs cell suspension from patients with colorectal cancer, with the hypothesis that these genes` mutations are of great importance regarding the generation of CTCs subpopulations. Subsequently, we compared CTCs mutational status with that of the corresponding primary tumor, in order to access the possibility of tumor cells characterization without biopsy. CTCs were detected and isolated from blood drawn from 52 colorectal cancer (CRC patients using a quantum-dot-labelled magnetic immunoassay method. Mutations were detected by PCR-RFLP or allele-specific PCR and confirmed by direct sequencing. In 52 patients, discordance between primary tumor and CTCs was 5.77% for KRAS, 3.85% for BRAF, 11.54% for CD133 rs3130, 7.69% for CD133 rs2286455 and 11.54% for PLS3 rs6643869 mutations. Our results support that DNA mutational analysis of CTCs may enable non-invasive, specific biomarker diagnostics and expand the scope of personalized medicine for cancer patients.

  15. A Case of Recurrent Solid Pseudopapillary Tumor of the Pancreas with Involvement of the Spleen and Kidney

    OpenAIRE

    Park, Sang Eun; Park, Nam Sook; Chun, Jae Min; Park, Nam Whan; Yang, Young Joon; Yun, Gak Won; Lee, Hyo Jin; Yun, Hwan Jung; Jo, Deog Yeon; Song, Kyu Sang; Kim, Samyong

    2006-01-01

    Solid pseudopapillary tumor of the pancreas (SPTP) is a rare primary pancreatic tumor of an unknown etiology that is usually diagnosed in adolescent girls and young women. Most SPTPs are considered to be benign and only rarely metastasize. We report here on a 27-year old woman with recurrent SPTP with involvement of both the spleen and left kidney at the time of the initial diagnosis, and with aggressive behavior. In July 1995, she was admitted with abdominal discomfort and mass. She underwen...

  16. Pan-cancer stratification of solid human epithelial tumors and cancer cell lines reveals commonalities and tissue-specific features of the CpG island methylator phenotype.

    Science.gov (United States)

    Sánchez-Vega, Francisco; Gotea, Valer; Margolin, Gennady; Elnitski, Laura

    2015-01-01

    The term CpG island methylator phenotype (CIMP) has been used to describe widespread DNA hypermethylation at CpG-rich genomic regions affecting clinically distinct subsets of cancer patients. Even though there have been numerous studies of CIMP in individual cancer types, a uniform analysis across tissues is still lacking. We analyze genome-wide patterns of CpG island hypermethylation in 5,253 solid epithelial tumors from 15 cancer types from TCGA and 23 cancer cell lines from ENCODE. We identify differentially methylated loci that define CIMP+ and CIMP- samples, and we use unsupervised clustering to provide a robust molecular stratification of tumor methylomes for 12 cancer types and all cancer cell lines. With a minimal set of 89 discriminative loci, we demonstrate accurate pan-cancer separation of the 12 CIMP+/- subpopulations, based on their average levels of methylation. Tumor samples in different CIMP subclasses show distinctive correlations with gene expression profiles and recurrence of somatic mutations, copy number variations, and epigenetic silencing. Enrichment analyses indicate shared canonical pathways and upstream regulators for CIMP-targeted regions across cancer types. Furthermore, genomic alterations showing consistent associations with CIMP+/- status include genes involved in DNA repair, chromatin remodeling genes, and several histone methyltransferases. Associations of CIMP status with specific clinical features, including overall survival in several cancer types, highlight the importance of the CIMP+/- designation for individual tumor evaluation and personalized medicine. We present a comprehensive computational study of CIMP that reveals pan-cancer commonalities and tissue-specific differences underlying concurrent hypermethylation of CpG islands across tumors. Our stratification of solid tumors and cancer cell lines based on CIMP status is data-driven and agnostic to tumor type by design, which protects against known biases that have hindered

  17. Diagnostic accuracy of diffusion-weighted imaging with conventional MR imaging for differentiating complex solid and cystic ovarian tumors at 1.5T

    Directory of Open Access Journals (Sweden)

    Zhang Ping

    2012-11-01

    Full Text Available Abstract Background Preoperative characterization of complex solid and cystic adnexal masses is crucial for informing patients about possible surgical strategies. Our study aims to determine the usefulness of apparent diffusion coefficients (ADC for characterizing complex solid and cystic adnexal masses. Methods One-hundred and 91 patients underwent diffusion-weighted (DW magnetic resonance (MR imaging of 202 ovarian masses. The mean ADC value of the solid components was measured and assessed for each ovarian mass. Differences in ADC between ovarian masses were tested using the Student’s t-test. The receiver operating characteristic (ROC was used to assess the ability of ADC to differentiate between benign and malignant complex adnexal masses. Results Eighty-five patients were premenopausal, and 106 were postmenopausal. Seventy-four of the 202 ovarian masses were benign and 128 were malignant. There was a significant difference between the mean ADC values of benign and malignant ovarian masses (p -3 mm2/s may be the optimal one for differentiating between benign and malignant tumors. Conclusions A high signal intensity within the solid component on T2WI was less frequently in benign than in malignant adnexal masses. The combination of DW imaging with ADC value measurements and T2-weighted signal characteristics of solid components is useful for differentiating between benign and malignant ovarian masses.

  18. Aberrant paramagnetic signals outside the tumor volume on routine surveillance MRI of brain tumor patients.

    Science.gov (United States)

    Yust-Katz, Shlomit; Inbar, Edna; Michaeli, Natalia; Limon, Dror; Siegal, Tali

    2017-09-01

    Late complications of cerebral radiation therapy (RT) involve vascular injury with acquired cavernous malformation, telangiectasias and damage to vascular walls which are well recognized in children. Its incidence in adults is unknown. Blood products and iron deposition that accompany vascular injury create paramagnetic effects on MRI. This study retrospectively investigated the frequency of paramagnetic lesions on routine surveillance MRI of adult brain tumor patients. MRI studies of 115 brain tumor patients were reviewed. Only studies containing sequences of either susceptibility weighted images or gradient echo or blood oxygenation level dependent imaging were included. Lesions inside the tumor volume were not considered. 68 studies fulfilled the above criteria and included 48 patients with previous RT (35 followed for >2 years and 13 for 1 year) and 20 patients who were not treated with RT. The median age at time of irradiation was 47 years. Aberrant paramagnetic lesions were found in 23/35 (65%) patients followed for >2 years after RT and in only 1/13 (8%) patients followed for 1-year after radiation (p = 0.03). The 1-year follow-up group did not differ from the control group [2/20 (9%)]. Most lesions were within the radiation field and none of the patients had related symptomatology. The number and incidence of these lesions increased with time and amounted to 75% over 3 years post RT. MRI paramagnetic signal aberrations are common findings in adult brain tumor patients that evolve over time after RT. The clinical significance of these lesions needs further investigation.

  19. Factors affecting intellectual outcome in pediatric brain tumor patients

    International Nuclear Information System (INIS)

    Ellenberg, L.; McComb, J.G.; Siegel, S.E.; Stowe, S.

    1987-01-01

    A prospective study utilizing repeated intellectual testing was undertaken in 73 children with brain tumors consecutively admitted to Childrens Hospital of Los Angeles over a 3-year period to determine the effect of tumor location, extent of surgical resection, hydrocephalus, age of the child, radiation therapy, and chemotherapy on cognitive outcome. Forty-three patients were followed for at least two sequential intellectual assessments and provide the data for this study. Children with hemispheric tumors had the most general cognitive impairment. The degree of tumor resection, adequately treated hydrocephalus, and chemotherapy had no bearing on intellectual outcome. Age of the child affected outcome mainly as it related to radiation. Whole brain radiation therapy was associated with cognitive decline. This was especially true in children below 7 years of age, who experienced a very significant loss of function after whole brain radiation therapy

  20. 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

  1. Effect of Au-dextran NPs as anti-tumor agent against EAC and solid tumor in mice by biochemical evaluations and histopathological investigations.

    Science.gov (United States)

    Medhat, Dalia; Hussein, Jihan; El-Naggar, Mehrez E; Attia, Mohamed F; Anwar, Mona; Latif, Yasmine Abdel; Booles, Hoda F; Morsy, Safaa; Farrag, Abdel Razik; Khalil, Wagdy K B; El-Khayat, Zakaria

    2017-07-01

    Dextran-capped gold nanoparticles (Au-dextran NPs) were prepared exploiting the natural polysaccharide polymer as both reducing and stabilizing agent in the synthesis process, aiming at studying their antitumor effect on solid carcinoma and EAC-bearing mice. To this end, Au-dextran NPs were designed via simple eco-friendly chemical reaction and they were characterized revealing the monodispersed particles with narrow distributed size of around 49nm with high negative charge. In vivo experiments were performed on mice. Biochemical analysis of liver and kidney functions and oxidation stress ratio in addition to histopathological investigations of such tumor tissues were done demonstrating the potentiality of Au-dextran NPs as antitumor agent. The obtained results revealed that EAC and solid tumors caused significant increase in liver and kidney functions, liver oxidant parameters, alpha feto protein levels and diminished liver antioxidant accompanied by positive expression of tumor protein p53 of liver while the treatment with Au-dextran NPs for both types caused improvement in liver and kidney functions, increased liver antioxidant, increased the expression level of B-cell lymphoma 2 gene and subsequently suppressed the apoptotic pathway. As a result, the obtained data provides significant antitumor effects of the Au-dextran NPs in both Ehrlich ascites and solid tumor in mice models. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. On complex preparation for radiotherapy of prostatic tumor patients

    International Nuclear Information System (INIS)

    Tkachev, S.I.

    1980-01-01

    An experience with the treatment of 62 patients with prostatic gland tumor has contributed to the elaboration of some approaches to the utilization of modern diagnostic facilities in order to define the spread of neoplastic process and select therapeutic tactics. A sequence of methods to be used has been described, including clinical and X-ray, radioisotope and ultrasonic methods of examination. The matter of particular attention is a newly developed method of the prostatic gland cranio-caudal size determination. The latter together with ultrasonic data enable one to detect the size of the tumor and select an adequate physico-technical regime of irradiation for each individual patient

  3. Regorafenib in Treating Patients With Advanced or Metastatic Neuroendocrine Tumors

    Science.gov (United States)

    2017-04-18

    Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Pancreatic Polypeptide Tumor; Pulmonary Carcinoid Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Somatostatinoma

  4. Field distribution and DNA transport in solid tumors during electric field-mediated gene delivery.

    Science.gov (United States)

    Henshaw, Joshua W; Yuan, Fan

    2008-02-01

    Gene therapy has a great potential in cancer treatment. However, the efficacy of cancer gene therapy is currently limited by the lack of a safe and efficient means to deliver therapeutic genes into the nucleus of tumor cells. One method under investigation for improving local gene delivery is based on the use of pulsed electric field. Despite repeated demonstration of its effectiveness in vivo, the underlying mechanisms behind electric field-mediated gene delivery remain largely unknown. Without a thorough understanding of these mechanisms, it will be difficult to further advance the gene delivery. In this review, the electric field-mediated gene delivery in solid tumors will be examined by following individual transport processes that must occur in vivo for a successful gene transfer. The topics of examination include: (i) major barriers for gene delivery in the body, (ii) distribution of electric fields at both cell and tissue levels during the application of external fields, and (iii) electric field-induced transport of genes across each of the barriers. Through this approach, the review summarizes what is known about the mechanisms behind electric field-mediated gene delivery and what require further investigations in future studies.

  5. Radiation Therapy Intensification for Solid Tumors: A Systematic Review of Randomized Trials

    Energy Technology Data Exchange (ETDEWEB)

    Yamoah, Kosj [Department of Radiation Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL (United States); Showalter, Timothy N. [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Ohri, Nitin, E-mail: ohri.nitin@gmail.com [Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York (United States)

    2015-11-15

    Purpose: To systematically review the outcomes of randomized trials testing radiation therapy (RT) intensification, including both dose escalation and/or the use of altered fractionation, as a strategy to improve disease control for a number of malignancies. Methods and Materials: We performed a literature search to identify randomized trials testing RT intensification for cancers of the central nervous system, head and neck, breast, lung, esophagus, rectum, and prostate. Findings were described qualitatively. Where adequate data were available, pooled estimates for the effect of RT intensification on local control (LC) or overall survival (OS) were obtained using the inverse variance method. Results: In primary central nervous system tumors, esophageal cancer, and rectal cancer, randomized trials have not demonstrated that RT intensification improves clinical outcomes. In breast cancer and prostate cancer, dose escalation has been shown to improve LC or biochemical disease control but not OS. Radiation therapy intensification may improve LC and OS in head and neck and lung cancers, but these benefits have generally been limited to studies that did not incorporate concurrent chemotherapy. Conclusions: In randomized trials, the benefits of RT intensification have largely been restricted to trials in which concurrent chemotherapy was not used. Novel strategies to optimize the incorporation of RT in the multimodality treatment of solid tumors should be explored.

  6. Novel systemic treatment options for advanced solid tumors with or without central nervous system metastases or malignant glioma

    NARCIS (Netherlands)

    Milojkovic Kerklaan, B.

    2015-01-01

    Chemotherapy is a very frequently used therapy in patients with advanced tumors with or without central nervous system (CNS) metastases or primary brain tumors. Despite the significant progress in drug development, the survival of patients is limited with an unmet need for more effective

  7. Selective changes in expression of HLA class I polymorphic determinants in human solid tumors

    International Nuclear Information System (INIS)

    Natali, P.G.; Nicotra, M.R.; Bigotti, A.; Venturo, I.; Giacomini, P.; Marcenaro, L.; Russo, C.

