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Sample records for tumor consortium phase

  1. Brain Tumor Epidemiology Consortium (BTEC)

    Science.gov (United States)

    The Brain Tumor Epidemiology Consortium is an open scientific forum organized to foster the development of multi-center, international and inter-disciplinary collaborations that will lead to a better understanding of the etiology, outcomes, and prevention of brain tumors.

  2. An operational perspective of challenging statistical dogma while establishing a modern, secure distributed data management and imaging transport system: the Pediatric Brain Tumor Consortium phase I experience.

    Science.gov (United States)

    Onar, Arzu; Ramamurthy, Uma; Wallace, Dana; Boyett, James M

    2009-04-01

    The Pediatric Brain Tumor Consortium (PBTC) is a multidisciplinary cooperative research organization devoted to the study of correlative tumor biology and new therapies for primary central nervous system (CNS) tumors of childhood. The PBTC was created in 1999 to conduct early-phase studies in a rapid fashion in order to provide sound scientific foundation for the Children's Oncology Group to conduct definitive trials. The Operations and Biostatistics Center (OBC) of the PBTC is responsible for centrally administering study design and trial development, study conduct and monitoring, data collection and management as well as various regulatory and compliance processes. The phase I designs utilized for the consortium trials have accommodated challenges unique to pediatric trials such as body surface area (BSA)-based dosing in the absence of pediatric formulations of oral agents. Further during the past decade, the OBC has developed and implemented a state-of-the-art secure and efficient internet-based paperless distributed data management system. Additional web-based systems are also in place for tracking and distributing correlative study data as well as neuroimaging files. These systems enable effective communications among the members of the consortium and facilitate the conduct and timely reporting of multi-institutional early-phase clinical trials.

  3. Continual reassessment method vs. traditional empirically based design: modifications motivated by Phase I trials in pediatric oncology by the Pediatric Brain Tumor Consortium.

    Science.gov (United States)

    Onar, Arzu; Kocak, Mehmet; Boyett, James M

    2009-01-01

    In this article we provide additional support for the use of a model-based design in pediatric Phase I trials and present our modifications to the continual reassessment method (CRM), which were largely motivated by specific challenges we encountered in the context of the Pediatric Brain Tumor Consortium trials. We also summarize the results of our extensive simulations studying the operating characteristics of our modified approach and contrasting it to the empirically based traditional method (TM). Compared to the TM, our simulations indicate that the modified version of CRM is more accurate, exposes fewer patients to potentially toxic doses, and tends to require fewer patients. Further, the CRM-based MTD has a consistent definition across trials, which is important, especially in a consortium setting where multiple agents are being tested in studies that are often running simultaneously and accruing from the same patient population.

  4. Phase I Trial of MK-0752 in Children With Refractory CNS Malignancies: A Pediatric Brain Tumor Consortium Study

    Science.gov (United States)

    Fouladi, Maryam; Stewart, Clinton F.; Olson, James; Wagner, Lars M.; Onar-Thomas, Arzu; Kocak, Mehmet; Packer, Roger J.; Goldman, Stewart; Gururangan, Sridharan; Gajjar, Amar; Demuth, Tim; Kun, Larry E.; Boyett, James M.; Gilbertson, Richard J.

    2011-01-01

    Purpose To estimate the maximum-tolerated dose (MTD), describe dose-limiting toxicities (DLTs), and characterize pharmacokinetic properties of MK-0752, a gamma secretase inhibitor, in children with refractory or recurrent CNS malignancies. Patients and Methods MK-0752 was administered once daily for 3 consecutive days of every 7 days at escalating dosages starting at 200 mg/m2. The modified continual reassessment method was used to estimate the MTD. A course was 28 days in duration. Pharmacokinetic analysis was performed during the first course. Expression of NOTCH and hairy enhancer of split (HES) proteins was assessed in peripheral-blood mononuclear cells (PBMCs) before and following treatment with MK-0752. Results Twenty-three eligible patients were enrolled: 10 males (median age, 8.1 years; range, 2.6 to 17.7 years) with diagnoses of brainstem glioma (n = 6), ependymoma (n = 8), medulloblastoma/primitive neuroectodermal tumor (n = 4), glioblastoma multiforme (n = 2), atypical teratoid/rhabdoid tumor (n = 1), malignant glioma (n = 1), and choroid plexus carcinoma, (n = 1). Seventeen patients were fully evaluable for toxicity. No DLTs occurred in the three patients enrolled at 200 mg/m2/dose. At 260 mg/m2/dose, DLTs occurred in two of six patients, both of whom experienced grade 3 ALT and AST. There were no grade 4 toxicities; non–dose-limiting grade 3 toxicities included hypokalemia and lymphopenia. Population pharmacokinetic values (% coefficient of variation) for MK-0752 were apparent oral clearance, 0.444 (38%) L/h/m2; apparent volume of distribution, 7.36 (24%) L/m2; and ka, 0.358 (99%) hr−1. Conclusion MK-0752 is well-tolerated in children with recurrent CNS malignancies. The recommended phase II dose using the 3 days on followed by 4 days off schedule is 260 mg/m2/dose once daily. PMID:21825264

  5. Phase 1 trial of ontuxizumab (MORAb-004) in children with relapsed or refractory solid tumors: A report from the Children's Oncology Group Phase 1 Pilot Consortium (ADVL1213).

    Science.gov (United States)

    Norris, Robin E; Fox, Elizabeth; Reid, Joel M; Ralya, Andrew; Liu, Xiaowei W; Minard, Charles; Weigel, Brenda J

    2018-05-01

    Ontuxizumab is a humanized IgG monoclonal antibody that targets the cell-surface glycoprotein endosialin (tumor endothelial marker-1[TEM-1]/CD248) found on activated mesenchymal cells and certain tumors. Ontuxizumab binding to endosialin may interfere with platelet-derived growth factor signaling, prevent tumor stroma organization, and prevent new vessel formation. Ontuxizumab was administered intravenously on days 1, 8, 15, and 22 of a 28-day cycle at three dose levels (4, 8, and 12 mg/kg). Further dose escalation to 16 mg/kg was planned if the maximum tolerated dose (MTD) was not reached and the ontuxizumab systemic clearance was ≥30% higher in children compared to adults. Following determination of the MTD/recommended phase 2 dose, an additional cohort of six patients (children with relapsed or refractory solid tumors. The PK of ontuxizumab does not appear to be significantly different in children compared to adults. © 2018 Wiley Periodicals, Inc.

  6. A pediatric phase 1 trial of vorinostat and temozolomide in relapsed or refractory primary brain or spinal cord tumors: a Children's Oncology Group phase 1 consortium study.

    Science.gov (United States)

    Hummel, Trent R; Wagner, Lars; Ahern, Charlotte; Fouladi, Maryam; Reid, Joel M; McGovern, Renee M; Ames, Matthew M; Gilbertson, Richard J; Horton, Terzah; Ingle, Ashish M; Weigel, Brenda; Blaney, Susan M

    2013-09-01

    We conducted a pediatric phase I study to estimate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetic properties of vorinostat, a histone deacetylase (HDAC) inhibitor, when given in combination with temozolomide in children with refractory or recurrent CNS malignancies. Vorinostat, followed by temozolomide approximately 1 hour later, was orally administered, once daily, for 5 consecutive days every 28 days at three dose levels using the rolling six design. Studies of histone accumulation in peripheral blood mononuclear cells were performed on Day 1 at 0, 6, and 24 hours after vorinostat dosing. Vorinostat pharmacokinetics (PK) and serum MGMT promoter status were also assessed. Nineteen eligible patients were enrolled and 18 patients were evaluable for toxicity. There were no DLTs observed at dose level 1 or 2. DLTs occurred in four patients at dose level 3: thrombocytopenia (4), neutropenia (3), and leucopenia (1). Non-dose limiting grade 3 or 4 toxicities related to protocol therapy were also hematologic and included neutropenia, lymphopenia, thrombocytopenia, anemia, and leucopenia. Three patients exhibited stable disease and one patient had a partial response. There was no clear relationship between vorinostat dosage and drug exposure over the dose range studied. Accumulation of acetylated H3 histone in PBMC was observed after administration of vorinostat. Five-day cycles of vorinostat in combination with temozolomide are well tolerated in children with recurrent CNS malignancies with myelosuppression as the DLT. The recommended phase II combination doses are vorinostat, 300 mg/m(2) /day and temozolomide, 150 mg/m(2) /day. Copyright © 2013 Wiley Periodicals, Inc.

  7. Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report1

    Science.gov (United States)

    Pollack, Ian F.; Jakacki, Regina I.; Blaney, Susan M.; Hancock, Michael L.; Kieran, Mark W.; Phillips, Peter; Kun, Larry E.; Friedman, Henry; Packer, Roger; Banerjee, Anu; Geyer, J. Russell; Goldman, Stewart; Poussaint, Tina Young; Krasin, Matthew J.; Wang, Yanfeng; Hayes, Michael; Murgo, Anthony; Weiner, Susan; Boyett, James M.

    2007-01-01

    This study estimated the maximum tolerated dose (MTD) of imatinib with irradiation in children with newly diagnosed brainstem gliomas, and those with recurrent malignant intracranial gliomas, stratified according to use of enzyme-inducing anticonvulsant drugs (EIACDs). In the brainstem glioma stratum, imatinib was initially administered twice daily during irradiation, but because of possible association with intratumoral hemorrhage (ITH) was subsequently started two weeks after irradiation. The protocol was also amended to exclude children with prior hemorrhage. Twenty-four evaluable patients received therapy before the amendment, and three of six with a brainstem tumor experienced dose-limiting toxicity (DLT): one had asymptomatic ITH, one had grade 4 neutropenia and, one had renal insufficiency. None of 18 patients with recurrent glioma experienced DLT. After protocol amendment, 3 of 16 patients with brainstem glioma and 2 of 11 patients with recurrent glioma who were not receiving EIACDs experienced ITH DLTs, with three patients being symptomatic. In addition to the six patients with hemorrhages during the DLT monitoring period, 10 experienced ITH (eight patients were symptomatic) thereafter. The recommended phase II dose for brainstem gliomas was 265 mg/m2. Three of 27 patients with brainstem gliomas with imaging before and after irradiation, prior to receiving imatinib, had new hemorrhage, excluding their receiving imatinib. The MTD for recurrent high-grade gliomas without EIACDs was 465 mg/m2, but the MTD was not established with EIACDs, with no DLTs at 800 mg/m2. In summary, recommended phase II imatinib doses were determined for children with newly diagnosed brainstem glioma and recurrent high-grade glioma who were not receiving EIACDs. Imatinib may increase the risk of ITH, although the incidence of spontaneous hemorrhages in brainstem glioma is sufficiently high that this should be considered in studies of agents in which hemorrhage is a concern. PMID

  8. Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog-Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032.

    Science.gov (United States)

    Robinson, Giles W; Orr, Brent A; Wu, Gang; Gururangan, Sridharan; Lin, Tong; Qaddoumi, Ibrahim; Packer, Roger J; Goldman, Stewart; Prados, Michael D; Desjardins, Annick; Chintagumpala, Murali; Takebe, Naoko; Kaste, Sue C; Rusch, Michael; Allen, Sariah J; Onar-Thomas, Arzu; Stewart, Clinton F; Fouladi, Maryam; Boyett, James M; Gilbertson, Richard J; Curran, Tom; Ellison, David W; Gajjar, Amar

    2015-08-20

    Two phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB). Adult patients enrolled onto PBTC-025B and pediatric patients enrolled onto PBTC-032 were treated with vismodegib (150 to 300 mg/d). Protocol-defined response, which had to be sustained for 8 weeks, was confirmed by central neuroimaging review. Molecular tests to identify patterns of response and insensitivity were performed when tissue was available. A total of 31 patients were enrolled onto PBTC-025B, and 12 were enrolled onto PBTC-032. Three patients in PBTC-025B and one in PBTC-032, all with SHH-subgroup MB (SHH-MB), exhibited protocol-defined responses. Progression-free survival (PFS) was longer in those with SHH-MB than in those with non-SHH-MB, and prolonged disease stabilization occurred in 41% of patient cases of SHH-MB. Among those with SHH-MB, loss of heterozygosity of PTCH1 was associated with prolonged PFS, and diffuse staining of P53 was associated with reduced PFS. Whole-exome sequencing identified mutations in SHH genes downstream from SMO in four of four tissue samples from nonresponders and upstream of SMO in two of four patients with favorable responses. Vismodegib exhibits activity against adult recurrent SHH-MB but not against recurrent non-SHH-MB. Inadequate accrual of pediatric patients precluded conclusions in this population. Molecular analyses support the hypothesis that SMO inhibitor activity depends on the genomic aberrations within the tumor. Such inhibitors should be advanced in SHH-MB studies; however, molecular and genomic work remains imperative to identify target populations that will truly benefit. © 2015 by American Society of Clinical Oncology.

  9. Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog–Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032

    Science.gov (United States)

    Robinson, Giles W.; Orr, Brent A.; Wu, Gang; Gururangan, Sridharan; Lin, Tong; Qaddoumi, Ibrahim; Packer, Roger J.; Goldman, Stewart; Prados, Michael D.; Desjardins, Annick; Chintagumpala, Murali; Takebe, Naoko; Kaste, Sue C.; Rusch, Michael; Allen, Sariah J.; Onar-Thomas, Arzu; Stewart, Clinton F.; Fouladi, Maryam; Boyett, James M.; Gilbertson, Richard J.; Curran, Tom; Ellison, David W.; Gajjar, Amar

    2015-01-01

    Purpose Two phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB). Patients and Methods Adult patients enrolled onto PBTC-025B and pediatric patients enrolled onto PBTC-032 were treated with vismodegib (150 to 300 mg/d). Protocol-defined response, which had to be sustained for 8 weeks, was confirmed by central neuroimaging review. Molecular tests to identify patterns of response and insensitivity were performed when tissue was available. Results A total of 31 patients were enrolled onto PBTC-025B, and 12 were enrolled onto PBTC-032. Three patients in PBTC-025B and one in PBTC-032, all with SHH-subgroup MB (SHH-MB), exhibited protocol-defined responses. Progression-free survival (PFS) was longer in those with SHH-MB than in those with non-SHH–MB, and prolonged disease stabilization occurred in 41% of patient cases of SHH-MB. Among those with SHH-MB, loss of heterozygosity of PTCH1 was associated with prolonged PFS, and diffuse staining of P53 was associated with reduced PFS. Whole-exome sequencing identified mutations in SHH genes downstream from SMO in four of four tissue samples from nonresponders and upstream of SMO in two of four patients with favorable responses. Conclusion Vismodegib exhibits activity against adult recurrent SHH-MB but not against recurrent non-SHH–MB. Inadequate accrual of pediatric patients precluded conclusions in this population. Molecular analyses support the hypothesis that SMO inhibitor activity depends on the genomic aberrations within the tumor. Such inhibitors should be advanced in SHH-MB studies; however, molecular and genomic work remains imperative to identify target populations that will truly benefit. PMID:26169613

  10. Phase I study of vorinostat in combination with temozolomide in patients with high-grade gliomas: North American Brain Tumor Consortium Study 04-03.

    Science.gov (United States)

    Lee, Eudocia Q; Puduvalli, Vinay K; Reid, Joel M; Kuhn, John G; Lamborn, Kathleen R; Cloughesy, Timothy F; Chang, Susan M; Drappatz, Jan; Yung, W K Alfred; Gilbert, Mark R; Robins, H Ian; Lieberman, Frank S; Lassman, Andrew B; McGovern, Renee M; Xu, Jihong; Desideri, Serena; Ye, Xiabu; Ames, Matthew M; Espinoza-Delgado, Igor; Prados, Michael D; Wen, Patrick Y

    2012-11-01

    A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG). This phase I, dose-finding, investigational study was conducted in two parts. Part 1 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days every 28 days. Part 2 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days of the first cycle and 200 mg/m(2)/day for 5 days of the subsequent 28-day cycles. In part 1, the MTD of vorinostat administered on days 1 to 7 and 15 to 21 of every 28-day cycle, in combination with TMZ, was 500 mg daily. Dose-limiting toxicities (DLT) included grade 3 anorexia, grade 3 ALT, and grade 5 hemorrhage in the setting of grade 4 thrombocytopenia. In part 2, the MTD of vorinostat on days 1 to 7 and 15 to 21 of every 28-day cycle, combined with TMZ, was 400 mg daily. No DLTs were encountered, but vorinostat dosing could not be escalated further due to thrombocytopenia. The most common serious adverse events were fatigue, lymphopenia, thrombocytopenia, and thromboembolic events. There were no apparent pharmacokinetic interactions between vorinostat and TMZ. Vorinostat treatment resulted in hyperacetylation of histones H3 and H4 in peripheral mononuclear cells. Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway. ©2012 AACR.

  11. Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of Tumors From Patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group

    Science.gov (United States)

    Yeo, Winnie; Chung, Hyun C.; Chan, Stephen L.; Wang, Ling Z.; Lim, Robert; Picus, Joel; Boyer, Michael; Mo, Frankie K.F.; Koh, Jane; Rha, Sun Y.; Hui, Edwin P.; Jeung, Hei C.; Roh, Jae K.; Yu, Simon C.H.; To, Ka F.; Tao, Qian; Ma, Brigette B.; Chan, Anthony W.H.; Tong, Joanna H.M.; Erlichman, Charles; Chan, Anthony T.C.; Goh, Boon C.

    2012-01-01

    Purpose Epigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II. Patients and Methods Major eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score ≤ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m2 per day (level 1), 900 mg/m2 per day (level 2), 1,200 mg/m2 per day (level 3), and 1,400 mg/m2 per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response. Results Belinostat pharmacokinetics were linear from 600 to 1,400 mg/m2 without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P = .036). Conclusion Epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. HR23B

  12. 18F-FDG PET and MR Imaging Associations Across a Spectrum of Pediatric Brain Tumors: A Report from the Pediatric Brain Tumor Consortium

    Science.gov (United States)

    Zukotynski, Katherine; Fahey, Frederic; Kocak, Mehmet; Kun, Larry; Boyett, James; Fouladi, Maryam; Vajapeyam, Sridhar; Treves, Ted; Poussaint, Tina Y.

    2014-01-01

    The purpose of this study was to describe 18F-FDG uptake across a spectrum of pediatric brain tumors and correlate 18F-FDG PET with MR imaging variables, progression-free survival (PFS), and overall survival (OS). Methods A retrospective analysis was conducted of children enrolled in phase I/II clinical trials through the Pediatric Brain Tumor Consortium from August 2000 to June 2010. PET variables were summarized within diagnostic categories using descriptive statistics. Associations of PET with MR imaging variables and PFS and OS by tumor types were evaluated. Results Baseline 18F-FDG PET was available in 203 children; 66 had newly diagnosed brain tumors, and 137 had recurrent/refractory brain tumors before enrolling in a Pediatric Brain Tumor Consortium trial. MR imaging was performed within 2 wk of PET and before therapy in all cases. The 18F-FDG uptake pattern and MR imaging contrast enhancement (CE) varied by tumor type. On average, glioblastoma multiforme and medulloblastoma had uniform, intense uptake throughout the tumor, whereas brain stem gliomas (BSGs) had low uptake in less than 50% of the tumor and ependymoma had low uptake throughout the tumor. For newly diagnosed BSG, correlation of 18F-FDG uptake with CE portended reduced OS (P = 0.032); in refractory/recurrent BSG, lack of correlation between 18F-FDG uptake and CE suggested decreased PFS (P = 0.023). In newly diagnosed BSG for which more than 50% of the tumor had 18F-FDG uptake, there was a suggestion of lower apparent diffusion coefficient (P = 0.061) and decreased PFS (P = 0.065). Conclusion 18F-FDG PET and MR imaging showed a spectrum of patterns depending on tumor type. In newly diagnosed BSG, the correlation of 18F-FDG uptake and CE suggested decreased OS, likely related to more aggressive disease. When more than 50% of the tumor had 18F-FDG uptake, the apparent diffusion coefficient was lower, consistent with increased cellularity. In refractory/recurrent BSG, poor correlation between 18F

  13. 25 CFR 1000.50 - What must a Tribe/Consortium seeking a planning grant submit in order to meet the planning phase...

    Science.gov (United States)

    2010-04-01

    ... submit in order to meet the planning phase requirements? 1000.50 Section 1000.50 Indians OFFICE OF THE... seeking a planning grant submit in order to meet the planning phase requirements? A Tribe/Consortium must... the Tribe/Consortium is free from material audit exceptions. In order to meet this requirement, a...

  14. Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients

    Science.gov (United States)

    Mazcko, Christina; Brown, Diane E.; Koehler, Jennifer W.; Miller, Andrew D.; Miller, C. Ryan; Bentley, R. Timothy; Packer, Rebecca A.; Breen, Matthew; Boudreau, C. Elizabeth; Levine, Jonathan M.; Simpson, R. Mark; Halsey, Charles; Kisseberth, William; Rossmeisl, John H.; Dickinson, Peter J.; Fan, Timothy M.; Corps, Kara; Aldape, Kenneth; Puduvalli, Vinay; Pluhar, G. Elizabeth; Gilbert, Mark R.

    2016-01-01

    On September 14–15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed. PMID:27179361

  15. Pediatric phase I trial and pharmacokinetic study of dasatinib: a report from the children's oncology group phase I consortium.

    Science.gov (United States)

    Aplenc, Richard; Blaney, Susan M; Strauss, Lewis C; Balis, Frank M; Shusterman, Suzanne; Ingle, Ashish Mark; Agrawal, Shruti; Sun, Junfeng; Wright, John J; Adamson, Peter C

    2011-03-01

    PURPOSE Dasatinib is an orally available tyrosine kinase inhibitor with low nanomolar activity against SRC family kinases, BCR-ABL, c-KIT, EPHA2, and the PDGF-β receptor. Dasatinib was found to have selective activity in several tumor models in the Pediatric Preclinical Testing Program. PATIENTS AND METHODS A phase I study of dasatinib in pediatric patients with refractory solid tumors or imatinib-refractory, Philadelphia chromosome-positive leukemia was performed. Dose levels of 50, 65, 85, and 110 mg/m²/dose, administered orally twice daily for 28 days, with courses repeated without interruption, were studied. Pharmacokinetic studies were performed with the initial dose. A total of 39 patients (solid tumors, n = 28; chronic myeloid leukemia [CML], n = 9; acute lymphoblastic leukemia, n = 2) were enrolled. No dose-limiting toxicities (DLTs) were observed at the 50, 65, and 85 mg/m² dose levels. At 110 mg/m², two of six patients experienced DLT including grade 2 diarrhea and headache. In children with leukemia, grade 4 hypokalemia (50 mg/m²), grade 3 diarrhea (85 mg/m²), and grade 2 creatinine elevation (50 mg/m²) were observed. DLT in later courses included pleural effusions, hemangiomatosis, and GI hemorrhage. There were three complete cytogenetic responses, three partial cytogenetic responses, and two partial/minimal cytogenetic responses observed in evaluable patients with CML. CONCLUSION Overall, drug disposition and tolerability of dasatinib were similar to those observed in adult patients.

  16. Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium

    DEFF Research Database (Denmark)

    Muranen, Taru A; Blomqvist, Carl; Dörk, Thilo

    2016-01-01

    BACKGROUND: P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival...... and characteristics of breast tumors of germ line p.I157T carriers. METHODS: We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer...... characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models...

  17. Massachusetts Institute of Technology Consortium Agreement

    National Research Council Canada - National Science Library

    Asada, Haruhiko

    1999-01-01

    ... of Phase 2 of the Home Automation and Healthcare Consortium. This report describes all major research accomplishments within the last six months since we launched the second phase of the consortium...

  18. Exploratory evaluation of MR permeability with 18F-FDG PET mapping in pediatric brain tumors: a report from the Pediatric Brain Tumor Consortium.

    Science.gov (United States)

    Zukotynski, Katherine A; Fahey, Frederic H; Vajapeyam, Sridhar; Ng, Sarah S; Kocak, Mehmet; Gururangan, Sridharan; Kun, Larry E; Poussaint, Tina Y

    2013-08-01

    The purpose of this study was to develop a method of registering (18)F-FDG PET with MR permeability images for investigating the correlation of (18)F-FDG uptake, permeability, and cerebral blood volume (CBV) in children with pediatric brain tumors and their relationship with outcome. Twenty-four children with brain tumors in a phase II study of bevacizumab and irinotecan underwent brain MR and (18)F-FDG PET within 2 wk. Tumor types included supratentorial high-grade astrocytoma (n = 7), low-grade glioma (n = 9), brain stem glioma (n = 4), medulloblastoma (n = 2), and ependymoma (n = 2). There were 33 cases (pretreatment only [n = 12], posttreatment only [n = 3], and both pretreatment [n = 9] and posttreatment [n = 9]). (18)F-FDG PET images were registered to MR images from the last time point of the T1 perfusion time series using mutual information. Three-dimensional regions of interest (ROIs) drawn on permeability images were automatically transferred to registered PET images. The quality of ROI registration was graded (1, excellent; 2, very good; 3, good; 4, fair; and 5, poor) by 3 independent experts. Spearman rank correlations were used to assess correlation of maximum tumor permeability (Kps(max)), maximum CBV (CBV(max)), and maximum (18)F-FDG uptake normalized to white matter (T/W(max)). Cox proportional hazards models were used to investigate associations of these parameters with progression-free survival (PFS). The quality of ROI registration between PET and MR was good to excellent in 31 of 33 cases. There was no correlation of baseline Kps(max) with CBV(max) (Spearman rank correlation = 0.018 [P = 0.94]) or T/W(max) (Spearman rank correlation = 0.07 [P = 0.76]). Baseline CBV(max) was correlated with T/W(max) (Spearman rank correlation = 0.47 [P = 0.036]). Baseline Kps(max), CBV(max), and T/W(max) were not significantly associated with PFS (P = 0.42, hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.90-1.045, and number of events [n(events)] = 15

  19. Associations of Breast Cancer Risk Factors With Tumor Subtypes : A Pooled Analysis From the Breast Cancer Association Consortium Studies

    NARCIS (Netherlands)

    Yang, Xiaohong R.; Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomaeki, Kristiina; Heikkilae, Paeivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J.; Van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O'Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M. S.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Doerk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Perez, Jose Ignacio; Menendez Rodriguez, Primitiva; Zamora, Pilar; Bentez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Bruening, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Byrski, Tomasz; Gorski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collee, Margriet; Wang-Gohrke, Shan; Pylkaes, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Paeivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Orsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Borge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; Mckay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P. E. A.; Tollenaar, R. A. E. M.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients

  20. Evaluation of the Safety and Benefit of Phase I Oncology Trials for Patients With Primary CNS Tumors.

    Science.gov (United States)

    Gounder, Mrinal M; Nayak, Lakshmi; Sahebjam, Solmaz; Muzikansky, Alona; Sanchez, Armando J; Desideri, Serena; Ye, Xiaobu; Ivy, S Percy; Nabors, L Burt; Prados, Michael; Grossman, Stuart; DeAngelis, Lisa M; Wen, Patrick Y

    2015-10-01

    Patients with high-grade gliomas (HGG) are frequently excluded from first-in-human solid tumor trials because of perceived poor prognosis, excessive toxicities, concomitant drug interactions, and poor efficacy. We conducted an analysis of outcomes from select, single-agent phase I studies in patients with HGG. We compared outcomes to pooled analysis of published studies in solid tumors with various molecular and cytotoxic drugs evaluated as single agents or as combinations. Individual records of patients with recurrent HGG enrolled onto Adult Brain Tumor Consortium trials of single-agent, cytotoxic or molecular agents from 2000 to 2008 were analyzed for baseline characteristics, toxicities, responses, and survival. Our analysis included 327 patients with advanced, refractory HGG who were enrolled onto eight trials involving targeted molecular (n=5) and cytotoxic (n=3) therapies. At enrollment, patients had a median Karnofsky performance score of 90 and median age of 52 years; 62% were men, 63% had glioblastoma, and the median number of prior systemic chemotherapies was one. Baseline laboratory values were in an acceptable range to meet eligibility criteria. Patients were on the study for a median of two cycles (range, Patients with HGG who meet standard eligibility criteria may be good candidates for solid tumor phase I studies with single-agent molecular or cytotoxic drugs with favorable preclinical rationale and pharmacokinetic properties in this population. © 2015 by American Society of Clinical Oncology.

  1. DTI assessment of the brainstem white matter tracts in pediatric BSG before and after therapy: a report from the Pediatric Brain Tumor Consortium.

    Science.gov (United States)

    Prabhu, Sanjay P; Ng, Sarah; Vajapeyam, Sridhar; Kieran, Mark W; Pollack, Ian F; Geyer, Russell; Haas-Kogan, Daphne; Boyett, James M; Kun, Larry; Poussaint, Tina Young

    2011-01-01

    To assess changes in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values in brainstem gliomas (BSG) in children and to observe the temporal evolution of changes in the white matter tracts following therapy using diffusion tensor imaging (DTI) analysis. Serial ADC and FA measurements were obtained in three patients with newly diagnosed BSG on two approved treatment protocols. Values were compared with a set of normative ADC, FA, and eigenvalues of age-matched children of the corticospinal, transverse pontine and medial lemniscal tracts. Fiber tracking of the tracts coursing through the brainstem was performed using standard diffusion tractography analysis. We found increased ADC values within tumor at baseline compared to age-matched controls, with subsequent drop following treatment and subsequent increase with recurrence. Correspondingly, FA values were reduced at presentation, but transiently recovered during the phase of tumor response to treatment, and finally decreased significantly during tumor progression. These changes were concordant with the tractography analysis of white matter tracts in the brainstem. Based on these results, we suggest that initial changes in ADC and FA values reflects tract infiltration by tumor, but not complete disruption, whereas tumor progression results in complete loss of anisotropy possibly due to tract disruption. Serial changes in ADC and FA values and tractography data in pediatric BSG suggest initial tumor infiltration, with transient improvement on treatment and subsequent loss of tract anisotropy during tumor progression. This technique may have potential use in assessing response to treatment regimens for pediatric BSG.

  2. Exploratory evaluation of two-dimensional and three-dimensional methods of FDG PET quantification in pediatric anaplastic astrocytoma: a report from the Pediatric Brain Tumor Consortium (PBTC)

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Gethin; Treves, S. Ted [Harvard Medical School, Joint Program in Nuclear Medicine, Children' s Hospital Boston, Boston, MA (United States); Fahey, Frederic H. [Harvard Medical School, Joint Program in Nuclear Medicine, Children' s Hospital Boston, Boston, MA (United States); Harvard Medical School, Division of Nuclear Medicine, Department of Radiology, Children' s Hospital Boston, Boston, MA (United States); Kocak, Mehmet; Boyett, James M.; Kun, Larry E. [St Jude Children' s Research Hospital, Memphis, TN (United States); Pollack, Ian F. [Children' s Hospital Pittsburgh, Pittsburgh, PA (United States); Young Poussaint, Tina [Harvard Medical School, Division of Neuroradiology, Department of Radiology, Children' s Hospital Boston, Boston, MA (United States)

    2008-09-15

    The rationale of this study was to investigate the feasibility of three-dimensional (3D) methods to analyze {sup 18}F-fluoro-deoxy-glucose (FDG) uptake in children with anaplastic astrocytoma (AA) in a multi-institutional trial, to compare 3D and two-dimensional (2D) methods and explore data associations with progression-free survival (PFS). 3D tumor volumes from pretreatment MR images (fluid attenuation inversion recovery and postgadolinium) of children with recurrent AA on a phase I trial of imatinib mesylate were coregistered to FDG positron emission tomography (PET) images. PET data were normalized. Four metrics were defined: the maximum ratio (maximum pixel value within the 3D tumor volume, normalized), the total ratio (cumulative pixel values within the tumor volume, normalized) and tumor mean ratio (total pixel value divided by volume, normalized). 2D analysis methods were compared. Cox proportional hazards models were used to estimate the association between these methods and PFS. Strongest correlations between 2D and 3D methods were with analyses using postcontrast T1 images for volume of interest (VOI). The analyses suggest 3D maximum tumor and mean tumor ratios, whether normalized by gray matter or white matter, were associated with PFS. This study of a series of pretreatment AA patients suggests that 3D PET methods using VOIs based on postcontrast T1 correlate with 2D methods and are related to PFS. These methods yield an estimate of metabolically active tumor burden and may add prognostic information after tumor grade is determined. Future rigorous multi-institutional protocols with larger numbers of patients will be required for validation. (orig.)

  3. BACTERIAL CONSORTIUM

    Directory of Open Access Journals (Sweden)

    Payel Sarkar

    2013-01-01

    Full Text Available Petroleum aromatic hydrocarbons like benzen e, toluene, ethyl benzene and xylene, together known as BTEX, has almost the same chemical structure. These aromatic hydrocarbons are released as pollutants in th e environment. This work was taken up to develop a solvent tolerant bacterial cons ortium that could degrade BTEX compounds as they all share a common chemical structure. We have isolated almost 60 different types of bacterial strains from different petroleum contaminated sites. Of these 60 bacterial strains almost 20 microorganisms were screene d on the basis of capability to tolerate high concentration of BTEX. Ten differe nt consortia were prepared and the compatibility of the bacterial strains within the consortia was checked by gram staining and BTEX tolerance level. Four successful mi crobial consortia were selected in which all the bacterial strains concomitantly grew in presence of high concentration of BTEX (10% of toluene, 10% of benzene 5% ethyl benzene and 1% xylene. Consortium #2 showed the highest growth rate in pr esence of BTEX. Degradation of BTEX by consortium #2 was monitored for 5 days by gradual decrease in the volume of the solvents. The maximum reduction observed wa s 85% in 5 days. Gas chromatography results also reveal that could completely degrade benzene and ethyl benzene within 48 hours. Almost 90% degradation of toluene and xylene in 48 hours was exhibited by consortium #2. It could also tolerate and degrade many industrial solvents such as chloroform, DMSO, acetonitrile having a wide range of log P values (0.03–3.1. Degradation of aromatic hydrocarbon like BTEX by a solvent tolerant bacterial consortium is greatly significant as it could degrade high concentration of pollutants compared to a bacterium and also reduces the time span of degradation.

  4. Anxiety in the preoperative phase of awake brain tumor surgery.

    Science.gov (United States)

    Ruis, Carla; Wajer, Irene Huenges; Robe, Pierre; van Zandvoort, Martine

    2017-06-01

    Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we analyzed the prevalence and potential clinical predictors of anxiety in the pre-operative phase of an awake brain tumor surgery. Seventy consecutive candidates for an awake brain tumor surgery were included. All patients received a neuropsychological pre-operative work-up. The Hospital Anxiety and Depression Scale (HADS) was administrated to investigate symptoms of anxiety. Demographic and medical data were extracted from patients' charts. Linear regression analyses, multiple regression analyses, t-tests for parametric and Mann-Whitney U tests for non-parametric data were used to analyze the relation between demographic and medical variables and pre-operative anxiety. Mean score on the anxiety scale of the HADS was 6.1 (SD=4.2, range 1-19) and 25% of the patients scored on or above the cut-off for anxiety symptoms (score >7). Women reported higher levels of anxiety than men (p<0.01). Furthermore, younger patient were more anxious than older patients (p<0.05). No other variables were significantly related to pre-operative anxiety. Merely, one in every four patients reported significant anxiety symptoms in the pre-operative phase. Besides gender and age, none of the other demographic or medical factors were significantly associated with the level of anxiety. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  6. Estimation of Breast Tumor Conductivity using Parabolic Phase Fitting

    NARCIS (Netherlands)

    Katscher, U.; Djamshidi, K.; Voigt, T.; Ivancevic, M.; Abe, H.; Newstead, G.; Keupp, J.

    2012-01-01

    According to ex vivo studies, breast tumors exhibit a significantlyaltered electric conductivity. This feature opens the chance to increase the specificity of breast tumor characterization with MRI. Theelectric conductivity can be measured in vivo using “Electric Properties Tomography (EPT). EPT has

  7. International Lymphoma Epidemiology Consortium

    Science.gov (United States)

    The InterLymph Consortium, or formally the International Consortium of Investigators Working on Non-Hodgkin's Lymphoma Epidemiologic Studies, is an open scientific forum for epidemiologic research in non-Hodgkin's lymphoma.

  8. Anxiety in the preoperative phase of awake brain tumor surgery

    NARCIS (Netherlands)

    Ruis, Carla; Huenges Wajer, I.M.C.; Robe, Pierre; van Zandvoort, Martine

    OBJECTIVE: Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we

  9. Anxiety in the preoperative phase of awake brain tumor surgery

    NARCIS (Netherlands)

    Ruis, C.; Huenges Wajer, I.M.C.; Robe, Pierre; van Zandvoort, M.J.E.

    Objective Awake surgery emerges as a standard of care for brain tumors located in or near eloquent areas. Levels of preoperative anxiety in patients are important, because anxiety can influence cognitive performance and participation, hence altering the outcome of the procedure. In this study we

  10. MRI as a central component of clinical trials analysis in brainstem glioma: a report from the Pediatric Brain Tumor Consortium (PBTC)

    Science.gov (United States)

    Poussaint, Tina Young; Kocak, Mehmet; Vajapeyam, Sridhar; Packer, Roger I.; Robertson, Richard L.; Geyer, Russell; Haas-Kogan, Daphne; Pollack, Ian F.; Vezina, Gilbert; Zimmerman, Robert; Cha, Soonmee; Patay, Zoltan; Boyett, James M.; Kun, Larry E.

    2011-01-01

    We report MRI findings from 2 pediatric clinical trials of diffuse intrinsic brainstem glioma (BSG) incorporating concurrent radiation therapy (RT) with molecularly targeted agents (gefitinib and tipifarnib). We determined associations of MRI variables with progression-free survival and overall survival and investigated effects of treatment on these variables. MRI (including diffusion and perfusion) was done before treatment, every 8 weeks (first year), every 12 weeks (thereafter), and at the end of treatment or disease progression. Reduced tumor volume (P < .0001) and tumor diffusion values (P <.0001) were apparent on the first post-RT/drug studies. Decreases in tumor volume correlated with pre-RT volume (P < .0001) and pre-RT diffusion values (P < .0001); larger decreases were noted for tumors with higher volumes and diffusion values. Patients with larger pre-RT tumors had longer progression-free survival (P < .0001). Patients with ≥25% decrease in tumor volume and diffusion values after RT had longer progression-free survival (P = .028) and overall survival (P = .0009). Enhancement at baseline and over time was significantly associated with shorter survival. Tumor diffusion values with baseline enhancement were significantly lower than those without (P = .0002). RT of BSG is associated with decreased tumor volume and intralesional diffusion values; patients with ≥25% decrease in values post-RT had relatively longer survival intervals, apparently providing an early imaging-based surrogate for relative outcomes. Patients with larger tumors and greater decreases in tumor volume and diffusion values had longer survival intervals. Tumor enhancement was associated with shorter survival, lower tumor diffusion values (increased cellularity), and a smaller drop in diffusion values after RT (P = .006). These associations justify continued investigation in other large clinical trials of brainstem glioma patients. PMID:21297126

  11. Effective genetic vaccination with a widely shared endogenous retroviral tumor antigen requires CD40 stimulation during tumor rejection phase.

    Science.gov (United States)

    Bronte, Vincenzo; Cingarlini, Sara; Apolloni, Elisa; Serafini, Paolo; Marigo, Ilaria; De Santo, Carmela; Macino, Beatrice; Marin, Oriano; Zanovello, Paola

    2003-12-15

    Endogenous retrovirus (ERV) products are recognized by T lymphocytes in mice and humans. As these Ags are preferentially expressed by neoplastic tissues, they might represent an ideal target for active immunization by genetic vaccination. However, i.m. inoculation of plasmid DNA encoding mouse gp70 or p15E, two products of the env gene of an endogenous murine leukemia virus, elicited a weak Ag-specific T lymphocyte response and resulted in partial protection from challenge with mouse tumors possessing these Ags. Depletion experiments showed that CD8(+), but not CD4(+), T lymphocytes were crucial for the antitumor activity of the vaccines. Systemic administration of agonistic anti-CD40 mAb increased the therapeutic potential of genetic vaccination, but only when given during the tumor rejection phase and not at the time of immunization. This effect correlated with a dramatic increase in the number of ERV-specific CD8(+) T lymphocytes. Adjuvant activity of CD40 agonists thus seems to be relevant to enhance the CD8(+) T cell-dependent response in tumor-bearing hosts, suggesting that sustaining tumor-specific T lymphocyte survival in subjects undergoing vaccination might be a key event in the successful vaccination with weak tumor Ags.

  12. MinION Analysis and Reference Consortium: Phase 2 data release and analysis of R9.0 chemistry.

    Science.gov (United States)

    Jain, Miten; Tyson, John R; Loose, Matthew; Ip, Camilla L C; Eccles, David A; O'Grady, Justin; Malla, Sunir; Leggett, Richard M; Wallerman, Ola; Jansen, Hans J; Zalunin, Vadim; Birney, Ewan; Brown, Bonnie L; Snutch, Terrance P; Olsen, Hugh E

    2017-01-01

    Long-read sequencing is rapidly evolving and reshaping the suite of opportunities for genomic analysis. For the MinION in particular, as both the platform and chemistry develop, the user community requires reference data to set performance expectations and maximally exploit third-generation sequencing. We performed an analysis of MinION data derived from whole genome sequencing of Escherichia coli K-12 using the R9.0 chemistry, comparing the results with the older R7.3 chemistry. We computed the error-rate estimates for insertions, deletions, and mismatches in MinION reads. Run-time characteristics of the flow cell and run scripts for R9.0 were similar to those observed for R7.3 chemistry, but with an 8-fold increase in bases per second (from 30 bps in R7.3 and SQK-MAP005 library preparation, to 250 bps in R9.0) processed by individual nanopores, and less drop-off in yield over time. The 2-dimensional ("2D") N50 read length was unchanged from the prior chemistry. Using the proportion of alignable reads as a measure of base-call accuracy, 99.9% of "pass" template reads from 1-dimensional ("1D")  experiments were mappable and ~97% from 2D experiments. The median identity of reads was ~89% for 1D and ~94% for 2D experiments. The total error rate (miscall + insertion + deletion ) decreased for 2D "pass" reads from 9.1% in R7.3 to 7.5% in R9.0 and for template "pass" reads from 26.7% in R7.3 to 14.5% in R9.0. These Phase 2 MinION experiments serve as a baseline by providing estimates for read quality, throughput, and mappability. The datasets further enable the development of bioinformatic tools tailored to the new R9.0 chemistry and the design of novel biological applications for this technology. K: thousand, Kb: kilobase (one thousand base pairs), M: million, Mb: megabase (one million base pairs), Gb: gigabase (one billion base pairs).

  13. Delay equations modeling the effects of phase-specific drugs and immunotherapy on proliferating tumor cells.

    Science.gov (United States)

    Barbarossa, Maria Vittoria; Kuttler, Christina; Zinsl, Jonathan

    2012-04-01

    In this work we present a mathematical model for tumor growth based on the biology of the cell cycle. For an appropriate description of the effects of phase-specific drugs, it is necessary to look at the cell cycle and its phases. Our model reproduces the dynamics of three different tumor cell populations: quiescent cells, cells during the interphase and mitotic cells. Starting from a partial differential equations (PDEs) setting, a delay differential equations (DDE) model is derived for an easier and more realistic approach. Our equations also include interactions of tumor cells with immune system effectors. We investigate the model both from the analytical and the numerical point of view, give conditions for positivity of solutions and focus on the stability of the cancer-free equilibrium. Different immunotherapeutic strategies and their effects on the tumor growth are considered, as well.

  14. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  15. X-ray phase contrast with injected gas for tumor microangiography

    International Nuclear Information System (INIS)

    Lundström, U; Larsson, D H; Burvall, A; Hertz, H M; Westermark, U K; Henriksson, M Arsenian

    2014-01-01

    We show that the microvasculature of mouse tumors can be visualized using propagation-based phase-contrast x-ray imaging with gas as the contrast agent. The large density difference over the gas–tissue interface provides high contrast, allowing the imaging of small-diameter blood vessels with relatively short exposure times and low dose using a compact liquid-metal-jet x-ray source. The method investigated is applied to tumors (E1A/Ras-transformed mouse embryonic fibroblasts) grown in mouse ears, demonstrating sub-15-µm-diameter imaging of their blood vessels. The exposure time for a 2D projection image is a few seconds and a full tomographic 3D map takes some minutes. The method relies on the strength of the vasculature to withstand the gas pressure. Given that tumor vessels are known to be more fragile than normal vessels, we investigate the tolerance of the vasculature of 12 tumors to gas injection and find that a majority withstand 200 mbar pressures, enough to fill 12-µm-diameter vessels with gas. A comparison of the elasticity of tumorous and non-tumorous vessels supports the assumption of tumor vessels being more fragile. Finally, we conclude that the method has the potential to be extended to the imaging of 15 µm vessels in thick tissue, including mouse imaging, making it of interest for, e.g., angiogenesis research. (paper)

  16. Grating-based phase-contrast imaging of tumor angiogenesis in lung metastases.

    Directory of Open Access Journals (Sweden)

    Huimin Lin

    Full Text Available To assess the feasibility of the grating-based phase-contrast imaging (GPI technique for studying tumor angiogenesis in nude BALB/c mice, without contrast agents.We established lung metastatic models of human gastric cancer by injecting the moderately differentiated SGC-7901 gastric cancer cell line into the tail vein of nude mice. Samples were embedded in a 10% formalin suspension and dried before imaging. Grating-based X-ray phase-contrast images were obtained at the BL13W beamline of the Shanghai Synchrotron Radiation Facility (SSRF and compared with histological sections.Without contrast agents, grating-based X-ray phase-contrast imaging still differentiated angiogenesis within metastatic tumors with high spatial resolution. Vessels, down to tens of microns, showed gray values that were distinctive from those of the surrounding tumors, which made them easily identifiable. The vessels depicted in the imaging study were similar to those identified on histopathology, both in size and shape.Our preliminary study demonstrates that grating-based X-ray phase-contrast imaging has the potential to depict angiogenesis in lung metastases.

  17. Community Hospital Telehealth Consortium

    National Research Council Canada - National Science Library

    Williams, Elton

    2003-01-01

    The Community Hospital Telehealth Consortium is a unique, forward-thinking, community-based healthcare service project organized around 5 not-for-profit community hospitals located throughout Louisiana and Mississippi...

  18. Community Hospital Telehealth Consortium

    National Research Council Canada - National Science Library

    Williams, Jr, Elton L

    2007-01-01

    The Community Hospital Telehealth Consortium is a unique, forward-thinking, community-based healthcare service project organized around 5 not-for-profit community hospitals located throughout Louisiana and Mississippi...

  19. Results of a Phase II Study of the Italian Group on Rare Tumors

    Directory of Open Access Journals (Sweden)

    Armando Santoro

    1999-01-01

    Full Text Available Purpose. The prognosis of advanced soft tissue sarcoma is poor, only a few drugs showing some activity with response rates around 15– 25%. Consequently drug development seems mandatory to improve treatment outcome. Following previous favourable EORTC experience, the Italian Group on Rare Tumors started a phase II study with docetaxel to confirm the activity of this drug in soft tissue sarcoma.

  20. Prospects and challenges of quantitative phase imaging in tumor cell biology

    Science.gov (United States)

    Kemper, Björn; Götte, Martin; Greve, Burkhard; Ketelhut, Steffi

    2016-03-01

    Quantitative phase imaging (QPI) techniques provide high resolution label-free quantitative live cell imaging. Here, prospects and challenges of QPI in tumor cell biology are presented, using the example of digital holographic microscopy (DHM). It is shown that the evaluation of quantitative DHM phase images allows the retrieval of different parameter sets for quantification of cellular motion changes in migration and motility assays that are caused by genetic modifications. Furthermore, we demonstrate simultaneously label-free imaging of cell growth and morphology properties.

  1. Dosimetric effect of intrafraction tumor motion in phase gated lung stereotactic body radiotherapy

    International Nuclear Information System (INIS)

    Zhao Bo; Yang Yong; Li Tianfang; Li Xiang; Heron, Dwight E.; Huq, M. Saiful

    2012-01-01

    Purpose: A major concern for lung intensity modulated radiation therapy delivery is the deviation of actually delivered dose distribution from the planned one due to simultaneous movements of multileaf collimator (MLC) leaves and tumor. For gated lung stereotactic body radiotherapy treatment (SBRT), the situation becomes even more complicated because of SBRT's characteristics such as fewer fractions, smaller target volume, higher dose rate, and extended fractional treatment time. The purpose of this work is to investigate the dosimetric effect of intrafraction tumor motion during gated lung SBRT delivery by reconstructing the delivered dose distribution with real-time tumor motion considered. Methods: The tumor motion data were retrieved from six lung patients. Each of them received three fractions of stereotactic radiotherapy treatments with Cyberknife Synchrony (Accuray, Sunnyvale, CA). Phase gating through an external surrogate was simulated with a gating window of 5 mm. The resulting residual tumor motion curves during gating (beam-on) were retrieved. Planning target volume (PTV) was defined as physician-contoured clinical target volume (CTV) surrounded by an isotropic 5 mm margin. Each patient was prescribed with 60 Gy/3 fractions. The authors developed an algorithm to reconstruct the delivered dose with tumor motion. The DMLC segments, mainly leaf position and segment weighting factor, were recalculated according to the probability density function of tumor motion curve. The new DMLC sequence file was imported back to treatment planning system to reconstruct the dose distribution. Results: Half of the patients in the study group experienced PTV D95% deviation up to 26% for fractional dose and 14% for total dose. CTV mean dose dropped by 1% with tumor motion. Although CTV is almost covered by prescribed dose with 5 mm margin, qualitative comparison on the dose distributions reveals that CTV is on the verge of underdose. The discrepancy happens due to tumor

  2. The Consortium for Higher Education Tax Reform Report

    Science.gov (United States)

    Center for Postsecondary and Economic Success, 2014

    2014-01-01

    This White Paper presents the work of the Consortium for Higher Education Tax Reform, a partnership funded by the Bill & Melinda Gates Foundation as part of the second phase of its Reimagining Aid Design and Delivery (RADD) initiative. Consortium partners are the Center for Postsecondary and Economic Success at CLASP, the Education Trust, New…

  3. Using X-ray in-line phase-contrast imaging for the investigation of nude mouse hepatic tumors.

    Directory of Open Access Journals (Sweden)

    Qiang Tao

    Full Text Available The purpose of this paper is to report the noninvasive imaging of hepatic tumors without contrast agents. Both normal tissues and tumor tissues can be detected, and tumor tissues in different stages can be classified quantitatively. We implanted BEL-7402 human hepatocellular carcinoma cells into the livers of nude mice and then imaged the livers using X-ray in-line phase-contrast imaging (ILPCI. The projection images' texture feature based on gray level co-occurrence matrix (GLCM and dual-tree complex wavelet transforms (DTCWT were extracted to discriminate normal tissues and tumor tissues. Different stages of hepatic tumors were classified using support vector machines (SVM. Images of livers from nude mice sacrificed 6 days after inoculation with cancer cells show diffuse distribution of the tumor tissue, but images of livers from nude mice sacrificed 9, 12, or 15 days after inoculation with cancer cells show necrotic lumps in the tumor tissue. The results of the principal component analysis (PCA of the texture features based on GLCM of normal regions were positive, but those of tumor regions were negative. The results of PCA of the texture features based on DTCWT of normal regions were greater than those of tumor regions. The values of the texture features in low-frequency coefficient images increased monotonically with the growth of the tumors. Different stages of liver tumors can be classified using SVM, and the accuracy is 83.33%. Noninvasive and micron-scale imaging can be achieved by X-ray ILPCI. We can observe hepatic tumors and small vessels from the phase-contrast images. This new imaging approach for hepatic cancer is effective and has potential use in the early detection and classification of hepatic tumors.

  4. Phase transitions in tumor growth: IV relationship between metabolic rate and fractal dimension of human tumor cells

    Science.gov (United States)

    Betancourt-Mar, J. A.; Llanos-Pérez, J. A.; Cocho, G.; Mansilla, R.; Martin, R. R.; Montero, S.; Nieto-Villar, J. M.

    2017-05-01

    By the use of thermodynamics formalism of irreversible processes, complex systems theory and systems biology, it is derived a relationship between the production of entropy per unit time, the fractal dimension and the tumor growth rate for human tumors cells. The thermodynamics framework developed demonstrates that, the dissipation function is a Landau potential and also the Lyapunov function of the dynamical behavior of tumor growth, which indicate the directional character, stability and robustness of the phenomenon. The entropy production rate may be used as a quantitative index of the metastatic potential of tumors. The current theoretical framework will hopefully provide a better understanding of cancer and contribute to improvements in cancer treatment.

  5. Detection of hepatic VX2 tumors in rabbits: comparison of conventional US and phase- inversion harmonic US during the liver- specific late phase of contrast enhancement

    International Nuclear Information System (INIS)

    Lee, Jeong Min; Youk, Ji Hyun; Lee, Young Hwan; Kim, Young Kon; Kim, Chong Soo; Li, Chun Ai

    2003-01-01

    To compare phase-inversion sonography during the liver-specific phase of contrast enhancement using a microbubble contrast agent with conventional B-mode sonography for the detection of VX2 liver tumors. Twenty-three rabbits, 18 of which had VX2 liver tumor implants, received a bolus injection of 0.6 g of Levovist (200 mg/ml). During the liver-specific phase of this agent, they were evaluated using both conventional sonography and contrast-enhanced phase-inversion harmonic imaging (CEPIHI). Following sacrifice of the animals, pathologic analysis was performed and the reference standard thus obtained. The conspicuity, size and number of the tumors before and after contrast administration, as determined by a sonographer, were compared between the two modes and with the pathologic findings. CE-PIHI demonstrated marked hepatic parenchymal enhancement in all rabbits. For VX2 tumors detected at both conventional US and CE- PIHI, conspicuity was improved by contrast-enhanced PIHI. On examination of gross specimens, 52 VX2 tumors were identified. Conventional US correctly detected 18 of the 52 (34.6%), while PIHI detected 35 (67.3%) (p < 0.05). In particular, conventional US detected only three (8.3%) of the 36 tumors less than 10 mm in diameter, but CE-PIHI detected 19 such tumors (52.8%) (p < 0.05). Compared to conventional sonography, PIHI performed during the liver-specific phase after intravenous injection of Levovist is markedly better at detecting VX2 liver tumors

  6. Capture of circulating tumor cells using photoacoustic flowmetry and two phase flow.

    Science.gov (United States)

    O'Brien, Christine M; Rood, Kyle D; Bhattacharyya, Kiran; DeSouza, Thiago; Sengupta, Shramik; Gupta, Sagar K; Mosley, Jeffrey D; Goldschmidt, Benjamin S; Sharma, Nikhilesh; Viator, John A

    2012-06-01

    Melanoma is the deadliest form of skin cancer, yet current diagnostic methods are unable to detect early onset of metastatic disease. Patients must wait until macroscopic secondary tumors form before malignancy can be diagnosed and treatment prescribed. Detection of cells that have broken off the original tumor and travel through the blood or lymph system can provide data for diagnosing and monitoring metastatic disease. By irradiating enriched blood samples spiked with cultured melanoma cells with nanosecond duration laser light, we induced photoacoustic responses in the pigmented cells. Thus, we can detect and enumerate melanoma cells in blood samples to demonstrate a paradigm for a photoacoustic flow cytometer. Furthermore, we capture the melanoma cells using microfluidic two phase flow, a technique that separates a continuous flow into alternating microslugs of air and blood cell suspension. Each slug of blood cells is tested for the presence of melanoma. Slugs that are positive for melanoma, indicated by photoacoustic waves, are separated from the cytometer for further purification and isolation of the melanoma cell. In this paper, we evaluate the two phase photoacoustic flow cytometer for its ability to detect and capture metastatic melanoma cells in blood.

  7. Isolation of circulating tumor cells using photoacoustic flowmetry and two phase flow

    Science.gov (United States)

    O'Brien, Christine M.; Rood, Kyle D.; Gupta, Sagar K.; Mosley, Jeffrey D.; Goldschmidt, Benjamin S.; Sharma, Nikhilesh; Sengupta, Shramik; Viator, John A.

    2011-03-01

    Melanoma is the deadliest form of skin cancer, yet current diagnostic methods are inadequately sensitive. Patients must wait until secondary tumors form before malignancy can be diagnosed and treatment prescribed. Detection of cells that have broken off the original tumor and flow through the blood or lymph system can provide data for diagnosing and monitoring cancer. Our group utilizes the photoacoustic effect to detect metastatic melanoma cells, which contain the pigmented granule melanin. As a rapid laser pulse irradiates melanoma, the melanin undergoes thermo-elastic expansion and ultimately creates a photoacoustic wave. Thus, melanoma patient's blood samples can be enriched, leaving the melanoma in a white blood cell (WBC) suspension. Irradiated melanoma cells produce photoacoustic waves, which are detected with a piezoelectric transducer, while the optically transparent WBCs create no signals. Here we report an isolation scheme utilizing two-phase flow to separate detected melanoma from the suspension. By introducing two immiscible fluids through a t-junction into one flow path, the analytes are compartmentalized. Therefore, the slug in which the melanoma cell is located can be identified and extracted from the system. Two-phase immiscible flow is a label free technique, and could be used for other types of pathological analytes.

  8. DNA ploidy and S phase fraction of breast and ovarian tumor cells treated with a natural anthracycline analog (aloin).

    Science.gov (United States)

    Esmat, Amr Y; El-Gerzawy, Shadia M; Rafaat, Amira

    2005-01-01

    DNA ploidy and S phase fraction analysis by flow cytometry on breast and ovarian tumor cells continuously exposed to aloin, a natural anthraquinone, at two concentrations (20-60 microg/ml) was done. Untreated breast and ovarian tumor cells (control) showed an aneuploid pattern, with a mean DNA index of 2.10+/-0.10 and S phase fraction of 28.46+/-1.5 and 17.40+/-0.75%, respectively. Treatment of breast and ovarian tumor cells with aloin showed a persistent aneuploid pattern and a significantly dose-dependent increase in the percentage of S phase fraction and in the proportion of cells cycling at a higher ploidy level (>G2M). The polyploidization indicates that aloin does not inhibit initiation of DNA synthesis and that cells replicated a full complement of DNA but had difficulty in M phase.

  9. Kansas Wind Energy Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Gruenbacher, Don [Kansas State Univ., Manhattan, KS (United States)

    2015-12-31

    This project addresses both fundamental and applied research problems that will help with problems defined by the DOE “20% Wind by 2030 Report”. In particular, this work focuses on increasing the capacity of small or community wind generation capabilities that would be operated in a distributed generation approach. A consortium (KWEC – Kansas Wind Energy Consortium) of researchers from Kansas State University and Wichita State University aims to dramatically increase the penetration of wind energy via distributed wind power generation. We believe distributed generation through wind power will play a critical role in the ability to reach and extend the renewable energy production targets set by the Department of Energy. KWEC aims to find technical and economic solutions to enable widespread implementation of distributed renewable energy resources that would apply to wind.

  10. IPD-Work consortium

    DEFF Research Database (Denmark)

    Kivimäki, Mika; Singh-Manoux, Archana; Virtanen, Marianna

    2015-01-01

    of countries. The aim of the consortium is to estimate reliably the associations of work-related psychosocial factors with chronic diseases, disability, and mortality. Our findings are highly cited by the occupational health, epidemiology, and clinical medicine research community. However, some of the IPD-Work......'s findings have also generated disagreement as they challenge the importance of job strain as a major target for coronary heart disease (CHD) prevention, this is reflected in the critical discussion paper by Choi et al (1). In this invited reply to Choi et al, we aim to (i) describe how IPD-Work seeks......Established in 2008 and comprising over 60 researchers, the IPD-Work (individual-participant data meta-analysis in working populations) consortium is a collaborative research project that uses pre-defined meta-analyses of individual-participant data from multiple cohort studies representing a range...

  11. The BADER Consortium

    Science.gov (United States)

    2013-10-01

    BiOM: The Director of the BADER Consortium was invited to participate in a local (Newark, DE) demonstration of the BiOM Bionic Lower Leg System. BiOM...trials of the DEKA Arm and have agreed to facilitate upcoming and future clinical trials. Dr. Tim Brindle of the VA attended the BADER Annual Meeting...clinical care for members of the Armed Forces, veterans, and civilians who have undergone amputation, traumatic brain injury, and other serious

  12. Phase I study of the Hedgehog pathway inhibitor IPI-926 in adult patients with solid tumors.

    Science.gov (United States)

    Jimeno, Antonio; Weiss, Glen J; Miller, Wilson H; Gettinger, Scott; Eigl, Bernard J C; Chang, Anne Lynne S; Dunbar, Joi; Devens, Shannon; Faia, Kerrie; Skliris, Georgios; Kutok, Jeff; Lewis, Karl D; Tibes, Raoul; Sharfman, William H; Ross, Robert W; Rudin, Charles M

    2013-05-15

    To conduct a first-in-human phase I study to determine the dose-limiting toxicities (DLT), characterize the pharmacokinetic profile, and document the antitumor activity of IPI-926, a new chemical entity that inhibits the Hedgehog pathway (HhP). Patients with solid tumors refractory to standard therapy were given IPI-926 once daily (QD) by mouth in 28-day cycles. The starting dose was 20 mg, and an accelerated titration schedule was used until standard 3 + 3 dose-escalation cohorts were implemented. Pharmacokinetics were evaluated on day -7 and day 22 of cycle 1. Ninety-four patients (32F, 62M; ages, 39-87) received doses ranging from 20 to 210 mg QD. Dose levels up to and including 160 mg administered QD were well tolerated. Toxicities consisted of reversible elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin, fatigue, nausea, alopecia, and muscle spasms. IPI-926 was not associated with hematologic toxicity. IPI-926 pharmacokinetics were characterized by a slow absorption (T(max) = 2-8 hours) and a terminal half-life (t(1/2)) between 20 and 40 hours, supporting QD dosing. Of those HhP inhibitor-naïve patients with basal cell carcinoma (BCC) who received more than one dose of IPI-926 and had a follow-up clinical or Response Evaluation Criteria in Solid Tumors (RECIST) assessment, nearly a third (8 of 28 patients) showed a response to IPI-926 at doses ≥130 mg. IPI-926 was well tolerated up to 160 mg QD within 28-day cycles, which was established as the recommended phase II dose and schedule for this agent. Single-agent activity of IPI-926 was observed in HhP inhibitor-naïve patients with BCC. ©2013 AACR

  13. A phase 1 study of oral ridaforolimus in pediatric patients with advanced solid tumors.

    Science.gov (United States)

    Pearson, Andrew D J; Federico, Sara M; Aerts, Isabelle; Hargrave, Darren R; DuBois, Steven G; Iannone, Robert; Geschwindt, Ryan D; Wang, Ruixue; Haluska, Frank G; Trippett, Tanya M; Geoerger, Birgit

    2016-12-20

    Ridaforolimus is an investigational, potent, selective mTOR inhibitor. This study was conducted to determine the recommended phase 2 dose (RP2D), maximum tolerated dose, safety, pharmacokinetics, and antitumor activity of oral ridaforolimus in children with advanced solid tumors. In this phase 1, multicenter, open-label study in children aged 6 to orally for 5 consecutive days/week in 28-day cycles until progression, unacceptable toxicity, or consent withdrawal. Dose started at 22 mg/m2 and increased to 28 mg/m2 and 33 mg/m2, followed by expansion at the RP2D. Twenty patients were treated; 18 were evaluable for dose-limiting toxicities. One dose-limiting toxicity (grade 3 increased alanine aminotransferase) occurred in 1 patient at 33 mg/m2. Dose escalation concluded at 33 mg/m2; the maximum tolerated dose was not determined. The most common treatment-related adverse events (frequency ≥40%) were manageable grade 1-2 stomatitis, thrombocytopenia, hypertriglyceridemia, increased alanine aminotransferase, fatigue, hypercholesterolemia, anemia, and increased aspartate aminotransferase. Ridaforolimus exposure at 28 mg/m2 and 33 mg/m2 exceeded adult target levels. The RP2D for oral ridaforolimus in children was defined as 33 mg/m2. Four patients received at least 4 cycles; 2 with pineoblastoma and diffuse intrinsic pontine glioma had stable disease for 12 and 46 cycles, respectively. Ridaforolimus is orally bioavailable and well tolerated in children with advanced solid tumors. The RP2D (33 mg/m2, 5 days/week) exceeds the adult RP2D. The favorable toxicity and pharmacokinetic profiles may allow for combination therapy, a promising therapeutic option in pediatric malignancies.