    1989-01-01

    Analysis of surgical biopsies with monoclonal antibodies (mAbs) to framework determinants of major histocompatibility complex class I antigens has shown that malignant transformation is frequently associated with a marked loss of these cell surface molecules. The present study sought to determine whether more selective losses of major histocompatibility complex class I expression occur. Multiple specimens from 13 different types of primary and metastatic tumors were tested utilizing mAb BB7.2, which recognizes a polymorphic HLA-A2 epitope. In each case, expression of HLA-A,B,C molecules was determined by testing with mAb W6/32 directed to a framework HLA class I determinant. The authors have found that in HLA-A2-positive patients, HLA-A2 products are not detectable or are reduced in their expression in 70-80% of endometrial, colorectal, mammary, and renal tumors; in 40-60% of soft-tissue, skin, ovary, urinary bladder, prostate, and stomach tumors; and in 25-30% of melanomas and lung carcinomas tested. All tumors expressed the framework HLA-A,B.C determinant. The HLA-A2 epitope recognized by mAb BB7.2 is located in a portion of the HLA-A2 molecule postulated to react with the T-cell receptor. The selective loss of an HLA class I polymorphic epitope shown in this study may explain the mechanism by which tumor cells escape both T-cell recognition and natural killer cell surveillance

  8. Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis.

    Science.gov (United States)

    Wu, Jiayuan; Hu, Liren; Wu, Fenping; Zou, Lei; He, Taiping

    2017-05-09

    Several previous studies have reported the prognostic value of hexokinase 2 (HK2) in digestive system tumors. However, these studies were limited by the small sample sizes and the results were inconsistent among them. Therefore, we conducted a meta-analysis based on 15 studies with 1932 patients to assess the relationship between HK2 overexpression and overall survival (OS) of digestive system malignancies. The relationship of HK2 and clinicopathological features was also evaluated. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CI) were calculated to estimate the effect size. Positive HK2 expression showed poor OS in all tumor types (HR = 1.75 [1.41-2.18], P digestive system cancers.

  9. Caring for patients with brain tumor: The patient and care giver ...

    African Journals Online (AJOL)

    Background: Patients with brain tumors form a heterogeneous group in terms of clinical presentation and pathology. However, the impact of the disease on patients' families is often more homogenous and frequently quite profound. A considerable body of literature is available on the management of brain tumors and ...

  10. Investigation of the effects of long-term infusion of 125I-iododeoxyuridine on tumor growth in mice (solid mouse tumor sarcoma-180)

    International Nuclear Information System (INIS)

    Wirtz, F.

    1987-05-01

    The present experiments were designed to test the therapeutic qualification of 125 I incorporated in DNA of tumor cells. The tumor-host system used was the solid mouse tumor sarcoma-180 growing on female albino mice (NMRI). A device was built which makes it possible to intravenously infuse tumor bearing mice with solutions of 125 IUdR for several weeks. Three or, respectively, 5 days before the onset of the infusions the mice were inocculated into the right hind leg with 3x10 5 tumor cells in 0.1 ml physiological salt solution. The total activity administered per mouse was 100 μCi infused during a period of 10 days. After termination of the infusions tumor sizes and retained radioactivities were measured every 5 days until death of the animals occured. In comparison with tumors of control animals tumors of mice infused with 125 IUdR showed a mean retardation in growth of about 27% of the volumes of control tumors during the total period of post-infusion observation (25 days). Extension of life expectancy and an increase of the rate of final tumor regression did not occur. Likewise, no significant differences were observed between tumors which were 3 or 5 days old on the first day of infusion. After termination of the infusions the residual whole-body radioactivity per mouse was about 1% of the total activity infused per animal. This was in good agreement with calculations considering rates of incorporation and excretion and confirmed earlier assumptions that only about 5% of the administered IUdR is incorporated initially. The number further confirmed that, during the first 10 days after incorporation, the daily loss of activity - due to cell death - is about 30%. Control animals without tumors showed a faster decrease of incorporated activity or, respectively, loss of cells than tumor bearing mice. This difference could in part be explained by an exhaution of the short-lived cell populations of the reticulo-endothelial system of tumor bearing animals. (orig

  11. Antitumor Effect of Selenium and Modified Pectin Nano Particles and Gamma Radiation on Ehrilch Solid Tumor in Female Mice

    International Nuclear Information System (INIS)

    Mansour, S. Z.; Anis, L.M.; EI- Batal, A.I.

    2010-01-01

    Selenium nano particle (Nano- Se) is a novel Se species with novel biological activities with low toxicity. The aim of the present work was to evaluate the antitumor activity of a novel Nano- Se compound with or without gamma irradiation of female mice. Selenium size- controlled Nano-Se was prepared by a simple method by adding modified pectin to the selenious acid and ascorbic acid. The antitumor activity of Selenium and Modified Pectin Nano Particles (Se-Mp- NPs) were evaluated against Ehrilch ascites carcinoma (In vitro) and Ehrilch solid tumor model (In vivo). The antioxidant states of the novel compound were assessed measuring parameters in blood and tumor tissue of female mice. Malonaldehydoyl (MDA) end product of lipid peroxidation was evaluated in plasma and tumor tissue. Glutathione -S- transferase (GST) and cytochrome P450 (Cyto P450) were determined in tumor tissue homogenate. Tumor necrosis factor alpha (TNF- a) concentration and interleukin 10 (IL- 10) concentrations was evaluated in plasma of female mice. The effect of tumor inoculation and different treatments on liver enzymes (ALT and AST) and kidney Function (urea and creatinine) were detected in the plasma of animals. Apoptosis was shown and estimated in tumor tissue of animals histopathological of tumor in different groups of mice were examined. Ehrilch solid tumor induced a significant increase in MDA content, GSH-Px and GST activities level and in the amount of metabolites of CYP 450. Moreover, a significant decrease was observed in GSH content, SOD activity level in the tumor tissue, INF- a concentration, IL- 10 concentration in the plasma. Also, a significant alteration in kidney and liver functions was occurred as compared to control group. The results showed a significant antitumor activity of selenium and Modified Pectin Nano Particles (Se-Mp- NPs) at the concentration 2.25 μg / ml was 70%

  12. One Hundred Twenty-One Resected Solid Pseudopapillary Tumors of the Pancreas: An 8-Year Single-Institution Experience at Zhongshan Hospital, Shanghai, China.

    Science.gov (United States)

    Xu, Yadong; Zhao, Guochao; Pu, Ning; Nuerxiati, Abulimiti; Ji, Yuan; Zhang, Lei; Rong, Yefei; Lou, Wenhui; Wang, Dansong; Kuang, Tiantao; Xu, Xuefeng; Wu, Wenchuan

    2017-09-01

    The aims of this study were to introduce our experience with treating patients with pancreatic solid pseudopapillary tumors (SPTs) and to investigate the clinical risk factors for recurrence of SPTs because no consensus has been established to date. One hundred twenty-one patients underwent surgical resection from January 2008 to December 2015 in our institution. Clinical data were collected from the standardized reports. Of the 121 patients, 93 (76.9%) were women, 28 (23.1%) were men, and the mean age at diagnosis was 33.7 years (range, 11-68 years). Sixty patients were subjected to short-term complications, and 8 patients experienced long-term complications, some of whom may require surgery. The tumor located in the distal pancreas (P = 0.02), and a Ki-67 index value > 1.5 (P = 0.01) indicated malignancy according to the World Health Organization 2000 classification. One hundred three patients responded to follow-up, and 3 cases (2.9%) were subject to liver metastases. Recurrence was more frequently observed in tumors classified as high-grade malignancies according to the World Health Organization 2010 classification (P = 0.013), synchronous metastases (P < 0.001), peripancreatic fat infiltration (P = 0.018), and lymphovascular invasion (P < 0.001). Evaluating the risk of the recurrence of SPTs still requires systematic and multicenter trials in the future, even some pathological features showed statistical differences.

  13. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors

    DEFF Research Database (Denmark)

    Sempere, Lorenzo F; Preis, Meir; Yezefski, Todd

    2010-01-01

    of altered miRNA expression in solid tumors, we developed a sensitive fluorescence-based in situ hybridization (ISH) method to visualize miRNA accumulation within individual cells in formalin-fixed, paraffin-embedded tissue specimens. This ISH method was implemented to be compatible with routine clinical...

  14. Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

    Science.gov (United States)

    Lassau, Nathalie; Bonastre, Julia; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe-Devilliers, Catherine; Gallix, Benoit; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis-Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Feutray, Sylvaine; Uzan-Augui, Joëlle; Coiffier, Benedicte; Benastou, Baya; Koscielny, Serge

    2014-12-01

    Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it

  15. Incidence of second solid cancer in patients after treatment of Hodgkin's disease

    International Nuclear Information System (INIS)

    Glanzmann, C.; Veraguth, A.; Luetolf, U.M.

    1994-01-01

    340 patients had curative treatment with mantle or paraaortic and pelvic radiotherapy (1964 to 1972) or mantle plus paraaortic and spleen or splenic pedicle or total nodal radiotherapy with or without chemotherapy (1973 to 1992). Since 1987, after chemotherapy only modified involved fields were irradiated. All seconds tumors have been histologically verified. The cumulative incidence of second solid cancer of the patients have been compared with the age and sex specific expected rates according to the ''Zuercher Krebsregister 1980 to 1990''. We observed seven patients with leucemia after radiotherapy plus chemotherapy, five patients with non-Hodgkin-lymphoma and 21 patients with solid cancers after radiotherapy or radiotherapy and chemotherapy with a cumulative risk of all second malignancies of 7,0% (ten years), 30.7% (20 years) and 40,5% (24 years). Cumulative risk of second solid cancer was 3,1% (ten years), 9,3% (15 years), 23,5% (20 years) and 34,3% (24 years). Cumulative risk of second solid cancer was significantly higher than expected with no decrease of the relative risk after more than 20 years of follow-up. We observed a significantly higher risk of breast cancer in women less than 30 years of age at treatment. Relative risk of second solid cancer was higher after radiotherapy plus chemotherapy compared to radiotherapy alone, but the difference was not statistically significant. Nearly all patients with radiotherapy plus chemotherapy and a follow-up of ten years or more had radiotherapy with large fields. (orig./MG) [de

  16. Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

    Science.gov (United States)

    Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

    2016-09-01

    Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

  17. Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

    International Nuclear Information System (INIS)

    Valous, Nektarios A.; Lahrmann, Bernd; Halama, Niels; Grabe, Niels; Bergmann, Frank; Jäger, Dirk

    2016-01-01

    not only on percentage content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. Conclusions: The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

  18. Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors.

    Science.gov (United States)

    Valous, Nektarios A; Lahrmann, Bernd; Halama, Niels; Bergmann, Frank; Jäger, Dirk; Grabe, Niels

    2016-06-01

    content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

  19. Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Valous, Nektarios A. [Applied Tumor Immunity Clinical Cooperation Unit, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg 69120 (Germany); Lahrmann, Bernd; Halama, Niels; Grabe, Niels [Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg 69120 (Germany); Bergmann, Frank [Institute of Pathology, Heidelberg University Hospital, Heidelberg 69120 (Germany); Jäger, Dirk [Department of Medical Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg 69120, Germany and National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg 69120 (Germany)

    2016-06-15

    not only on percentage content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. Conclusions: The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance.

  20. CD 99 immunocytochemistry in solid pseudopapillary tumor of pancreas: A study on fine-needle aspiration cytology smears.

    Science.gov (United States)

    Ghosh, Ranajoy; Mallik, Saumya R; Mathur, Sandeep R; Iyer, Venkateswaran K

    2013-07-01

    Solid pseudopapillary tumor of pancreas (SPTP) is a rare pancreatic tumor of uncertain histogenesis usually affecting young women. Though these tumors have characteristic cytomorphology, it is sometimes difficult to differentiate them from neuroendocrine tumors of the pancreas. We reviewed cases of SPTP to delineate the diagnostic cytological features and also observed utility of CD 99 (MIC 2) immunostaining to aid in the diagnosis of this tumor. This study was designed to demonstrate the utility of CD 99 immunostaining along with cytological features for making a pre-operative diagnosis and delineating it from the neuroendocrine tumor of pancreas which is a close mimic. Cytomorphological features of 11 cases of solid pseudopapillary neoplasm diagnosed by pre-operative fine-needle aspiration cytology (FNAC) at our institute were reviewed. Immunocytochemistry for CD 99 was also performed on the smears. All the cases had cellular smears with monomorphic cells lying singly, as loosely cohesive clusters as well as forming delicate pseudopapillae. Presence of intra and extra-cellular basement membrane material, background foamy macrophages and nuclear grooves were the other salient features. Immunocytochemistry for CD 99 could be performed on eight cases and demonstrated typical paranuclear dot-like positivity. Pre-operative early diagnosis of SPTP can be made by FNAC which can further be aided by CD 99 immunocytochemistry.

  1. Serum IgE levels in patients with intracranial tumors

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    George A Alexiou

    2015-03-01

    Full Text Available Aim: Several epidemiological studies have shown an inverse correlation between allergy and brain cancer. The purpose of this study was to compare the serum IgE levels between patients with gliomas and nonglial tumors and their possible prognostic role. Methods: A total of 84 patients with intracranial tumors were included in this study. At clinical presentation, estimation of serum IgE levels was assessed by nephelometry. Detailed information regarding the history of allergies was collected by interview. Results: Of the 84 cases, 42 were gliomas, 23 were meningiomas, 16 were metastases and 3 were primary central nervous system lymphomas. Patients with high-grade glioma had lower IgE levels than patients with low-grade glioma. Patients with glioma and meningioma had statistical significant lower serum IgE levels than patients with metastases. Patients with glioblastoma with serum IgE levels greater than 24 U/mL had a better survival. Conclusion: Patients with glioma and meningioma had lower IgE levels than patients with metastatic lesions. A prognostic role of serum IgE levels was found in glioblastoma. Further studies in larger patient series are required in order to verify our preliminary observations.