  14. Phase I study of pazopanib plus TH-302 in advanced solid tumors.

    Science.gov (United States)

    Riedel, Richard F; Meadows, Kellen L; Lee, Paula H; Morse, Michael A; Uronis, Hope E; Blobe, Gerard C; George, Daniel J; Crawford, Jeffrey; Niedzwiecki, Donna; Rushing, Christel N; Arrowood, Christy C; Hurwitz, Herbert I

    2017-03-01

    To define the maximum tolerated dose (MTD), recommended phase II dose (RPTD), and assess safety and tolerability for the combination of pazopanib plus TH-302, an investigational hypoxia-activated prodrug (HAP), in adult patients with advanced solid tumors. This was an open-label, non-randomized, single-center, phase I trial consisting 2 stages. Stage 1 was a standard "3 + 3" dose escalation design to determine safety and the RPTD for TH-302 plus pazopanib combination. Stage 2 was an expanded cohort to better describe the tolerability and toxicity profile at the MTD. Pazopanib was orally dosed at 800 mg daily on days 1-28 for all cohorts. TH-302 was administered intravenously on days 1, 8 and 15 of a 28-day cycle at doses of 340 mg/m 2 (cohort 1) or 480 mg/m 2 (cohort 2). Dose limiting toxicity (DLT) was assessed in the first 28-day cycle. Efficacy was assessed every 2 cycles. Thirty patients were enrolled between December 2011 and September 2013. In the dose escalation stage, 7 patients were enrolled in the 340 mg/m 2 TH-302 cohort and 6 patients in the 480 mg/m 2 TH-302 cohort. Ten patients were evaluable for DLT. DLTs included grade 2 intolerable esophagitis (n = 1) in the 340 mg/m 2 TH-302 cohort, and grade 3 vaginal inflammation (n = 1) and grade 3 neutropenia with grade 3 thrombocytopenia (n = 1, same patient) in the 480 mg/m 2 TH-302 cohort. The 340 mg/m 2 TH-302 cohort was determined to be MTD and RPTD. The most common treatment-related adverse events were hematologic (anemia, neutropenia, and thrombocytopenia), nausea/vomiting, palmar-plantar erythrodysesthesia syndrome, constipation, fatigue, mucositis, anorexia, pain, and hypertension. Partial response (PR) was observed in 10% (n = 3) of patients, stable disease (SD) in 57% (n = 17), and progressive disease (PD) in 23% (n = 7). Due to toxicity, 3 patients were discontinued from study drug prior to first radiographic assessment but were included in these calculations

  15. Phase I dose-escalation study of long-acting pasireotide in patients with neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Yao JC

    2017-06-01

    Full Text Available James C Yao,1 Jennifer A Chan,2 Alain C Mita,3 Madan G Kundu,4 Karina Hermosillo Reséndiz,4 Ke Hu,4 Shoba Ravichandran,4 Jonathan R Strosberg,5 Edward M Wolin6 1GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2Gastrointestinal Cancer Center, Dana–Farber Cancer Institute, Boston, MA, 3Experimental Therapeutics, Cedars-Sinai Medical Center, Los Angeles, CA, 4Oncology, Novartis Pharmaceuticals Corporation, East Hanover, NJ, 5Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 6Oncology, Montefiore Einstein Center for Cancer Care, Bronx, NY, USA Abstract: This phase I study aimed at determining the maximum tolerated dose (MTD and characterizing the safety, tolerability, pharmacokinetics (PKs, and efficacy of pasireotide in patients with advanced neuroendocrine tumors (NETs. Patients were enrolled in two phases: dose-escalation phase (to determine the MTD at a starting dose of 80 mg pasireotide long-acting release (LAR i.m. followed by a dose-expansion phase (to evaluate safety and preliminary efficacy. Associations between PK/pharmacodynamic parameters and clinical outcomes were evaluated using linear regression analysis. A total of 29 patients were treated with 80 mg (n=13 and 120 mg (n=16 doses. Most common primary tumor sites included small intestine (44.8%, pancreas (24.1%, and lung (17.2%. No protocol-defined dose-limiting toxicities were observed in the study; however, in post hoc analysis, a higher incidence of bradycardia (heart rate [HR] <40 beats per minute [bpm] was observed with 120 mg (31.3% vs 80 mg (0%. Two partial responses (PRs were observed, both in the 120 mg dose cohort. Pasireotide concentrations correlated with tumor shrinkage, although the association was not statistically significant (P=0.08. Among the biomarkers analyzed, insulin-like growth factor 1 (IGF-1 showed a decreasing trend with increasing pasireotide concentration

  16. Effect of normal and tumor factors on different phases of cell populations cycle.

    Science.gov (United States)

    Inda, A M; García, A L; Errecalde, A L; Badrán, A F

    1999-12-01

    In the present experiments we studied the effect of extracts from intact liver (LE), ES2 tumor extract (TE), plasmas from intact mice (PI), and from tumor bearing animals (PT) on different phases of hepatocytes and renocytes cell cycles. C3HS 28-day-old male mice, standardized for periodicity analysis, were injected at 16:00 hours and killed every 4 hours during a circadian cycle at 20:00/04; 00:00/08; 04:00/12; 08:00/16; 12:00/20 and 16:00/24 (time of day/hours post treatment). Colchicine (2 microg/g) was injected 4 hours before killing them. Samples of livers and kidneys were processed for histology and mitotic index determinations. The results were expressed as colchicine arrested metaphases per 1000 nuclei. The TE, LE and PI had a promoting effect on the mitotic activity of hepatocytes during the first 12 hours post treatment. During the subsequent 12 hours, not only these treatments but also the PI had an inhibiting effect on the mitotic activity of the same cell population. Also the TE and the PT had a promoting effect on the mitotic activity of the renocytes during the first 12 hours while the effect of all treatments showed a clear inhibition of the mitotic activity studied during the last 12 hours. Taking into account the time elapsed between the injections and the measurements made in these light-dark synchronized animals, we conclude that the increase in mitotic index observed in those tissues stemmed from a reinitiation of cell-cycle traverse in a subpopulation of G2-arrested, noncycling cells.

  17. A phase II trial with bevacizumab and irinotecan for patients with primary brain tumors and progression after standard therapy

    DEFF Research Database (Denmark)

    Møller, Søren; Grunnet, Kirsten; Hansen, Steinbjørn

    2012-01-01

    The combination of irinotecan and bevacizumab has shown efficacy in the treatment of recurrent glioblastoma multiforme (GBM). A prospective, phase II study of 85 patients with various recurrent brain tumors was carried out. Primary endpoints were progression free survival (PFS) and response rate....

  18. Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system

    Directory of Open Access Journals (Sweden)

    Oh KS

    2014-06-01

    Full Text Available Keun Sang Oh,1 Ji Young Yhee,2 Dong-Eun Lee,3 Kwangmeyung Kim,2 Ick Chan Kwon,2 Jae Hong Seo,4 Sang Yoon Kim,5 Soon Hong Yuk1,4 1College of Pharmacy, Korea University, Sejong, 2Biomedical Research Center, Korea Institute of Science and Technology, Seoul, 3Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeonbuk, 4Biomedical Research Center, Korea University Guro Hospital, Seoul, 5Department of Otolaryngology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea Abstract: Primary tumor and tumor-associated metastatic lymphatics have emerged as new targets for anticancer therapy, given that these are difficult to treat using traditional chemotherapy. In this study, docetaxel-loaded Pluronic nanoparticles with Flamma™ (FPR-675, fluorescence molecular imaging dye; DTX/FPR-675 Pluronic NPs were prepared using a temperature-induced phase transition for accurate detection of metastatic lymphatics. Significant accumulation was seen at the primary tumor and in metastatic lymph nodes within a short time. Particle size, maximum drug loading capacity, and drug encapsulation efficiency of the docetaxel-loaded Pluronic NPs were approximately 10.34±4.28 nm, 3.84 wt%, and 94±2.67 wt%, respectively. Lymphatic tracking after local and systemic delivery showed that DTX/FPR-675 Pluronic NPs were more potent in tumor-bearing mice than in normal mice, and excised mouse lymphatics showed stronger near-infrared fluorescence intensity on the tumor-bearing side than on the non-tumor-bearing side at 60 minutes post-injection. In vivo cytotoxicity and efficacy data for the NPs demonstrated that the systemically administered NPs caused little tissue damage and had minimal side effects in terms of slow renal excretion and prolonged circulation in tumor-bearing mice, and rapid renal excretion in non-tumor-bearing mice using an in vivo real-time near-infrared fluorescence imaging system. These results

  19. The International Human Epigenome Consortium

    DEFF Research Database (Denmark)

    Stunnenberg, Hendrik G; Hirst, Martin

    2016-01-01

    The International Human Epigenome Consortium (IHEC) coordinates the generation of a catalog of high-resolution reference epigenomes of major primary human cell types. The studies now presented (see the Cell Press IHEC web portal at http://www.cell.com/consortium/IHEC) highlight the coordinated...

  20. Hawaii Space Grant Consortium

    Science.gov (United States)

    Flynn, Luke P.

    2005-01-01

    The Hawai'i Space Grant Consortium is composed of ten institutions of higher learning including the University of Hawai'i at Manoa, the University of Hawai'i at Hilo, the University of Guam, and seven Community Colleges spread over the 4 main Hawaiian islands. Geographic separation is not the only obstacle that we face as a Consortium. Hawai'i has been mired in an economic downturn due to a lack of tourism for almost all of the period (2001 - 2004) covered by this report, although hotel occupancy rates and real estate sales have sky-rocketed in the last year. Our challenges have been many including providing quality educational opportunities in the face of shrinking State and Federal budgets, encouraging science and technology course instruction at the K-12 level in a public school system that is becoming less focused on high technology and more focused on developing basic reading and math skills, and assembling community college programs with instructors who are expected to teach more classes for the same salary. Motivated people can overcome these problems. Fortunately, the Hawai'i Space Grant Consortium (HSGC) consists of a group of highly motivated and talented individuals who have not only overcome these obstacles, but have excelled with the Program. We fill a critical need within the State of Hawai'i to provide our children with opportunities to pursue their dreams of becoming the next generation of NASA astronauts, engineers, and explorers. Our strength lies not only in our diligent and creative HSGC advisory board, but also with Hawai'i's teachers, students, parents, and industry executives who are willing to invest their time, effort, and resources into Hawai'i's future. Our operational philosophy is to FACE the Future, meaning that we will facilitate, administer, catalyze, and educate in order to achieve our objective of creating a highly technically capable workforce both here in Hawai'i and for NASA. In addition to administering to programs and

  1. Comparison of the gross tumor volume in end-expiration/end-inspiration (2 Phase) and summated all phase volume captured in four-dimensional computed tomography in carcinoma lung patients.

    Science.gov (United States)

    Sharma, Pramod Kumar; Srivastava, Roopam; Munshi, Anusheel; Chomal, Manish; Saini, Gagan; Garg, Madhur; Manjhi, Jayanand; Rai, D V

    2016-01-01

    The aim of this study was to compare the delineation and treatment planning of 2 Phase based (end-expiration and end-inspiration) internal gross tumor volume (IGTV) with 10-phase based (four-dimensional [4D]) IGTV. Patients with lung tumors at different sites were selected for the study. The location of the tumor in Groups A, B, C were at the upper lobe (attached to the chest wall), middle lobe, and lower lobe, respectively. We contoured the GTV on each of the 10 respiratory phases of the 4D computed tomography (4DCT) data set. The combination of these GTVs produced the IGTV "All Phases." GTV was also generated on the extreme respiratory phases. The combination of these two GTVs produced IGTV "2 Phases." Treatment planning was done, and dose to organs at risks (OARs) were compared in both cases. The average volume of IGTV "2 Phases" and IGTV "All Phases" for Group A were nearly same. However, for Group B and Group C, IGTV "2 Phases" were smaller than the IGTV "All Phases." Lung-GTV doses were less in "exp-insp" phases than in "4DCT" for Groups B, C, whereas it was same for "expiration-inspiration" and "4DCT" in Patient A. Patients with tumor upper lobe tumor have no difference in tumor coverage and OARs sparing in the 2 Phase and all phases but middle lobe and lower lobe have a greater excursion during respiration and hence greater all phases IGTV.

  2. Gas Storage Technology Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Joel L. Morrison; Sharon L. Elder

    2007-06-30

    Gas storage is a critical element in the natural gas industry. Producers, transmission and distribution companies, marketers, and end users all benefit directly from the load balancing function of storage. The unbundling process has fundamentally changed the way storage is used and valued. As an unbundled service, the value of storage is being recovered at rates that reflect its value. Moreover, the marketplace has differentiated between various types of storage services and has increasingly rewarded flexibility, safety, and reliability. The size of the natural gas market has increased and is projected to continue to increase towards 30 trillion cubic feet over the next 10 to 15 years. Much of this increase is projected to come from electric generation, particularly peaking units. Gas storage, particularly the flexible services that are most suited to electric loads, is crucial in meeting the needs of these new markets. To address the gas storage needs of the natural gas industry, an industry-driven consortium was created--the Gas Storage Technology Consortium (GSTC). The objective of the GSTC is to provide a means to accomplish industry-driven research and development designed to enhance the operational flexibility and deliverability of the nation's gas storage system, and provide a cost-effective, safe, and reliable supply of natural gas to meet domestic demand. This report addresses the activities for the quarterly period of April 1, 2007 through June 30, 2007. Key activities during this time period included: (1) Organizing and hosting the 2007 GSTC Spring Meeting; (2) Identifying the 2007 GSTC projects, issuing award or declination letters, and begin drafting subcontracts; (3) 2007 project mentoring teams identified; (4) New NETL Project Manager; (5) Preliminary planning for the 2007 GSTC Fall Meeting; (6) Collecting and compiling the 2005 GSTC project final reports; and (7) Outreach and communications.

  3. Nuclear Fabrication Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Levesque, Stephen [EWI, Columbus, OH (United States)

    2013-04-05

    This report summarizes the activities undertaken by EWI while under contract from the Department of Energy (DOE) Office of Nuclear Energy (NE) for the management and operation of the Nuclear Fabrication Consortium (NFC). The NFC was established by EWI to independently develop, evaluate, and deploy fabrication approaches and data that support the re-establishment of the U.S. nuclear industry: ensuring that the supply chain will be competitive on a global stage, enabling more cost-effective and reliable nuclear power in a carbon constrained environment. The NFC provided a forum for member original equipment manufactures (OEM), fabricators, manufacturers, and materials suppliers to effectively engage with each other and rebuild the capacity of this supply chain by : Identifying and removing impediments to the implementation of new construction and fabrication techniques and approaches for nuclear equipment, including system components and nuclear plants. Providing and facilitating detailed scientific-based studies on new approaches and technologies that will have positive impacts on the cost of building of nuclear plants. Analyzing and disseminating information about future nuclear fabrication technologies and how they could impact the North American and the International Nuclear Marketplace. Facilitating dialog and initiate alignment among fabricators, owners, trade associations, and government agencies. Supporting industry in helping to create a larger qualified nuclear supplier network. Acting as an unbiased technology resource to evaluate, develop, and demonstrate new manufacturing technologies. Creating welder and inspector training programs to help enable the necessary workforce for the upcoming construction work. Serving as a focal point for technology, policy, and politically interested parties to share ideas and concepts associated with fabrication across the nuclear industry. The report the objectives and summaries of the Nuclear Fabrication Consortium

  4. Gas Storage Technology Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Joel L. Morrison; Sharon L. Elder

    2006-05-10

    Gas storage is a critical element in the natural gas industry. Producers, transmission and distribution companies, marketers, and end users all benefit directly from the load balancing function of storage. The unbundling process has fundamentally changed the way storage is used and valued. As an unbundled service, the value of storage is being recovered at rates that reflect its value. Moreover, the marketplace has differentiated between various types of storage services, and has increasingly rewarded flexibility, safety, and reliability. The size of the natural gas market has increased and is projected to continue to increase towards 30 trillion cubic feet (TCF) over the next 10 to 15 years. Much of this increase is projected to come from electric generation, particularly peaking units. Gas storage, particularly the flexible services that are most suited to electric loads, is critical in meeting the needs of these new markets. In order to address the gas storage needs of the natural gas industry, an industry-driven consortium was created--the Gas Storage Technology Consortium (GSTC). The objective of the GSTC is to provide a means to accomplish industry-driven research and development designed to enhance operational flexibility and deliverability of the Nation's gas storage system, and provide a cost effective, safe, and reliable supply of natural gas to meet domestic demand. This report addresses the activities for the quarterly period of January 1, 2006 through March 31, 2006. Activities during this time period were: (1) Organize and host the 2006 Spring Meeting in San Diego, CA on February 21-22, 2006; (2) Award 8 projects for co-funding by GSTC for 2006; (3) New members recruitment; and (4) Improving communications.

  5. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children’s Oncology Group phase 1 consortium study

    Science.gov (United States)

    Mossé, Yael P; Lim, Megan S; Voss, Stephan D; Wilner, Keith; Ruffner, Katherine; Laliberte, Julie; Rolland, Delphine; Balis, Frank M; Maris, John M; Weigel, Brenda J; Ingle, Ashish M; Ahern, Charlotte; Adamson, Peter C; Blaney, Susan M

    2013-01-01

    Summary Background Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as anaplastic large-cell lymphoma, inflammatory myofibroblastic tumours, non-small-cell lung cancer (NSCLC), and neuroblastoma. Therefore, ALK inhibition could be a useful therapeutic strategy in children. We aimed to determine the safety, recommended phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma. Methods In this open-label, phase 1 dose-escalation trial, patients older than 12 months and younger than 22 years with measurable or evaluable solid or CNS tumours, or anaplastic large-cell lymphoma, refractory to therapy and for whom there was no known curative treatment were eligible. Crizotinib was given twice daily without interruption. Six dose levels (100, 130, 165, 215, 280, 365 mg/m2 per dose) were assessed in the dose-finding phase of the study (part A1), which is now completed. The primary endpoint was to estimate the maximum tolerated dose, to define the toxic effects of crizotinib, and to characterise the pharmacokinetics of crizotinib in children with refractory cancer. Additionally, patients with confirmed ALK translocations, mutations, or amplification (part A2 of the study) or neuroblastoma (part A3) could enrol at one dose level lower than was currently given in part A1. We assessed ALK genomic status in tumour tissue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood samples of patients with anaplastic large-cell lymphoma. All patients who received at least one dose of crizotinib were evaluable for response; patients completing at least one cycle of therapy or experiencing dose limiting toxicity before that were considered fully evaluable for toxicity. This study is registered with ClinicalTrials. gov, NCT00939770. Findings 79 patients were enrolled in the study from Oct 2, 2009, to May 31, 2012. The median age was 10

  6. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study.

    Science.gov (United States)

    Mossé, Yael P; Lim, Megan S; Voss, Stephan D; Wilner, Keith; Ruffner, Katherine; Laliberte, Julie; Rolland, Delphine; Balis, Frank M; Maris, John M; Weigel, Brenda J; Ingle, Ashish M; Ahern, Charlotte; Adamson, Peter C; Blaney, Susan M

    2013-05-01

    Various human cancers have ALK gene translocations, amplifications, or oncogenic mutations, such as anaplastic large-cell lymphoma, inflammatory myofibroblastic tumours, non-small-cell lung cancer (NSCLC), and neuroblastoma. Therefore, ALK inhibition could be a useful therapeutic strategy in children. We aimed to determine the safety, recommended phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma. In this open-label, phase 1 dose-escalation trial, patients older than 12 months and younger than 22 years with measurable or evaluable solid or CNS tumours, or anaplastic large-cell lymphoma, refractory to therapy and for whom there was no known curative treatment were eligible. Crizotinib was given twice daily without interruption. Six dose levels (100, 130, 165, 215, 280, 365 mg/m(2) per dose) were assessed in the dose-finding phase of the study (part A1), which is now completed. The primary endpoint was to estimate the maximum tolerated dose, to define the toxic effects of crizotinib, and to characterise the pharmacokinetics of crizotinib in children with refractory cancer. Additionally, patients with confirmed ALK translocations, mutations, or amplification (part A2 of the study) or neuroblastoma (part A3) could enrol at one dose level lower than was currently given in part A1. We assessed ALK genomic status in tumour tissue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood samples of patients with anaplastic large-cell lymphoma. All patients who received at least one dose of crizotinib were evaluable for response; patients completing at least one cycle of therapy or experiencing dose limiting toxicity before that were considered fully evaluable for toxicity. This study is registered with ClinicalTrials.gov, NCT00939770. 79 patients were enrolled in the study from Oct 2, 2009, to May 31, 2012. The median age was 10.1 years (range 1.1-21.4); 43

  7. Human Adipose Derived Stem Cells Induced Cell Apoptosis and S Phase Arrest in Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2015-01-01

    Full Text Available The aim of this study was to determine the effect of human adipose derived stem cells (ADSCs on the viability and apoptosis of human bladder cancer cells. EJ and T24 cells were cocultured with ADSCs or cultured with conditioned medium of ADSCs (ADSC-CM, respectively. The cell counting and colony formation assay showed ADSCs inhibited the proliferation of EJ and T24 cells. Cell viability assessment revealed that the secretions of ADSCs, in the form of conditioned medium, were able to decrease cancer cell viability. Wound-healing assay suggested ADSC-CM suppressed migration of T24 and EJ cells. Moreover, the results of the flow cytometry indicated that ADSC-CM was capable of inducing apoptosis of T24 cells and inducing S phase cell cycle arrest. Western blot revealed ADSC-CM increased the expression of cleaved caspase-3 and cleaved PARP, indicating that ADSC-CM induced apoptosis in a caspase-dependent way. PTEN/PI3K/Akt pathway and Bcl-2 family proteins were involved in the mechanism of this reaction. Our study indicated that ADSCs may provide a promising and practicable manner for bladder tumor therapy.

  8. Gross tumor volume dependency on phase sorting methods of four-dimensional computed tomography images for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Soo Yong; Lim, Sang Wook; Ma, Sun Young; Yu, Je Sang [Dept. of Radiation Oncology, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan (Korea, Republic of)

    2017-09-15

    To see the gross tumor volume (GTV) dependency according to the phase selection and reconstruction methods, we measured and analyzed the changes of tumor volume and motion at each phase in 20 cases with lung cancer patients who underwent image-guided radiotherapy. We retrospectively analyzed four-dimensional computed tomography (4D-CT) images in 20 cases of 19 patients who underwent image-guided radiotherapy. The 4D-CT images were reconstructed by the maximum intensity projection (MIP) and the minimum intensity projection (Min-IP) method after sorting phase as 40%–60%, 30%–70%, and 0%–90%. We analyzed the relationship between the range of motion and the change of GTV according to the reconstruction method. The motion ranges of GTVs are statistically significant only for the tumor motion in craniocaudal direction. The discrepancies of GTV volume and motion between MIP and Min-IP increased rapidly as the wider ranges of duty cycles are selected. As narrow as possible duty cycle such as 40%–60% and MIP reconstruction was suitable for lung cancer if the respiration was stable. Selecting the reconstruction methods and duty cycle is important for small size and for large motion range tumors.

  9. Accumulation of Phase-Shift Nanoemulsions to Enhance MR-Guided Ultrasound-Mediated Tumor Ablation In Vivo

    Directory of Open Access Journals (Sweden)

    Jonathan A. Kopechek

    2013-01-01

    Full Text Available Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU is being explored as a non-invasive technology to treat solid tumors. However, the clinical use of HIFU for tumor ablation applications is currently limited by the long treatment times required. Phase-shift nanoemulsions (PSNE, consisting of liquid perfluorocarbon droplets that can be vaporized into microbubbles, are being developed to accelerate HIFU-mediated heating. The purpose of this study was to examine accumulation of PSNE in intramuscular rabbit tumors in vivo. MR images were acquired before and after intravenous injection of gadolinium-containing PSNE. MR signal enhancement was observed in rabbit tumors up to six hours after injection, indicating that PSNE accumulated in the tumors. In addition, PSNE vaporization was detected in the tumor with B-mode ultrasound imaging, and MR thermometry measurements indicated that PSNE accelerated the rate of HIFU-mediated heating. These results suggest that PSNE could dramatically improve the efficiency and clinical feasibility of MRgHIFU.

  10. Applying functional metagenomics to search for novel lignocellulosic enzymes in a microbial consortium derived from a thermophilic composting phase of sugarcane bagasse and cow manure.

    Science.gov (United States)

    Colombo, Lívia Tavares; de Oliveira, Marcelo Nagem Valério; Carneiro, Deisy Guimarães; de Souza, Robson Assis; Alvim, Mariana Caroline Tocantins; Dos Santos, Josenilda Carlos; da Silva, Cynthia Canêdo; Vidigal, Pedro Marcus Pereira; da Silveira, Wendel Batista; Passos, Flávia Maria Lopes

    2016-09-01

    Environments where lignocellulosic biomass is naturally decomposed are sources for discovery of new hydrolytic enzymes that can reduce the high cost of enzymatic cocktails for second-generation ethanol production. Metagenomic analysis was applied to discover genes coding carbohydrate-depleting enzymes from a microbial laboratory subculture using a mix of sugarcane bagasse and cow manure in the thermophilic composting phase. From a fosmid library, 182 clones had the ability to hydrolyse carbohydrate. Sequencing of 30 fosmids resulted in 12 contigs encoding 34 putative carbohydrate-active enzymes belonging to 17 glycosyl hydrolase (GH) families. One third of the putative proteins belong to the GH3 family, which includes β-glucosidase enzymes known to be important in the cellulose-deconstruction process but present with low activity in commercial enzyme preparations. Phylogenetic analysis of the amino acid sequences of seven selected proteins, including three β-glucosidases, showed low relatedness with protein sequences deposited in databases. These findings highlight microbial consortia obtained from a mixture of decomposing biomass residues, such as sugar cane bagasse and cow manure, as a rich resource of novel enzymes potentially useful in biotechnology for saccharification of lignocellulosic substrate.

  11. Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

    Science.gov (United States)

    Kopechek, Jonathan A.; Park, Eun-Joo; Zhang, Yong-Zhi; Vykhodtseva, Natalia I.; McDannold, Nathan J.; Porter, Tyrone M.

    2014-07-01

    Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 s using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650 kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P W of acoustic power was 46 ± 22% with PSNE injection. The results indicate that PSNE nucleates cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could potentially be used to reduce the time and/or acoustic intensity required for HIFU-mediated heating, thereby increasing the feasibility and clinical efficacy of HIFU thermal ablation therapy.

  12. Gas Storage Technology Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Joel Morrison; Elizabeth Wood; Barbara Robuck

    2010-09-30

    The EMS Energy Institute at The Pennsylvania State University (Penn State) has managed the Gas Storage Technology Consortium (GSTC) since its inception in 2003. The GSTC infrastructure provided a means to accomplish industry-driven research and development designed to enhance the operational flexibility and deliverability of the nation's gas storage system, and provide a cost-effective, safe, and reliable supply of natural gas to meet domestic demand. The GSTC received base funding from the U.S. Department of Energy's (DOE) National Energy Technology Laboratory (NETL) Oil & Natural Gas Supply Program. The GSTC base funds were highly leveraged with industry funding for individual projects. Since its inception, the GSTC has engaged 67 members. The GSTC membership base was diverse, coming from 19 states, the District of Columbia, and Canada. The membership was comprised of natural gas storage field operators, service companies, industry consultants, industry trade organizations, and academia. The GSTC organized and hosted a total of 18 meetings since 2003. Of these, 8 meetings were held to review, discuss, and select proposals submitted for funding consideration. The GSTC reviewed a total of 75 proposals and committed co-funding to support 31 industry-driven projects. The GSTC committed co-funding to 41.3% of the proposals that it received and reviewed. The 31 projects had a total project value of $6,203,071 of which the GSTC committed $3,205,978 in co-funding. The committed GSTC project funding represented an average program cost share of 51.7%. Project applicants provided an average program cost share of 48.3%. In addition to the GSTC co-funding, the consortium provided the domestic natural gas storage industry with a technology transfer and outreach infrastructure. The technology transfer and outreach were conducted by having project mentoring teams and a GSTC website, and by working closely with the Pipeline Research Council International (PRCI) to

  13. MinION Analysis and Reference Consortium: Phase 2 data release and analysis of R9.0 chemistry [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Miten Jain

    2017-05-01

    Full Text Available Background: Long-read sequencing is rapidly evolving and reshaping the suite of opportunities for genomic analysis. For the MinION in particular, as both the platform and chemistry develop, the user community requires reference data to set performance expectations and maximally exploit third-generation sequencing. We performed an analysis of MinION data derived from whole genome sequencing of Escherichia coli K-12 using the R9.0 chemistry, comparing the results with the older R7.3 chemistry. Methods: We computed the error-rate estimates for insertions, deletions, and mismatches in MinION reads. Results: Run-time characteristics of the flow cell and run scripts for R9.0 were similar to those observed for R7.3 chemistry, but with an 8-fold increase in bases per second (from 30 bps in R7.3 and SQK-MAP005 library preparation, to 250 bps in R9.0 processed by individual nanopores, and less drop-off in yield over time. The 2-dimensional (“2D” N50 read length was unchanged from the prior chemistry. Using the proportion of alignable reads as a measure of base-call accuracy, 99.9% of “pass” template reads from 1-dimensional (“1D”  experiments were mappable and ~97% from 2D experiments. The median identity of reads was ~89% for 1D and ~94% for 2D experiments. The total error rate (miscall + insertion + deletion decreased for 2D “pass” reads from 9.1% in R7.3 to 7.5% in R9.0 and for template “pass” reads from 26.7% in R7.3 to 14.5% in R9.0. Conclusions: These Phase 2 MinION experiments serve as a baseline by providing estimates for read quality, throughput, and mappability. The datasets further enable the development of bioinformatic tools tailored to the new R9.0 chemistry and the design of novel biological applications for this technology. Abbreviations: K: thousand, Kb: kilobase (one thousand base pairs, M: million, Mb: megabase (one million base pairs, Gb: gigabase (one billion base pairs.

  14. Atlantic Coast Environmental Indicators Consortium

    Data.gov (United States)

    Federal Laboratory Consortium — n 2000, the US EPA granted authority to establish up to five Estuarine Indicator Research Programs. These Programs were designed to identify, evaluate, recommend and...

  15. COnsortium of METabolomics Studies (COMETS)

    Science.gov (United States)

    The COnsortium of METabolomics Studies (COMETS) is an extramural-intramural partnership that promotes collaboration among prospective cohort studies that follow participants for a range of outcomes and perform metabolomic profiling of individuals.

  16. NCI Pediatric Preclinical Testing Consortium

    Science.gov (United States)

    NCI has awarded grants to five research teams to participate in its Pediatric Preclinical Testing Consortium, which is intended to help to prioritize which agents to pursue in pediatric clinical trials.

  17. Phase I study of oral CP-4126, a gemcitabine derivative, in patients with advanced solid tumors.

    Science.gov (United States)

    Stuurman, F E; Voest, E E; Awada, A; Witteveen, P O; Bergeland, T; Hals, P-A; Rasch, W; Schellens, J H M; Hendlisz, A

    2013-08-01

    CP-4126 is a gemcitabine (2',2'-difluorodeoxycytidine; dFdC) 5' elaidic acid ester. The purpose of this dose-escalating study was to assess safety, pharmacokinetics (PK) and preliminary antitumor activity of the oral formulation and to determine the recommended dose (RD) for phase II studies. The study had a two-step design: a non-randomized dose-escalating step I with oral CP-4126 alone, followed by a randomized, cross-over step II that compared oral CP-4126 with dFdC i.v.. CP-4126 was given on days 1,8,15 in a 4-week schedule with increasing doses until the RD was established. 26 patients with different solid tumours were enrolled in step I at seven dose levels (100-3,000 mg/day). The most frequent drug-related AEs were fatigue and dysgeusia, the majority being grade 1-2. One patient experienced a dose limiting toxicity after one dose of CP-4126 at 1,300 mg/day (ASAT grade 3). PK of CP-4126 could not be determined. The metabolites dFdC and dFdU obeyed dose-dependent pharmacokinetics. Exposures to dFdC were about ten-fold lower compared to exposures after comparable doses of dFdC i.v.. Nine patients reached stable disease as best response, whereby in one patient with vaginal carcinoma a 25 % reduction of tumor volume was reached. This study demonstrates that CP-4126 can be safely administered orally to patients up to 3,000 mg/day in a d1,8,15 q4w schedule with a tolerable safety profile. CP-4126 acts as a prodrug for dFdC when given orally, but because of the poor absorption and the rapid pre-systemic metabolism the study was terminated early and no RD could be determined.

  18. Phase II trial of temozolomide for leptomeningeal metastases in patients with solid tumors.

    Science.gov (United States)

    Segura, Pedro Pérez; Gil, Miguel; Balañá, Carmen; Chacón, Ignacio; Langa, José Muñoz; Martín, María; Bruna, Jordi

    2012-08-01

    There is a current unmet medical need for treatment of leptomeningeal metastases (LMD). To analyze the efficacy and safety of systemic temozolomide (TMZ) for first-line treatment of patients with LMD associated with solid tumors, a phase II, non-randomized, multicenter, prospective study was conducted. The planned duration of treatment was a maximum of six cycles (24 weeks) or until unacceptable toxicity was reported. One cycle of oral TMZ (100 mg/m(2) daily) consisted of one week on treatment/one week off treatment for four weeks. The study was stopped early because of poor accrual. Nineteen patients (median age 51(33-72); 32 % male) were enrolled. The LMD source was breast cancer (53 %) and non-small-cell lung cancer (37 %). Previous treatment was chemotherapy (100 %), surgery 74 %, radiotherapy 79 %, and hormone therapy 42 %. The average last dose of TMZ received by patients was 171 mg and only one patient required dose reduction. Three of 19 patients (15.8 %) had clinical benefit and 16 of 19 patients (84.2 %) progressed. Of the two patients completing the study (six cycles, 24 weeks), one had a partial response and the other stable disease. Median survival was 43 days (95 % CI 28.7-57.3); there were 18 deaths. Median TTP was 28 days (95 % CI 14-42). The most common adverse event was vomiting (52.6 %); nine patients (47.4 %) reported at least one serious adverse event but only one episode of thrombocytopenia was drug related. Median Karnofsky score remained at or above 70 % throughout the study, and was 75 % at the end of the study. First-line TMZ was well tolerated, and did not adversely affect the quality of life of patients with LMD. Future studies are needed to verify the efficacy results of this pilot trial.

  19. Swiss Industrial Biocatalysis Consortium (SIBC).

    Science.gov (United States)

    Wirz, Beat; Kittelmann, Matthias; Meyer, Hans-Peter; Wohlgemuth, Roland

    2010-01-01

    Taking up the common challenges in biocatalysis, a group of industrialists decided to react with a bottom-up solution, and created the Swiss Industrial Biocatalysis Consortium (SIBC). The Swiss Industrial Biocatalysis Consortium is a pre-competitive working group to better implement and utilize existing know-how and resources in biocatalysis, and to influence and shape the economic and educational political environment. Recent examples of activities are outlined.

  20. Hickory Consortium 2001 Final Report

    Energy Technology Data Exchange (ETDEWEB)

    2003-02-01

    As with all Building America Program consortia, systems thinking is the key to understanding the processes that Hickory Consortium hopes to improve. The Hickory Consortium applies this thinking to more than the whole-building concept. Their systems thinking embraces the meta process of how housing construction takes place in America. By understanding the larger picture, they are able to identify areas where improvements can be made and how to implement them.

  1. California Verbal Learning Test-II performance in schizophrenia as a function of ascertainment strategy: comparing the first and second phases of the Consortium on the Genetics of Schizophrenia (COGS).

    Science.gov (United States)

    Stone, William S; Mesholam-Gately, Raquelle I; Braff, David L; Calkins, Monica E; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Seidman, Larry J

    2015-04-01

    The first phase of the Consortium on the Genetics of Schizophrenia (COGS-1) showed performance deficits in learning and memory on the California Verbal Learning Test, Second Edition (CVLT-II) in individuals with schizophrenia (SZ), compared to healthy comparison subjects (HCS). A question is whether the COGS-1 study, which used a family study design (i.e. studying relatively intact families), yielded "milder" SZ phenotypes than those acquired subsequently in the COGS-2 case-control design that did not recruit unaffected family members. CVLT-II performance was compared for the COGS-1 and COGS-2 samples. Analyses focused on learning, recall and recognition variables, with age, gender and education as covariates. Analyses of COGS-2 data explored effects of additional covariates and moderating factors in CVLT-II performance. 324 SZ subjects and 510 HCS had complete CVLT-II and covariate data in COGS-1, while 1356 SZ and 1036 HCS had complete data in COGS-2. Except for recognition memory, analysis of covariance showed significantly worse performance in COGS-2 on all CVLT-II variables for SZ and HCS, and remained significant in the presence of the covariates. Performance in each of the 5 learning trials differed significantly. However, effect sizes comparing cases and controls were comparable across the two studies. COGS-2 analyses confirmed SZ performance deficits despite effects of multiple significant covariates and moderating factors. CVLT-II performance was worse in COGS-2 than in COGS-1 for both the SZ and the HCS in this large cohort, likely due to cohort effects. Demographically corrected data yield a consistent pattern of performance across the two studies in SZ. Copyright © 2014. Published by Elsevier B.V.

  2. Combustion Byproducts Recycling Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Ziemkiewicz, Paul; Vandivort, Tamara; Pflughoeft-Hassett, Debra; Chugh, Y Paul; Hower, James

    2008-08-31

    Each year, over 100 million tons of solid byproducts are produced by coal-burning electric utilities in the United States. Annual production of flue gas desulfurization (FGD) byproducts continues to increase as the result of more stringent sulfur emission restrictions. In addition, stricter limits on NOx emissions mandated by the 1990 Clean Air Act have resulted in utility burner/boiler modifications that frequently yield higher carbon concentrations in fly ash, which restricts the use of the ash as a cement replacement. Controlling ammonia in ash is also of concern. If newer, “clean coal” combustion and gasification technologies are adopted, their byproducts may also present a management challenge. The objective of the Combustion Byproducts Recycling Consortium (CBRC) is to develop and demonstrate technologies to address issues related to the recycling of byproducts associated with coal combustion processes. A goal of CBRC is that these technologies, by the year 2010, will lead to an overall ash utilization rate from the current 34% to 50% by such measures as increasing the current rate of FGD byproduct use and increasing in the number of uses considered “allowable” under state regulations. Another issue of interest to the CBRC would be to examine the environmental impact of both byproduct utilization and disposal. No byproduct utilization technology is likely to be adopted by industry unless it is more cost-effective than landfilling. Therefore, it is extremely important that the utility industry provide guidance to the R&D program. Government agencies and privatesector organizations that may be able to utilize these materials in the conduct of their missions should also provide input. The CBRC will serve as an effective vehicle for acquiring and maintaining guidance from these diverse organizations so that the proper balance in the R&D program is achieved.

  3. Capture of circulating tumor cells using photoacoustic flowmetry and two phase flow

    OpenAIRE

    O’Brien, Christine M.; Rood, Kyle D.; Bhattacharyya, Kiran; DeSouza, Thiago; Sengupta, Shramik; Gupta, Sagar K.; Mosley, Jeffrey D.; Goldschmidt, Benjamin S.; Sharma, Nikhilesh; Viator, John A.

    2012-01-01

    Melanoma is the deadliest form of skin cancer, yet current diagnostic methods are unable to detect early onset of metastatic disease. Patients must wait until macroscopic secondary tumors form before malignancy can be diagnosed and treatment prescribed. Detection of cells that have broken off the original tumor and travel through the blood or lymph system can provide data for diagnosing and monitoring metastatic disease. By irradiating enriched blood samples spiked with cultured melanoma cell...

  4. Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study

    Energy Technology Data Exchange (ETDEWEB)

    Milosevic, Michael F., E-mail: mike.milosevic@rmp.uhn.ca [Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Townsley, Carol A. [Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Chaudary, Naz [Department of Advanced Molecular Oncology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Clarke, Blaise [Department of Pathology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Laboratory Medicine and Pathology, University of Toronto, Toronto (Canada); Pintilie, Melania [Department of Clinical Study Coordination and Biostatistics, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Fan, Stacy; Glicksman, Rachel [Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Haider, Masoom [Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto (Canada); Department of Medical Imaging, University of Toronto, Toronto (Canada); Kim, Sunmo [Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); MacKay, Helen [Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Medicine, University of Toronto, Toronto (Canada); Yeung, Ivan [Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Hill, Richard P. [Department of Radiation Oncology, University of Toronto, Toronto (Canada); Department of Advanced Molecular Oncology, Princess Margaret Cancer Center, University Health Network, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); and others

    2016-01-01

    Purpose: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). Methods and Materials: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. Results: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. Conclusions: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.

  5. Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

    DEFF Research Database (Denmark)

    Mulligan, Anna Marie; Couch, Fergus J; Barrowdale, Daniel

    2011-01-01

    ABSTRACT: INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes...... in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumor. METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumor......, to assess the associations of twelve loci with breast cancer tumor characteristics. Associations were evaluated using a retrospective cohort approach. RESULTS: The results suggested stronger associations with ER-positive breast cancer than ER-negative for eleven loci in both BRCA1 and BRCA2 carriers. Among...

  6. Shape memory alloy consortium (SMAC)

    Science.gov (United States)

    Jacot, A. Dean

    1999-07-01

    The application of smart structures to helicopter rotors has received widespread study in recent years. This is one of the major thrusts of the Shape Memory Alloy Consortium (SMAC) program. SMAC includes 3 companies and 4 Universities in a cost sharing consortium funded under DARPA Smart Materials and Structures program. This paper describes the objective of the SMAC effort, and its relationship to a previous DARPA smart structure rotorcraft program from which it originated. The SMAC program includes NiTinol fatigue/characterization studies, SMA actuator development, and ferromagnetic SMA material development. The paper summarizes the SMAC effort, and includes background and details on Boeing's development of a SMA torsional actuator for rotorcraft applications. SMA actuation is used to retwist the rotorcraft blade in flight, and result in a significant payload increase for either helicopters or tiltrotors. This paper is also augmented by several other papers in this conference with specific results from other SMAC consortium members.

  7. Combustion Byproducts Recycling Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Paul Ziemkiewicz; Tamara Vandivort; Debra Pflughoeft-Hassett; Y. Paul Chugh; James Hower

    2008-08-31

    The Combustion Byproducts Recycling Consortium (CBRC) program was developed as a focused program to remove and/or minimize the barriers for effective management of over 123 million tons of coal combustion byproducts (CCBs) annually generated in the USA. At the time of launching the CBRC in 1998, about 25% of CCBs were beneficially utilized while the remaining was disposed in on-site or off-site landfills. During the ten (10) year tenure of CBRC (1998-2008), after a critical review, 52 projects were funded nationwide. By region, the East, Midwest, and West had 21, 18, and 13 projects funded, respectively. Almost all projects were cooperative projects involving industry, government, and academia. The CBRC projects, to a large extent, successfully addressed the problems of large-scale utilization of CCBs. A few projects, such as the two Eastern Region projects that addressed the use of fly ash in foundry applications, might be thought of as a somewhat smaller application in comparison to construction and agricultural uses, but as a novel niche use, they set the stage to draw interest that fly ash substitution for Portland cement might not attract. With consideration of the large increase in flue gas desulfurization (FGD) gypsum in response to EPA regulations, agricultural uses of FGD gypsum hold promise for large-scale uses of a product currently directed to the (currently stagnant) home construction market. Outstanding achievements of the program are: (1) The CBRC successfully enhanced professional expertise in the area of CCBs throughout the nation. The enhanced capacity continues to provide technology and information transfer expertise to industry and regulatory agencies. (2) Several technologies were developed that can be used immediately. These include: (a) Use of CCBs for road base and sub-base applications; (b) full-depth, in situ stabilization of gravel roads or highway/pavement construction recycled materials; and (c) fired bricks containing up to 30%-40% F

  8. The ocean sampling day consortium

    DEFF Research Database (Denmark)

    Kopf, Anna; Bicak, Mesude; Kottmann, Renzo

    2015-01-01

    Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate...... the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our...

  9. Smart Nanoparticles Undergo Phase Transition for Enhanced Cellular Uptake and Subsequent Intracellular Drug Release in a Tumor Microenvironment.

    Science.gov (United States)

    Ye, Guihua; Jiang, Yajun; Yang, Xiaoying; Hu, Hongxiang; Wang, Beibei; Sun, Lu; Yang, Victor C; Sun, Duxin; Gao, Wei

    2018-01-10

    Inefficient cellular uptake and intracellular drug release at the tumor site are two major obstacles limiting the antitumor efficacy of nanoparticle delivery systems. To overcome both problems, we designed a smart nanoparticle that undergoes phase transition in a tumor microenvironment (TME). The smart nanoparticle is generated using a lipid-polypetide hybrid nanoparticle, which comprises a PEGylated lipid monolayer shell and a pH-sensitive hydrophobic poly-l-histidine core and is loaded with the antitumor drug doxorubicin (DOX). The smart nanoparticle undergoes a two-step phase transition at two different pH values in the TME: (i) At the TME (pH e : 7.0-6.5), the smart nanoparticle swells, and its surface potential turns from negative to neutral, facilitating the cellular uptake; (ii) After internalization, at the acid endolysosome (pH endo : 6.5-4.5), the smart nanoparticle dissociates and induces endolysosome escape to release DOX into the cytoplasm. In addition, a tumor-penetrating peptide iNRG was modified on the surface of the smart nanoparticle as a tumor target moiety. The in vitro studies demonstrated that the iNGR-modified smart nanoparticles promoted cellular uptake in the acidic environment (pH 6.8). The in vivo studies showed that the iNGR-modified smart nanoparticles exerted more potent antitumor efficacy against late-stage aggressive breast carcinoma than free DOX. These data suggest that the smart nanoparticles may serve as a promising delivery system for sequential uptake and intracellular drug release of antitumor agents. The easy preparation of these smart nanoparticles may also have advantages in the future manufacture for clinical trials and clinical use.

  10. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    International Nuclear Information System (INIS)

    Mimura, Hidefumi; Arai, Yasuaki; Yamakado, Koichiro; Sone, Miyuki; Takeuchi, Yoshito; Miki, Tsuneharu; Gobara, Hideo; Sakuhara, Yusuke; Yamamoto, Takanobu; Sato, Yozo; Kanazawa, Susumu

    2016-01-01

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  11. A phase I study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors.

    Directory of Open Access Journals (Sweden)

    Oren J Becher

    Full Text Available The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label dose-escalation study to assess pharmacokinetics, describe toxicities, and identify the MTD for single-agent perifosine. Five dose levels were investigated, ranging from 25 to 125 mg/m2/day for 28 days per cycle. Twenty-three patients (median age 10 years, range 4-18 years with CNS tumors (DIPG [n = 3], high-grade glioma [n = 5], medulloblastoma [n = 2], ependymoma [n = 3], neuroblastoma (n = 8, Wilms tumor (n = 1, and Ewing sarcoma (n = 1 were treated. Only one DLT occurred (grade 4 hyperuricemia at dose level 4. The most common grade 3 or 4 toxicity at least possibly related to perifosine was neutropenia (8.7%, with the remaining grade 3 or 4 toxicities (fatigue, hyperglycemia, fever, hyperuricemia, and catheter-related infection occurring in one patient each. Pharmacokinetics was dose-saturable at doses above 50 mg/m2/day with significant inter-patient variability, consistent with findings reported in adult studies. One patient with DIPG (dose level 5 and 4 of 5 patients with high-grade glioma (dose levels 2 and 3 experienced stable disease for two months. Five subjects with neuroblastoma (dose levels 1 through 4 achieved stable disease which was prolonged (≥11 months in three. No objective responses were noted. In conclusion, the use of perifosine was safe and feasible in patients with recurrent/refractory pediatric CNS and solid tumors. An MTD was not defined by the 5 dose levels investigated. Our RP2D is 50 mg/m2/day.

  12. Phase I/II Study of Radiofrequency Ablation for Malignant Renal Tumors: Japan Interventional Radiology in Oncology Study Group 0701

    Energy Technology Data Exchange (ETDEWEB)

    Mimura, Hidefumi, E-mail: mimura@marianna-u.ac.jp [St. Marianna University School of Medicine, Department of Radiology (Japan); Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Yamakado, Koichiro, E-mail: yama@clin.medic.mie-u.ac.jp [Mie University School of Medicine, Department of Interventional Radiology (Japan); Sone, Miyuki, E-mail: msone@me.com; Takeuchi, Yoshito, E-mail: yotake62@qg8.so-net.ne.jp [National Cancer Center Hospital, Department of Diagnostic Radiology (Japan); Miki, Tsuneharu, E-mail: tmiki@koto.kpu-m.ac.jp [Kyoto Prefectural University of Medicine, Department of Urology (Japan); Gobara, Hideo, E-mail: gobara@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan); Sakuhara, Yusuke, E-mail: yusaku@med.hokudai.ac.jp [Hokkaido University School of Medicine, Department of Diagnostic and Interventional Radiology (Japan); Yamamoto, Takanobu, E-mail: tyamamot@tcc.pref.tochigi.lg.jp [Tochigi Cancer Center, Department of Radiology (Japan); Sato, Yozo, E-mail: ysato@aichi-cc.jp [Aichi Cancer Center Hospital, Department of Diagnostic and Interventional Radiology (Japan); Kanazawa, Susumu, E-mail: susumu@cc.okayama-u.ac.jp [Okayama University Medical School, Department of Radiology (Japan)

    2016-05-15

    PurposeThis multicenter phase I/II study evaluated the safety, feasibility, and initial efficacy of radiofrequency ablation (RFA) for small malignant renal tumors.MethodsThirty-three patients were enrolled in the study. A single session of RFA was performed in patients with a renal tumor of 1–3 cm in greatest diameter, with the exception of lesions adjacent to the renal hilum. The primary endpoint was the safety of renal RFA, and the secondary endpoints were its feasibility and initial efficacy for local control, as well as the incidence and grade of adverse events. Clinical efficacy was evaluated by CT scans within 1 week and at a further 4 weeks after the procedure using the criteria adapted from the Response Evaluation Criteria in Solid Tumors.ResultsThe RFA procedure was completed in 100 % (95 % confidence interval [CI] 89–100 %) of all 33 patients. There were no severe adverse events (0 % [95 % CI 0–11 %]). Among the 33 patients, a complete response, partial response, progressive disease, and stable disease were seen in 28 (85 %), 0 (0 %), one (3 %), and one (3 %) patient(s), respectively, with a tumor response rate of 85 % [95 % CI 68–95 %]). Three patients (9 %), including one ineligible patient (3 %), were not evaluable. Out of 30 evaluable patients, a complete response was achieved in 28 (93 %).ConclusionThe current multicenter trial revealed that RFA is a safe, feasible, and effective treatment for small malignant renal tumors in patients who are not candidates for surgery.

  13. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Hamid Omid

    2011-11-01

    Full Text Available Abstract Background Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4, has demonstrated an improvement in overall survival in two phase III trials of patients with advanced melanoma. The primary objective of the current trial was to prospectively explore candidate biomarkers from the tumor microenvironment for associations with clinical response to ipilimumab. Methods In this randomized, double-blind, phase II biomarker study (ClinicalTrials.gov NCT00261365, 82 pretreated or treatment-naïve patients with unresectable stage III/IV melanoma were induced with 3 or 10 mg/kg ipilimumab every 3 weeks for 4 doses; at Week 24, patients could receive maintenance doses every 12 weeks. Efficacy was evaluated per modified World Health Organization response criteria and safety was assessed continuously. Candidate biomarkers were evaluated in tumor biopsies collected pretreatment and 24 to 72 hours after the second ipilimumab dose. Polymorphisms in immune-related genes were also evaluated. Results Objective response rate, response patterns, and safety were consistent with previous trials of ipilimumab in melanoma. No associations between genetic polymorphisms and clinical activity were observed. Immunohistochemistry and histology on tumor biopsies revealed significant associations between clinical activity and high baseline expression of FoxP3 (p = 0.014 and indoleamine 2,3-dioxygenase (p = 0.012, and between clinical activity and increase in tumor-infiltrating lymphocytes (TILs between baseline and 3 weeks after start of treatment (p = 0.005. Microarray analysis of mRNA from tumor samples taken pretreatment and post-treatment demonstrated significant increases in expression of several immune-related genes, and decreases in expression of genes implicated in cancer and melanoma. Conclusions Baseline expression of immune-related tumor biomarkers and a post-treatment increase in TILs may be positively associated with

  14. A comparison of safety and efficacy of cytotoxic versus molecularly targeted drugs in pediatric phase I solid tumor oncology trials.

    Science.gov (United States)

    Dorris, Kathleen; Liu, Chunyan; Li, Dandan; Hummel, Trent R; Wang, Xia; Perentesis, John; Kim, Mi-Ok; Fouladi, Maryam

    2017-03-01

    Prior reviews of phase I pediatric oncology trials involving primarily cytotoxic agents have reported objective response rates (ORRs) and toxic death rates of 7.9-9.6% and 0.5%, respectively. These data may not reflect safety and efficacy in phase I trials of molecularly targeted (targeted) drugs. A systematic review of pediatric phase I solid tumor trials published in 1990-2013 was performed. The published reports were evaluated for patient characteristics, toxicity information, and response numbers. A total of 143 phase I pediatric clinical trials enrolling 3,896 children involving 53 targeted and 48 cytotoxic drugs were identified. A meta-analysis demonstrated that the ORR is 2.1-fold higher with cytotoxic drugs (0.066 vs. 0.031 per subject; P = 0.007). By contrast, the pooled estimate of the stable disease rate (SDR) is similar for cytotoxic and targeted drugs (0.2 vs. 0.23 per subject; P = 0.27).  The pooled estimate of the dose-limiting toxicity rate is 1.8-fold larger with cytotoxic drugs (0.24 vs. 0.13 per subject; P = 0.0003). The hematologic grade 3-4 (G3/4) toxicity rate is 3.6-fold larger with cytotoxic drugs (0.43 vs. 0.12 per treatment course; P = 0.0001); however, the nonhematologic G3/4 toxicities and toxic deaths occur at similar rates for cytotoxic and targeted drugs. In phase I pediatric solid tumor trials, ORRs were significantly higher for cytotoxic versus targeted agents. SDRs were similar in targeted and cytotoxic drug trials. Patients treated with cytotoxic agents were more likely to experience hematologic G3/4 toxicities than those patients receiving targeted drugs. © 2016 Wiley Periodicals, Inc.

  15. Community Hospital Telehealth Consortium (CHTC)

    Science.gov (United States)

    2003-12-30

    technology to improve and expand the opportunity for rural and urban underserved populations to receive quality, affordable health care....The Community Hospital Telehealth Consortium (CHTC) is a unique, forward-thinking, community-based healthcare service project organized around 6 not

  16. East bay fire chiefs' consortium

    Science.gov (United States)

    Michael Bradley

    1995-01-01

    The traditional approach to planning for public fire protection has been based on independent actions by each fire department or district. The county fire chiefs’ associations, while providing interagency communication, were not adequate to deal with the regional nature of the wildland urban interface problem. The formation of the East Bay Fire Chiefs’ Consortium grew...

  17. Photoacoustic radar phase-filtered spatial resolution and co-registered ultrasound image enhancement for tumor detection.

    Science.gov (United States)

    Dovlo, Edem; Lashkari, Bahman; Mandelis, Andreas; Shi, Wei; Liu, Fei-Fei

    2015-03-01

    Co-registered ultrasound (US) and frequency-domain photoacoustic radar (FD-PAR) imaging is reported for the first time in this paper. The merits of ultrasound and cross-correlation (radar) frequency-domain photoacoustic imaging are leveraged for accurate tumor detection. Commercial US imagers possess sophisticated, optimized software for rapid image acquisition that could dramatically speed-up PA imaging. The PAR image generated from the amplitude of the cross-correlation between detected and input signals was filtered by the standard deviation (SD) of the phase of the correlation signal, resulting in strong improvement of image spatial resolution, signal-to-noise ratio (SNR) and contrast. Application of phase-mediated image improvement is illustrated by imaging a cancer cell-injected mouse. A 14-15 dB SNR gain was recorded for the phase-filtered image compared to the amplitude and phase independently, while ~340 μm spatial resolution was seen for the phase PAR image compared to ~840 μm for the amplitude image.

  18. Tumor Biology and Immunology | Center for Cancer Research

    Science.gov (United States)

    Tumor Biology and Immunology The Comparative Brain Tumor Consortium is collaborating with National Center for Advanced Translational Sciences to complete whole exome sequencing on canine meningioma samples. Results will be published and made publicly available.

  19. Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo.

    Science.gov (United States)

    Zhao, Tiejun; Sun, Qiang; del Rincon, Sonia V; Lovato, Amanda; Marques, Maud; Witcher, Michael

    2014-01-01

    Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn) has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1) as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP) injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

  20. Gallotannin imposes S phase arrest in breast cancer cells and suppresses the growth of triple-negative tumors in vivo.

    Directory of Open Access Journals (Sweden)

    Tiejun Zhao

    Full Text Available Triple-negative breast cancers are associated with poor clinical outcomes and new therapeutic strategies are clearly needed. Gallotannin (Gltn has been previously demonstrated to have potent anti-tumor properties against cholangiocarcinoma in mice, but little is known regarding its capacity to suppress tumor outgrowth in breast cancer models. We tested Gltn for potential growth inhibitory properties against a variety of breast cancer cell lines in vitro. In particular, triple-negative breast cancer cells display higher levels of sensitivity to Gltn. The loss of proliferative capacity in Gltn exposed cells is associated with slowed cell cycle progression and S phase arrest, dependent on Chk2 phosphorylation and further characterized by changes to proliferation related genes, such as cyclin D1 (CcnD1 as determined by Nanostring technology. Importantly, Gltn administered orally or via intraperitoneal (IP injections greatly reduced tumor outgrowth of triple-negative breast cells from mammary fat pads without signs of toxicity. In conclusion, these data strongly suggest that Gltn represents a novel approach to treat triple-negative breast carcinomas.

  1. BIODEGRADATION OF MTBE BY A MICROORGANISM CONSORTIUM

    Directory of Open Access Journals (Sweden)

    M. Alimohammadi, A. R. Mesdaghinia, M. Mahmoodi, S. Nasseri, A. H. Mahvi and J. Nouri

    2005-10-01

    Full Text Available Methyl Tert-Butyl Ether (MTBE is one of the ether oxygenates which its use has been increased within the last twenty years. This compound is produced from isobutylene and methanol reaction that is used as octane index enhancer and also increases dissolved oxygen in gasoline and decreases carbon monoxide emission in four phased motors because of better combustion of gasoline. High solubility in water (52 g/L, high vapor pressure (0.54 kg/cm3, low absorption to organic carbon of soil and presence of MTBE in the list of potentially-carcinogens of U.S EPA has made its use of great concern. The culture media used in this study was Mineral Salt Medium (MSM. The study lasted for 236 days and in three different concentrations of MTBE of 200, 5 and 0.8 mg/L. A control sample was also used to compare the results. This research studied the isolation methods of microbial consortium in the MTBE polluted soils in Tehran and Abadan petroleum refinery besides MTBE degradation. The results showed the capability of bacteria in consuming MTBE as carbon source. Final microbial isolation was performed with several microbial passages as well as keeping consortium in a certain amount of MTBE as the carbon source.

  2. Clinical phase II study with Gd-DTPA (dimeglumine gadopentetate, SHL 451 A) in brain tumor and cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, Kohki; Aoki, Shigeki; Machida, Tohru and others

    1988-06-01

    A clinical phase II study with Gd-DTPA, the first contrast medium for MRI, was performed in 109 cases, a total of 114 studies mainly with brain tumor. In this study, one of the three concentrations of Gd-DTPA, 0.05 mmol/kg, 0.10 mmol/kg or 0.15 mmol/kg was used in each patient. It was elucidated that especially 0.10 and 0.15 Gd-DTPA were useful in detecting disruption or abscence of BBB and distinguishing tumor from edema. The side-effect observed was only a slight urticaria which was seen with 0.15 mmol/kg Gd-DTPA. Accordingly, it was estimated that the standard concentration of Gd-DTPA would be 0.10 mmol/kg. As this contrast medium was safe, and clinically useful in detecting diseases of the central nervous system, it was concluded that the shift to the clinical phase III trial is possible.