  2. SERTOLI-LEYDIG CELL TUMOR; A RARE CASE IN A POSTMENOPAUSAL PATIENT – CASE REPORT

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    Petra Krajnc

    2018-02-01

    Full Text Available Background. Sertoli-Leydig cell tumors belong to the group of sex cord stromal tumors of the ovary. They account for less than 0.5 % of all ovarian tumors and occur primarily in young women between 20 and 30 years of age. This type of tumors can secrete androgens, causing virilisation, and are extremely rarely presented in postmenopausis. Methods. A 73-year old multiparous woman was presented to our institution with complaints of abdominal distention and abdominal pain in her lower abdomen. On physical examination, she had a large, fixed palpable abdominal mass, approximately 20 cm in diameter, arising from the pelvis. The laboratoric tests revealed an elevated level of CA125 of 221.3 U/ml of serum. The ultrasound showed a complex cystic and solid pelvic tumor. There was no sign of ascites. Her hormonal status was within normal range and she also showed no signs of virilisation. On laparotomy a complex left ovarian mass, measuring 30 × 27 × 15 cm was found and sent to frozen section. The result of frozen section was a malignant tumor of unknown origin, therefore a radical surgical procedure was performed. The histopathological examination established the diagnosis of a malignant Sertoli-Leydig cell tumor of the left ovary, of intermediate differentiation. Other removed tissue was free of malignant cells. The early postoperative course was uneventful and the patient was released from hospital 10 days after surgery. However, she returned to our institution 16 days after surgery due to a proximal thrombosis of v. saphena magna. The patient was treated with low-molecularweight heparin and later warfarin for 6 weeks post operation. 16 months after the operation she was symptomatically treated for severe microcytic anemia. She showed no signs of a relapse. 27 months after primary surgery she was operated for the second time due to acute bowel obstruction. She had large masses of necrotic tumor removed from abdomen and transversostomia was performed

  3. Application of 10BSH entrapped transferrin-PEG-liposome to boron neutron-capture therapy (BNCT) for solid tumor

    International Nuclear Information System (INIS)

    Maruyama, K.; Ishida, O.; Iwatsuru, M.; Yanagie, H.; Eriguchi, M.; Kobayashi, H.

    2000-01-01

    The successful treatment of cancer by BNCT requires the selective concentration of 10 B within malignant tumor cells. Intracellular targeting ability and cytotoxic effects of 10 B entrapped TF-PEG-liposomes, in which TF is covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes, were examined in Colon 26 tumor-bearing mice. TF-PEG-liposomes readily bound to tumor cells in vivo, and were internalized by receptor-mediated endocytosis. 10 B-PEG-liposomes and 10 B-TF-PEG-liposomes showed prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue and reached high level of 10 B content in tumor. After thermal neutron irradiation of mice injected with 10 B-PEG-liposomes or 10 B-TF-PEG-liposome, tumor growth was suppressed relative to controls. These results suggest that intravenous injection of 10 B TF-PEG-liposome can increase the intracellular retention of 10 B atoms, which were introduced by receptor mediated endocytosis after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. (author)

  4. Pelvic pain in a young patient: Sclerosing stromal tumor

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    Huriye Ayşe Parlakgümüş

    2013-03-01

    Full Text Available Introduction: Sclerosing stromal tumors are rare, benign sex chord stromal tumors. They are usually unilateral and are seen in second or third decades. The complaint at admission may be menstrual irregularity, pelvic pain, palpable pelvic mass, precocious puberty and postmenopausal bleeding. Because the complaint at admission and radiological findings are not specific to SSTs preoperative diagnosis is challenging. Herein we present the sonographical, intraoperative and histopathological findings of a SST diagnosed during laparoscopy in a patient who admitted with chronic pelvic pain and received pelvic inflammatory disease and endometriosis treatment and differential diagnosis of SSTs with the other ovarian tumors. Case report: 24 years old nulliparous patient first admitted to the gynecology department with the complaint of foul smelling vaginal discharge and pelvic pain. The diagnosis was pelvic inflammatory disease and the patient received antibiotics. The pelvic examination was normal except the mass in the right ovary which had similar echogenity to the ovary. Because of the pelvic pain the mass was assumed to be an endometrioma and the patient was prescribed an oral contraceptive treatment for 3 months. Because of the persistent pelvic pain a diagnostic laparoscopy was performed which revealed a 2 cm, pinkish- white, exophytic lesion originating from the right ovary. Pathological examination reported the mass to be a sclerosing stromal tumor. After the treatment the patient no longer complained of vaginal discharge but pelvic pain still persisted. After the operation the patient no longer complained of pelvic pain. Conclusion: Although SSTs are rare, they should be kept in mind when a young patient admits with menstrual irregularity, pelvic pain and hirsutism, particularly if the pain is refractory to treatment.

  5. Anemia prevalence and treatment practice in patients with non-myeloid tumors receiving chemotherapy

    International Nuclear Information System (INIS)

    Merlini, Laura; Cartenì, Giacomo; Iacobelli, Stefano; Stelitano, Caterina; Airoldi, Mario; Balcke, Peter; Keil, Felix; Haslbauer, Ferdinand; Belton, Laura; Pujol, Beatriz

    2013-01-01

    To describe the prevalence and management of anemia in cancer patients. This cross-sectional, observational survey was conducted in Italy and Austria. Centers prespecified one day, during a 4-month enrollment window, to report specific data collected during normal clinical practice for patients with non-myeloid tumors attending for chemotherapy (±radiotherapy) treatment. The primary endpoint was the prevalence of anemia as determined using a prespecified algorithm: hemoglobin (Hb) ≤10 g/dL on/within 3 days prior to visit; ongoing anemia treatment; physician diagnosis of anemia, together with ≥1 anemia symptom. Between November 18, 2010 and March 18, 2011, data for 1412 patients were collected (Italy n = 1130; Austria n = 282). Most patients (n = 1136; 80%) had solid tumors; 809 (57%) had received ≤3 chemotherapy cycles. The prevalence of anemia was 32% (95% confidence interval: 29.4%–34.2%); 196 patients (14%) were deemed anemic based on Hb ≤10 g/dL, 131 (9%) on ongoing anemia treatment, and 121 (9%) on physician diagnosis/anemia symptom. Overall, 1153 patients (82%) had Hb data; mean (standard deviation [SD]) Hb levels were 11.7 (1.7) g/dL. In total, 456 patients (32%) had anemia symptoms: fatigue (n = 392; 28%), depression (n = 122; 9%), and dyspnea (n = 107; 8%) were most common. Fifty-one patients (4%) had had their current chemotherapy cycle delayed due to anemia. On visit day, or ≤28 days prior, 91 (6%), 188 (13%), and 81 patients (6%) had evidence of whole blood/red blood cell transfusion, erythropoiesis-stimulating agent use, or iron use, respectively. On the prespecified study day, one-third of patients with non-myeloid tumors undergoing chemotherapy were found to be anemic and 13% had evidence of erythropoiesis-stimulating agent use then or in the 28 days prior

  6. A fluid biopsy as investigating technology for the fluid phase of solid tumors

    Science.gov (United States)

    Kuhn, Peter; Bethel, Kelly

    2012-02-01

    has been made in fighting cancer, the victories are limited. Current medical and surgical strategies are very good at controlling local disease in cancer patients. We can successfully eradicate primary tumors in the sites where they arise and we can effectively control local recurrences in the nearby tissues. However, distant spread of cancer via the bloodstream (figure 1), known as hematogenous metastasis, has always been the fatal loophole. Like an evil humor, this process of hematogenous metastasis is mysterious to us. We do not understand its timing or its variability in terms of establishing new tumors at distant sites. It is invisible while it is happening, just as infectious transmission of Yersinia pestis is invisible. And like the resultant boils of bubonic plague in the pre-antibiotic era, by the time we see the ominous swellings, it is far too late. figure 1 Figure 1. Hematogenous metastasis from a primary lung tumor. The inset shows the spread of cancer cells via the bloodstream. Consequently, despite furious effort to treat and cure cancer, we are frustrated at our poor ability to detect and predict the deadly phenomenon of hematogenous spread, and we are disheartened by the apparent impenetrability of the process. Persistent helplessness in the face of this randomness tempts us toward fatalistic acceptance of cancer deaths as a natural consequence of improved longevity, just as death from childbed fever was once accepted as a frequent natural consequence of delivering a child. Finally, however, we are in the process of refining methods to reliably detect, measure and characterize this internal biological process. The cells that are spreading cancer are in the bloodstream and must therefore be found and studied in samples from the bloodstream. Such circulating tumor cells (CTCs) are the focus of the evolving field of CTC biology and have proved a wily target. Early intimations of their nature came with the application of the Cellsearch® methodology

  7. Prevalence of benign tumors among patients with multiple sclerosis

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    Aryan Rafiee Zadeh

    2015-10-01

    Full Text Available Multiple sclerosis (MS, an inflammatory autoimmune disease, affects almost 1% of world’s population in which myelin sheaths of neurons are targeted by immune cells. Association of different factors and diseases with MS provides new insights into possible pathogenesis and treatment for this disease. In this regard, we investigated the association of benign tumors with MS disease by studying total Isfehan multiple sclerosis (TIMS records for MS patients registered in Isfahan Multiple Sclerosis Society (IMSS who had developed any kind of benign tumors whether before MS diagnosis or after it. This study was performed in Isfahan province, third large province of Iran, with 4,815,863 populations located 1590 meters above sea level between latitudes 30 and 34 degrees north of the equator, and longitude 49-55 east. Among 4950 registered patients, 28 patients were discovered to have three types of benign tumors; pituitary adenoma in 22, meningioma in 5 and lipoma in 1 patient. The incidence rate of developing pituitary adenoma and meningioma were higher than in general population (OR 95%CI: 1.110; range: 0.731-1.685 and 1.035; range: 0.431-2.487 respectively but these findings were not statistically significant (p= 0.624 for pituitary adenoma and p= 0.939 for meningioma. But the incidence rate for lipoma was lower among MS patients (OR 95%CI: 0.020; range: 0.003-0.143 which was statistically significant (p <0.001.

  8. Clinical outcomes for 14 consecutive patients with solid pseudopapillary neoplasms who underwent laparoscopic distal pancreatectomy.

    Science.gov (United States)

    Nakamura, Yoshiharu; Matsushita, Akira; Katsuno, Akira; Yamahatsu, Kazuya; Sumiyoshi, Hiroki; Mizuguchi, Yoshiaki; Uchida, Eiji

    2016-02-01

    The postoperative results of laparoscopic distal pancreatectomy for solid pseudopapillary neoplasm of the pancreas (SPN), including the effects of spleen-preserving resection, are still to be elucidated. Of the 139 patients who underwent laparoscopic pancreatectomy for non-cancerous tumors, 14 consecutive patients (average age, 29.6 years; 1 man, 13 women) with solitary SPN who underwent laparoscopic distal pancreatectomy between March 2004 and June 2015 were enrolled. The tumors had a mean diameter of 4.8 cm. Laparoscopic spleen-preserving distal pancreatectomy was performed in eight patients (spleen-preserving group), including two cases involving pancreatic tail preservation, and laparoscopic spleno-distal pancreatectomy was performed in six patients (standard resection group). The median operating time was 317 min, and the median blood loss was 50 mL. Postoperatively, grade B pancreatic fistulas appeared in two patients (14.3%) but resolved with conservative treatment. No patients had postoperative complications, other than pancreatic fistulas, or required reoperation. The median postoperative hospital stay was 11 days, and the postoperative mortality was zero.None of the patients had positive surgical margins or lymph nodes with metastasis. The median follow-up period did not significantly differ between the two groups (20 vs 39 months, P = 0.1368). All of the patients are alive and free from recurrent tumors without major late-phase complications. Laparoscopic distal pancreatectomy might be a suitable treatment for patients with SPN. A spleen-preserving operation is preferable for younger patients with SPN, and this study demonstrated the non-inferiority of the procedure compared to spleno-distal pancreatectomy. © 2015 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  9. Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets

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    Neimar de Paula Silva

    2017-04-01

    Full Text Available ABSTRACT Objective To analyze the relationship between the development of childhood solid tumors and 1 birth weight and 2 fetal growth, using two Brazilian population-based data sets. Methods A case–cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC and 14 population-based cancer registries (PBCRs was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS, non-CNS embryonal, and other tumors (“miscellaneous”. Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region. Odds ratios (ORs with 95% confidence intervals (CIs were computed using unconditional logistic regression analysis. Results In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00–1.24 and the adjusted OR was 1.02 (CI: 0.90–1.16 for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00–1.55 and the adjusted OR was 1.04 (CI: 0.82–1.34 for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. Conclusions The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with “miscellaneous” tumors.

  10. Birth weight and risk of childhood solid tumors in Brazil: a record linkage between population-based data sets.

    Science.gov (United States)

    de Paula Silva, Neimar; de Souza Reis, Rejane; Cunha, Rafael Garcia; Oliveira, Julio Fernando; da Silva de Lima, Fernanda Cristina; Pombo-de-Oliveira, Maria Socorro; Santos, Marceli Oliveira; de Camargo, Beatriz

    2017-04-20

    To analyze the relationship between the development of childhood solid tumors and 1) birth weight and 2) fetal growth, using two Brazilian population-based data sets. A case-cohort study was performed using two population-based data sets, and linkage between the Live Birth Information System (Sistema de Informação sobre Nascidos Vivos, SINASC) and 14 population-based cancer registries (PBCRs) was established. Four controls per case were chosen randomly from the SINASC data set. Tumors were classified as central nervous system (CNS), non-CNS embryonal, and other tumors ("miscellaneous"). Adjustments were made for potential confounders (maternal age, mode of delivery, maternal education, birth order, gestational age, sex, and geographic region). Odds ratios (ORs) with 95% confidence intervals (CIs) were computed using unconditional logistic regression analysis. In a trend analysis, for every 500 g of additional birth weight, the crude OR was 1.12 (CI: 1.00-1.24) and the adjusted OR was 1.02 (CI: 0.90-1.16) for all tumors. For every 1 000 g of additional birth weight, the crude OR was 1.25 (CI: 1.00-1.55) and the adjusted OR was 1.04 (CI: 0.82-1.34) for all tumors. Among children diagnosed after reaching the age of 3 years, in the miscellaneous tumor category, the OR was significantly increased for every additional 500 g and 1 000 g of birth weight. The study data suggested that increased birth weight was associated with childhood solid tumor development, especially among children more than 3 years old with "miscellaneous" tumors.

  11. Malignant oral tumors in iran: ten-year analysis on patient and tumor characteristics of 1042 patients in Tehran.

    Science.gov (United States)

    Sargeran, Katayoun; Murtomaa, Heikki; Safavi, Seyed Mohammad Reza; Vehkalahti, Miira; Teronen, Olli

    2006-11-01

    This study analyzed characteristics of oral cancer patients from Tehran, Iran, and their tumors. Data came from the patient records of 30 major hospitals in Tehran. Patients (n = 1042), diagnosed with invasive oral cancer in 1993-2003, were classified by primary tumor site according to ICD-10 (C00-C10). Data were analyzed separately for lip, oral cavity and salivary gland tumors. Statistical evaluation included chi and t-test. Of all cases, 59% were male. Age for all cases ranged from 6-103 years, mean age was 58.8 years (SD 16; median 62); 89% were older than 40. Tumor site breakdown was 65% oral cavity, 21% major salivary glands and 14% lip. A clear gender difference (P dominated in oral cavity cancers and men in lip cancers. The most common cancer site was the tongue (32%), accounting for 50% of the oral cavity cancers. Histologically, 88% of all oral cavity and lip cancers were squamous cell carcinomas, 10% of those were in age /= age 65. At the time of diagnosis, 59% of oral cavity cancers and 29% of lip cancers were at stage III or IV (P < 0.001). The results emphasize an urgent need for a national program focusing on early detection of oral cancers, including educational information addressed to oral health professionals.

  12. Diagnostic Study of Tumor Characteristics in Patients With Ewing's Sarcoma

    Science.gov (United States)

    2013-06-20

    Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

  13. Brown tumor of the maxilla in patient with secondary hyperparathyroidism

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    Jović Nebojša

    2004-01-01

    Full Text Available Brown tumor or parathyroid osteopathy is a kind of bony lesion caused by hyperparathyroidism. It appears as an expansive osteolytic lesion mostly in mandible, ribs, pelvis and femur, but rarely in the upper jaw. Bone resorption is the result of osteoclastic activity due to an increased activity of parathyroid hormone. A 25-years-old male patient was operated on due to clinicaly and radiographicaly obvious maxillary tumor and increased values of parathyroid hormon (PTH - 1 050 ng/l. The level of calcium in blood was normal (Ca 2.34 mEq/L. The patient was dialyzed for years because of the chronic renal failure. Histopathologic analysis confirmed brown tumor, that appeared as bony lesion of secondary hyperparathyroidism due to the chronic renal failure. The operation of the upper jaw had been performed before parathyroidectomy, due to an excessive growth of tumor followed by heavy epistaxes. The subsequent parathyroidectomy was followed by the regression of remaining bony lesions.

  14. Familial tumoral calcinosis in two Chinese patients: a case series

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    Cheng Xiaoli

    2011-08-01

    Full Text Available Abstract Introduction Tumoral calcinosis is a rare and benign condition characterized by massive subcutaneous soft tissue deposits of calcium phosphate predominantly around large joints. Case presentation Familial tumoral calcinosis was present in two members of a Han Chinese family, namely, the son and daughter. The 14-year-old son had the first operation on his right sole of the foot at the age of six, and then experienced subsequent surgeries at a lesion in his right sole of the foot and left hip, respectively. The 16-year-old daughter underwent her first operation at the age of six in her left gluteal region, and subsequent surgeries were performed due to recurrence at the same lesion. Pathologic diagnoses of surgical specimens in both of the patients were reported as tumoral calcinosis. The laboratory results showed hyperphosphatemia with normal levels of serum calcium and alkaline phosphatase. Only surgical treatment was performed in both patients with satisfactory prognosis. Conclusion This is the first report of Chinese familial tumoral calcinosis. The etiopathogenisis and treatment are discussed.

  15. An Unusual Case of Hepatic Tumor in an Elderly Patient

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    Huan-Lin Chen

    2009-09-01

    Full Text Available Malignant epithelioid hemangioendothelioma is a rare hepatic tumor of vascular origin. It is most commonly found in young to middle-aged women, and the tumors vary in their reported potential for malignancy. The etiologic factors are not yet clear, and some investigators have suggested an association with oral contraceptives, whereas others have noted an association with exposure to vinyl chloride, asbestos, thorotrast, major trauma to the liver, viral hepatitis, primary biliary cirrhosis, and alcohol consumption. The clinical manifestations are nonspecific, and most are asymptomatic. Among symptomatic patients, the most common symptom is right upper quadrant pain, followed by jaundice, weight loss, fatigue, ascites, hepatomegaly, and fever. The only definitive diagnosis requires immunohistochemical evidence of endothelial differentiation, which is demonstrated by the presence of factor VIII-related antigen and cytokeratins. As with most mesenchymal tumors, surgical resection is the most effective means of controlling local disease and preventing distant metastasis, although adjuvant therapies have been offered for patients with unresectable tumors or who are not transplant candidates. We present the case of an elderly man with a hepatic malignant epithelioid hemangioendothelioma, and we reviewed the English-language literature.

  16. American brain tumor patients treated with BNCT in Japan

    International Nuclear Information System (INIS)

    Laramore, G.E.; Griffin, B.R.; Spence, A.

    1995-01-01

    The purpose of this work is to establish and maintain a database for patients from the United States who have received BNCT in Japan for malignant gliomas of the brain. This database will serve as a resource for the DOE to aid in decisions relating to BNCT research in the United States, as well as assisting the design and implementation of clinical trials of BNCT for brain cancer patients in this country. The database will also serve as an information resource for patients with brain tumors and their families who are considering this form of therapy

  17. Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer.

    Science.gov (United States)

    Ghaghada, Ketan B; Sato, Amy F; Starosolski, Zbigniew A; Berg, John; Vail, David M

    2016-01-01

    Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I) for computed tomography (CT) imaging of solid tumors in companion dogs with naturally occurring cancer. The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years) with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose). Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study. Liposomal-I resulted in significant (p contrast agent was demonstrated. Liposomal-I enabled visualization of primary and metastatic liver tumors. Sub-cm sized liver lesions grossly appeared as hypo-enhanced compared to the surrounding normal parenchyma with improved lesion conspicuity in the post-24 hour scan. Large liver tumors (> 1 cm) demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan. The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of

  18. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

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    M Soltani

    Full Text Available Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  19. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Science.gov (United States)

    Soltani, M; Chen, P

    2013-01-01

    Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries) are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  20. [Pseudomeigs syndrome in a patient with Krukenberg's tumor].

    Science.gov (United States)

    Bayod, M J Herráiz; Carlón, M Elorz; Idoate, M A

    2007-01-01

    We report the case of a fiftyone-year-old woman with a past medical history of Linfoma no Hodking and a gastric adenocarcinoma with signet ring cells. She came to our institution with a twenty month history of dysnea secondary to pleural effussion, bilateral lower extremity edema and probably had ascitis. On CT and US two bilateral pelvic masses were found and biopsied. The anatomopathological analysis showed bilateral ovarian implants from signet ring cell adenocarcinoma (Krukenberg tumor). This patient developed a PseudoMeigs syndrome consisting on malignant ovarian tumor asociated with ascitis and pleural effusion without malignant cells. Oncological patients who present with ascitis and benign pleural effusion, the diagnosis of PseudoMeigs syndrome should be considered.

  1. Radiation as an inducer of in-situ autologous vaccine in the treatment of solid tumors

    International Nuclear Information System (INIS)

    Ahmed, Mansoor M.

    2013-01-01

    Radiation therapy (RT) is conventionally used for local tumor control. Although local control of the primary tumor can prevent the development of subsequent systemic metastases, tumor irradiation is not effective in controlling pre-existing systemic disease. The concept of radiation-enhanced antigen presentation and immunomodulation allows the harnessing of tumor cell death induced by radiation as a potential source of tumor antigens for immunotherapy. Immunomodulation using RT is a novel strategy of in situ tumor vaccination where primary tumor irradiation can contribute to the control of pre-existing systemic metastatic disease. The absence of systemic immunosuppression (often associated with chemotherapy) and the generally lower toxicity makes radiation a desirable adjuvant regimen for immunotherapy and tumor vaccination strategies. Increased understanding of tumor immunology and the biology of radiation-mediated immune modulation should enhance the efficacy of combining these therapeutic modalities. Here we aim to provide an overview of the biology of radiation-induced immune modulation. (author)

  2. Factors that predict residual tumors in re-TUR patients

    African Journals Online (AJOL)

    H. Türk

    2015-11-30

    Nov 30, 2015 ... Abstract. Introduction: Thefirstandforemostruleinthetreatmentofsuperficialbladdercanceriscorrectandcomplete resection of the tumor. Histopathological analysis of the resected tumor will help to define the correct tumor stage, thus delaying or, ideally, avoiding tumor recurrence and progression. Objectives: ...

  3. Contrast Dose and Radiation Dose Reduction in Abdominal Enhanced Computerized Tomography Scans with Single-phase Dual-energy Spectral Computerized Tomography Mode for Children with Solid Tumors.

    Science.gov (United States)

    Yu, Tong; Gao, Jun; Liu, Zhi-Min; Zhang, Qi-Feng; Liu, Yong; Jiang, Ling; Peng, Yun

    2017-04-05

    Contrast dose and radiation dose reduction in computerized tomography (CT) scan for adult has been explored successfully, but there have been few studies on the application of low-concentration contrast in pediatric abdominal CT examinations. This was a feasibility study on the use of dual-energy spectral imaging and adaptive statistical iterative reconstruction (ASiR) for the reduction of radiation dose and iodine contrast dose in pediatric abdominal CT patients with solid tumors. Forty-five patients with solid tumors who had initial CT (Group B) and follow-up CT (Group A) after chemotherapy were enrolled. The initial diagnostic CT scan (Group B) was performed using the standard two-phase enhanced CT with 320 mgI/ml concentration contrast, and the follow-up scan (Group A) was performed using a single-phase enhanced CT at 45 s after the beginning of the 270 mgI/ml contrast injection using spectral mode. Forty percent ASiR was used for the images in Group B and monochromatic images with energy levels ≥60 keV in Group A. In addition, filtered back-projection (FBP) reconstruction was used for monochromatic images hounsfield unit (HU). The abdominal organs of Groups A and B had similar degrees of absolute and relative enhancement (t = 0.36 and -1.716 for liver, -0.153 and -1.546 for pancreas, and 2.427 and 0.866 for renal cortex, all P> 0.05). Signal-to-noise ratio of the abdominal organs was significantly lower in Group A than in Group B (t = -8.11 for liver, -7.83 for pancreas, and -5.38 for renal cortex, all P 3, indicating clinically acceptable image quality. Single-phase, dual-energy spectral CT used for children with solid abdominal tumors can reduce contrast dose and radiation dose and can also maintain clinically acceptable image quality.

  4. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    Directory of Open Access Journals (Sweden)

    Thamm Reinhard

    2006-06-01

    Full Text Available Abstract Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical

  5. Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

    International Nuclear Information System (INIS)

    Nieder, Carsten; Grosu, Anca L; Astner, Sabrina; Thamm, Reinhard; Molls, Michael

    2006-01-01

    Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical implementation. A potential chemotherapy

  6. Radiobiologic significance of apoptosis and micronucleation in quiescent cells within solid tumors following γ-ray irradiation

    International Nuclear Information System (INIS)

    Masunaga, Shin-ichiro; Ono, Koji; Suzuki, Minoru; Kinashi, Yuko; Takagaki, Masao

    2001-01-01

    Purpose: To determine the frequency of apoptosis in quiescent (Q) cells within solid tumors following γ-ray irradiation, using four different tumor cell lines. In addition, to assess the significance of detecting apoptosis in these cell lines. Methods and Materials: C3H/He mice bearing SCC VII or FM3A tumors, Balb/c mice bearing EMT6/KU tumors, and C57BL mice bearing EL4 tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received γ-ray irradiation at a dose of 4-25 Gy while alive or after tumor clamping. Immediately after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (=Q cells) was determined using immunofluorescence staining for BrdU. Meanwhile, 6 hours after irradiation, tumor cell suspensions obtained in the same manner were fixed. The apoptosis frequency in Q cells was also determined with immunofluorescence staining for BrdU. The MN and apoptosis frequency in total (P+Q) tumor cells were determined from the tumors that were not pretreated with BrdU. Results: In total cells, SCC VII, FM3A, and EMT6/KU cells showed reasonable relationships between MN frequency and surviving fraction (SF). However, fewer micronuclei were induced in EL4 cells than the other cell lines. In contrast, a comparatively close relationship between apoptosis frequency and SF was found in total cells of EL4 cell line. Less apoptosis was observed in the other cell lines. Quiescent tumor cells exhibited significantly lower values of MN and apoptosis frequency probably due to their large hypoxic fraction, similar to total tumor cells on clamped irradiation. Conclusion: γ-ray irradiation induced MN formation in SCC VII, FM3A, and EMT6/KU tumor cells, and the apoptosis was marked in EL4 cells compared with

  7. Values of tumor markers (AFP, β-HCG and CEA) and gamma-camera scintigraphy in patients with testicular tumors

    International Nuclear Information System (INIS)

    Milkov, V.; Sultanov, S.; Tsvetkov, D.

    1989-01-01

    Complex gamma-camera and radioimmunologic study of the tumor markers AFP, β-HCG and CEA was performed in 7 patients with testicular tumors. In all tested patients gamma-camera scintigraphy of the testes clearly delineated the zone of the pathological process. Gamma-camera examination very well differentiates malignant from nonmalignant processes in the testes. The serum levels of the tumor markers AFP and β-HCG proved elevated in 3 of the tested patients during the preoperative period. The histological types of the tumors in these patients were: teratocarcinoma in one and embryonal carcinoma in the other two. It is believed that investigation of the three tumor markers may gain acceptance as additonal method in the complex diagnosis of these diseases

  8. Osteopontin is a tumor autoantigen in prostate cancer patients

    Science.gov (United States)

    TILLI, TATIANA M.; SILVA, ELOÍSIO A.; MATOS, LÍVIA C.; FAGET, DOUGLAS V.; DIAS, BIANCA F.P.; VASCONCELOS, JULIANA S.P.; YOKOSAKI, YASUYUKI; GIMBA, ETEL R.P.