  3. Corn in consortium with forages

    Directory of Open Access Journals (Sweden)

    Cássia Maria de Paula Garcia

    2013-12-01

    Full Text Available The basic premises for sustainable agricultural development with focus on rural producers are reducing the costs of production and aggregation of values through the use crop-livestock system (CLS throughout the year. The CLS is based on the consortium of grain crops, especially corn with tropical forages, mainly of the genus Panicum and Urochloa. The study aimed to evaluate the grain yield of irrigated corn crop intercropped with forage of the genus Panicum and Urochloa. The experiment was conducted at the Fazenda de Ensino, Pesquisa e Extensão – FEPE  of the Faculdade de Engenharia - UNESP, Ilha Solteira in an Oxisol in savannah conditions and in the autumn winter of 2009. The experimental area was irrigated by a center pivot and had a history of no-tillage system for 8 years. The corn hybrid used was simple DKB 390 YG at distances of 0.90 m. The seeds of grasses were sown in 0.34 m spacing in the amount of 5 kg ha-1, they were mixed with fertilizer minutes before sowing  and placed in a compartment fertilizer seeder and fertilizers were mechanically deposited in the soil at a depth of 0.03 m. The experimental design used was a randomized block with four replications and five treatments: Panicum maximum cv. Tanzania sown during the nitrogen fertilization (CTD of the corn; Panicum maximum cv. Mombaça sown during the nitrogen fertilization (CMD of the corn; Urochloa brizantha cv. Xaraés sown during the occasion of nitrogen fertilization (CBD of the corn; Urochloa ruziziensis cv. Comumsown during the nitrogen fertilization (CRD of the corn and single corn (control. The production components of corn: plant population per hectare (PlPo, number of ears per hectare (NE ha-1, number of rows per ear (NRE, number of kernels per row on the cob (NKR, number of grain in the ear (NGE and mass of 100 grains (M100G were not influenced by consortium with forage. Comparing grain yield (GY single corn and maize intercropped with forage of the genus Panicum

  4. Bortezomib in combination with celecoxib in patients with advanced solid tumors: a phase I trial

    Directory of Open Access Journals (Sweden)

    Salzer Shanta

    2007-12-01

    Full Text Available Abstract Background COX-2 inhibitors, such as celecoxib, and ubiquitin-proteasome pathway inhibitors, such as bortezomib, can down-regulate NF-κB, a transcription factor implicated in tumor growth. The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of bortezomib in combination with celecoxib in patients with advanced solid tumors. Methods Patients received escalating doses of bortezomib either on a weekly schedule (days 1, 8, 15, 22, and 29 repeated every 42 days or on a twice-weekly administration schedule (days 1, 4, 8, and 11 repeated every 21 days, in combination with escalating doses of celecoxib twice daily throughout the study period from 200 mg to 400 mg twice daily. Results No dose-limiting toxicity was observed during the study period. Two patients had stable disease lasting for four and five months each, and sixteen patients developed progressive disease. Conclusion The combination of bortezomib and celecoxib was well tolerated, without dose limiting toxicities observed throughout the dosing ranges tested, and will be studied further at the highest dose levels investigated. Trial registration number NCT00290680.

  5. Corn in consortium with forages

    OpenAIRE

    Cássia Maria de Paula Garcia; Marcelo Andreotti; Marcelo Carvalho Minhoto Teixeira Filho; Keny Samejima Mascarenha Lopes; Ciniro Costa; Erikelly Aline Ribeiro de Santana

    2013-01-01

    The basic premises for sustainable agricultural development with focus on rural producers are reducing the costs of production and aggregation of values through the use crop-livestock system (CLS) throughout the year. The CLS is based on the consortium of grain crops, especially corn with tropical forages, mainly of the genus Panicum and Urochloa. The study aimed to evaluate the grain yield of irrigated corn crop intercropped with forage of the genus Panicum and Urochloa. The experiment was c...

  6. John Glenn Biomedical Engineering Consortium

    Science.gov (United States)

    Nall, Marsha

    2004-01-01

    The John Glenn Biomedical Engineering Consortium is an inter-institutional research and technology development, beginning with ten projects in FY02 that are aimed at applying GRC expertise in fluid physics and sensor development with local biomedical expertise to mitigate the risks of space flight on the health, safety, and performance of astronauts. It is anticipated that several new technologies will be developed that are applicable to both medical needs in space and on earth.

  7. Appalachian clean coal technology consortium

    Energy Technology Data Exchange (ETDEWEB)

    Kutz, K.; Yoon, Roe-Hoan [Virginia Polytechnic Institute and State Univ., Blacksburg, VA (United States)

    1995-11-01

    The Appalachian Clean Coal Technology Consortium (ACCTC) has been established to help U.S. coal producers, particularly those in the Appalachian region, increase the production of lower-sulfur coal. The cooperative research conducted as part of the consortium activities will help utilities meet the emissions standards established by the 1990 Clean Air Act Amendments, enhance the competitiveness of U.S. coals in the world market, create jobs in economically-depressed coal producing regions, and reduce U.S. dependence on foreign energy supplies. The research activities will be conducted in cooperation with coal companies, equipment manufacturers, and A&E firms working in the Appalachian coal fields. This approach is consistent with President Clinton`s initiative in establishing Regional Technology Alliances to meet regional needs through technology development in cooperation with industry. The consortium activities are complementary to the High-Efficiency Preparation program of the Pittsburgh Energy Technology Center, but are broader in scope as they are inclusive of technology developments for both near-term and long-term applications, technology transfer, and training a highly-skilled work force.

  8. A fluid biopsy as investigating technology for the fluid phase of solid tumors

    Science.gov (United States)

    Kuhn, Peter; Bethel, Kelly

    2012-02-01

    Reliable measurement of internal bodily substances and structures is one of the cornerstones of modern medicine. Progress in cancer medicine, like that in many medical fields, must encompass and take advantage of progress in the physical sciences. Historically, the development and refinement of physical sciences-based detection of biological entities precedes periods of great advancements in therapies. To treat broken limbs and arthritis, we are indebted to Conrad Roentgen's discovery of x-rays by which we can evaluate the bones; to apply gamma knife therapy for cancer, we are indebted to Marie Curie's discoveries about radioactivity by which we can eradicate tumors; to manage the complications of diabetes, we are indebted to Tom Clemens, Ames Pharmaceuticals and Dick Bernstein's refinement of direct blood glucose measurement technology by which we can count, hour-to-hour, the waxing and waning of blood sugar levels; to understand anything at all on the cellular level, we are indebted to Antonie van Leeuwenhoek's microscope, by which we can see our cells. The application of physical sciences perspectives to biological and medical problems has a long and productive history. As of late, however, the increasing compartmentalization of science and exponential increases of knowledge in both arenas has resulted in a rift between the two. The NCI has initiated a research network establishing multiple centers of investigation, the Physical Sciences in Oncology Centers (http://physics.cancer.gov), which seek to mend the rift. Each headed by a pair of investigators, one in the physical sciences and one in the biological sciences, the centers seek to bring the advances and breakthroughs of the physical sciences world to bear on the question of cancer. This issue of physical biology contains a series of articles exploring the utility and applicability of a new method for measuring cancer as it spreads, developed at the Scripps Physical Oncology Center. Although some progress

  9. Lanreotide autogel every 6 weeks compared with Lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: a Phase III Study.

    Science.gov (United States)

    Bajetta, Emilio; Procopio, Giuseppe; Catena, Laura; Martinetti, Antonia; De Dosso, Sara; Ricci, Sergio; Lecchi, Alberto S; Boscani, Paolo F; Iacobelli, Stefano; Carteni, Giacomo; De Braud, Filippo; Loli, Paola; Tartaglia, Andreas; Bajetta, Roberto; Ferrari, Leonardo

    2006-11-15

    The noninferiority of a 6-week dosing schedule of lanreotide Autogel (Lan ATG) at a dose of 120 mg compared with a 3-week dosing schedule of lanreotide microparticles (Lan MP) at a dose of 60 mg was investigated in patients with neuroendocrine tumors (NET). Patients who had sporadic, well differentiated NET with a low grade of malignancy were recruited for this open-label, Phase III, multicenter trial. Patients were randomized to receive either 3 deep subcutaneous injections of Lan ATG (120 mg, every 6 weeks) or 6 intramuscular injections of Lan MP (60 mg, every 3 weeks). Tumor markers, tumor size, and symptoms were assessed between baseline and Week 18. Success was classified as a response that ranged from disappearance to an increase <25% in tumor marker, tumor size, or symptom frequency. Sixty patients were randomized, and 46 patients completed the study. Both for tumor markers and for tumor size, Lan ATG was not inferior to Lan MP (55% and 59% of patients responded on tumor markers, respectively; 68% and 66% of patients responded on tumor size, respectively). There were too few symptomatic patients to compare carcinoid symptoms. Both treatments were tolerated well, and no safety concerns were identified. Lan ATG at a dose of 120 mg every 6 weeks was as effective for controlling NET as Lan MP at a dose of 60 mg every 3 weeks.

  10. Techniques for heating eccentrically located tumors with the BSD annular phased array system (APAS): Clinical experience

    International Nuclear Information System (INIS)

    Samulski, T.V.; Kapp, D.S.; Bagshaw, M.A.; Fessenden, P.; Lee, E.R.; Lohrbach, A.W.

    1985-01-01

    The authors are currently investigating the potential for treatment optimization with the BSD APAS in tumors which are eccentrically located within the lower abdomen and pelvis. Attempts have been made to manipulate electric field (E-field) distribution during treatments through frequency changes and partial array activation (driving less than all four quadrants). Field shifts are qualitatively documented using the manufacturer's supplied diode array probes located at the patient/bolus interface in anterior, posterior and bilateral positions. Preliminary findings indicate that the internal E-field distributions can be manipulated to result in better treatment tolerance and better temperature distributions in selected target volumes. Phantom and clinical data are presented demonstrating the utility of these approaches

  11. Donepezil for Irradiated Brain Tumor Survivors: A Phase III Randomized Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    Rapp, Stephen R; Case, L Doug; Peiffer, Ann; Naughton, Michelle M; Chan, Michael D; Stieber, Volker W; Moore, Dennis F; Falchuk, Steven C; Piephoff, James V; Edenfield, William J; Giguere, Jeffrey K; Loghin, Monica E; Shaw, Edward G

    2015-05-20

    Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments. © 2015 by American Society of Clinical Oncology.

  12. Phase I study of bryostatin 1: assessment of interleukin 6 and tumor necrosis factor alpha induction in vivo. The Cancer Research Campaign Phase I Committee.

    Science.gov (United States)

    Philip, P A; Rea, D; Thavasu, P; Carmichael, J; Stuart, N S; Rockett, H; Talbot, D C; Ganesan, T; Pettit, G R; Balkwill, F

    1993-11-17

    Many oncogenes have been shown to code for growth factor receptors that are involved in regulation of cell growth and proliferation and can activate transcription via protein kinase C. Bryostatin 1, a partial agonist of protein kinase C, has demonstrated potent antitumor activity in vitro and in vivo in human tumor xenografts. The aim of this phase I study was to determine the optimal dosage and toxicity profile of bryostatin 1 and its influence on cytokine release in vivo. Three successive cohorts consisting of 35 patients with various malignant tumors were treated with bryostatin 1 by intravenous infusion over 1 hour as follows: cohort A--35 micrograms/m2 (three patients) or 50 micrograms/m2 (eight patients) once every 2 weeks; cohort B--25 micrograms/m2 once a week (eight patients); and cohort C--25 micrograms/m2 once a week for 3 weeks, with no treatment during the 4th week (16 patients). Plasma levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) were measured by immunoradiometric assay and by radioimmunoassay, respectively. The dose-limiting toxicity was grade 3 or 4 myalgia in four of 11 patients in cohort A, in two of eight in cohort B, and in none of 16 in cohort C. Occurrence of myalgia was dose related. There was no significant myelosuppression, apart from a small and transient fall in platelet count. Six patients experienced acute but transient skin flushing, dyspnea, hypotension, and bradycardia, probably related to the bryostatin 1 vehicle. TNF-alpha and IL-6 were detected in plasma at 2 and 24 hours after treatment, respectively, and the levels were dose related (P = .02). Two patients with metastatic malignant melanoma had partial remission after three or four cycles of therapy; remission lasted 6 weeks and 10+ months, respectively. The dose-limiting toxicity of bryostatin 1 was myalgia. Plasma IL-6 and TNF-alpha concentrations were increased within 24 hours of therapy. Antitumor activity against malignant melanoma was observed

  13. A phase I dose-escalation study of MEDI-575, a PDGFRα monoclonal antibody, in adults with advanced solid tumors.

    Science.gov (United States)

    Becerra, Carlos R; Conkling, Paul; Vogelzang, Nicholas; Wu, Hilary; Hong, Shengyan; Narwal, Rajesh; Liang, Meina; Tavakkoli, Fatemeh; Pandya, Naimish

    2014-11-01

    The purpose of the study was to evaluate safety and determine the maximum tolerated dose (MTD) of MEDI-575, a fully human monoclonal antibody that selectively binds to platelet-derived growth factor receptor-α (PDGFRα), in patients with advanced solid tumors. This phase I multicenter, open-label, single-arm study enrolled adults in a 3 + 3 dose escalation design to receive MEDI-575 (3, 6, 9, 12, or 15 mg/kg) once weekly (QW) until toxicity or disease progression occurred. One 0.5-mg/kg dose was given before the first dose in the 3-mg/kg cohort to determine pharmacokinetics (PK) and pharmacodynamics under unsaturated conditions. After completion of dose escalation in the QW cohorts, patients were enrolled in two additional cohorts and received MEDI-575 25 or 35 mg/kg every 3 weeks (Q3W). Secondary measures included assessments of PK, immunogenicity, and antitumor activity. A total of 35 patients received MEDI-575 QW (n = 23) or Q3W (n = 12). Most treatment-related adverse events were grade 1 or 2 in severity across all dose levels, with fatigue (n = 12) and nausea (n = 8) being reported most frequently. With no reports of dose-limiting toxicities (DLTs), the MTD was not reached. MEDI-575 exhibited a nonlinear PK profile and increased plasma platelet-derived growth factor-AA levels in a dose-dependent manner with limited immunogenicity. Stable disease was reported as the best tumor response in 9 of 29 evaluable patients; however, no objective responses were reported. Administration of MEDI-575 QW or Q3W resulted in a favorable safety profile, including a lack of DLTs, but without evidence of antitumor activity in patients with refractory solid tumors.

  14. Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors.

    Science.gov (United States)

    Annunziata, Christina M; Kohn, Elise C; LoRusso, Patricia; Houston, Nicole D; Coleman, Robert L; Buzoianu, Manuela; Robbie, Gabriel; Lechleider, Robert

    2013-02-01

    Targeting the cell-surface receptor EphA2, which is highly expressed in some solid tumors, is a novel approach for cancer therapy. We aimed to evaluate the safety profile, maximum tolerated dose (MTD), pharmacokinetics, and antitumor activity of MEDI-547, an antibody drug conjugate composed of the cytotoxic drug auristatin (toxin) linked to a human anti-EphA2 monoclonal antibody (1C1), in patients with solid tumors relapsed/refractory to standard therapy. In this phase 1, open-label study with planned dose-escalation and dose-expansion cohorts, patients received a 1-h intravenous infusion of MEDI-547 (0.08 mg/kg) every 3 weeks. Six patients received 0.08 mg/kg; all discontinued treatment. Dose escalation was not pursued. The study was stopped before cohort 2 enrollment due to treatment-related bleeding and coagulation events (hemorrhage-related, n = 3; epistaxis, n = 2). Therefore, lower doses were not explored and an MTD could not be selected. The most frequently reported treatment-related adverse events (AEs) were increased liver enzymes, decreased hemoglobin, decreased appetite, and epistaxis. Three patients (50%) experienced treatment-related serious AEs, including conjunctival hemorrhage, pain (led to study drug discontinuation), liver disorder, and hemorrhage. Best response included progressive disease (n = 5; 83.3%) and stable disease (n = 1; 16.7%). Minimal or no dissociation of toxin from 1C1 conjugate occurred in the blood. Serum MEDI-547 concentrations decreased rapidly, ~70% by 3 days post-dose. No accumulation of MEDI-547 was observed at 0.08 mg/kg upon administration of a second dose 3 weeks following dose 1. The safety profile of MEDI-547 does not support further clinical investigation in patients with advanced solid tumors.

  15. A Phase I study of MEDI-575, a PDGFRα monoclonal antibody, in Japanese patients with advanced solid tumors.

    Science.gov (United States)

    Murakami, Haruyasu; Ikeda, Masafumi; Okusaka, Takuji; Inaba, Yoshitaka; Iguchi, Haruo; Yagawa, Katsuro; Yamamoto, Nobuyuki

    2015-09-01

    MEDI-575 is a fully human monoclonal antibody that selectively binds to platelet-derived growth factor receptor alpha (PDGFRα). This open-label Phase I study assessed the safety and tolerability of MEDI-575 in Japanese patients with advanced solid tumors. The study comprised two parts: Part A, dose escalation; Part B, dose expansion in patients with hepatocellular cancer. In Part A, patients were enrolled into three cohorts: MEDI-575 was administered intravenously over a 21-day treatment cycle at doses of 9 and 15 mg/kg/week (cohorts 1, 2) and 35 mg/kg/3-weekly (cohort 3). In Part B, MEDI-575 25 mg/kg/3-weekly was administered. Secondary measures included assessment of the maximum tolerated dose, pharmacokinetics, immunogenicity and anti-tumor activity. Ten and 12 patients were treated in Parts A and B, respectively. There were no dose-limiting toxicities; the maximum tolerated dose was not determined. Common treatment-related adverse events were fatigue (30%) and decreased appetite (20%) in Part A and decreased appetite (33.3%) in Part B. All treatment-related adverse events were grade 1 or 2 in severity. No patients discontinued MEDI-575 because of an adverse event and there were no patient deaths due to adverse events. MEDI-575 binding with PDGFRα resulted in a dose-dependent increase in PDGF-AA ligand, with plateau levels observed within 2 days and sustained during the dosing interval. None of the patients in Part A or B experienced complete or partial responses to treatment. MEDI-575 once weekly and 3-weekly was well tolerated with a favorable pharmacokinetic profile in Japanese patients with advanced solid tumors. ClinicalTrials.gov, NCT01102400.

  16. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.

    Science.gov (United States)

    Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano

    2014-08-21

    The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response

  17. Consortium for Health and Military Performance (CHAMP)

    Data.gov (United States)

    Federal Laboratory Consortium — The Center's work addresses a wide scope of trauma exposure from the consequences of combat, operations other than war, terrorism, natural and humanmade disasters,...

  18. Enhancement pattern analysis of hypervascular hepatocellular carcinoma on dynamic MR imaging with histopathological correlation: Validity of portal phase imaging for predicting tumor grade

    International Nuclear Information System (INIS)

    Okamoto, Daisuke; Yoshimitsu, Kengo; Nishie, Akihiro; Tajima, Tsuyoshi; Asayama, Yoshiki; Ishigami, Kousei; Hirakawa, Masakazu; Ushijima, Yasuhiro; Kakihara, Daisuke; Nakayama, Tomohiro; Nishihara, Yunosuke; Aishima, Shinichi; Taketomi, Akinobu; Kishimoto, Junji; Honda, Hiroshi

    2012-01-01

    Purpose: To elucidate the correlation between hypervascular hepatocellular carcinoma (HCC) enhancement patterns on dynamic MR imaging and histological findings. Materials and methods: Surgically proven 46 hypervascular HCCs of forty-one patients were enrolled. For each HCC, the signal intensity in the portal phase (SIPP) was evaluated. In this study, high, iso-, or low intensity in the portal phase was hypothesized as late, moderate, or early washout pattern, respectively. The SIPP of each HCC was correlated to histological grade and architectural subtypes that represent degrees of trabecular structure. For the trabecular HCCs, the thickness of tumor plate was also correlated for indirect estimation of tumor sinusoid. Results: There was a significant correlation between the SIPP vs. histological grade and also vs. architectural subtypes, namely the degree of trabecular structure. Washout of hypervascular HCC occurred earlier as the histological grade advanced and the histological architecture got closer to pure trabecular HCC. For the trabecular HCCs, the thickness of tumor plate correlated significantly with SIPP or histological grade. Hypervascular HCCs with thicker tumor plates showed worse histological grade and earlier washout pattern. Conclusions: Histological grade of hypervascular HCC may be predicted using SIPP. The thickness of tumor plate, resultantly the size of sinusoid between tumor plates, can account for the relationship between washout pattern and histological grade in the trabecular HCCs.

  19. Phase I study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor in patients with refractory solid tumors.

    Science.gov (United States)

    Beutel, Gernot; Glen, Hilary; Schöffski, Patrick; Chick, Jon; Gill, Stan; Cassidy, James; Twelves, Chris

    2005-08-01

    OSI-7904L is a liposomal formulation of a potent noncompetitive thymidylate synthase inhibitor (TSI) that does not require polyglutamation for activity. This phase I study was done to establish the safety, tolerability, maximum tolerated dose, recommended dose, and pharmacokinetics of OSI-7904L in patients with advanced solid tumors refractory to standard therapy. OSI-7904L was given as a 30-minute i.v. infusion every 21 days to 31 patients at eight dose levels from 0.4 to 15.0 mg/m(2), using three patients per dose level, up to 10 patients at the recommended dose. Baseline plasma homocysteine and 2'-deoxyuridine and genotype polymorphism were measured as potential predictors of biological activity. Minimal toxicity was reported up to 9.6 mg/m(2), but dose-limiting toxicity was seen in both patients at 15 mg/m(2) including stomatitis, fatigue, tachyarrhythmia, rash and hand-foot syndrome, diarrhea, and fatal neutropenic sepsis. Other toxicity such as nausea and vomiting was mild or moderate. This resulted in the investigation of an intermediate dose level of 12 mg/m(2), identified as the recommended dose for phase II studies. Prolonged disease stabilization was reported in 11 of 31 heavily pretreated patients. Pharmacokinetic data indicate that this liposomal formulation alters the disposition properties of the parent drug resulting in a prolonged plasma residence time. OSI-7904L given as a 30-minute i.v. infusion every 21 days is feasible and well tolerated at the recommended phase II dose of 12 mg/m(2). The main toxicities are rash, pruritus, lethargy, stomatitis, and myelosuppression. Observed toxicities were predictable and characteristic for TSIs.

  20. The Mustard Consortium’s Elucidation of the Pathophysiology of Sulfur Mustard and Antidote Development

    Science.gov (United States)

    2006-09-01

    A. M. Hossini, L. F. Fecker, C. E. Orfanos, and B. Tebbe (2002). The role of nuclear factor-kappa B and melanogenesis in tumor necrosis factor...chemical warfare agents. A further goal in conjunction with consortium members is to design rat and mouse microarrays and QPCR reagents , which will be

  1. Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium

    NARCIS (Netherlands)

    Stevens, Wendy B. C.; Mendeville, Matias; Redd, Robert; Clear, Andrew J.; Bladergroen, Reno; Calaminici, Maria; Rosenwald, Andreas; Hoster, Eva; Hiddemann, Wolfgang; Gaulard, Philippe; Xerri, Luc; Salles, Gilles; Klapper, Wolfram; Phreundschuh, Michael; Jack, Andrew; Gascoyne, Randy D.; Natkunam, Yasodha; Advani, Ranjana; Kimby, Eva; Sander, Birgitta; Sehn, Laurie; Hagenbeek, Anton; Raemaekers, John; Gribben, John; Kersten, Marie Jose'; Ylstra, Bauke; Weller, Edie; de Jong, Daphne

    2017-01-01

    In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a

  2. Tri-District Arts Consortium Summer Program.

    Science.gov (United States)

    Kirby, Charlotte O.

    1990-01-01

    The Tri-District Arts Consortium in South Carolina was formed to serve artistically gifted students in grades six-nine. The consortium developed a summer program offering music, dance, theatre, and visual arts instruction through a curriculum of intense training, performing, and hands-on experiences with faculty members and guest artists. (JDD)

  3. Global Consortium on Security Transformation | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The proposed Global Consortium on Security Transformation emerged from discussions between members of an informal network of scholars and practitioners in the fields of security reform and governance in different regions of the South. This grant will establish the Consortium as a joint venture between the Institute of ...

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

    Directory of Open Access Journals (Sweden)

    Anthoney D

    2012-11-01

    Full Text Available Abstract Background 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. Methods 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. Results 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients and 10 mg/m2 (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 Cmax from 1–10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. Conclusions 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. Trial registration EU-CTR2006-001345-33

  5. B cell activating factor of the tumor necrosis factor family (BAFF behaves as an acute phase reactant in acute pancreatitis.

    Directory of Open Access Journals (Sweden)

    Georg Pongratz

    Full Text Available To determine if B cell activating factor of the tumor necrosis factor family (BAFF acts as an acute phase reactant and predicts severity of acute pancreatitis.40 patients with acute pancreatitis were included in this single center cohort pilot study. Whole blood and serum was analyzed on day of admission and nine consecutive days for BAFF, c-reactive protein (CRP, interleukin-6 (IL-6, procalcitonin (PCT, and leucocyte numbers. Different severity Scores (Ranson, APACHE II, SAPS II, SAPS III and the clinical course of the patient (treatment, duration of stay, duration ICU were recorded.Serum BAFF correlates with CRP, an established marker of severity in acute pancreatitis at day of admission with a timecourse profil similar to IL-6 over the first nine days. Serum BAFF increases with Ranson score (Kruskal-Wallis: Chi2 = 10.8; p = 0.03 similar to CRP (Kruskal-Wallis: Chi2 = 9.4; p = 0.05 . Serum BAFF, IL-6, and CRP levels are elevated in patients that need intensive care for more than seven days and in patients with complicated necrotizing pancreatitis. Discriminant analysis and receiver operator characteristics show that CRP (wilks-lambda = 0.549; ROC: AUC 0.948 and BAFF (wilks-lambda = 0.907; ROC: AUC 0.843 serum levels at day of admission best predict severe necrotizing pancreatitis or death, outperforming IL-6, PCT, and number of leucocytes.This study establishes for the first time BAFF as an acute phase reactant with predictive value for the course of acute pancreatitis. BAFF outperforms established markers in acute pancreatitis, like IL-6 and PCT underscoring the important role of BAFF in the acute inflammatory response.

  6. B cell activating factor of the tumor necrosis factor family (BAFF) behaves as an acute phase reactant in acute pancreatitis.

    Science.gov (United States)

    Pongratz, Georg; Hochrinner, Hannah; Straub, Rainer H; Lang, Stefanie; Brünnler, Tanja

    2013-01-01

    To determine if B cell activating factor of the tumor necrosis factor family (BAFF) acts as an acute phase reactant and predicts severity of acute pancreatitis. 40 patients with acute pancreatitis were included in this single center cohort pilot study. Whole blood and serum was analyzed on day of admission and nine consecutive days for BAFF, c-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and leucocyte numbers. Different severity Scores (Ranson, APACHE II, SAPS II, SAPS III) and the clinical course of the patient (treatment, duration of stay, duration ICU) were recorded. Serum BAFF correlates with CRP, an established marker of severity in acute pancreatitis at day of admission with a timecourse profil similar to IL-6 over the first nine days. Serum BAFF increases with Ranson score (Kruskal-Wallis: Chi2 = 10.8; p = 0.03) similar to CRP (Kruskal-Wallis: Chi2 = 9.4; p = 0.05 ). Serum BAFF, IL-6, and CRP levels are elevated in patients that need intensive care for more than seven days and in patients with complicated necrotizing pancreatitis. Discriminant analysis and receiver operator characteristics show that CRP (wilks-lambda = 0.549; ROC: AUC 0.948) and BAFF (wilks-lambda = 0.907; ROC: AUC 0.843) serum levels at day of admission best predict severe necrotizing pancreatitis or death, outperforming IL-6, PCT, and number of leucocytes. This study establishes for the first time BAFF as an acute phase reactant with predictive value for the course of acute pancreatitis. BAFF outperforms established markers in acute pancreatitis, like IL-6 and PCT underscoring the important role of BAFF in the acute inflammatory response.

  7. Circulating Tumor Cell Enumeration in a Phase II Trial of a Four-Drug Regimen in Advanced Colorectal Cancer.

    Science.gov (United States)

    Krebs, Matthew G; Renehan, Andrew G; Backen, Alison; Gollins, Simon; Chau, Ian; Hasan, Jurjees; Valle, Juan W; Morris, Karen; Beech, Janette; Ashcroft, Linda; Saunders, Mark P; Dive, Caroline

    2015-06-01

    Multidrug regimens are active against advanced colorectal cancer (ACRC). However, the increased toxicity requires the use of biomarkers to select the patients who will derive the most benefit. We assessed circulating tumor cells (CTCs) as a prognostic biomarker in patients treated with a 4-drug regimen. A single-arm phase II trial (Erbitux Study of CPT11, Oxaliplatin, UFToral Targeted-therapy [eSCOUT]) was undertaken in patients with previously untreated KRAS wild-type ACRC using a regimen of irinotecan, oxaliplatin, and tegafur-uracil with leucovorin and cetuximab. Baseline CTCs were enumerated using CellSearch. The endpoints were an objective response rate (ORR) and overall survival (OS). We modeled our results and compared them with those modeled for the capecitabine, oxaliplatin, bevacizumab +/- cetuximab (CAIRO2) trial, stratifying patients a priori into low (< 3) and high (≥ 3) CTC groups. For 48 eligible patients, the best ORR from the 4-drug regimen was 71%, with a disease control rate of 98%. The median OS for patients with a high and low CTC count was 18.7 and 22.3 months (log-rank test, P = .038), respectively. In our modeled data, for patients with a low CTC count, no differences were found between the median OS in the eSCOUT trial and that in the CAIRO2 trial (22.2 vs. 22.0 months). However, for the high CTC group, a clinically relevant improvement was seen in median OS (eSCOUT vs. CAIRO2, 18.7 vs. 13.7 months; P = .001). These data are hypothesis generating-for patients with ACRC, stratification by CTC count can identify those who might benefit the most from an intensive 4-drug regimen, avoiding high-toxicity regimens in low CTC groups. This hypothesis warrants validation in a phase III biomarker-driven trial. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. The use of phase sequence image sets to reconstruct the total volume occupied by a mobile lung tumor

    International Nuclear Information System (INIS)

    Gagne, Isabelle M.; Robinson, Don M.; Halperin, Ross; Roa, Wilson

    2005-01-01

    The use of phase sequence image (PSI) sets to reveal the total volume occupied by a mobile target is presented. Isocontrast composite clinical target volumes (CCTVs) may be constructed from PSI sets in order to reveal the total volume occupied by a mobile target during the course of its travel. The ability of the CCTV technique to properly account for target motion is demonstrated by comparison to contours of the true total volume occupied (TVO) for a number of experimental phantom geometries. Finally, using real patient data, the clinical utility of the CCTV technique to properly account for internal tumor motion while minimizing the volume of healthy lung tissue irradiated is assessed by comparison to the standard approach of applying safety margins. Results of the phantom study reveal that CCTV cross sections constructed at the 20% isocontrast level yield good agreement with the total cross sections (TXO) of mobile targets. These CCTVs conform well to the TVOs of the moving targets examined whereby the addition of small uniform margins ensures complete circumscription of the TVO with the inclusion of minimal amounts of surrounding external volumes. The CCTV technique is seen to be clearly superior to the common practice of the addition of safety margins to individual CTV contours in order to account for internal target motion. Margins required with the CCTV technique are eight to ten times smaller than those required with individual CTVs

  9. First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors

    Directory of Open Access Journals (Sweden)

    Barry H. Smith

    2016-01-01

    Full Text Available Purpose Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival, which is the secondary objective. Methods Thirty-one patients underwent up to four intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg via laparoscopy in this single-arm trial (FDA BB-IND 10091; NCT 00283075. Serial physical examinations, laboratory testing, and PET-CT imaging were performed before and three months after each implant. Results RMBs were well tolerated at both dose levels (mean 660.9 per implant. AEs were (Grade 1/2 with no treatment-related SAEs. Conclusion The data support the safety of RMB therapy in advanced-malignancy patients, and the preliminary evidence for their potential efficacy is encouraging. A Phase 2 efficacy trial is ongoing.