    2011-01-01

    Anti-tumor antibodies act as biomarkers for the early diagnosis of prostate cancer (PCa). Osteopontin (OPN) is overexpressed in PCa cells and contributes to the progression of the disease. This study aimed to evaluate whether OPN evokes a humoral immune response in PCa patients and whether the reactivity levels of anti-OPN antibodies may be used to better differentiate PCa from benign and healthy donor plasma samples. Plasma samples from biopsy-proven PCa patients (29), benign prostate hyperplasia (BPH) (18) and control healthy donors (HD) (30) were tested by immunoblots using the recombinant human OPN. The frequency of anti-OPN antibodies was significantly higher in PCa (66%) plasma samples as compared to BPH (33%) and HD controls (10%). Anti-OPN antibodies were detected in a high proportion of plasma samples from patients with a Gleason score of less than 6 (57%), prostate-specific antigen levels lower than 10 ng/ml (67%) and pT2 organ-confined disease (70%), suggesting that anti-OPN antibodies may be used as an early serum marker for PCa. To the best of our knowledge, this is the first description of OPN as a tumor autoantigen and one of the most reactive individual autoantigens described thus far. These data support the inclusion of OPN in a multiplex of tumor antigens in order to perform antibody profiling in PCa as well as in other malignancies overexpressing OPN. PMID:22870138

  9. A Tumor-stroma Targeted Oncolytic Adenovirus Replicated in Human Ovary Cancer Samples and Inhibited Growth of Disseminated Solid Tumors in Mice

    Science.gov (United States)

    Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

    2012-01-01

    Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 1010 v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15–40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression. PMID:22948673

  10. Novel Therapeutic Strategies for Solid Tumor Based on Body's Intrinsic Antitumor Immune System.

    Science.gov (United States)

    Duan, Haifeng

    2018-05-22

    The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. © 2018 The Author(s). Published by S. Karger AG, Basel.

  11. Nutritional status and nutritional risk in patients with neuroendocrine tumors

    DEFF Research Database (Denmark)

    Borre, Mette; Dam, Gitte Aarøe; Knudsen, Anne Wilkens

    2018-01-01

    BACKGROUND: Malnutrition is frequent among patients with malignancies and associated with impaired function, reduced quality of life and increased mortality. Few data are available in patients with neuroendocrine tumors (NET) on nutritional status, nutritional risk, and nutrition impact symptoms...... (NIS). We aimed to assess nutritional status (NS) and risk, level of function and associations with NIS in NET patients. METHODS: In a cross-sectional study of NET patients, we measured body mass index (BMI) and handgrip strength (HGS) as markers of NS and muscle function assessed by HGS....... The nutritional risk score (NRS) was determined by NRS-2002. NIS was assessed by the eating symptoms questionnaire (ESQ), and disease-related appetite questionnaire (DRAQ). RESULTS: We included 186 patients (51% women), median age 66 years. We observed low BMI (

  12. The observation about the change of the body weight for tumor patients and the bearing tumor mice in radiotherapy

    International Nuclear Information System (INIS)

    Wu Dijun; Ju Yongjian; Ning Liyan; Wu Hong; Wang Gaoren; Gao Xuan; Tang Yahong

    2010-01-01

    Objective: To observe the change of the body weight for tumor patients and the bearing tumor mice in radiotherapy. Methods: For 63 tumor patients, the body weight (BW) were measured before and after radiotherapy respectively, and then the change of BW were compared and analyzed with that of 23 healthy volunteers at the median treatment period. Also 45 mice bearing human galactophore tumor cells SK-BR-3 were divided into irradiation and non-irradiation groups, and the change of BW for these two groups were measured and analyzed. Results: The average BW decreases in the irradiation groups' mice but increase in the non-irradiation groups' mice, and the change of BW in these two groups has the statistical significance respectively, also the difference between these two groups has the statistical significance. For the four groups' tumor patients including 63 tumor patients as a whole, the nasopharynx cancer, esophagus cancer and lung cancer, the average BW decreases, but only in nasopharynx cancer and lung cancer groups the statistical significance are found. And at the same period, the BW of healthy volunteers are maintained. Compared change of BW in the four tumor groups with that in the healthy volunteers respectively, except the esophagus cancer group, the statistical significance are found in the other three groups. Conclusion: For tumor patients,perhaps the BW will lose in the period of radiotherapy, so the effect of lose of BW must be cared about. (authors)

  13. Acute hypopituitarism associated with periorbital swelling and cardiac dysfunction in a patient with pituitary tumor apoplexy: a case report.

    Science.gov (United States)

    Ohara, Nobumasa; Yoneoka, Yuichiro; Seki, Yasuhiro; Akiyama, Katsuhiko; Arita, Masataka; Ohashi, Kazumasa; Suzuki, Kazuo; Takada, Toshinori

    2017-08-24

    Pituitary tumor apoplexy is a rare clinical syndrome caused by acute hemorrhage or infarction in a preexisting pituitary adenoma. It typically manifests as an acute episode of headache, visual disturbance, mental status changes, cranial nerve palsy, and endocrine pituitary dysfunction. However, not all patients present with classical symptoms, so it is pertinent to appreciate the clinical spectrum of pituitary tumor apoplexy presentation. We report an unusual case of a patient with pituitary tumor apoplexy who presented with periorbital edema associated with hypopituitarism. An 83-year-old Japanese man developed acute anterior hypopituitarism; he showed anorexia, fatigue, lethargy, severe bilateral periorbital edema, and mild cardiac dysfunction in the absence of headache, visual disturbance, altered mental status, and cranial nerve palsy. Magnetic resonance imaging showed a 2.5-cm pituitary tumor containing a mixed pattern of solid and liquid components indicating pituitary tumor apoplexy due to hemorrhage in a preexisting pituitary adenoma. Replacement therapy with oral hydrocortisone and levothyroxine relieved his symptoms of central adrenal insufficiency, central hypothyroidism, periorbital edema, and cardiac dysfunction. Common causes of periorbital edema include infections, inflammation, trauma, allergy, kidney or cardiac dysfunction, and endocrine disorders such as primary hypothyroidism. In the present case, the patient's acute central hypothyroidism was probably involved in the development of both periorbital edema and cardiac dysfunction. The present case highlights the need for physicians to consider periorbital edema as an unusual predominant manifestation of pituitary tumor apoplexy.

  14. Yolk sac tumor in a patient with transverse testicular ectopia

    Directory of Open Access Journals (Sweden)

    Zhu Yi-Ping

    2011-08-01

    Full Text Available Abstract Transverse testicular ectopia (TTE is a rare anomaly in which both testes descend through a single inguinal canal. We report a case of yolk sac tumor in the ectopic testis of a patient with TTE. A 24-year-old man presented to our hospital with a left inguinal-mass, right cryptorchidism and elevated alpha-fetoprotein (AFP. A left herniotomy 3 years earlier demonstrated both testes in the left scrotum, one above another positionally. Four months ago, a left scrotal mass appeared and radical orchiectomy of both testes revealed testicular yolk sac tumor of the ectopic testis. An enlarging left inguinal-mass appeared 2 months ago and he was referred to our hospital. Laboratory data showed an elevation of AFP (245.5 ng/ml and a 46 XY karyotype. He underwent bilateral retroperitoneal lymph node dissection and simultaneous left inguinal mass dissection. Histopathologic examination revealed a diagnosis of recurrent yolk sac tumor in the left inguinal mass. The retroperitoneal lymph node was not enlarged and, on histopathology, was not involved. The patient has now been followed up for 8 months without evidence of biochemical or radiological recurrence.

  15. Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

    Directory of Open Access Journals (Sweden)

    Hyun-Kyoung Kim

    Full Text Available BACKGROUND: The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs, which are abundant in solid tumors, can be utilized for identification of rearranged ends. METHOD: As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP microarray method entailing CNB-region refinement by competitor DNA. RESULT: Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9% were identified, and two polymerase chain reaction (PCR-amplifiable rearrangements were obtained in six cases (66.7%. And significantly, TNGS-CNB, with its high positive identification rate (82.6% of PCR-amplifiable rearrangements at candidate sites (19/23, just from filtering of aligned sequences, requires little effort for validation. CONCLUSION: Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

  16. Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

    Science.gov (United States)

    Kim, Hyun-Kyoung; Park, Won Cheol; Lee, Kwang Man; Hwang, Hai-Li; Park, Seong-Yeol; Sorn, Sungbin; Chandra, Vishal; Kim, Kwang Gi; Yoon, Woong-Bae; Bae, Joon Seol; Shin, Hyoung Doo; Shin, Jong-Yeon; Seoh, Ju-Young; Kim, Jong-Il; Hong, Kyeong-Man

    2014-01-01

    The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS) for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can be utilized for identification of rearranged ends. As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB) in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region refinement by competitor DNA. Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)-amplifiable rearrangements were obtained in six cases (66.7%). And significantly, TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable rearrangements at candidate sites (19/23), just from filtering of aligned sequences, requires little effort for validation. Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

  17. Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 patients

    NARCIS (Netherlands)

    de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

    2013-01-01

    Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

  18. Low Accuracy of Tumor Markers for Diagnosing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 Patients

    NARCIS (Netherlands)

    de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

    2013-01-01

    Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

  19. Radiotherapy, especially at young age, increases the risk for de novo brain tumors in patients treated for pituitary tumors

    NARCIS (Netherlands)

    Burman, Pia; Van Beek, André P.; Biller, Beverly M.K.; Camacho-Hubner, Cecilia; Mattsson, Anders F.

    Background: Excess mortality due to de novo malignant brain tumors was recently found in a national study of patients with hypopituitarism following treatment of pituitary tumors. Here, we examined a larger multi-national cohort to corroborate and extend this observation. Objective: To investigate

  20. Cytotoxic drug sensitivity testing of tumor cells from patients with ovarian carcinoma using the fluorometric microculture cytotoxicity assay (FMCA).

    Science.gov (United States)

    Csoka, K; Larsson, R; Tholander, B; Gerdin, E; de la Torre, M; Nygren, P

    1994-08-01

    The automated fluorometric microculture cytotoxicity assay (FMCA) is based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein by viable cells after a 72-hr culture period in microtiter plates. The FMCA was adopted for chemosensitivity testing of tumor cells from patients with ovarian carcinoma. Thirty-seven samples of solid tumors and malignant effusions were obtained from 35 patients at diagnosis or relapse. Tumor cells from solid samples and effusions were prepared by enzymatic digestion and centrifugation, respectively, followed by Percoll or Ficoll purification. The fluorescence was proportional to the number of cells/well and considerably higher in tumor cells than in contaminating normal cells. The effect of up to 19 cytotoxic drugs was successfully assessed in 70% of the samples and there was a good correlation between drug sensitivity data reported by the FMCA and the DiSC assay performed in parallel. The overall drug sensitivity pattern in vitro corresponded well to the clinical experience. The effect of cisplatin varied considerably between patients and resistance was found also in cases not previously exposed to cytotoxic drugs. The FMCA is a rapid and simple method that seems to report clinically relevant cytotoxic drug sensitivity data in ovarian carcinomas. In the future, this method may contribute to optimizing chemotherapy by assisting in individualized drug selection and new drug development.

  1. In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening.

    Science.gov (United States)

    Mazzocchi, Andrea R; Rajan, Shiny A P; Votanopoulos, Konstantinos I; Hall, Adam R; Skardal, Aleksander

    2018-02-13

    Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models with which treatment optimization can be performed before initiation of therapy. We demonstrate the initial implementation of this platform using tumor biospecimens surgically removed from two mesothelioma patients. First, we show the ability to biofabricate and maintain viable 3D tumor constructs within a tumor-on-a-chip microfluidic device. Second, we demonstrate that results of on-chip chemotherapy screening mimic those observed in subjects themselves. Finally, we demonstrate mutation-specific drug testing by considering the results of precision medicine genetic screening and confirming the effectiveness of the non-standard compound 3-deazaneplanocin A for an identified mutation. This patient-derived tumor organoid strategy is adaptable to a wide variety of cancers and may provide a framework with which to improve efforts in precision medicine oncology.

  2. Gastric emptying of solid food in patients with gastroesophageal reflux

    International Nuclear Information System (INIS)

    Shay, S.; Eggli, D.; Van Nostrand, D.; Johnson, L.

    1985-01-01

    While delayed solid gastric emptying (GE) has been reported in patients with gastroesophageal reflux (GER), the relationship of GE to daytime and/or nighttime reflux patterns, and the severity of endoscopic esophagitis are unknown. The authors measured GE in a study population of symptomatic patients (n=33) with abnormal 24 hour pH monitoring (24 hr pH). The study population was divided into two groups by esophagoscopy; those with (E+=22); and 2) those without (E-=11) erosive esophagitis and/or Barrett's esophagus. GE was measured in all patients and in 15 normal volunteers (NL) by the in vivo labelling of chicken liver with Tc-99m-SC, which was in turn diced into 1 cm. cubes and given in 7 1/2 oz. of beef stew. Upright one minute anterior and posterior digital images were obtained every 15 min. for 2.5 hours. 24 hour pH was divided into daytime (upright) and nighttime (supine) segments, and acid exposure was defined as % time pH < 4 for that posture. There was no correlation between GE T 1/2 and acid exposure, daytime or nighttime, for the patient population as a whole. However, patients with the longest GE T1/2 tended to have severe daytime reflux. The authors rarely found delayed solid food gastric emptying in patients with reflux; moreover, they found no association between GE and either diurnal reflux patterns on 24 hr pH or the severity of endoscopic esophagitis

  3. Correlation between radiosensitivity of transplanted solid tumor and nutritive condition of host animal

    Energy Technology Data Exchange (ETDEWEB)

    Ando, K [Showa Univ., Tokyo (Japan). School of Medicine

    1975-04-01

    Studies on radiosensitivity of the transplanted tumor were carried out and the following results were obtained: 1. Radiosensitivity of the tumor ran parallel to the growth rate. 2. Malnutrition of the host after irradiation made the tumor radiosensitive, probably because the sublethally damaged tumor cell did not recover. 3. Mitotic index correlated well with radiosensitivity, and the low mitotic index caused by starvation made the tumor cell recover poorly. 4. The DNA synthetic rate measured by means of iodine labeled IUdR did not successfully correlate with the mitotic rate, presumably because of the role of thymidine pool size in this experiment. 5. The serum protein level possibly with the tumor growth, which modified the radiosensitivity. 6. Serum oxygen was difficult to interpret, however, it might be compensated by erythrocytosis in a starved condition.

  4. Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Lardon Filip

    2010-04-01

    Full Text Available Abstract Background There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor associated antigens possibly inducing a cellular anti-tumor immune response. It is well recognized that cytotoxic lymphocytes constitute one of the most important effector mechanisms of anti-tumor-immunity. However, their potential prognostic influence in colorectal cancer remains controversial. Aim of the study was to examine infiltration of CD3+ and CD8+ lymphocytes in colorectal cancer and their prognostic potential. Two-hundred-fifteen colorectal cancer cases, previously analyzed for microsatellite instability (MSI, were selected for immunohistochemical detection of CD3+, CD8+ infiltration and the expression of granzyme B. Prognostic relevance was assessed by survival analysis. Results Strong correlations were found between the infiltration of lymphocytes and several clinicopathological variables. Survival analysis revealed that intra-epithelial infiltration of CD3+ and CD8+ T lymphocytes and stromal infiltration of CD3+ lymphocytes had a major impact on the patients' overall survival in the univariate analysis, however independent of their association with MSI-status. In addition, it was also demonstrated that there was an important disease specific survival advantage for patients with microsatellite stable (MSS tumors containing intraepithelial CD8+ tumor infiltrating lymphocytes. When samples were analyzed for colon cancer and rectal cancer separately, the results of the overall population were confirmed in colon cancer only. When entered into a multiple Cox regression analysis adjusting for other possible important confounding factors, the strong impact of lymphocyte infiltration on overall survival was not maintained. Only early stage and young age

  5. Detection of tumor recurrence using technetium99m-tetrofosmin brain SPECT in patients with previously irradiated brain tumors

    International Nuclear Information System (INIS)

    Llamas A; Reyes A; Uribe, L F; Martinez T

    2004-01-01

    Objective: to assess the clinical utility of brain SPECT with Tc-99m Tetrofosmin to differentiate between tumor recurrence and radionecrosis in patients with primary brain tumors previously treated with external beam radiotherapy. Materials and methods: thirteen patients with clinical or radiological suspicion of tumor recurrence were studied with brain SPECT using 20-mCi of Tc-99m Tetrofosmin. Obtained images were interpreted by consensus between two experienced observers and subsequently classified as positive or negative for tumor viability. Results were compared to those of conventional diagnostic imaging techniques. Diagnostic test values and 95% confidence intervals were quantified. Results: SPECT results included 7 true-positives, 5 true-negatives and 1 false negative result. Conclusions: Tc-99m Tetrofosmin brain SPECT night be a useful alternative to diagnose recurrent brain tumors, especially with non-conclusive clinical and radiological findings

  6. Particle radiotherapy for patients with H and N malignant tumor

    International Nuclear Information System (INIS)

    Murakami, Masao; Demizu, Yusuke; Niwa, Yasue; Terashima, Kazuki; Fujii, Osamu; Mima, Masayuki; Hashimoto, Naoki; Jin, Dongcun

    2011-01-01

    Particle beams have a characteristic called the Bragg peak, which is a peak formed at a fixed depth in the body depending on the acceleration energy. Utilizing this property, a high dose can be concentrated in the target tumor while minimizing damage to surrounding normal tissues. Proton and carbon ion beams have a higher linear energy transfer (LET) than X-rays. The relative biological effectiveness of proton and carbon ion beams compared with X-rays (=1) is estimated to be 1.1 and 3.0, respectively. Therefore, we can expect particle radiotherapy to be effective for patients with radio-resistant tumors such as malignant melanoma, adenoidcystic carcinoma and adenocarcinoma. As of the end of July 2011, there were 9 particle institutes operating in Japan; the Hyogo Ion Beam Medical Center was established in May 2001 as a leading project of the ''Hyogo Cancer Strategy''. One major characteristic is that the Center can generate both proton and carbon ion beams. Locally advanced nasal, paranasal or salivary gland cell tumors are good candidates for particle radiotherapy. Downsizing of the accelerator, price reduction of the machine, broad use of particle therapy in the field of clinical oncology, and intensity modulated particle therapy are future challenges. (author)

  7. Solid pseudopapillary tumor of the pancreas: Experience at a tertiary care centre of Northern India

    Directory of Open Access Journals (Sweden)

    Namita Bhutani

    2017-01-01

    Conclusion: SPT is rare, but treatable pancreatic tumor. While clinical signs and symptoms are relatively nonspecific, characteristic findings on imaging and histology separate these tumors from the more malignant pancreatic tumors. The prognosis is favorable even in the presence of distant metastasis. Although surgical resection is generally curative, a close follow-up is advised in order to diagnose a local recurrence or distant metastasis.

  8. Polyphenon-E encapsulated into chitosan nanoparticles inhibited proliferation and growth of Ehrlich solid tumor in mice

    Directory of Open Access Journals (Sweden)

    Azza I. Othman

    2018-03-01

    Full Text Available Limited bioavailability of green tea polyphenols hampered their delivery to tumor and hence therapeutic effectiveness. This study investigated the antitumor activity of polyphenon-E (PE encapsulated into chitosan nanoparticles (CSNPs in Ehrlich solid tumor in mice. CSNPs-PE, with a particle size of 53–69 nm showed 83% entrapment efficiency and a sustained release of PE in pH = 7.4 at 37 °C. The data demonstrated a higher percentage of released drug in case of less crosslinked formulations. Ehrlich ascites carcinoma (EAC cells (2.5 × 106/0.2 ml/mouse were injected subcutaneously in the back of mice. Oral administration of CSNPs-PE for 30 days produced a significant decrease in tumor volume (53% and weight (60% compared with free PE and voids CSNPs (72%. Compared with free PE and control, cell cycle revealed G0/G1 arrest associated with decrease in proliferating cell nuclear antigen (PCNA. In tumor tissue of CSNPs-PE treated mice, compared with free PE, there were; 1 induction of Bax and p53, 2 activation of caspases-3,-8 and -9, and CD95, 3 decrease in Bcl-2 expression of 4 inhibition of VEGF and CD31 expressions in tumor tissue. In conclusion, encapsulation of PE into CSNPs provided a good platform for cancer chemotherapy and raised existing application of different polyphenols for nanochemotherapy/prevention.

  9. Phase I study of the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat in advanced renal cell carcinoma and other solid tumors.

    Science.gov (United States)

    Zibelman, Matthew; Wong, Yu-Ning; Devarajan, Karthik; Malizzia, Lois; Corrigan, Alycia; Olszanski, Anthony J; Denlinger, Crystal S; Roethke, Susan K; Tetzlaff, Colleen H; Plimack, Elizabeth R

    2015-10-01

    Drugs inhibiting the mammalian target of rapamycin (mTOR) are approved in the treatment of renal cell carcinoma (RCC), but resistance inevitably emerges. Proposed escape pathways include increased phosphorylation of Akt, which can be down regulated by histone deacetylase (HDAC) inhibitors. We hypothesized that co-treatment with the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat may abrogate resistance in RCC. This phase 1 study evaluated the co-administration of ridaforolimus and vorinostat in patients with advanced solid tumors. The primary objective was to determine the maximum tolerated dose (MTD) in RCC patients. Although all solid tumors were allowed, prior cytotoxic chemotherapy was limited to 1 regimen. Using a modified 3 + 3 dose escalation design, various dose combinations were tested concurrently in separate cohorts. Efficacy was a secondary endpoint. Fifteen patients were treated at one of three dose levels, thirteen with RCC (10 clear cell, 3 papillary). Dosing was limited by thrombocytopenia. The MTD was determined to be ridaforolimus 20 mg daily days 1-5 with vorinostat 100 mg BID days 1-3 weekly, however late onset thrombocytopenia led to a lower recommended phase II dose: ridaforolimus 20 mg daily days 1-5 with vorinostat 100 mg daily days 1-3 weekly. Two patients, both with papillary RCC, maintained disease control for 54 and 80 weeks, respectively. The combination of ridaforolimus and vorinostat was tolerable at the recommended phase II dose. Two patients with papillary RCC experienced prolonged disease stabilization, thus further study of combined HDAC and mTOR inhibition in this population is warranted.

  10. Applications of lipid nanocarriers for solid tumors therapy: literature review; Aplicacoes das nanoparticulas lipidicas no tratamento de tumores solidos: revisao de literatura

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lidiane Correia de; Souza, Leonardo Gomes; Marreto, Ricardo Neves; Lima, Eliana Martins; Taveira, Stephania Fleury [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Fac. de Farmacia; Taveira, Eliseu Jose Fleury, E-mail: stephaniafleury@gmail.com [Hospital Erasto Gaertner, Curitiba, PR (Brazil). Oncologia Clinica

    2012-07-01

    Introduction: Lipid nanocarriers are systems used to target drugs to its site of action and have attracted attention of the scientific community because they are biocompatible and biodegradable. These systems can target drugs to solid tumors, providing sustained drug release in the site of action, thus increasing the utility of the antineoplastic chemotherapy. Objective: To review the available literature on in vivo experiments with lipid nanocarriers containing cytotoxic drugs for solid tumors treatment. Method: A search study was carried out in Pubmed{sup R} database from 2007 to 2011, with subject descriptors: liposomes, lipid nanoparticles, cancer and in vivo, with the boolean operator 'and' among them, in English. Results: 1,595 papers related to the use of liposomes and 77 related to lipid nanoparticles were found. Few studies reported in vivo experiments with lipid nanoparticles (28 papers) compared to liposomes (472 papers), since liposomes were developed two decades before lipid nanoparticles. Four liposomal medicines have already been approved and are used in the clinic while only one medicine containing lipid nanoparticles is in phase I of clinical studies. Conclusion: The number of papers related to the use of nanotechnology for cancer treatment is increasing rapidly, making important to know the different kinds of nanocarriers and, especially, those which are already used in the clinic. There are only few clinical studies on lipid nanocarriers; however, these systems present an enormous potential to improve the clinical practice in oncology. (author)

  11. The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition

    International Nuclear Information System (INIS)

    Peddaboina, Chander; Smythe, W Roy; Cao, Xiaobo; Jupiter, Daniel; Fletcher, Steven; Yap, Jeremy L; Rai, Arun; Tobin, Richard P; Jiang, Weihua; Rascoe, Philip; Rogers, M Karen Newell

    2012-01-01

    It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. Mcl-1 is a critical survival protein in a variety of cell lineages and is critically regulated via ubiquitination. The Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon adenocarcinomas were evaluated via immunohistochemistry. Interaction between USP9X and Mcl-1 was demonstrated by immunoprecipitation-western blotting. The protein expression profiles of Mcl-1, Bcl-xL and USP9X in multiple cancer cell lines were determined by western blotting. Annexin-V staining and cleaved PARP western blotting were used to assay for apoptosis. The cellular toxicities after various treatments were measured via the XTT assay. In our current analysis of colon and lung cancer samples, we demonstrate that Mcl-1 and Bcl-xL are overexpressed and also co-exist in many tumors and that the expression levels of both genes correlate with the clinical staging. The downregulation of Mcl-1 or Bcl-xL via RNAi was found to increase the sensitivity of the tumor cells to chemotherapy. Furthermore, our analyses revealed that USP9X expression correlates with that of Mcl-1 in human cancer tissue samples. We additionally found that the USP9X inhibitor WP1130 promotes Mcl-1 degradation and increases tumor cell sensitivity to chemotherapies. Moreover, the combination of WP1130 and ABT-737, a well-documented Bcl-xL inhibitor, demonstrated a chemotherapeutic synergy and promoted apoptosis in different tumor cells. Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors

  12. Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

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    Maciej H Swat

    Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

  13. Tumor markers and bone scan in breast cancer patients

    International Nuclear Information System (INIS)

    Ugrinska, A.; Vaskova, O.; Kraleva, S.; Petrova, D.; Smickova, S.