  10. Evaluation of some tumor markers, acute phase proteins, sialic acid and lipid bound sialic acid before and after chemotherapy in patients with stomach cancer

    OpenAIRE

    Cebi, Aysegul; Mert, Handan; Mert, Nihat

    2016-01-01

    Objective:  It was aimed to compare the some tumor markers, acute phase proteins, sialic acid and lipid bound sialic acid levels in patients with stomach cancer before and after chemotherapy to the healthy controls.Material and Methods:  Forty-eight patients with stomach adenocarcinoma and 20 healthy controls, totally 68 subjects were used. Blood samples were taken from all patients before and after chemotherapy and controls to analyse the levels of tumor markers (CA 125, CA 15-3, CA 19-9, CE...

  11. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors

    Directory of Open Access Journals (Sweden)

    Spugnini Enrico P

    2011-12-01

    Full Text Available Abstract Background The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. Mechanisms underlying this resistance are far from being entirely known. A very efficient mechanism of tumor resistance to drugs is related to the modification of tumour microenvironment through changes in the extracellular and intracellular pH. The acidification of tumor microenvironment depends on proton pumps that actively pump protons outside the cells, mostly to avoid intracellular acidification. In fact, we have shown in pre-clinical settings as pre-treatment with proton-pumps inhibitors (PPI increase tumor cell and tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer proven refractory to conventional chemotherapy have been recruited in a compassionate study. Methods Thirty-four companion animals (27 dogs and 7 cats were treated adding to their chemotherapy protocols the pump inhibitor lansoprazole at high dose, as suggested by pre-clinical experiments. Their responses have been compared to those of seventeen pets (10 dogs and 7 cats whose owners did not pursue any other therapy than continuing the currently ongoing chemotherapy protocols. Results The drug was overall well tolerated, with only four dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response twenty-three pets out of 34 had partial or complete responses (67.6% the remaining patients experienced no response or progressive disease however most owners reported improved quality of life in most of the non responders. On the other hand, only three animals in the control group (17% experienced short lived partial responses (1-3 months duration while all the others died of progressive disease within two months. Conclusions high dose proton pump inhibitors have been shown to induce reversal of tumor chemoresistance as well as improvement of

  12. Gene Ontology Consortium: going forward.

    Science.gov (United States)

    2015-01-01

    The Gene Ontology (GO; http://www.geneontology.org) is a community-based bioinformatics resource that supplies information about gene product function using ontologies to represent biological knowledge. Here we describe improvements and expansions to several branches of the ontology, as well as updates that have allowed us to more efficiently disseminate the GO and capture feedback from the research community. The Gene Ontology Consortium (GOC) has expanded areas of the ontology such as cilia-related terms, cell-cycle terms and multicellular organism processes. We have also implemented new tools for generating ontology terms based on a set of logical rules making use of templates, and we have made efforts to increase our use of logical definitions. The GOC has a new and improved web site summarizing new developments and documentation, serving as a portal to GO data. Users can perform GO enrichment analysis, and search the GO for terms, annotations to gene products, and associated metadata across multiple species using the all-new AmiGO 2 browser. We encourage and welcome the input of the research community in all biological areas in our continued effort to improve the Gene Ontology. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Phase I study of intraoperative radiotherapy with photon radiosurgery system in children with recurrent brain tumors: Preliminary report of first dose level (10 Gy)

    International Nuclear Information System (INIS)

    Kalapurakal, John A.; Goldman, Stewart; Stellpflug, Wendy; Curran, John; Sathiaseelan, Vythialingam; Marymont, Maryanne H.; Tomita, Tadanori

    2006-01-01

    Purpose: To describe the preliminary results after intraoperative radiotherapy (IORT) with the photon radiosurgery system in children with recurrent brain tumors treated at the first dose level (10 Gy) of a Phase I protocol. Methods and Materials: A Phase I IORT dose escalation protocol was initiated at Children's Memorial Hospital to determine the maximal tolerated IORT dose in children with recurrent brain tumors. Results: Fourteen children have received IORT thus far. Eight had been previously irradiated. Thirteen children had ependymoma. The median follow-up was 16 months. Three patients (21%) developed radiation necrosis on follow-up MRI scans 6 to 12 months after IORT. They had not been previously irradiated and had received 10 Gy to a depth of 5 mm. One required surgery and the other two had resolution of their lesions without treatment. All 3 patients were asymptomatic at the last follow-up. No other late toxicity was observed at the last follow-up visit. Eight patients (57%) had tumor control within the surgical bed after IORT. Conclusion: Our findings have demonstrated the safety and feasibility of IORT to a dose of 10 Gy to 2 mm in children with previously irradiated brain tumors. IORT to a dose of 10 Gy at 5 mm was associated with a greater complication rate

  14. NASA space radiation transport code development consortium

    International Nuclear Information System (INIS)

    Townsend, L. W.

    2005-01-01

    Recently, NASA established a consortium involving the Univ. of Tennessee (lead institution), the Univ. of Houston, Roanoke College and various government and national laboratories, to accelerate the development of a standard set of radiation transport computer codes for NASA human exploration applications. This effort involves further improvements of the Monte Carlo codes HETC and FLUKA and the deterministic code HZETRN, including developing nuclear reaction databases necessary to extend the Monte Carlo codes to carry out heavy ion transport, and extending HZETRN to three dimensions. The improved codes will be validated by comparing predictions with measured laboratory transport data, provided by an experimental measurements consortium, and measurements in the upper atmosphere on the balloon-borne Deep Space Test Bed (DSTB). In this paper, we present an overview of the consortium members and the current status and future plans of consortium efforts to meet the research goals and objectives of this extensive undertaking. (authors)

  15. International Radical Cystectomy Consortium: A way forward

    Directory of Open Access Journals (Sweden)

    Syed Johar Raza

    2014-01-01

    Full Text Available Robot-assisted radical cystectomy (RARC is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC. Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.

  16. The LBNL/JSU/AGMUS Science Consortium

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-04-01

    This report discusses the 11 year of accomplishments of the science consortium of minority graduates from Jackson State University and Ana G. Mendez University at the Lawrence Berkeley National Laboratory.

  17. Oil Production by a Consortium of Oleaginous Microorganisms grown on primary effluent wastewater

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Jacqueline; Hetrick, Mary; French, Todd; Hernandez, Rafael; Donaldson, Janet; Mondala, Andro; Holmes, William

    2011-01-01

    Municipal wastewater could be a potential growth medium that has not been considered for cultivating oleaginous microorganisms. This study is designed to determine if a consortium of oleaginous microorganism can successfully compete for carbon and other nutrients with the indigenous microorganisms contained in primary effluent wastewater. RESULTS: The oleaginous consortium inoculated with indigenous microorganisms reached stationary phase within 24 h, reaching a maximum cell concentration of 0.58 g L -1. Water quality post-oleaginous consortium growth reached a maximum chemical oxygen demand (COD) reduction of approximately 81%, supporting the consumption of the glucose within 8 h. The oleaginous consortium increased the amount of oil produced per gram by 13% compared with indigenous microorganisms in raw wastewater. Quantitative polymerase chain reaction (qPCR) results show a substantial population increase in bacteria within the first 24 h when the consortium is inoculated into raw wastewater. This result, along with the fatty acid methyl esters (FAMEs) results, suggests that conditions tested were not sufficient for the oleaginous consortium to compete with the indigenous microorganisms.

  18. Apoptosis in the transplanted canine transmissible venereal tumor during growth and regression phases Apoptose no tumor venéreo transmissível canino durante as fases de crescimento e regressão

    Directory of Open Access Journals (Sweden)

    F.G.A. Santos

    2008-06-01

    Full Text Available Twelve male, mongrel, adult dogs were subcutaneously transplanted with cells originated from two canine transmissible venereal tumors (TVT. The aim was to demonstrate and to quantify the occurrence of apoptosis in the TVT regression. After six months of transplantation, a tumor sample was obtained from each dog, being six dogs with TVT in the growing phase and six in the regression phase as verified by daily measurements. Samples were processed for histological and ultrastructural purposes as well as for DNA extraction. Sections of 4µm were stained by HE, Shorr, methyl green pyronine, Van Gieson, TUNEL reaction and immunostained for P53. The Shorr stained sections went through morphometry that demonstrated an increase of the apoptotic cells per field in the regressive tumors. It was also confirmed by transmission electron microscopy, which showed cells with typical morphology of apoptosis and by the TUNEL reaction that detected in situ the 3'OH nick end labeling mainly in the regressive tumors. The regressive TVTs also showed an intensified immunostaining for P53 besides a more intense genomic DNA fragmentation detected by the agarose gel electrophoresis. In conclusion, apoptosis has an important role in the regression of the experimental TVT in a way that is P53-dependent.Doze cães, adultos, machos e sem raça definida foram transplantados subcutaneamente, na região hipogástrica, com células originadas de dois tumores venéreos transmissíveis caninos (TVT. O objetivo do estudo foi demonstrar e quantificar a ocorrência de apoptose na regressão do TVT. Após seis meses, foi obtido um tumor de cada animal, totalizando seis em crescimento e seis em regressão. Fragmentos dos tumores foram processados para avaliação histológica, ultra-estrutural e também para extração de DNA. Cortes de 4µm foram corados em HE, Shorr, verde de metila pironina e Van Gieson e alguns foram submetidos à reação do TUNEL e à imunoistoquímica para P53

  19. Clinical impact of tumor location on the colon cancer survival and recurrence: analyses of pooled data from three large phase III randomized clinical trials.

    Science.gov (United States)

    Aoyama, Toru; Kashiwabara, Kosuke; Oba, Koji; Honda, Michitaka; Sadahiro, Sotaro; Hamada, Chikuma; Maeda, Hiromichi; Mayanagi, Shuhei; Kanda, Mitsuro; Sakamoto, Junichi; Saji, Shigetoyo; Yoshikawa, Takaki

    2017-11-01

    The aim of the present study was to determine whether or not the overall survival (OS) and disease-free survival (DFS) were affected by the tumor location in patients who underwent curative resection for colon cancer in a pooled analysis of three large phase III studies performed in Japan. In total, 4029 patients were included in the present study. Patients were classified as having right-side colon cancer (RC) if the primary tumor was located in the cecum, ascending colon, hepatic flexure or transverse colon, and left-side colon cancer (LCC) if the tumor site was within the splenic flexure, descending colon, sigmoid colon or recto sigmoid junction. The risk factors for the OS and DFS were analyzed. In the present study, 1449 patients were RC, and 2580 were LCC. The OS rates at 3 and 5 years after surgery were 87.6% and 81.6% in the RC group and 91.5% and 84.5% in the LCC group, respectively. Uni- and multivariate analyses showed that RRC increased the risk of death by 19.7% (adjusted hazard ratio = 1.197; 95% confidence interval, 1.020-1.408; P = 0.0272). In contrast, the DFS was similar between the two locations. The present study confirmed that the tumor location was a risk factor for the OS in patients who underwent curative treatment for colon cancer. Tumor location may, therefore, need to be considered a stratification factor in future phase III trials of colon cancer. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  20. Diagnostic Accuracy of Split-Bolus Single-Phase Contrast-Enhanced Cone-Beam CT for the Detection of Liver Tumors before Transarterial Chemoembolization.

    Science.gov (United States)

    Jonczyk, Martin; Chapiro, Julius; Collettini, Federico; Geisel, Dominik; Schnapauff, Dirk; Streitparth, Florian; Schmidt, Thomas; Hamm, Bernd; Gebauer, Bernhard; Wieners, Gero

    2017-10-01

    To evaluate detectability of hepatocellular carcinoma (HCC) using split-bolus cone-beam CT in intraindividual comparison between cone-beam CT and contrast-enhanced MR imaging. In a retrospective, single-center study, 28 patients with 85 HCC tumors were treated with transarterial chemoembolization between May 2015 and June 2016. All patients underwent arterial and hepatobiliary phase (HBP) MR imaging within 1 month before transarterial chemoembolization. Cone-beam CT images were acquired using a split-bolus contrast injection with 2 contrast injections and 1 cone-beam CT acquisition. Statistical analyses included Friedman 2-way analysis, Kendall coefficient of concordance, and Wilcoxon test. Tumor detectability was scored using a 5-point system (1 = best; 5 = worst) by 2 independent readers resulting in 170 evaluated tumors. Quantitative analysis included signal-to-noise and contrast-to-noise ratio and contrast measurements. P values cone-beam CT (2.91/2.73) and HBP MR imaging (2.93/2.21) compared with arterial MR imaging (3.72/3.05; P cone-beam CT and HBP MR imaging in terms of detectability (P = .154) and sensitivity for hypervascularized tumors. More tumors were identified on cone-beam CT (n = 121/170) than on arterial MR imaging (n = 94/170). Average contrast-to-noise ratio values of arterial and HBP MR imaging were higher than for cone-beam CT (7.79, 8.58, 4.43), whereas contrast values were higher for cone-beam CT than for MR imaging (0.11, 0.13, 0.97). Split-bolus cone-beam CT showed excellent detectability of HCC. Sensitivity is comparable to HBP MR imaging and better than arterial phase MR imaging. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  1. Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat (EZH2 Histone Methyl Transferase [HMT] Inhibitor) as a Single Agent in Subjects With Adv. Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With DLBCL

    Science.gov (United States)

    2018-04-12

    B-cell Lymphomas (Phase 1); Advanced Solid Tumors (Phase 1); Diffuse Large B-cell Lymphoma (Phase 2); Follicular Lymphoma (Phase 2); Transformed Follicular Lymphoma; Primary Mediastinal Large B-Cell Lymphoma

  2. Randomized phase II trial of autologous dendritic cell vaccines versus autologous tumor cell vaccines in metastatic melanoma: 5-year follow up and additional analyses.

    Science.gov (United States)

    Dillman, Robert O; Cornforth, Andrew N; Nistor, Gabriel I; McClay, Edward F; Amatruda, Thomas T; Depriest, Carol

    2018-03-06

    Despite improved survival following checkpoint inhibitors, there is still a potential role for anti-cancer therapeutic vaccines. Because of biological heterogeneity and neoantigens resulting from each patient's mutanome, autologous tumor may be the best source of tumor-associated antigens (TAA) for vaccines. Ex vivo loading of autologous dendritic cells with TAA may be associated with superior clinical outcome compared to injecting irradiated autologous tumor cells. We conducted a randomized phase II trial to compare autologous tumor cell vaccines (TCV) and autologous dendritic cell vaccines (DCV) loaded with autologous TAA. Short-term autologous tumor cell lines were established from metastatic tumor. Vaccines were admixed with 500 micrograms of GM-CSF and injected weekly for 3 weeks, then at weeks 8, 12,16, 20, and 24. The primary endpoint was overall survival. Secondary objectives were identification of adverse events, and results of delayed type hypersensitivity (DTH) reactions to intradermal tumor cell injections. Forty-two patients were randomized. All were followed from randomization until death or for five years; none were lost to follow-up. DCV was associated with longer survival: median 43.4 versus 20.5 months (95% CI, 18.6 to > 60 versus 9.3 to 32.3 months) and a 70% reduction in the risk of death (hazard ratio = 0.304, p = 0.0053, 95% CI, 0.131 to 0.702). Tumor DTH reactions were neither prognostic nor predictive. The most common treatment-related adverse events were mild to moderate local injection site reactions and flu-like symptoms; but grade 2 treatment-related adverse events were more frequent with TCV. Serum marker analyses at week-0 and week-4 showed that serum markers were similar at baseline in each arm, but differed after vaccination. This is the only human clinical trial comparing DCV and TCV as platforms for autologous TAA presentation. DCV was associated with minimal toxicity and long-term survival in patients with metastatic

  3. Combining a focused air-puff system with phase-sensitive optical coherence tomography for the detection of soft-tissue tumors based on elasticity measurement

    Science.gov (United States)

    Wang, Shang; Li, Jiasong; Vantipalli, Srilatha; Manapuram, Ravi Kiran; Ingram, Davis R.; Twa, Michael D.; Lazar, Alexander J.; Lev, Dina C.; Pollock, Raphael E.; Larin, Kirill V.

    2013-03-01

    We combine a focused air-puff system with phase-sensitive optical coherence tomography (PhS-OCT) to measure the elasticity of soft tissues. Surface waves (SWs) on soft tissues are induced by a low-pressure, short-duration air stream from an air-puff system and measured using a high-sensitivity PhS-OCT imaging system. Young's modulus of soft tissues can be quantified based on the group velocity of SWs. To precisely control the excitation pressure, the air-puff system was characterized with a high-resolution analog pressure transducer. We studied the feasibility of this method for the non-contact detection of soft-tissue tumors. Ex vivo human fat and myxoma were used for these pilot experiments. Results demonstrate that this optical non-contact technique can be used to differentiate soft-tissue tumors from normal tissues based on measurements of their elasticity.

  4. A phase I/II study on stereotactic body radiotherapy with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm for lung tumors.

    Science.gov (United States)

    Iwata, Hiromitsu; Ishikura, Satoshi; Murai, Taro; Iwabuchi, Michio; Inoue, Mitsuhiro; Tatewaki, Koshi; Ohta, Seiji; Yokota, Naoki; Shibamoto, Yuta

    2017-08-01

    In this phase I/II study, we assessed the safety and initial efficacy of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm. Study subjects had histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the incidence of Grade ≥3 radiation pneumonitis (RP) within 180 days of the start of SBRT. The secondary endpoint was local control and overall survival rates. Five patients were initially enrolled at level 1 [50 Gy/4 fractions (Fr)]; during the observation period, level 0 (45 Gy/4 Fr) was opened. The dose was escalated to the next level when grade ≥3 RP was observed in 0 out of 5 or 1 out of 10 patients. Virtual quality assurance planning was performed for 60 Gy/4 Fr; however, dose constraints for the organs at risk did not appear to be within acceptable ranges. Therefore, level 2 (55 Gy/4 Fr) was regarded as the upper limit. After the recommended dose (RD) was established, 15 additional patients were enrolled at the RD. The prescribed dose was normalized at the 95% volume border of the planning target volume based on the Monte Carlo algorithm. Between September 2011 and September 2015, 40 patients (primary 30; metastasis 10) were enrolled. Five patients were enrolled at level 0, 15 at level 1, and 20 at level 2. Only one grade 3 RP was observed at level 1. Two-year local control and overall survival rates were 98 and 81%, respectively. The RD was 55 Gy/4 Fr. SBRT with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm was tolerated well and appeared to be effective for solitary lung tumors.

  5. Tumor interstitial fluid

    DEFF Research Database (Denmark)

    Gromov, Pavel; Gromova, Irina; Olsen, Charlotta J.

    2013-01-01

    Tumor interstitial fluid (TIF) is a proximal fluid that, in addition to the set of blood soluble phase-borne proteins, holds a subset of aberrantly externalized components, mainly proteins, released by tumor cells and tumor microenvironment through various mechanisms, which include classical secr...

  6. A Phase I study of the Heat Shock Protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced solid tumors

    Science.gov (United States)

    Pacey, Simon; Wilson, Richard H.; Walton, Mike; Eatock, Martin M.; Hardcastle, Anthea; Zetterlund, Anna; Arkenau, Hendrik-Tobias; Moreno-Farre, Javier; Banerji, Udai; Roels, Belle; Peachey, Heidi; Aherne, Wynne; de Bono, Johan S.; Raynaud, Florence; Workman, Paul; Judson, Ian

    2010-01-01

    Purpose A Phase I study to define toxicity and recommend a Phase II dose of the HSP90 inhibitor alvespimycin (17-DMAG; 17-dimethylaminoethylamino-17-demethoxygeldanamycin). Secondary endpoints included evaluation of pharmacokinetic profile, tumor response and definition of a biologically effective dose (BED). Patients and Methods Patients with advanced solid cancers were treated with weekly, intravenous (IV) 17-DMAG. An accelerated titration dose escalation design was used. The maximum tolerated dose (MTD) was the highest dose at which ≤ 1/6 patients experienced dose limiting toxicity (DLT). Dose de-escalation from the MTD was planned with mandatory, sequential tumor biopsies to determine a BED. Pharmacokinetic and pharmacodynamic assays were validated prior to patient accrual. Results Twenty five patients received 17-DMAG (range 2.5 to 106 mg/m2). At 106mg/m2 of 17-DMAG 2/4 patients experienced DLT, including one treatment related death. No DLT occurred at 80mg/m2. Common adverse events were gastrointestinal, liver function changes and ocular. AUC and Cmax increased proportionally with 17-DMAG doses ≤ 80mg/m2. In peripheral blood mononuclear cells significant (p disease (chondrosarcoma, CRPC and renal cancer for 28, 59 and 76 weeks respectively). Conclusion The recommended Phase II dose of 17-DMAG is 80mg/m2 weekly, IV. PMID:21278242

  7. A Comparison of Amplitude-Based and Phase-Based Positron Emission Tomography Gating Algorithms for Segmentation of Internal Target Volumes of Tumors Subject to Respiratory Motion

    Energy Technology Data Exchange (ETDEWEB)

    Jani, Shyam S., E-mail: sjani@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California (United States); Robinson, Clifford G. [Department of Radiation Oncology, Siteman Cancer Center, Washington University in St Louis, St Louis, Missouri (United States); Dahlbom, Magnus [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California (United States); White, Benjamin M.; Thomas, David H.; Gaudio, Sergio; Low, Daniel A.; Lamb, James M. [Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, California (United States)

    2013-11-01

    Purpose: To quantitatively compare the accuracy of tumor volume segmentation in amplitude-based and phase-based respiratory gating algorithms in respiratory-correlated positron emission tomography (PET). Methods and Materials: List-mode fluorodeoxyglucose-PET data was acquired for 10 patients with a total of 12 fluorodeoxyglucose-avid tumors and 9 lymph nodes. Additionally, a phantom experiment was performed in which 4 plastic butyrate spheres with inner diameters ranging from 1 to 4 cm were imaged as they underwent 1-dimensional motion based on 2 measured patient breathing trajectories. PET list-mode data were gated into 8 bins using 2 amplitude-based (equal amplitude bins [A1] and equal counts per bin [A2]) and 2 temporal phase-based gating algorithms. Gated images were segmented using a commercially available gradient-based technique and a fixed 40% threshold of maximum uptake. Internal target volumes (ITVs) were generated by taking the union of all 8 contours per gated image. Segmented phantom ITVs were compared with their respective ground-truth ITVs, defined as the volume subtended by the tumor model positions covering 99% of breathing amplitude. Superior-inferior distances between sphere centroids in the end-inhale and end-exhale phases were also calculated. Results: Tumor ITVs from amplitude-based methods were significantly larger than those from temporal-based techniques (P=.002). For lymph nodes, A2 resulted in ITVs that were significantly larger than either of the temporal-based techniques (P<.0323). A1 produced the largest and most accurate ITVs for spheres with diameters of ≥2 cm (P=.002). No significant difference was shown between algorithms in the 1-cm sphere data set. For phantom spheres, amplitude-based methods recovered an average of 9.5% more motion displacement than temporal-based methods under regular breathing conditions and an average of 45.7% more in the presence of baseline drift (P<.001). Conclusions: Target volumes in images generated

  8. A Comparison of Amplitude-Based and Phase-Based Positron Emission Tomography Gating Algorithms for Segmentation of Internal Target Volumes of Tumors Subject to Respiratory Motion

    International Nuclear Information System (INIS)

    Jani, Shyam S.; Robinson, Clifford G.; Dahlbom, Magnus; White, Benjamin M.; Thomas, David H.; Gaudio, Sergio; Low, Daniel A.; Lamb, James M.

    2013-01-01

    Purpose: To quantitatively compare the accuracy of tumor volume segmentation in amplitude-based and phase-based respiratory gating algorithms in respiratory-correlated positron emission tomography (PET). Methods and Materials: List-mode fluorodeoxyglucose-PET data was acquired for 10 patients with a total of 12 fluorodeoxyglucose-avid tumors and 9 lymph nodes. Additionally, a phantom experiment was performed in which 4 plastic butyrate spheres with inner diameters ranging from 1 to 4 cm were imaged as they underwent 1-dimensional motion based on 2 measured patient breathing trajectories. PET list-mode data were gated into 8 bins using 2 amplitude-based (equal amplitude bins [A1] and equal counts per bin [A2]) and 2 temporal phase-based gating algorithms. Gated images were segmented using a commercially available gradient-based technique and a fixed 40% threshold of maximum uptake. Internal target volumes (ITVs) were generated by taking the union of all 8 contours per gated image. Segmented phantom ITVs were compared with their respective ground-truth ITVs, defined as the volume subtended by the tumor model positions covering 99% of breathing amplitude. Superior-inferior distances between sphere centroids in the end-inhale and end-exhale phases were also calculated. Results: Tumor ITVs from amplitude-based methods were significantly larger than those from temporal-based techniques (P=.002). For lymph nodes, A2 resulted in ITVs that were significantly larger than either of the temporal-based techniques (P<.0323). A1 produced the largest and most accurate ITVs for spheres with diameters of ≥2 cm (P=.002). No significant difference was shown between algorithms in the 1-cm sphere data set. For phantom spheres, amplitude-based methods recovered an average of 9.5% more motion displacement than temporal-based methods under regular breathing conditions and an average of 45.7% more in the presence of baseline drift (P<.001). Conclusions: Target volumes in images generated

  9. A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone.

    Science.gov (United States)

    Resta, Lee P; Pili, Roberto; Eisenberger, Mario A; Spitz, Avery; King, Serina; Porter, Jennifer; Franke, Amy; Boinpally, Ramesh; Carducci, Michael A; Sweeney, Christopher J

    2011-02-01

    To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors. This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m(2) given on Day 1 of each 21-day cycle. OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response. The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued.

  10. A Staff Education Consortium: One Model for Collaboration.

    Science.gov (United States)

    Stetler, Cheryl Beth; And Others

    1983-01-01

    Discusses the development, organization, activities, problems, and future of a staff education consortium of five medical center hospitals in Boston. The purposes of the consortium are mutual sharing, reduction in duplication, and cost containment of educational programing. (JOW)

  11. 76 FR 20690 - International Consortium of Orthopedic Registries; Public Workshop

    Science.gov (United States)

    2011-04-13

    ... HUMAN SERVICES Food and Drug Administration International Consortium of Orthopedic Registries; Public... Administration (FDA) is announcing a public workshop entitled ``International Consortium of Orthopedic Registries... orthopedic registries that have orthopedic implant information and create a research network to advance the...

  12. 24 CFR 943.118 - What is a consortium?

    Science.gov (United States)

    2010-04-01

    ... DEVELOPMENT PUBLIC HOUSING AGENCY CONSORTIA AND JOINT VENTURES Consortia § 943.118 What is a consortium? A consortium consists of two or more PHAs that join together to perform planning, reporting, and other...

  13. Midwest Transportation Consortium : 2003-2004 annual report.

    Science.gov (United States)

    2004-01-01

    Introduction: The Midwest Transportation Consortium (MTC) recently completed its fifth year : of operation. In doing so, the consortium has established itself as an effective : network that promotes the education of future transportation professional...

  14. The Consortium Method of Educational Change.

    Science.gov (United States)

    Maynes, Bill; McIntosh, Gordon

    1979-01-01

    In offering an alternative approach to organizing major curriculum changes, this paper presents a case study and analysis of a consortium project in which the need for change, the change process, and the curriculum writing all took place at the local level. (Author/IRT)

  15. Primary Immune Deficiency Treatment Consortium (PIDTC) report

    NARCIS (Netherlands)

    L.M. Griffith (Linda); M. Cowan (Morton); L.D. Notarangelo (Luigi Daniele); R. Kohn (Robert); J. Puck (Jennifer); S.-Y. Pai (Sung-Yun); B. Ballard (Barbara); S.C. Bauer (Sarah); J. Bleesing (Jack); M. Boyle (Marcia); R.W. Brower (Ronald); R.H. Buckley (Rebecca); M. van der Burg (Mirjam); L.M. Burroughs (Lauri); F. Candotti (Fabio); A. Cant (Andrew); T. Chatila (Talal); C. Cunningham-Rundles (Charlotte); M.C. Dinauer (Mary); J. Dvorak (Jennie); A. Filipovich (Alexandra); L.A. Fleisher (Lee); H.B. Gaspar (Bobby); T. Gungor (Tayfun); E. Haddad (Elie); E. Hovermale (Emily); F. Huang (Faith); A. Hurley (Alan); M. Hurley (Mary); S.K. Iyengar (Sudha); E.M. Kang (Elizabeth); B.R. Logan (Brent); J.R. Long-Boyle (Janel); H. Malech (Harry); S.A. McGhee (Sean); S. Modell (Sieglinde); S. Modell (Sieglinde); H.D. Ochs (Hans); R.J. O'Reilly (Richard); R. Parkman (Robertson); D. Rawlings (D.); J.M. Routes (John); P. Shearer (P.); T.N. Small (Trudy); H. Smith (H.); K.E. Sullivan (Kathleen); P. Szabolcs (Paul); A.J. Thrasher (Adrian); D. Torgerson; P. Veys (Paul); K. Weinberg (Kenneth); J.C. Zuniga-Pflucker (Juan Carlos)

    2014-01-01

    textabstractThe Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency

  16. A JASTRO study group report. A randomized phase III trial of hyperthermia in combination with radiotherapy for superficial tumors

    International Nuclear Information System (INIS)

    Hiraoka, Masahiro; Nishimura, Yasumasa; Mitsumori, Michihide

    1998-01-01

    Result of study about local effect of hyperthermia in combination with radiotherapy for superficial tumors was reported. The irradiation was more than 90% isodose for lesion, and total dose was 60 Gy in cases with anamnesis and 40-50 Gy and without anamnesis at a rate of five times a week and 2 Gy at one time. Hyperthermia was carried out four times; once a week, at 42.5 degrees on tumor side edge, and for 40 minutes. Total 53 cases (neck lymph node metastasis 30 cases, relapse breast cancer 11, advanced breast cancer 1, other superficial tumor 11) were divided into 2 groups. Radiotherapy without hyperthermia (group R) was 27 cases, radiotherapy with hyperthermia (group H) was 26 cases. CR and CR+PR within 2 months after treatment were as follows: Group R: 50%, 85%, Group H: 64%, 100%. The CR+PR was superior in group H (p=0.0497). The CR at maximum effect after treatment was 65% of group R and 86% of group H (p=0.17). The local control rate after CR was not different in both groups. (K.H.)

  17. El xeroderma pigmentoso en su fase de proliferación cutánea tumoral The xeroderma pigmentosum in its phase of tumoral cutaneous proliferation

    Directory of Open Access Journals (Sweden)

    Ernesto Melardo Taño Espinosa

    2012-03-01

    evolution of a girl aged 10 presenting with xeroderma pigmentosum with a very advanced phase of the disease and a significant growth of cutaneous carcinomas. The objective of this paper is to present a uncommon clinical case not much frequent of xeroderma pigmentosum and at the same time, to make a bibliographic review to direct towards the early diagnosis and the appropriate treatment in this type of cases.

  18. Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.