    2004-01-01

    Full text: The objective of this study was to compare the levels of CA15-3 and CEA with the bone scan findings in patients with breast cancer. Retrospective analysis of 76 bone scans from 61 patients diagnosed with breast cancer in the last 5 years was performed by two nuclear medicine specialists. All bone scans were performed after surgical treatment of the disease. Patients with loco-regional residual disease or distant metastases in the liver, lung or the brain were excluded from the study. According to the bone scan the patients were divided in 5 groups: normal bone scan (N), equivocal bone scan (E), single metastasis (1MS), three metastases (3MS) and multiple metastases (MMS). Tumor markers were determined within a month before or after the bone scan was performed. Cut-off value for CA 15-3 was 35 U/ml, and for CEA 3 ng/ml. Statistical analysis was performed using descriptive statistic and Kolmogorov-Smirnov test. Bone metastases were revealed in 38% of the patients referred for bone scintigraphy out of which 26% had MMS, 7.8% had single MS and 4% had 3MS. The results of 6.5% of the patients were determined as equivocal. The values of CA15-3 were higher in all patient groups compared with the group that had normal bone scan, but this difference reached statistical significance only in groups with 3MS and MMS (p < 0.01). The values of CEA were significantly higher only in patients with multiple metastases when compared with group N (p < 0.01). Values higher than cut-off value for CA 15-3 was found in 9 patients out of 42 in the group with normal bone scan. The highest value of CA 15-3 in this group was 47 U/ml. Only one patient in this group showed elevated levels for CEA. Three patients in the group with single metastasis had normal CA 15-3, while CEA was elevated only in one patient. All patients in the group with 3MS had elevated levels of CA 15-3 while CEA was in the normal range. All patients with MMS had elevated CA 15-3 values while CEA was elevated in

  14. Consensus Contouring Guidelines for Postoperative Stereotactic Body Radiation Therapy for Metastatic Solid Tumor Malignancies to the Spine

    International Nuclear Information System (INIS)

    Redmond, Kristin J.; Robertson, Scott; Lo, Simon S.; Soltys, Scott G.; Ryu, Samuel; McNutt, Todd; Chao, Samuel T.; Yamada, Yoshiya; Ghia, Amol; Chang, Eric L.; Sheehan, Jason; Sahgal, Arjun

    2017-01-01

    Purpose: To develop consensus contouring guidelines for postoperative stereotactic body radiation therapy (SBRT) for spinal metastases. Methods and Materials: Ten spine SBRT specialists representing 10 international centers independently contoured the clinical target volume (CTV), planning target volume (PTV), spinal cord, and spinal cord planning organ at risk volume (PRV) for 10 representative clinical scenarios in postoperative spine SBRT for metastatic solid tumor malignancies. Contours were imported into the Computational Environment for Radiotherapy Research. Agreement between physicians was calculated with an expectation minimization algorithm using simultaneous truth and performance level estimation with κ statistics. Target volume definition guidelines were established by finding optimized confidence level consensus contours using histogram agreement analyses. Results: Nine expert radiation oncologists and 1 neurosurgeon completed contours for all 10 cases. The mean sensitivity and specificity were 0.79 (range, 0.71-0.89) and 0.94 (range, 0.90-0.99) for the CTV and 0.79 (range, 0.70-0.95) and 0.92 (range, 0.87-0.99) for the PTV), respectively. Mean κ agreement, which demonstrates the probability that contours agree by chance alone, was 0.58 (range, 0.43-0.70) for CTV and 0.58 (range, 0.37-0.76) for PTV (P<.001 for all cases). Optimized consensus contours were established for all patients with 80% confidence interval. Recommendations for CTV include treatment of the entire preoperative extent of bony and epidural disease, plus immediately adjacent bony anatomic compartments at risk of microscopic disease extension. In particular, a “donut-shaped” CTV was consistently applied in cases of preoperative circumferential epidural extension, regardless of extent of residual epidural extension. Otherwise more conformal anatomic-based CTVs were determined and described. Spinal instrumentation was consistently excluded from the CTV. Conclusions: We provide

  15. Evaluation of uptake and distribution of gold nanoparticles in solid tumors

    Science.gov (United States)

    England, Christopheri G.; Gobin, André M.; Frieboes, Hermann B.

    2015-11-01

    Although nanotherapeutics offer a targeted and potentially less toxic alternative to systemic chemotherapy in cancer treatment, nanotherapeutic transport is typically hindered by abnormal characteristics of tumor tissue. Once nanoparticles targeted to tumor cells arrive in the circulation of tumor vasculature, they must extravasate from irregular vessels and diffuse through the tissue to ideally reach all malignant cells in cytotoxic concentrations. The enhanced permeability and retention effect can be leveraged to promote extravasation of appropriately sized particles from tumor vasculature; however, therapeutic success remains elusive partly due to inadequate intra-tumoral transport promoting heterogeneous nanoparticle uptake and distribution. Irregular tumor vasculature not only hinders particle transport but also sustains hypoxic tissue kregions with quiescent cells, which may be unaffected by cycle-dependent chemotherapeutics released from nanoparticles and thus regrow tumor tissue following nanotherapy. Furthermore, a large proportion of systemically injected nanoparticles may become sequestered by the reticulo-endothelial system, resulting in overall diminished efficacy. We review recent work evaluating the uptake and distribution of gold nanoparticles in pre-clinical tumor models, with the goal to help improve nanotherapy outcomes. We also examine the potential role of novel layered gold nanoparticles designed to address some of these critical issues, assessing their uptake and transport in cancerous tissue.

  16. Solid pseudopapillary tumor of the pancreas (SPPT: Still an unsolved enigma Tumor sólido pseudopapilar del páncreas (TSSP: un enigma sin resolver

    Directory of Open Access Journals (Sweden)

    J. A. Cienfuegos

    2010-12-01

    Full Text Available Solid pseudo-papillary tumor (SPPT is a rare cystic tumor of the pancreas (1-3% of exocrine tumors of the pancreas which shows an "enigmatic" behavior on the clinical and molecular pattern. A retrospective analysis of the citological studies and resected specimens of pancreatic cystic tumors from May 1996 to February 2010 was carried out. Three cases of SPPT were found, which are the objective of this study. The diagnosis was established upon occasional finding in the abdominal CT, in spite of sizing between 3 and 6 cm of diameter. In the three cases the preoperative diagnosis was confirmed by citology and specific immunohistochemical staining. Cases 2 and 3 showed strong immunoreactivity for Beta-Catenina and E-Cadherina staining. Radical resection (R0 was carried out in the three cases. A young male -21 years of age (case 1- who had duodenal infiltration and two lymph nodes metastases died of hepatic and peritoneal recurrence 20 months following surgery. The other two cases are free of disease. The current review of the literature reports roughly 800 cases since the first report in 1959, and shows the enigmatic character of this tumor regarding the cellular origin, molecular pathways, prognostic factors and clinical behavior.El tumor pseudopapilar (TSPP es un tumor quístico del páncreas muy poco frecuente (1-3% de los tumores exocrinos del páncreas y que tiene un comportamiento oncológico y molecular "enigmático". Se realizó un análisis retrospectivo de las citologías de las lesiones quísticas del páncreas, así como de los tumores quísticos resecados entre mayo de 1996 y febrero de 2010, encontrándose tres tumores SSPP, motivo de este estudio. En los tres casos el diagnóstico fue ocasional en el TC abdominal a pesar de presentar unos tamaños entre 3 y 6 cm de diámetro. En los tres casos se confirmó el diagnóstico preoperatorio mediante citología e inmunohistoquímica. En los casos 2 y 3 se confirmó la positividad para Beta

  17. Exploring intra- and inter-reader variability in uni-dimensional, bi-dimensional, and volumetric measurements of solid tumors on CT scans reconstructed at different slice intervals

    International Nuclear Information System (INIS)

    Zhao, Binsheng; Tan, Yongqiang; Bell, Daniel J.; Marley, Sarah E.; Guo, Pingzhen; Mann, Helen; Scott, Marietta L.J.; Schwartz, Lawrence H.; Ghiorghiu, Dana C.

    2013-01-01

    Objective: Understanding magnitudes of variability when measuring tumor size may be valuable in improving detection of tumor change and thus evaluating tumor response to therapy in clinical trials and care. Our study explored intra- and inter-reader variability of tumor uni-dimensional (1D), bi-dimensional (2D), and volumetric (VOL) measurements using manual and computer-aided methods (CAM) on CT scans reconstructed at different slice intervals. Materials and methods: Raw CT data from 30 patients enrolled in oncology clinical trials was reconstructed at 5, 2.5, and 1.25 mm slice intervals. 118 lesions in the lungs, liver, and lymph nodes were analyzed. For each lesion, two independent radiologists manually and, separately, using computer software, measured the maximum diameter (1D), maximum perpendicular diameter, and volume (CAM only). One of them blindly repeated the measurements. Intra- and inter-reader variability for the manual method and CAM were analyzed using linear mixed-effects models and Bland–Altman method. Results: For the three slice intervals, the maximum coefficients of variation for manual intra-/inter-reader variability were 6.9%/9.0% (1D) and 12.3%/18.0% (2D), and for CAM were 5.4%/9.3% (1D), 11.3%/18.8% (2D) and 9.3%/18.0% (VOL). Maximal 95% reference ranges for the percentage difference in intra-reader measurements for manual 1D and 2D, and CAM VOL were (−15.5%, 25.8%), (−27.1%, 51.6%), and (−22.3%, 33.6%), respectively. Conclusions: Variability in measuring the diameter and volume of solid tumors, manually and by CAM, is affected by CT slice interval. The 2.5 mm slice interval provides the least measurement variability. Among the three techniques, 2D has the greatest measurement variability compared to 1D and 3D

  18. Tailored Beta-catenin mutational approach in extra-abdominal sporadic desmoid tumor patients without therapeutic intervention

    International Nuclear Information System (INIS)

    Broekhoven, Danique L.M. van; Grünhagenl, Dirk J.; Dalen, Thijs van; Coevorden, Frits van; Bonenkamp, Han J.; Been, Lukas B.; Bemelmans, Marc H.A.; Dijkstra, Sander D.S.; Colombo, Chiara; Gronchi, Alessandro; Verhoef, Cornelis

    2016-01-01

    The efficacy of the classical treatment modalities surgery and radiotherapy in the treatment of aggressive fibromatosis is presently disputed and there is a shift towards a more conservative approach. The aim of the present study is to objectify tumor growth in patients with extra-abdominal or abdominal wall aggressive fibromatosis, while adhering to a “watchful waiting” policy. Other objectives are to investigate quality of life and to identify factors associated with tumor growth, in particular the relation with the presence of a CTNNB1-gene mutation in the tumor. GRAFITI is a nationwide, multicenter, prospective registration trial. All patients with extra-abdominal or abdominal wall aggressive fibromatosis are eligible for inclusion in the study. Main exclusion criteria are: history of familiar adenomatous polyposis, severe pain, functional impairment, life/limb threating situations in case of progressive disease. Patients included in the study will be treated with a watchful waiting policy during a period of 5 years. Imaging studies with ultrasound and magnetic resonance imaging scan will be performed during follow-up to monitor possible growth: the first years every 3 months, the second year twice and the yearly. In addition patients will be asked to complete a quality of life questionnaire on specific follow-up moments. The primary endpoint is the rate of progression per year, defined by the Response Evaluation Criteria In Solid Tumors (RECIST). Secondary endpoints are quality of life and the rate of influence on tumor progression for several factors, such as CTNNB1-mutations, age and localization. This study will provide insight in tumor behavior, the effect on quality of life and clinicopathological factors predictive of tumor progression. The GRAFITI trial is registered in the Netherlands National Trial Register (NTR), number: NTR4714

  19. Preliminary Study of Oxygen-Enhanced Longitudinal Relaxation in MRI: A Potential Novel Biomarker of Oxygenation Changes in Solid Tumors

    International Nuclear Information System (INIS)

    O'Connor, James P.B.; Naish, Josephine H.; Parker, Geoff J.M.; Waterton, John C.; Watson, Yvonne; Jayson, Gordon C.; Buonaccorsi, Giovanni A.; Cheung, Sue; Buckley, David L.; McGrath, Deirdre M.; West, Catharine M.L.; Davidson, Susan E.; Roberts, Caleb; Mills, Samantha J.; Mitchell, Claire L.; Hope, Lynn; Ton, N. Chan; Jackson, Alan

    2009-01-01

    Purpose: There is considerable interest in developing non-invasive methods of mapping tumor hypoxia. Changes in tissue oxygen concentration produce proportional changes in the magnetic resonance imaging (MRI) longitudinal relaxation rate (R 1 ). This technique has been used previously to evaluate oxygen delivery to healthy tissues and is distinct from blood oxygenation level-dependent (BOLD) imaging. Here we report application of this method to detect alteration in tumor oxygenation status. Methods and materials: Ten patients with advanced cancer of the abdomen and pelvis underwent serial measurement of tumor R 1 while breathing medical air (21% oxygen) followed by 100% oxygen (oxygen-enhanced MRI). Gadolinium-based dynamic contrast-enhanced MRI was then performed to compare the spatial distribution of perfusion with that of oxygen-induced ΔR 1 . Results: ΔR 1 showed significant increases of 0.021 to 0.058 s -1 in eight patients with either locally recurrent tumor from cervical and hepatocellular carcinomas or metastases from ovarian and colorectal carcinomas. In general, there was congruency between perfusion and oxygen concentration. However, regional mismatch was observed in some tumor cores. Here, moderate gadolinium uptake (consistent with moderate perfusion) was associated with low area under the ΔR 1 curve (consistent with minimal increase in oxygen concentration). Conclusions: These results provide evidence that oxygen-enhanced longitudinal relaxation can monitor changes in tumor oxygen concentration. The technique shows promise in identifying hypoxic regions within tumors and may enable spatial mapping of change in tumor oxygen concentration.

  20. Changed adipocytokine concentrations in colorectal tumor patients and morbidly obese patients compared to healthy controls

    International Nuclear Information System (INIS)

    Hillenbrand, Andreas; Fassler, Juliane; Huber, Nadine; Xu, Pengfei; Henne-Bruns, Doris; Templin, Markus; Schrezenmeier, Hubert; Wolf, Anna Maria; Knippschild, Uwe

    2012-01-01

    Obesity has been associated with increased incidence of colorectal cancer. Adipose tissue dysfunction accompanied with alterations in the release of adipocytokines has been proposed to contribute to cancer pathogenesis and progression. The aim of this study was to analyze plasma concentrations of several adipose tissue expressed hormones in colorectal cancer patients (CRC) and morbidly obese (MO) patients and to compare these concentrations to clinicopathological parameters. Plasma concentrations of adiponectin, resistin, leptin, active plasminogen activator inhibitor (PAI)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1 alpha, and tumor necrosis factor (TNF)-alpha were determined in 67 patients operated on for CRC (31 rectal cancers, 36 colon cancers), 37 patients operated on for morbid obesity and 60 healthy blood donors (BD). Compared to BD, leptin concentrations were lowered in CRC patients whereas those of MO patients were elevated. Adiponectin concentrations were only lowered in MO patients. Concentrations of MCP-1, PAI-1, and IL-1 alpha were elevated in both CRC and MO patients, while resistin and TNF-alpha were similarly expressed in MO and CRC patients compared to BD. Resistin concentrations positively correlated with tumor staging (p<0.002) and grading (p=0.015) of rectal tumor patients. The results suggest that both MO and CRC have low-grade inflammation as part of their etiology

  1. Genomic Profiling on an Unselected Solid Tumor Population Reveals a Highly Mutated Wnt/β-Catenin Pathway Associated with Oncogenic EGFR Mutations

    Directory of Open Access Journals (Sweden)

    Jingrui Jiang

    2018-04-01

    Full Text Available Oncogenic epidermal growth factor receptors (EGFRs can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to mutations, oncogenic shift, alternative signaling, and other potential mechanisms. To further understand the genetic alterations associated with oncogenic EGFRs and to provide further insight into optimal and personalized therapeutic strategies, we applied a proprietary comprehensive next-generation sequencing (NGS-based assay of 435 genes to systematically study the genomic profiles of 1565 unselected solid cancer patient samples. We found that activating EGFR mutations were predominantly detected in lung cancer, particularly in non-small cell lung cancer (NSCLC. The mutational landscape of EGFR-driven tumors covered most key signaling pathways and biological processes. Strikingly, the Wnt/β-catenin pathway was highly mutated (48 variants detected in 46% of the EGFR-driven tumors, and its variant number topped that in the TP53/apoptosis and PI3K-AKT-mTOR pathways. Furthermore, an analysis of mutation distribution revealed a differential association pattern of gene mutations between EGFR exon 19del and EGFR L858R. Our results confirm the aggressive nature of the oncogenic EGFR-driven tumors and reassure that a combinational strategy should have advantages over an EGFR-targeted monotherapy and holds great promise for overcoming drug resistance.

  2. The quaternary state of polymerized human hemoglobin regulates oxygenation of breast cancer solid tumors: A theoretical and experimental study

    Science.gov (United States)

    Ju, Julia A.; Baek, Jin Hyen; Yalamanoglu, Ayla; Buehler, Paul W.; Gilkes, Daniele M.; Palmer, Andre F.

    2018-01-01

    A major constraint in the treatment of cancer is inadequate oxygenation of the tumor mass, which can reduce chemotherapeutic efficacy. We hypothesize that polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemotherapeutic outcomes. By locking PolyhHb in the relaxed (R) quaternary state, oxygen (O2) offloading at low O2 tensions (20 mm Hg) is facilitated with tense (T) state PolyhHb. Therefore, R-state PolyhHb may deliver significantly more O2 to hypoxic tissues. Biophysical parameters of T and R-state PolyhHb were used to populate a modified Krogh tissue cylinder model to assess O2 transport in a tumor. In general, we found that increasing the volume of transfused PolyhHb decreased the apparent viscosity of blood in the arteriole. In addition, we found that PolyhHb transfusion decreased the wall shear stress at large arteriole diameters (>20 μm), but increased wall shear stress for small arteriole diameters (state PolyhHb may be more effective than T-state PolyhHb for O2 delivery at similar transfusion volumes. Reduction in the apparent viscosity resulting from PolyhHb transfusion may result in significant changes in flow distributions throughout the tumor microcirculatory network. The difference in wall shear stress implies that PolyhHb may have a more significant effect in capillary beds through mechano-transduction. Periodic top-load transfusions of PolyhHb into mice bearing breast tumors confirmed the oxygenation potential of both PolyhHbs via reduced hypoxic volume, vascular density, tumor growth, and increased expression of hypoxia inducible genes. Tissue section analysis demonstrated primary PolyhHb clearance occurred in the liver and spleen indicating a minimal risk for renal damage. PMID:29414985

  3. Treatment and outcomes of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors: retrospective review of 12 patients.

    Science.gov (United States)

    Zuo, Qing-Yao; Wang, Hong; Li, Wei; Niu, Xiao-Hui; Huang, Yan-Hong; Chen, Jia; You, Yu-Hua; Liu, Bao-Yue; Cui, Ai-Min; Deng, Wei

    2017-09-21

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. Nonspecific symptoms make the diagnosis elusive. In addition, locating the responsible tumor(s) is challenging. The aim of this study was to investigate the clinical management and outcomes of TIO. The clinical features, diagnostic procedures, treatment, and outcomes of 12 patients were reviewed retrospectively. The cohort comprised six men and six women (mean age 45.5 ± 9.9 years, range 23-61 years). The mean duration of disease was 3.7 ± 2.6 years. All patients manifested progressive bone pain, muscle weakness, and/or difficulty walking. Serum phosphorus concentrations were low in all patients (mean 0.42 ± 0.12 mmol/L). Technetium-99m octreotide scintigraphy was performed in 11 patients and showed lesions in the right distal femur, left femoral head, and right tibial plateau, respectively, in three patients. Magnetic resonance imaging (MRI) was negative for lesions in one patient. Two patients underwent biopsies that showed negative histopathology. Two patients, at 2 years and 8 months, respectively, after having negative technetium-99m octreotide studies, underwent 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (CT), which revealed lesions in the sacrum and soft tissue of the left palm, respectively. One tumor was detected by CT and MRI. Overall, lesion sites were the head (two patients, 16.7%), thoracic and lumbar region (two, 16.7%), pelvis (three, 25%), lower limbs (four, 33.3%), and upper limbs (one, 8.3%). All patients underwent surgery, and histopathology showed phosphaturic mesenchymal tumors in each. Postoperatively, serum phosphorus concentrations normalized within 2-7 days in 11 patients. With follow-ups of 1-41 months, surgery was effective in 10 patients. One patient developed local recurrence and another had metastases. Locating tumors responsible for tumor-induced osteomalacia is

  4. Clinical course of non-operated patients with spinal cord tumor

    International Nuclear Information System (INIS)

    Kamata, Michihiro; Kinouchi, Junnosuke; Maruiwa, Hirofumi; Nakamura, Masaya; Matsumoto, Morio; Chiba, Kazuhiro; Toyama, Yoshiaki

    2003-01-01

    The clinical course of spinal cord tumors in 24 non-operated patients who were followed by MRI for more than 1 year was investigated retrospectively. Only 7 patients were positive in neurological symptoms. 7 patients had multiple tumors, and the histopathologic diagnosis in 16 patients was neurinoma. The MRI findings changed in 4 patients, and follow-up MR images showed rapid growth of 2 neurinomas. The clinical manifestations did not change in 17 patients, but they improved in 3 patients whose symptoms were not caused by tumors and improved after temporary worsening caused by tumor growth in 2 patients. They worsened in 2 patients with intramedullary tumors associated with neurological symptoms. The diameter of the spinal cord of the patients with intramedullary tumors increased, making the spinal cord susceptible to both anterior and posterior compression. Finally, the clinical course of the patients with spinal cord tumors did not deteriorate rapidly, except in the patients with intramedullary tumor associated with neurological manifestations. We concluded that when spinal cord tumors that are asymptomatic or associated with minor symptoms are diagnosed as neurinoma or neurofibroma based on the MRI findings, early surgery should not be performed and followed by meticulous follow-up. (author)

  5. Radiation- and Photo-induced Activation of 5-Fluorouracil Prodrugs as a Strategy for the Selective Treatment of Solid Tumors

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    Sei-ichi Nishimoto

    2008-10-01

    Full Text Available 5-Fluorouracil (5-FU is used widely as an anticancer drug to treat solid cancers, such as colon, breast, rectal, and pancreatic cancers, although its clinical application is limited because 5-FU has gastrointestinal and hematological toxicity. Many groups are searching for prodrugs with functions that are tumor selective in their delivery and can be activated to improve the clinical utility of 5-FU as an important cancer chemotherapeutic agent. UV and ionizing radiation can cause chemical reactions in a localized area of the body, and these have been applied in the development of site-specific drug activation and sensitization. In this review, we describe recent progress in the development of novel 5-FU prodrugs that are activated site specifically by UV light and ionizing radiation in the tumor microenvironment. We also discuss the chemical mechanisms underlying this activation.

  6. Dependence of radiotherapeutic results on tumor size in patients with cervix uteri carcinoma

    International Nuclear Information System (INIS)

    Gabelov, A.A.; Zharinov, G.M.

    1981-01-01

    A method is suggested that permits specifying the primary tumor size on the basis of clinical examination of patients with cervix uteri carcinoma. The values of tumor size have been correlated with long-term results of concomitant radiotherapy in 1358 patients with cervix uteri carcinoma. The data obtained have shown that the primary tumor size is a factor that determines to a large extent radiotherapeutic results in patients with cervix uteri carcinoma. The specification of tumor size values makes it possible to considerably lessen prognostic uncertainty of present-day staging classifications. The structure of radiotherapeutic failures also turned out to be closely associated with the primary tumor size

  7. Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy

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    Garcia-Villa, Alejandra; Balasubramanian, Priya; Miller, Brandon L. [William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH (United States); Lustberg, Maryam B.; Ramaswamy, Bhuvaneswari [Department of Internal Medicine, Breast Medical Oncology, James Cancer Hospital and Ohio State University Comprehensive Cancer Center, Columbus, OH (United States); Chalmers, Jeffrey J., E-mail: chalmers.1@osu.edu [William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH (United States)

    2012-10-25

    Circulating tumor cells (CTCs) are prognostic markers in a variety of solid tumor malignancies. The potential of CTCs to be used as a “liquid biopsy” to monitor a patient’s condition and predict drug response and resistance is currently under investigation. Using a negative depletion, enrichment methodology, CTCs isolated from the peripheral blood of breast cancer patients with stage IV breast cancer undergoing DNA damaging therapy with platinum-based therapy were enriched. The enriched cell suspensions were stained with an optimized labeling protocol targeting: nuclei, cytokeratins 8, 18, and 19, the surface marker CD45, and the presence of the protein γ-H2AX. As a direct or indirect result of platinum therapy, double-strand break of DNA initiates phosphorylation of the histone H2AX, at serine 139; this phosphorylated form is referred to as γ-H2AX. In addition to γ-H2AX staining in specific locations with the cell nuclei, consistent with previous reports and referred to as foci, more general staining in the cell cytoplasm was also observed in some cells suggesting the potential of cell apoptosis. Our study underscores the utility and the complexity of investigating CTCs as predictive markers of response to various therapies. Additional studies are ongoing to evaluate the diverse γ-H2AX staining patterns we report here which needs to be further correlated with patient outcomes.

  8. A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy

    Directory of Open Access Journals (Sweden)

    Han LQ

    2016-11-01

    Full Text Available Leiqiang Han, Tianqi Wang, Jingliang Wu, Xiaolan Yin, Hao Fang, Na Zhang School of Pharmaceutical Science, Shandong University, Ji’nan, Shandong, People’s Republic of China Abstract: Small molecule-based nanodrugs with nanoparticles (NPs that are mainly composed of small molecules, have been considered as a promising candidate for a next-generation nanodrug, owing to their unique properties. Vorinostat (SAHA is a canonical US Food and Drug Administration-approved histone deacetylase (HDAC inhibitor for the treatment of cutaneous T-cell lymphoma. However, the lack of efficacy against solid tumors hinders its progress in clinical use. Herein, a novel nanodrug of SAHA was developed based on disulfide-linked prodrug SAHA-S-S-VE. SAHA-S-S-VE could self-assemble into 148 nm NPs by disulfide-induced mechanisms, which were validated by molecular dynamics simulations. Under reduced conditions, the redox-responsive behavior of SAHA-S-S-VE was investigated, and the HDAC inhibition results verified the efficient release of free SAHA. With a biocompatible d-a-tocopheryl polyethylene glycol succinate (TPGS functionalization, the SAHA-S-S-VE/TPGS NPs exhibited low critical aggregation concentration of 4.5 µM and outstanding stability in vitro with drug-loading capacity of 24%. In vitro biological assessment indicated that SAHA-S-S-VE/TPGS NPs had significant anticancer activity against HepG2. Further in vivo evaluation demonstrated that the resulting NPs could be accumulated in the tumor region and inhibit the tumor growth effectively. This approach, which turned SAHA into a self-assembled redox-responsive nanodrug, provided a new channel for the use of HDAC inhibitor in solid tumor therapy. Keywords: SAHA, HDAC, small molecule, nanoparticles, self-assemble, disulfide bond

  9. HUMAN NK CELLS: FROM SURFACE RECEPTORS TO THE THERAPY OF LEUKEMIAS AND SOLID TUMORS

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    LORENZO eMORETTA

    2014-03-01

    Full Text Available Natural Killer (NK cells are major effector cells of the innate immunity. The discovery, over two decades ago, of MHC-class I specific NK receptors and subsequently of activating receptors, recognizing ligands expressed by tumor or virus-infected cells, paved the way to our understanding of the mechanisms of selective recognition and killing of tumor cells. Although NK cells can efficiently kill tumor cells of different histotypes in vitro, their activity may be limited in vivo by their inefficient trafficking to tumor lesions and by the inhibition of their function induced by tumor cells themselves and by the tumor microenvironment. On the other hand, the important role of NK cells has been clearly demonstrated in the therapy of high risk leukemias in the haploidentical hematopoietic cell (HSC transplantation setting. NK cells derived from donor HSC kill leukemic cells residual after the conditioning regimen, thus preventing leukemia relapses. In addition, they also kill residual dendritic cells and T lymphocytes, thus preventing both GvHD and graft rejection.

  10. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients

    International Nuclear Information System (INIS)

    Medrek, Catharina; Pontén, Fredrik; Jirström, Karin; Leandersson, Karin

    2012-01-01

    Tumor associated macrophages (TAMs) are alternatively activated macrophages that enhance tumor progression by promoting tumor cell invasion, migration and angiogenesis. TAMs have an anti-inflammatory function resembling M2 macrophages. CD163 is regarded as a highly specific monocyte/macrophage marker for M2 macrophages. In this study we evaluated the specificity of using the M2 macrophage marker CD163 as a TAM marker and compared its prognostic value with the more frequently used pan-macrophage marker CD68. We also analyzed the prognostic value of the localization of CD163 + and CD68 + myeloid cells in human breast cancer. The extent of infiltrating CD163 + or CD68 + myeloid cells in tumor nest versus tumor stroma was evaluated by immunohistochemistry in tissue microarrays with tumors from 144 breast cancer cases. Spearman’s Rho and χ 2 tests were used to examine the correlations between CD163 + or CD68 + myeloid cells and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the impact of CD163 + and CD68 + myeloid cells in tumor stroma and tumor nest, respectively, on recurrence free survival, breast cancer specific and overall survival. We found that infiltration of CD163 + and CD68 + macrophages into tumor stroma, but not into tumor nest, were of clinical relevance. CD163 + macrophages in tumor stroma positively correlated with higher grade, larger tumor size, Ki67 positivity, estrogen receptor negativity, progesterone receptor negativity, triple-negative/basal-like breast cancer and inversely correlated with luminal A breast cancer. Some CD163 + areas lacked CD