    Science.gov (United States)

    Miwa, Shinji; Nishida, Hideji; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Hayashi, Katsuhiro; Yamamoto, Norio; Mizukoshi, Eishiro; Nakamoto, Yasunari; Kaneko, Shuichi; Tsuchiya, Hiroyuki

    2017-05-01

    There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas. Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed. In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively. Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society. © 2017 American Cancer Society.

  19. Efficacy and Safety of Bevacizumab in Recurrent Sex Cord-Stromal Ovarian Tumors: Results of a Phase II Trial of the Gynecologic Oncology Group

    Science.gov (United States)

    Brown, Jubilee; Brady, William E.; Schink, Julian; Van Le, Linda; Leitao, Mario; Yamada, S. Diane; de Geest, Koen; Gershenson, David M.

    2014-01-01

    BACKGROUND The Gynecologic Oncology Group conducted this phase II trial to estimate the anti-tumor activity of bevacizumab and to determine the nature and degree of toxicity in patients with recurrent sex cord-stromal tumors of the ovary. METHODS A prospective, multi-institutional cooperative group trial was performed in women with recurrent measurable ovarian stromal tumor. Patients were allowed to have unlimited prior therapy, excluding bevacizumab. Bevacizumab 15 mg/kg was administered intravenously on day one of every 21 day cycle until disease progression or adverse effects prohibited further treatment. The primary endpoint was response rate (RR). Inhibin A and B levels were measured prior to each cycle, and the values were examined in relation to response and progression. RESULTS Thirty-six patients were enrolled, all of whom were eligible and evaluable. Patients received a median of nine cycles of treatment (range, 2-37 cycles). Six patients (16.7%) had partial responses (90% CI: 7.5%, 30.3%), 28 patients (77.8%) had stable disease, and two patients (5.6%) had increasing disease. This met the criterion for declaring the regimen active. The median PFS was 9.3 months. The median OS has not been reached. Two grade 4 toxicities occurred: hypertension and proteinuria; the most common grade 3 toxicities were hypertension (n=5) and pain (n=5). Inhibin A and B values were lower in patients who responded to treatment. CONCLUSIONS Bevacizumab has activity in the treatment of recurrent sex cord-stromal tumors of the ovary; toxicity is acceptable. Further investigation is warranted. PMID:24166194

  20. Phase I and Pharmacokinetic Trial of PTC299 in Pediatric Patients with Refractory or Recurrent Central Nervous System Tumors: a PBTC Study

    Science.gov (United States)

    Packer, Roger J.; Rood, Brian R.; Turner, David C.; Stewart, Clinton F.; Fisher, Michael; Smith, Christopher; Young-Pouissant, Tina; Goldman, Stewart; Lulla, Rishi; Banerjee, Anu; Pollack, Ian; Kun, Larry; Onar-Thomas, Arzu; Wu, Shengjie; Boyett, James M.; Fouladi, Maryam

    2015-01-01

    Background PTC299 is a novel, orally-bioavailable small molecule that selectively inhibits vascular endothelial growth factor receptor protein synthesis at the post-transcriptional level. Based on promising preclinical results, we conducted a pediatric phase I study to estimate the maximum tolerated dose (MTD), describe dose-limiting toxicities (DLT) and characterize the pharmacokinetic profile of PTC299 in children with recurrent CNS tumors. Patients and Methods PTC299 was administered orally twice or three times daily, depending on the regimen. Four regimens were evaluated using the rolling 6 design, starting with 1.2 mg/kg/dose twice daily and escalating to 2 mg/kg/dose three times daily. Pharmacokinetic studies were performed during the first two courses. Results Twenty-seven children (14 male, median age 11.2, range 5.5–21 years) with recurrent brain tumors were treated; 21 were fully evaluable for toxicity assessment. Therapy was well-tolerated, and the only DLT was grade 3 hyponatremia. Grade three and grade four toxicities were uncommon in subsequent cycles. Median AUC0–Tlast values at the 2 mg/kg were similar to those observed in adults. The study was terminated while patients were being treated at the highest planned dose, due to hepatotoxicity encountered in the ongoing adult phase I studies. No complete or partial responses were observed. Two patients with low-grade gliomas were noted to have minor responses, and at the time of the study’s closure, 5 children with low-grade gliomas had been on therapy for 8 or more courses (range 8–16). Conclusion PTC299 was well-tolerated at the highest dose level tested (2 mg/kg/dose TID) in children with recurrent brain tumors and prolonged disease stabilization was seen in children with low-grade gliomas. PMID:25407389

  1. An open-label phase 1 dose-escalation clinical trial of a single intravenous administration of gemcitabine in dogs with advanced solid tumors.

    Science.gov (United States)

    Marconato, L; Finotello, R; Bonfanti, U; Dacasto, M; Beatrice, L; Pizzoni, S; Leone, V F; Balestra, G; Furlanello, T; Rohrer Bley, C; Aresu, L

    2015-01-01

    A broad range of gemcitabine dosages have been used in dogs. To determine maximally tolerated dose (MTD), dose-limiting toxicity (DLT), and preliminary antitumor activity of intravenous administration of gemcitabine in dogs with advanced solid tumors. Twenty-two client-owned dogs. Dogs with advanced cancer were prospectively enrolled in an open-label Phase 1 study of gemcitabine. Gemcitabine was administered as a 30-minute intravenous bolus starting at 800 mg/m(2), using escalation of 50 mg/m(2) increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Treatment continued until disease progression or unacceptable toxicosis. Additional dogs were enrolled at MTD to better characterize tolerability, and to assess the extent and duration of gemcitabine excretion. Twenty-two dogs were treated at 4 dose levels, ranging from 800 to 950 mg/m(2). Neutropenia was identified as DLT. MTD was 900 mg/m(2). DLT consisting of grade 4 febrile neutropenia was observed at 950 mg/m(2) in 2 dogs. There were no nonhematologic DLTs. Twenty dogs received multiple doses, and none had evidence of severe toxicosis from any of their subsequent treatments. At 900 mg/m(2), 2 complete and 5 partial responses were observed in dogs with measurable tumors. The amount of gemcitabine excreted in urine decreased over time, and was undetectable after the first 24 hours. The recommended dose of gemcitabine for future Phase 2 studies is weekly 900 mg/m(2). In chemotherapy-naïve dogs with advanced solid tumor this dose level merits further evaluation. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  2. Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations.

    Directory of Open Access Journals (Sweden)

    Laura A Laviolette

    Full Text Available The Birt-Hogg-Dube disease occurs as a result of germline mutations in the human Folliculin gene (FLCN, and is characterized by clinical features including fibrofolliculomas, lung cysts and multifocal renal neoplasia. Clinical and genetic evidence suggest that FLCN acts as a tumor suppressor gene. The human cell line UOK257, derived from the renal cell carcinoma of a patient with a germline mutation in the FLCN gene, harbors a truncated version of the FLCN protein. Reconstitution of the wild type FLCN protein into UOK257 cells delays cell cycle progression, due to a slower progression through the late S and G2/M-phases. Similarly, Flcn (-/- mouse embryonic fibroblasts progress more rapidly through the cell cycle than wild type controls (Flcn (flox/flox. The reintroduction of tumor-associated FLCN mutants (FLCN ΔF157, FLCN 1-469 or FLCN K508R fails to delay cell cycle progression in UOK257 cells. Additionally, FLCN phosphorylation (on Serines 62 and 73 fluctuates throughout the cell cycle and peaks during the G2/M phase in cells treated with nocodazole. In keeping with this observation, the reintroduction of a FLCN phosphomimetic mutant into the UOK257 cell line results in faster progression through the cell cycle compared to those expressing the wild type FLCN protein. These findings suggest that the tumor suppression function of FLCN may be linked to its impact on the cell cycle and that FLCN phosphorylation is important for this activity. Additionally, these observations describe a novel in vitro assay for testing the functional significance of FLCN mutations and/or genetic polymorphisms.

  3. Kansas Consortium Plug-in Hybrid Medium Duty

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2012-03-31

    On September 30, 2008, the US Department of Energy (DoE), issued a cooperative agreement award, DE-FC26-08NT01914, to the Metropolitan Energy Center (MEC), for a project known as “Kansas Consortium Plug-in Hybrid Medium Duty Certification” project. The cooperative agreement was awarded pursuant to H15915 in reference to H. R. 2764 Congressionally Directed Projects. The original agreement provided funding for The Consortium to implement the established project objectives as follows: (1) to understand the current state of the development of a test protocol for PHEV configurations; (2) to work with industry stakeholders to recommend a medium duty vehicle test protocol; (3) to utilize the Phase 1 Eaton PHEV F550 Chassis or other appropriate PHEV configurations to conduct emissions testing; (4) and to make an industry PHEV certification test protocol recommendation for medium duty trucks. Subsequent amendments to the initial agreement were made, the most significant being a revised Scope of Project Objectives (SOPO) that did not address actual field data since it was not available as originally expected. This project was mated by DOE with a parallel project award given to the South Coast Air Quality Management District (SCAQMD) in California. The SCAQMD project involved designing, building and testing of five medium duty plug-in hybrid electric trucks. SCAQMD had contracted with the Electric Power Research Institute (EPRI) to manage the project. EPRI provided the required match to the federal grant funds to both the SCAQMD project and the Kansas Consortium project. The rational for linking the two projects was that the data derived from the SCAQMD project could be used to validate the protocols developed by the Kansas Consortium team. At the same time, the consortium team would be a useful resource to SCAQMD in designating their test procedures for emissions and operating parameters and determining vehicle mileage. The years between award of the cooperative

  4. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  5. India Ink Incorporated Multifunctional Phase-transition Nanodroplets for Photoacoustic/Ultrasound Dual-modality Imaging and Photoacoustic Effect Based Tumor Therapy

    Science.gov (United States)

    Jian, Jia; Liu, Chengbo; Gong, Yuping; Su, Lei; Zhang, Bin; Wang, Zhigang; wang, Dong; Zhou, Yu; Xu, Fenfen; Li, Pan; Zheng, Yuanyi; Song, Liang; Zhou, Xiyuan

    2014-01-01

    The in vivo applications of gas-core microbubbles have been limited by gas diffusion, rapid body clearance, and poor vascular permeability. To overcome these limitations, using a modified three-step emulsion process, we have developed a first-of-its-kind India ink incorporated optically-triggerable phase-transition perfluorocarbon nanodroplets (INDs) that can provide not only three types of contrast mechanisms—conventional/thermoelastic photoacoustic, phase-transition/nonlinear photoacoustic, and ultrasound imaging contrasts, but also a new avenue for photoacoustic effect mediated tumor therapy. Upon pulsed laser illumination above a relatively low energy threshold, liquid-gas phase transition of the INDs has been demonstrated both in vitro and in vivo, offering excellent contrasts for photoacoustic and ultrasound dual-modality imaging. With further increased laser energy, the nanodroplets have been shown to be capable of destructing cancer cells in vivo, presumably due to the photoacoustic effect induced shock-wave generation from the carbon particles of the incorporated India ink. The demonstrated results suggest that the developed multifunctional phase-transition nanodroplets have a great potential for many theranostic biomedical applications, including photoacoustic/ultrasound dual-modality molecular imaging and targeted, localized cancer therapy. PMID:25161702

  6. India ink incorporated multifunctional phase-transition nanodroplets for photoacoustic/ultrasound dual-modality imaging and photoacoustic effect based tumor therapy.

    Science.gov (United States)

    Jian, Jia; Liu, Chengbo; Gong, Yuping; Su, Lei; Zhang, Bin; Wang, Zhigang; Wang, Dong; Zhou, Yu; Xu, Fenfen; Li, Pan; Zheng, Yuanyi; Song, Liang; Zhou, Xiyuan

    2014-01-01

    The in vivo applications of gas-core microbubbles have been limited by gas diffusion, rapid body clearance, and poor vascular permeability. To overcome these limitations, using a modified three-step emulsion process, we have developed a first-of-its-kind India ink incorporated optically-triggerable phase-transition perfluorocarbon nanodroplets (INDs) that can provide not only three types of contrast mechanisms-conventional/thermoelastic photoacoustic, phase-transition/nonlinear photoacoustic, and ultrasound imaging contrasts, but also a new avenue for photoacoustic effect mediated tumor therapy. Upon pulsed laser illumination above a relatively low energy threshold, liquid-gas phase transition of the INDs has been demonstrated both in vitro and in vivo, offering excellent contrasts for photoacoustic and ultrasound dual-modality imaging. With further increased laser energy, the nanodroplets have been shown to be capable of destructing cancer cells in vivo, presumably due to the photoacoustic effect induced shock-wave generation from the carbon particles of the incorporated India ink. The demonstrated results suggest that the developed multifunctional phase-transition nanodroplets have a great potential for many theranostic biomedical applications, including photoacoustic/ultrasound dual-modality molecular imaging and targeted, localized cancer therapy.

  7. Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium.

    Science.gov (United States)

    Shah, Manish A; Janjigian, Yelena Y; Stoller, Ronald; Shibata, Stephen; Kemeny, Margaret; Krishnamurthi, Smitha; Su, Yungpo Bernard; Ocean, Allyson; Capanu, Marinela; Mehrotra, Bhoomi; Ritch, Paul; Henderson, Charles; Kelsen, David P

    2015-11-20

    Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and is associated with significant toxicity. We examined the safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter phase II study. Previously untreated patients with metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either mDCF (fluorouracil 2,000 mg/m2 intravenously [IV] over 48 hours, docetaxel 40 mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 3, every 2 weeks) or parent DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, and fluorouracil 750 mg/m2 IV over 5 days with granulocyte colony-stimulating factor, every 3 weeks). The study had 90% power to differentiate between 6-month progression-free survival of 26% and 43%, with type I and II error rates of 10% each. An early stopping rule for toxicity was included, defined as grade 3 to 4 adverse event rate > 70% in the first 3 months. From November 2006 to June 2010, 85 evaluable patients were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31) closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52% hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI, 34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6 months; P = .007). mDCF is less toxic than parent DCF, even when supported with growth factors, and is associated with improved efficacy. mDCF should be considered a standard first-line option for patients with metastatic gastric or GEJ adenocarcinoma.

  8. 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.

  9. Consortium for Verification Technology Fellowship Report.

    Energy Technology Data Exchange (ETDEWEB)

    Sadler, Lorraine E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-06-01

    As one recipient of the Consortium for Verification Technology (CVT) Fellowship, I spent eight days as a visiting scientist at the University of Michigan, Department of Nuclear Engineering and Radiological Sciences (NERS). During this time, I participated in multiple department and research group meetings and presentations, met with individual faculty and students, toured multiple laboratories, and taught one-half of a one-unit class on Risk Analysis in Nuclear Arms control (six 1.5 hour lectures). The following report describes some of the interactions that I had during my time as well as a brief discussion of the impact of this fellowship on members of the consortium and on me/my laboratory’s technical knowledge and network.

  10. Midwest Nuclear Science and Engineering Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Wynn Volkert; Dr. Arvind Kumar; Dr. Bryan Becker; Dr. Victor Schwinke; Dr. Angel Gonzalez; Dr. DOuglas McGregor

    2010-12-08

    The objective of the Midwest Nuclear Science and Engineering Consortium (MNSEC) is to enhance the scope, quality and integration of educational and research capabilities of nuclear sciences and engineering (NS/E) programs at partner schools in support of the U.S. nuclear industry (including DOE laboratories). With INIE support, MNSEC had a productive seven years and made impressive progress in achieving these goals. Since the past three years have been no-cost-extension periods, limited -- but notable -- progress has been made in FY10. Existing programs continue to be strengthened and broadened at Consortium partner institutions. The enthusiasm generated by the academic, state, federal, and industrial communities for the MNSEC activities is reflected in the significant leveraging that has occurred for our programs.

  11. Midwest Nuclear Science and Engineering Consortium

    International Nuclear Information System (INIS)

    Volkert, Wynn; Kumar, Arvind; Becker, Bryan; Schwinke, Victor; Gonzalez, Angel; McGregor, Douglas

    2010-01-01

    The objective of the Midwest Nuclear Science and Engineering Consortium (MNSEC) is to enhance the scope, quality and integration of educational and research capabilities of nuclear sciences and engineering (NS/E) programs at partner schools in support of the U.S. nuclear industry (including DOE laboratories). With INIE support, MNSEC had a productive seven years and made impressive progress in achieving these goals. Since the past three years have been no-cost-extension periods, limited -- but notable -- progress has been made in FY10. Existing programs continue to be strengthened and broadened at Consortium partner institutions. The enthusiasm generated by the academic, state, federal, and industrial communities for the MNSEC activities is reflected in the significant leveraging that has occurred for our programs.

  12. Overview of the Inland California Translational Consortium

    Science.gov (United States)

    Malkas, Linda H.

    2017-05-01

    The mission of the Inland California Translational Consortium (ICTC), an independent research consortium comprising a unique hub of regional institutions (City of Hope [COH], California Institute of Technology [Caltech], Jet Propulsion Laboratory [JPL], University of California Riverside [UCR], and Claremont Colleges Keck Graduate Institute [KGI], is to institute a new paradigm within the academic culture to accelerate translation of innovative biomedical discoveries into clinical applications that positively affect human health and life. The ICTC actively supports clinical translational research as well as the implementation and advancement of novel education and training models for the translation of basic discoveries into workable products and practices that preserve and improve human health while training and educating at all levels of the workforce using innovative forward-thinking approaches.

  13. Phase I and pharmacologic study of oral (PEG-1000) 9-aminocamptothecin in adult patients with solid tumors

    NARCIS (Netherlands)

    de Jonge, M. J.; Punt, C. J.; Gelderblom, A. H.; Loos, W. J.; van Beurden, V.; Planting, A. S.; van der Burg, M. E.; van Maanen, L. W.; Dallaire, B. K.; Verweij, J.; Wagener, D. J.; Sparreboom, A.

    1999-01-01

    9-Amino-20(S)-camptothecin (9-AC) is a specific inhibitor of topoisomerase-I. Recently, a bioavailability of approximately 48% for the oral PEG-1000 formulation was reported. We conducted a phase I and pharmacokinetic study of the oral PEG-1000 formulation of 9-AC to define the maximum-tolerated

  14. 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

    Science.gov (United States)

    Tan, Wei; Hong, Chi-Chen; Admane, Sonal; Dozier, Askia; Siedlecki, Francine; Whitworth, Amy; DiRaddo, Ann Marie; DePaolo, Dawn; Jacob, Sandra M.; Ma, Wen Wee; Miller, Austin; Adjei, Alex A.; Dy, Grace K.

    2017-01-01

    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. PMID:28672850

  15. 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.

  16. Midwest superconductivity consortium. 1993 Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1994-01-01

    The Midwest Superconductivity Consortium, MISCON, in the fourth year of operations further strengthened its mission to advance the science and understanding of high T{sub c} superconductivity. The goals of the organization and the individual projects continue to reflect the current needs for new knowledge in the field and the unique capabilities of the institutions involved. Group efforts and cooperative laboratory interactions to achieve the greatest possible synergy under the Consortium continue to be emphasized. Industrial affiliations coupled with technology transfer initiatives were expanded. Activities of the participants during the past year achieved an interactive and high level of performance. The number of notable achievements in the field contributed by Consortium investigators increased. The programmatic research continues to focus upon key materials-related problems in two areas. The first area has a focus upon {open_quotes}Synthesis and Processing{close_quotes} while the second is centered around {open_quotes}Limiting Features in Transport Properties of High T{sub c} Materials{close_quotes}.

  17. Primary Immune Deficiency Treatment Consortium (PIDTC) report.

    Science.gov (United States)

    Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D; Kohn, Donald B; Puck, Jennifer M; Pai, Sung-Yun; Ballard, Barbara; Bauer, Sarah C; Bleesing, Jack J H; Boyle, Marcia; Brower, Amy; Buckley, Rebecca H; van der Burg, Mirjam; Burroughs, Lauri M; Candotti, Fabio; Cant, Andrew J; Chatila, Talal; Cunningham-Rundles, Charlotte; Dinauer, Mary C; Dvorak, Christopher C; Filipovich, Alexandra H; Fleisher, Thomas A; Bobby Gaspar, Hubert; Gungor, Tayfun; Haddad, Elie; Hovermale, Emily; Huang, Faith; Hurley, Alan; Hurley, Mary; Iyengar, Sumathi; Kang, Elizabeth M; Logan, Brent R; Long-Boyle, Janel R; Malech, Harry L; McGhee, Sean A; Modell, Fred; Modell, Vicki; Ochs, Hans D; O'Reilly, Richard J; Parkman, Robertson; Rawlings, David J; Routes, John M; Shearer, William T; Small, Trudy N; Smith, Heather; Sullivan, Kathleen E; Szabolcs, Paul; Thrasher, Adrian; Torgerson, Troy R; Veys, Paul; Weinberg, Kenneth; Zuniga-Pflucker, Juan Carlos

    2014-02-01

    The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives. Published by Mosby, Inc.

  18. Removal of Triphenylmethane Dyes by Bacterial Consortium

    Science.gov (United States)

    Cheriaa, Jihane; Khaireddine, Monia; Rouabhia, Mahmoud; Bakhrouf, Amina

    2012-01-01

    A new consortium of four bacterial isolates (Agrobacterium radiobacter; Bacillus spp.; Sphingomonas paucimobilis, and Aeromonas hydrophila)-(CM-4) was used to degrade and to decolorize triphenylmethane dyes. All bacteria were isolated from activated sludge extracted from a wastewater treatment station of a dyeing industry plant. Individual bacterial isolates exhibited a remarkable color-removal capability against crystal violet (50 mg/L) and malachite green (50 mg/L) dyes within 24 h. Interestingly, the microbial consortium CM-4 shows a high decolorizing percentage for crystal violet and malachite green, respectively, 91% and 99% within 2 h. The rate of chemical oxygen demand (COD) removal increases after 24 h, reaching 61.5% and 84.2% for crystal violet and malachite green, respectively. UV-Visible absorption spectra, FTIR analysis and the inspection of bacterial cells growth indicated that color removal by the CM-4 was due to biodegradation. Evaluation of mutagenicity by using Salmonella typhimurium test strains, TA98 and TA100 studies revealed that the degradation of crystal violet and malachite green by CM-4 did not lead to mutagenic products. Altogether, these results demonstrated the usefulness of the bacterial consortium in the treatment of the textile dyes. PMID:22623907

  19. Removal of Triphenylmethane Dyes by Bacterial Consortium

    Directory of Open Access Journals (Sweden)

    Jihane Cheriaa

    2012-01-01

    Full Text Available A new consortium of four bacterial isolates (Agrobacterium radiobacter; Bacillus spp.; Sphingomonas paucimobilis, and Aeromonas hydrophila-(CM-4 was used to degrade and to decolorize triphenylmethane dyes. All bacteria were isolated from activated sludge extracted from a wastewater treatment station of a dyeing industry plant. Individual bacterial isolates exhibited a remarkable color-removal capability against crystal violet (50 mg/L and malachite green (50 mg/L dyes within 24 h. Interestingly, the microbial consortium CM-4 shows a high decolorizing percentage for crystal violet and malachite green, respectively, 91% and 99% within 2 h. The rate of chemical oxygen demand (COD removal increases after 24 h, reaching 61.5% and 84.2% for crystal violet and malachite green, respectively. UV-Visible absorption spectra, FTIR analysis and the inspection of bacterial cells growth indicated that color removal by the CM-4 was due to biodegradation. Evaluation of mutagenicity by using Salmonella typhimurium test strains, TA98 and TA100 studies revealed that the degradation of crystal violet and malachite green by CM-4 did not lead to mutagenic products. Altogether, these results demonstrated the usefulness of the bacterial consortium in the treatment of the textile dyes.

  20. 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, Giovanni; Sansovini, Maddalena; Ambrosetti, Alice; Severi, Stefano; Ianniello, Annarita; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola, FC (Italy); Monti, Manuela; Scarpi, Emanuela [IRST IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Donati, Caterina [IRST IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Amadori, Dino [IRST IRCCS, Department of Medical Oncology, Meldola (Italy)

    2014-10-15

    We evaluated the activity and safety profile of {sup 177}Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced, well-differentiated (G1-G2) gastrointestinal neuroendocrine tumors (GI-NETs). Forty-three patients with radiological tumor progression at baseline and a positive Octreoscan registered completed the treatment with Lu-PRRT, resulting in the cumulative activity of 18.5 or 27.8 GBq in five cycles. Total activity was scheduled on the basis of kidney function or bone marrow reserve. Twenty-five (58 %) patients were treated with a ''standard'' Lu-PRRT full dosage (FD) of 25.7 GBq (range 22.2-27.8), while the remaining 18 patients (42 %) who, at enrolment, showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage (RD) of 18.4 GBq (range 14.4-20.4). According to SWOG criteria, the overall response was complete response (CR) in (7 %) cases and stable disease (SD) in 33 (77 %), with a disease control rate (DCR) of 84 %. Median response duration was 25 months (range 7-50). Median progression-free survival (PFS) was 36 months (95 % CI 24-nr), and median overall survival (OS) has not yet been reached. Remarkably, none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu-PRRT. Lu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs, showing an 84 % DCR (95 % CI 73-95) that lasted for 25 months and a PFS of 36 months. Both activities of 27.8 GBq and 18.5 GBq proved safe and effective in all patients, including those with a higher probability of developing kidney or bone marrow toxicity. (orig.)

  1. Mediastinal tumor

    Science.gov (United States)

    Thymoma - mediastinal; Lymphoma - mediastinal ... mediastinal tumors in adults occur in the anterior mediastinum. They are usually cancerous (malignant) lymphomas, germ cell tumors, or thymomas. These tumors are ...

  2. A phase 1 study of the heat shock protein 90 inhibitor retaspimycin hydrochloride (IPI-504) in patients with gastrointestinal stromal tumors or soft tissue sarcomas

    Science.gov (United States)

    Wagner, Andrew J.; Chugh, Rashmi; Rosen, Lee S.; Morgan, Jeffrey A.; George, Suzanne; Gordon, Michael; Dunbar, Joi; Normant, Emmanuel; Grayzel, David; Demetri, George D.

    2015-01-01

    Purpose Heat shock protein 90 (Hsp90) is required for the proper folding, function, and stability of various client proteins, two of which (KIT and PDGFRα) are critical in the pathogenesis and progression of gastrointestinal stromal tumors (GIST). This phase 1 study investigated the safety and maximum tolerated dose (MTD) of retaspimycin hydrochloride (IPI-504), a novel potent and selective Hsp90 inhibitor, in patients with metastatic and/or unresectable GIST or other soft-tissue sarcomas (STS). Experimental Design IPI-504 was administered intravenously at doses ranging from 90 to 500 mg/m2 twice weekly for 2 weeks on/1 week off. Safety, pharmacokinetic, and pharmacodynamic profiles were determined. Response was assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.0 and optionally via 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) imaging. Results Fifty-four patients received IPI-504; 37 with GIST and 17 with other STS. The MTD was 400 mg/m2 twice weekly for 2 weeks on/1 week off. Common related adverse events were fatigue (59%), headache (44%), and nausea (43%). Exposure to IPI-504, 17-AAG, and 17-AG increased with IPI-504 dose. Stable disease (SD) was observed in 70% (26/37) of patients with GIST and 59% (10/17) of patients with STS. There was one confirmed partial response (PR) in a patient with GIST and one PR in a patient with liposarcoma. Metabolic partial responses occurred in 11/29 (38%) of GIST patients. Conclusions In this study of advanced GIST or other STS, IPI-504 was generally well-tolerated with some evidence of anti-tumor activity, serving as a clinical proof-of-concept that HSP90 inhibition remains a promising strategy. PMID:24045182

  3. Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199

    Science.gov (United States)

    Adams, Sylvia; Gray, Robert J.; Demaria, Sandra; Goldstein, Lori; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Wang, Molin; Jones, Vicky E.; Saphner, Thomas J.; Wolff, Antonio C.; Wood, William C.; Davidson, Nancy E.; Sledge, George W.; Sparano, Joseph A.; Badve, Sunil S.

    2014-01-01

    Purpose Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG). Patients and Methods Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified. Results The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS. Conclusion In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter. PMID:25071121

  4. Dynamic tumor modeling of the dose–response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial

    International Nuclear Information System (INIS)

    Stein, Andrew; Wang, Wenping; Carter, Alison A; Chiparus, Ovidiu; Hollaender, Norbert; Kim, Hyewon; Motzer, Robert J; Sarr, Celine

    2012-01-01

    The phase 3 RECORD-1 trial (NCT00410124) established the efficacy and safety of everolimus in patients with metastatic renal cell carcinoma (mRCC) who progress on sunitinib or sorafenib. In RECORD-1, patients received 10 mg everolimus daily, with dose reduction to 5 mg daily allowed for toxicity. We have developed a model of tumor growth dynamics utilizing serial measurements of the sum of the longest tumor diameters (SLD) from individual RECORD-1 patients to define the dose–response relationship of everolimus. The model predicts that after 1 year of continuous dosing, the change in SLD of target lesions will be +142.1% ± 98.3%, +22.4% ± 17.2%, and –15.7% ± 11.5% in the average patient treated with placebo, 5 mg everolimus, and 10 mg everolimus, respectively. This nonlinear, mixed-effects modeling approach can be used to describe the dynamics of each individual patient, as well as the overall population. This allows evaluation of how an actual dosing history and individual covariates impact on the observed drug effect, and offers the possibility of predicting clinical observations as a function of time. In this pharmacodynamic model of tumor response, everolimus more effectively shrinks target lesions in mRCC when dosed 10 mg daily versus 5 mg daily, although a 5-mg dose still shows an antitumor effect. These data support earlier studies that established 10 mg daily as the preferred clinical dose of everolimus, and improve our understanding of the everolimus dose–response relationship

  5. Phase I study of intermittent oral dosing of the insulin-like growth factor-1 and insulin receptors inhibitor OSI-906 in patients with advanced solid tumors.

    Science.gov (United States)

    Jones, Robin L; Kim, Edward S; Nava-Parada, Pilar; Alam, Salma; Johnson, Faye M; Stephens, Andrew W; Simantov, Ronit; Poondru, Srinivasu; Gedrich, Rich; Lippman, Scott M; Kaye, Stan B; Carden, Craig P

    2015-02-15

    We determined the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and preliminary activity of OSI-906, a potent, oral, dual inhibitor of insulin-like growth factor-1 receptor (IGF1R) and insulin receptor (IR), in patients with advanced solid tumors. This was a multicenter, open-label, dose escalation phase I study evaluating three intermittent dosing schedules of once-daily OSI-906 [schedule (S) 1, days 1-3 every 14 days; S2, days 1-5 every 14 days; S3, days 1-7 every 14 days]. A fed-fasting expansion cohort was included in the study. Seventy-nine patients were enrolled: 62 in S1, 4 in S2, and 13 in S3. S2 was discontinued. Dose-limiting toxicity comprised grade 3-4 hyperglycemia, vomiting, fatigue, and prolonged QTc interval. The MTD and recommended phase II dose of OSI-906 was 600 mg for both S1 and S3 schedules. Other common adverse events were grade 1-2 nausea, vomiting, fatigue, and diarrhea. The pharmacokinetics of OSI-906 was dose linear, and the terminal half-life ranged between 2 and 6 hours. High-fat meals had a moderate effect on the pharmacokinetics of OSI-906. At the MTD, inhibition of IGF1R and IR was observed in peripheral blood mononuclear cells. An increase in plasma IGF1 concentrations, an indirect measure of IGF1R signaling inhibition, was seen at doses ≥ 450 mg. Two patients with adrenocortical carcinoma achieved partial responses. The MTD of 600 mg was well tolerated and associated with preliminary antitumor activity. These data support further evaluation of OSI-906 in solid tumors. ©2014 American Association for Cancer Research.

  6. TTI Phase 2 Institutional Support: Consortium pour la Recherche E ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    -maintain administration and financial management processes and procedures, including regular account audits, and adherence to IDRC financial reporting requirements -position itself on a path to long-term sustainability by diversifying and expanding its funding sources -follow measurement and evaluation processes to ...

  7. TTI Phase 2 Institutional Support: Consortium pour la Recherche E ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This will help them consolidate their role as credible development actors in their countries, and in some cases, regionally and internationally. For CRES, this project will help enhance its research quality, organizational performance, and policy engagement. Improved research, better performance. Through this support over ...

  8. TTI Phase 2 Institutional Support: Consortium pour la Recherche E ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    TTI is a multi-funder program dedicated to strengthening independent policy research institutions, or think tanks, in developing countries. ... -follow measurement and evaluation processes to ensure that internal targets are met and to inform CRES of the impact of its work ... TIC, croissance économique et pauvreté.

  9. Phase 1 Trial of Bevacizumab With Concurrent Chemoradiation Therapy for Squamous Cell Carcinoma of the Head and Neck With Exploratory Functional Imaging of Tumor Hypoxia, Proliferation, and Perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Nyflot, Matthew J., E-mail: nyflot@uw.edu [Department of Radiation Oncology, University of Washington, Seattle, Washington (United States); Kruser, Tim J. [Department of Radiation Oncology, Cadence Cancer Center at Delnor Hospital, Geneva, Illinois (United States); Traynor, Anne M. [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Khuntia, Deepak [Varian Medical Systems, Palo Alto, California (United States); Yang, David T. [Departments of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hartig, Gregory K.; McCulloch, Timothy M. [Department of Surgery-Otolaryngology, H& N Surgery Division, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Wiederholt, Peggy A. [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Gentry, Lindell R. [Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Hoang, Tien [Department of Medicine, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Jeraj, Robert [Department of Human Oncology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Radiology, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); Department of Medical Physics, University of Wisconsin Carbone Cancer Center and School of Medicine and Public Health, Madison, Wisconsin (United States); and others

    2015-04-01

    Purpose: A phase 1 trial was completed to examine the safety and feasibility of combining bevacizumab with radiation and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (HNSCC) treated with curative intent. Additionally, we assessed the capacity of bevacizumab to induce an early tumor response as measured by a series of biological imaging studies. Methods and Materials: All patients received a single induction dose of bevacizumab (15 mg/kg) delivered 3 weeks (±3 days) before the initiation of chemoradiation therapy. After the initial dose of bevacizumab, comprehensive head and neck chemoradiation therapy was delivered with curative intent to 70 Gy in 33 fractions with concurrent weekly cisplatin at 30 mg/m{sup 2} and bevacizumab every 3 weeks (weeks 1, 4, 7) with dose escalation from 5 to 10 to 15 mg/kg. All patients underwent experimental imaging with [{sup 18}F]fluorothymidine positron emission tomography (FLT-PET) (proliferation), [{sup 61}Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) PET (Cu-ATSM-PET) (hypoxia), and dynamic contrast-enhanced computed tomography (DCE-CT) (perfusion) at 3 time points: before bevacizumab monotherapy, after bevacizumab monotherapy, and during the combined therapy course. Results: Ten patients were enrolled. All had stage IV HNSCC, all achieved a complete response to treatment, and 9 of 10 remain alive, with a mean survival time of 61.3 months. All patients experienced grade 3 toxicity, but no dose-limiting toxicities or significant bleeding episodes were observed. Significant reductions were noted in tumor proliferation (FLT-PET), tumor hypoxia (Cu-ATSM-PET), and DCE-CT contrast enhancement after bevacizumab monotherapy, with further decreases in FLT-PET and Cu-ATSM-PET during the combined therapy course. Conclusions: The incorporation of bevacizumab into comprehensive chemoradiation therapy regimens for patients with HNSCC appears safe and feasible. Experimental imaging

  10. 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

  11. GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ...

    African Journals Online (AJOL)

    Pavel M.E., Baum U., Hahn E.G., Hensen J. Doxorubucin and streptozocin after failed biotherapy of Neuroendocrine tumors. Int J. Gastrointest Cancer 2005; 35 179-185. 33. Yao J.C., Phan A., Hoff P.M., et al. Targeting vas- cular endothelial growth factor in advanced carci- noid tumors: a random assignment phase II study.

  12. Pegylated liposomal mitomycin C prodrug enhances tolerance of mitomycin C: a phase 1 study in advanced solid tumor patients

    International Nuclear Information System (INIS)

    Golan, Talia; Grenader, Tal; Ohana, Patricia; Amitay, Yasmine; Shmeeda, Hilary; La-Beck, Ninh M; Tahover, Esther; Berger, Raanan; Gabizon, Alberto A

    2015-01-01

    Mitomycin C (MMC) has potent cytotoxicity but cumulative toxicity limits widespread use. In animals, pegylated liposomal mitomycin C lipid-based prodrug (PL-MLP) was well tolerated and more effective than free MMC. We evaluated PL-MLP in patients with advanced cancer. Twenty-seven patients were treated in escalating dose cohorts of 0.5–3.5 mg/kg (equivalent to 0.15–1.03 mg/kg MMC) every 4 weeks for up to 12 cycles, unless disease progression or unacceptable toxicity occurred. Pharmacokinetics were assessed during cycles 1 and 3. Per protocol maximum tolerated dose was not reached at 3.5 mg/kg. However, prolonged thrombocytopenia developed after repeated doses of 3 mg/kg or cumulative doses of 10–12 mg/kg. Dose-related grade 3 or higher adverse events included fatigue, anemia, and decreased platelets. C max and AUC 0-∞ increased linearly over the dose range 0.5–2.0 mg/kg, and greater than linearly from 2.5 to 3.5 mg/kg; there were no significant differences in clearance of MLP between cycles 1 and 3. Median t 1/2 was 23 h among dose cohorts, with no trend by dose or cycle. One patient had a partial response. Stable disease was observed in 10 patients across all dose levels. PL-MLP has a long circulation time, was well tolerated, and can be administered to heavily pretreated patients at a single dose of 3.0 mg/kg and cumulative dose of 10–12 mg/kg before development of prolonged thrombocytopenia; this is nearly threefold the equivalent dose of MMC tolerated historically. This formulation may be active in a variety of tumor types and is better tolerated than free MMC

  13. 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.

  14. Phase I trial of MEK 1/2 inhibitor pimasertib combined with mTOR inhibitor temsirolimus in patients with advanced solid tumors.

    Science.gov (United States)

    Mita, Monica; Fu, Siqing; Piha-Paul, Sarina Anne; Janku, Filip; Mita, Alain; Natale, Ronald; Guo, Wei; Zhao, Charles; Kurzrock, Razelle; Naing, Aung

    2017-10-01

    Background Dual inhibition of activated MAPK and mTOR signaling pathways may enhance the antitumor efficacy of the MEK 1/2 inhibitor pimasertib and the mTOR inhibitor temsirolimus given in combination. Methods In this phase I study, patients with refractory advanced solid tumors (NCT01378377) received once-weekly temsirolimus plus once-daily oral pimasertib in 21-day cycles in a modified 3 + 3 dose-escalation design. The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of pimasertib in combination with temsirolimus, safety and pharmacokinetics (PK) were investigated. Results Of 33 patients evaluated, all experienced ≥1 treatment-emergent adverse event (TEAE) and 31 had treatment-related TEAEs, most frequently stomatitis and thrombocytopenia. TEAEs were reversible. No deaths were attributed to treatment. Nine patients had dose-limiting toxicities (stomatitis, thrombocytopenia, serum creatinine phosphokinase increase, visual impairment) and the MTD was determined as 45 mg/day pimasertib plus 25 mg/week temsirolimus. However, due to overlapping toxicities no further investigations were performed and the RP2D was not defined. PK profiles of both agents were not adversely affected. Seventeen patients (17/26 patients) had a best response of stable disease; five had stable disease lasting >12 weeks. Conclusions The RP2D was not defined and the pimasertib plus temsirolimus combination investigated did not warrant further study.

  15. Latest Developments of the Isprs Student Consortium

    Science.gov (United States)

    Detchev, I.; Kanjir, U.; Reyes, S. R.; Miyazaki, H.; Aktas, A. F.

    2016-06-01

    The International Society for Photogrammetry and Remote Sensing (ISPRS) Student Consortium (SC) is a network for young professionals studying or working within the fields of photogrammetry, remote sensing, Geographical Information Systems (GIS), and other related geo-spatial sciences. The main goal of the network is to provide means for information exchange for its young members and thus help promote and integrate youth into the ISPRS. Over the past four years the Student Consortium has successfully continued to fulfil its mission in both formal and informal ways. The formal means of communication of the SC are its website, newsletter, e-mail announcements and summer schools, while its informal ones are multiple social media outlets and various social activities during student related events. The newsletter is published every three to four months and provides both technical and experiential content relevant for the young people in the ISPRS. The SC has been in charge or at least has helped with organizing one or more summer schools every year. The organization's e-mail list has over 1,100 subscribers, its website hosts over 1,300 members from 100 countries across the entire globe, and its public Facebook group currently has over 4,500 joined visitors, who connect among one another and share information relevant for their professional careers. These numbers show that the Student Consortium has grown into a significant online-united community. The paper will present the organization's on-going and past activities for the last four years, its current priorities and a strategic plan and aspirations for the future four-year period.

  16. University Research Consortium annual review meeting program

    International Nuclear Information System (INIS)

    1996-07-01

    This brochure presents the program for the first annual review meeting of the University Research Consortium (URC) of the Idaho National Engineering Laboratory (INEL). INEL is a multiprogram laboratory with a distinctive role in applied engineering. It also conducts basic science research and development, and complex facility operations. The URC program consists of a portfolio of research projects funded by INEL and conducted at universities in the United States. In this program, summaries and participant lists for each project are presented as received from the principal investigators

  17. University Research Consortium annual review meeting program

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-07-01

    This brochure presents the program for the first annual review meeting of the University Research Consortium (URC) of the Idaho National Engineering Laboratory (INEL). INEL is a multiprogram laboratory with a distinctive role in applied engineering. It also conducts basic science research and development, and complex facility operations. The URC program consists of a portfolio of research projects funded by INEL and conducted at universities in the United States. In this program, summaries and participant lists for each project are presented as received from the principal investigators.

  18. History of the Tinnitus Research Consortium.

    Science.gov (United States)

    Snow, James B

    2016-04-01

    This article describes the creation and accomplishments of the Tinnitus Research Consortium (TRC), founded and supported through philanthropy and intended to enrich the field of tinnitus research. Bringing together a group of distinguished auditory researchers, most of whom were not involved in tinnitus research, over the fifteen years of its life it developed novel research approaches and recruited a number of new investigators into the field. The purpose of this special issue is to highlight some of the significant accomplishments of the investigators supported by the TRC. This article is part of a Special Issue entitled "Tinnitus". Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Midwest Superconductivity Consortium: 1994 Progress report

    Energy Technology Data Exchange (ETDEWEB)

    1995-01-01

    The mission of the Midwest Superconductivity Consortium, MISCON, is to advance the science and understanding of high {Tc} superconductivity. During the past year, 27 projects produced over 123 talks and 139 publications. Group activities and interactions involved 2 MISCON group meetings (held in August and January); with the second MISCON Workshop held in August; 13 external speakers; 79 collaborations (with universities, industry, Federal laboratories, and foreign research centers); and 48 exchanges of samples and/or measurements. Research achievements this past year focused on understanding the effects of processing phenomena on structure-property interrelationships and the fundamental nature of transport properties in high-temperature superconductors.

  20. Midwest Superconductivity Consortium: 1994 Progress report

    International Nuclear Information System (INIS)

    1995-01-01

    The mission of the Midwest Superconductivity Consortium, MISCON, is to advance the science and understanding of high T c superconductivity. During the past year, 27 projects produced over 123 talks and 139 publications. Group activities and interactions involved 2 MISCON group meetings (held in August and January); with the second MISCON Workshop held in August; 13 external speakers; 79 collaborations (with universities, industry, Federal laboratories, and foreign research centers); and 48 exchanges of samples and/or measurements. Research achievements this past year focused on understanding the effects of processing phenomena on structure-property interrelationships and the fundamental nature of transport properties in high-temperature superconductors

  1. Resibufogenin Induces G1-Phase Arrest through the Proteasomal Degradation of Cyclin D1 in Human Malignant Tumor Cells.

    Directory of Open Access Journals (Sweden)

    Masami Ichikawa

    Full Text Available Huachansu, a traditional Chinese medicine prepared from the dried toad skin, has been used in clinical studies for various cancers in China. Resibufogenin is a component of huachansu and classified as bufadienolides. Resibufogenin has been shown to exhibit the anti-proliferative effect against cancer cells. However, the molecular mechanism of resibufogenin remains unknown. Here we report that resibufogenin induces G1-phase arrest with hypophosphorylation of retinoblastoma (RB protein and down-regulation of cyclin D1 expression in human colon cancer HT-29 cells. Since the down-regulation of cyclin D1 was completely blocked by a proteasome inhibitor MG132, the suppression of cyclin D1 expression by resibufogenin was considered to be in a proteasome-dependent manner. It is known that glycogen synthase kinase-3β (GSK-3β induces the proteasomal degradation of cyclin D1. The addition of GSK-3β inhibitor SB216763 inhibited the reduction of cyclin D1 caused by resibufogenin. These effects on cyclin D1 by resibufogenin were also observed in human lung cancer A549 cells. These findings suggest that the anti-proliferative effect of resibufogenin may be attributed to the degradation of cyclin D1 caused by the activation of GSK-3β.

  2. A phase I study of the HSP90 inhibitor retaspimycin hydrochloride (IPI-504) in patients with gastrointestinal stromal tumors or soft-tissue sarcomas.

    Science.gov (United States)

    Wagner, Andrew J; Chugh, Rashmi; Rosen, Lee S; Morgan, Jeffrey A; George, Suzanne; Gordon, Michael; Dunbar, Joi; Normant, Emmanuel; Grayzel, David; Demetri, George D

    2013-11-01

    Heat shock protein 90 (HSP90) is required for the proper folding, function, and stability of various client proteins, two of which (KIT and PDGFRα) are critical in the pathogenesis and progression of gastrointestinal stromal tumors (GIST). This phase I study investigated the safety and maximum tolerated dose (MTD) of retaspimycin hydrochloride (IPI-504), a novel potent and selective HSP90 inhibitor, in patients with metastatic and/or unresectable GIST or other soft-tissue sarcomas (STS). IPI-504 was administered intravenously at doses ranging from 90 to 500 mg/m(2) twice weekly for 2 weeks on/1 week off. Safety, pharmacokinetic, and pharmacodynamic profiles were determined. Response was assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.0 and optionally via 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) imaging. Fifty-four patients received IPI-504; 37 with GIST and 17 with other STS. The MTD was 400 mg/m(2) twice weekly for 2 weeks on/1 week off. Common related adverse events were fatigue (59%), headache (44%), and nausea (43%). Exposure to IPI-504, 17-AAG, and 17-AG increased with IPI-504 dose. Stable disease (SD) was observed in 70% (26 of 37) of patients with GIST and 59% (10 of 17) of patients with STS. There was one confirmed partial response (PR) in a patient with GIST and one PR in a patient with liposarcoma. Metabolic partial responses occurred in 11 of 29 (38%) patients with GIST. In this study of advanced GIST or other STS, IPI-504 was generally well-tolerated with some evidence of antitumor activity, serving as a clinical proof-of-concept that HSP90 inhibition remains a promising strategy.

  3. 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.

  4. A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment

    International Nuclear Information System (INIS)

    Herrera, Fernanda G.; Chan, Philip; Doll, Corinne; Milosevic, Michael; Oza, Amit; Syed, Amy; Pintilie, Melania; Levin, Wilfred; Manchul, Lee; Fyles, Anthony

    2007-01-01

    Purpose: To evaluate the toxicity and effectiveness of celecoxib in combination with definitive chemoradiotherapy (CRT) in women with locally advanced cervical cancer. Methods and Materials: Thirty-one patients were accrued to a phase I-II trial of celecoxib 400 mg by mouth twice per day for 2 weeks before and during CRT. Tumor oxygenation (HP 5 ) and interstitial fluid pressure (IFP) were measured before and 2 weeks after celecoxib administration alone. The median follow-up time was 2.7 years (range, 1.1-4.4 years). Results: The most common acute G3/4 toxicities were hematologic (4/31, 12.9%) and gastrointestinal (5/31, 16.1%) largely attributed to chemotherapy. Late G3/4 toxicity was seen in 4 of 31 patients (13.7% actuarial risk at 2 yr), including fistulas in 3 patients (9.7%). Within the first year of follow-up, 25 of 31 patients (81%) achieved complete response (CR), of whom 20 remained in CR at last follow-up. After 2 weeks of celecoxib administration before CRT, the median IFP decreased slightly (median absolute, -4.6 mm Hg; p = 0.09; relative, -21%; p = 0.07), whereas HP 5 did not change significantly (absolute increase, 3.6%; p = 0.51; median relative increase, 11%; p = 0.27). No significant associations were seen between changes in HP 5 or IFP and response to treatment (p = 0.2, relative HP 5 change and p = 0.14, relative IFP change). Conclusions: Celecoxib in combination with definitive CRT is associated with acceptable acute toxicity, but higher than expected late complications. Celecoxib is associated with a modest reduction in the angiogenic biomarker IFP, but this does not correspond with tumor response

  5. Phase 1 evaluation of EZN-2208, a polyethylene glycol conjugate of SN38, in children adolescents and young adults with relapsed or refractory solid tumors.

    Science.gov (United States)

    Norris, Robin E; Shusterman, Suzanne; Gore, Lia; Muscal, Jodi A; Macy, Margaret E; Fox, Elizabeth; Berkowitz, Noah; Buchbinder, Aby; Bagatell, Rochelle

    2014-10-01

    EZN-2208 is a water-soluble PEGylated conjugate of the topoisomerase inhibitor SN38, the active metabolite of irinotecan. Compared to irinotecan, EZN-2208 has a prolonged half-life permitting extended exposure to SN38. EZN-2208 has demonstrated clinical tolerability and antitumor activity in adults with advanced solid tumors. This Phase 1 study evaluated the safety, pharmacokinetics, and preliminary antitumor activity of EZN-2208 in children with relapsed or refractory solid tumors. EZN-2208 was administered as a 1-hour intravenous infusion once every 21 days at five dose levels (12-30 mg/m(2) ). Filgrastim or pegfilgrastim was administered 24-48 hours after treatment with EZN-2208. The rolling-six design was used for dose determination. Thirty eligible patients (15 females; median [range] age 11.5 years [2-21 years]) were treated with EZN-2208. Dose-limiting diarrhea occurred in one patient receiving 16 mg/m(2) and dose-limiting dehydration was seen in one patient receiving 24 mg/m(2) . At dose levels above 16 mg/m(2) , Grade ≥3 myelosuppression was demonstrated in the majority of patients. Additional adverse events included nausea, vomiting, and fatigue. The maximum tolerated dose was identified as 24 mg/m(2) due to dose-limiting thrombocytopenia in two patients receiving 30 mg/m(2) . Two of nine patients with neuroblastoma who were evaluable for response had partial responses. Five patients (four with neuroblastoma) remained on study for ≥8 cycles. EZN-2208 was generally well-tolerated and was associated with clinical benefit in patients with neuroblastoma. © 2014 Wiley Periodicals, Inc.

  6. Fermentative hydrogen production by microbial consortium

    Energy Technology Data Exchange (ETDEWEB)

    Maintinguer, Sandra I.; Fernandes, Bruna S.; Duarte, Iolanda C.S.; Saavedra, Nora Katia; Adorno, M. Angela T.; Varesche, M. Bernadete [Department of Hydraulics and Sanitation, School of Engineering of Sao Carlos, University of Sao Paulo, Av. Trabalhador Sao-carlense, 400, 13566-590 Sao Carlos-SP (Brazil)

    2008-08-15

    Heat pre-treatment of the inoculum associated to the pH control was applied to select hydrogen-producing bacteria and endospores-forming bacteria. The source of inoculum to the heat pre-treatment was from a UASB reactor used in the slaughterhouse waste treatment. The molecular biology analyses indicated that the microbial consortium presented microorganisms affiliated with Enterobacter cloacae (97% and 98%), Clostridium sp. (98%) and Clostridium acetobutyricum (96%), recognized as H{sub 2} and volatile acids' producers. The following assays were carried out in batch reactors in order to verify the efficiencies of sucrose conversion to H{sub 2} by the microbial consortium: (1) 630.0 mg sucrose/L, (2) 1184.0 mg sucrose/L, (3) 1816.0 mg sucrose/L and (4) 4128.0 mg sucrose/L. The subsequent yields were obtained as follows: 15% (1.2 mol H{sub 2}/mol sucrose), 20% (1.6 mol H{sub 2}/mol sucrose), 15% (1.2 mol H{sub 2}/mol sucrose) and 4% (0.3 mol H{sub 2}/mol sucrose), respectively. The intermediary products were acetic acid, butyric acid, methanol and ethanol in all of the anaerobic reactors. (author)

  7. The NIH Extracellular RNA Communication Consortium

    Directory of Open Access Journals (Sweden)

    Alexandra M. Ainsztein

    2015-08-01

    Full Text Available The Extracellular RNA (exRNA Communication Consortium, funded as an initiative of the NIH Common Fund, represents a consortium of investigators assembled to address the critical issues in the exRNA research arena. The overarching goal is to generate a multi-component community resource for sharing fundamental scientific discoveries, protocols, and innovative tools and technologies. The key initiatives include (a generating a reference catalogue of exRNAs present in body fluids of normal healthy individuals that would facilitate disease diagnosis and therapies, (b defining the fundamental principles of exRNA biogenesis, distribution, uptake, and function, as well as development of molecular tools, technologies, and imaging modalities to enable these studies, (c identifying exRNA biomarkers of disease, (d demonstrating clinical utility of exRNAs as therapeutic agents and developing scalable technologies required for these studies, and (e developing a community resource, the exRNA Atlas, to provide the scientific community access to exRNA data, standardized exRNA protocols, and other useful tools and technologies generated by funded investigators.

  8. 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.

  9. The MRI-Linear Accelerator Consortium : Evidence-Based Clinical Introduction of an Innovation in Radiation Oncology Connecting Researchers, Methodology, Data Collection, Quality Assurance, and Technical Development

    NARCIS (Netherlands)

    Kerkmeijer, LGW; Fuller, Clifton D; Verkooijen, Helena M; Verheij, Marcel; Choudhury, Ananya; Harrington, Kevin J; Schultz, Chris; Sahgal, Arjun; Frank, Steven J; Goldwein, Joel; Brown, Kevin J; Minsky, Bruce D; van Vulpen, Marco

    2016-01-01

    An international research consortium has been formed to facilitate evidence-based introduction of MR-guided radiotherapy (MR-linac) and to address how the MR-linac could be used to achieve an optimized radiation treatment approach to improve patients' survival, local, and regional tumor control and

  10. Heat shock protein 70 and tumor-infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

    Science.gov (United States)

    Stangl, Stefan; Tontcheva, Nikoletta; Sievert, Wolfgang; Shevtsov, Maxim; Niu, Minli; Schmid, Thomas E; Pigorsch, Steffi; Combs, Stephanie E; Haller, Bernhard; Balermpas, Panagiotis; Rödel, Franz; Rödel, Claus; Fokas, Emmanouil; Krause, Mechthild; Linge, Annett; Lohaus, Fabian; Baumann, Michael; Tinhofer, Inge; Budach, Volker; Stuschke, Martin; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Belka, Claus; Maihöfer, Cornelius; Mönnich, David; Zips, Daniel; Multhoff, Gabriele

    2018-05-01

    Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre-activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor-infiltrating CD56 + NK cells in formalin-fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin-based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3-4) showed significantly decreased overall survival (OS; p = 0.008), local progression-free survival (LPFS; p = 0.034) and distant metastases-free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0-2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16- (p = 0.001), p53- (p = 0.0003) and HPV16 DNA-negative (p = 0.001) tumors. The absence or low numbers of tumor-infiltrating CD56 + NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor-infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor-infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  11. Phase I Dose-Escalation Study of Linsitinib (OSI-906) and Erlotinib in Patients with Advanced Solid Tumors.

    Science.gov (United States)

    Macaulay, Valentine M; Middleton, Mark R; Eckhardt, S Gail; Rudin, Charles M; Juergens, Rosalyn A; Gedrich, Richard; Gogov, Sven; McCarthy, Sean; Poondru, Srinivasu; Stephens, Andrew W; Gadgeel, Shirish M

    2016-06-15

    Cross-talk between type I IGF receptor (IGF1R), insulin receptor (INSR), and epidermal growth factor receptor (EGFR) mediates resistance to individual receptor blockade. This study aimed to determine the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of linsitinib, a potent oral IGF1R/INSR inhibitor, with EGFR inhibitor erlotinib. This open-label, dose-escalation study investigated linsitinib schedules S1: once daily intermittent (days 1-3 weekly); S2, once daily continuous; S3, twice-daily continuous; each with erlotinib 100-150 mg once daily; and a non-small cell lung cancer (NSCLC) expansion cohort. Ninety-five patients were enrolled (S1, 44; S2, 24; S3, 12; expansion cohort, 15) and 91 treated. Seven experienced dose-limiting toxicities: QTc prolongation (3), abnormal liver function (2), hyperglycemia (1), and anorexia (1). Common adverse events included drug eruption (84%), diarrhea (73%), fatigue (68%), nausea (58%), vomiting (40%). MTDs for linsitinib/erlotinib were 450/150 mg (S1), 400/100 mg (S2). On the basis of prior monotherapy data, S3 dosing at 150 mg twice daily/150 mg once daily was the recommended phase II dose for the expansion cohort. There was no evidence of drug-drug interaction. Pharmacodynamic data showed IGF-1 elevation and reduced IGF1R/INSR phosphorylation, suggesting pathway inhibition. Across schedules, 5/75 (7%) evaluable patients experienced partial responses: spinal chordoma (268+ weeks), rectal cancer (36 weeks), three NSCLCs including 2 adenocarcinomas (16, 72 weeks), 1 squamous wild-type EGFR NSCLC (36 weeks). Disease control (CR+PR+SD) occurred in 38 of 75 (51%), and 28 of 91 (31%) patients were on study >12 weeks. The linsitinib/erlotinib combination was tolerable with preliminary evidence of activity, including durable responses in cases unlikely to respond to erlotinib monotherapy. Clin Cancer Res; 22(12); 2897-907. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. Institutional Support : Consortium for Economic and Social Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Institutional Support : Consortium for Economic and Social Research (CRES) Sénégal. The Consortium pour la recherche économique et sociale (CRES) is an association of a multidisciplinary team of researchers based in Dakar, Sénégal. Its activities are organized under five departments: growth, poverty and equity; local ...

  13. Urban Consortium Energy Task Force - Year 21 Final Report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2003-04-01

    The Urban Consortium Energy Task Force (UCETF), comprised of representatives of large cities and counties in the United States, is a subgroup of the Urban Consortium, an organization of the nation's largest cities and counties joined together to identify, develop and deploy innovative approaches and technological solutions to pressing urban issues.

  14. An isolated bacterial consortium for crude oil biodegradation

    African Journals Online (AJOL)

    GREGORY

    2011-12-16

    Dec 16, 2011 ... designed using DesignExpert 6.0.8 software by optimizing the amount of crude oil, microbial inoculum and sludge which are initially ... Key words: Crude oil, bacterial consortium, kinetics, bioremediation, biostimulation, natural attenuation. ... For the preparation of the consortiums, colonies were plated on.

  15. Aims, organization and activities of the consortium for underground storage

    International Nuclear Information System (INIS)

    Stucky, G.

    1977-01-01

    The consortium of Swiss authorities interested in underground storage (the petroleum oil and gas industries, for fuel storage; the nuclear industry for radioactive waste disposal), was initiated in 1972. The author outlines the motives behind the formation of the consortium and outlines its structure and objectives. The envisaged projects are outlined. (F.Q.)

  16. Metabolism of 3-methylindole by a methanogenic consortium

    Energy Technology Data Exchange (ETDEWEB)

    Jidong Gu; Berry, D.F. (Virginia Polytechnic Inst. and State Univ., Blacksburg (United States))

    1992-08-01

    A methanogenic 3-methylindole (3-MI)-degrading consortium, enriched from wetland soil, completely mineralized 3-MI. Degradation proceeded through an initial hydroxylation reaction forming 3-methyloxindole. The consortium was unable to degrade oxindole or isatin, suggesting a new pathway for 3-MI fermentation. 3-Methylindole was identified by mass spectroscopy, ultraviolet spectroscopy, and proton nuclear magnetic resonance spectrometry.

  17. Serum Calprotectin Versus Acute-Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors.

    Science.gov (United States)

    Inciarte-Mundo, José; Victoria Hernández, Maria; Ruiz-Esquide, Virginia; Raquel Cabrera-Villalba, Sonia; Ramirez, Julio; Cuervo, Andrea; Pascal, Mariona; Yagüe, Jordi; Cañete, Juan D; Sanmarti, Raimon

    2016-07-01

    To compare the accuracy of serum calprotectin and acute-phase reactants (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels. We conducted a cross-sectional study of 87 RA patients receiving adalimumab, etanercept (ETN), or infliximab (IFX); 56 psoriatic arthritis (PsA) patients and 40 healthy blood donors were included as controls. Associations between calprotectin, CRP, and ESR and composite articular indices (Disease Activity Score in 28 joints [DAS28], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index) were analyzed by correlation and linear regression and the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves (area under the curve [AUC]). Calprotectin levels correlated better with all composite activity indices than CRP and ESR (all r coefficients >0.70). Calprotectin levels were significantly lower in RA and PsA patients in clinical remission compared with those with low disease activity for all articular indices. In RA, ESR discriminated between remission and low disease activity only when using DAS28, and CRP only with SDAI. In RA patients in remission/low disease activity, calprotectin but not CRP or ESR distinguished between patients with no swollen joints and those with ≥1 swollen joint (1.74 μg/ml versus 3.04 μg/ml; P = 0.010). Using DAS28 ≥2.6 as the reference variable, calprotectin showed an AUC of 0.92; the best cutoff was ≥2.47 μg/ml with a likelihood ratio of 6.3 (95% confidence interval 2.5-15.8). Calprotectin serum levels inversely correlated with trough serum drug levels of ETN (ρ = -0.671, P acute-phase reactants, even in patients with low inflammatory activity. © 2016, American College of Rheumatology.

  18. A phase II trial of regorafenib in patients with metastatic and/or a unresectable gastrointestinal stromal tumor harboring secondary mutations of exon 17.

    Science.gov (United States)

    Yeh, Chun-Nan; Chen, Ming-Huang; Chen, Yen-Yang; Yang, Ching-Yao; Yen, Chueh-Chuan; Tzen, Chin-Yuan; Chen, Li-Tzong; Chen, Jen-Shi

    2017-07-04

    Gastrointestinal stromal tumors (GISTs) are caused by the constitutive activation of KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations. Imatinib selectively inhibits KIT and PDGFR, leading to disease control for 80%-90% of patients with metastatic GIST. Imatinib resistance can occur within a median of 2-3 years due to secondary mutations in KIT. According to preclinical studies, both imatinib and sunitinib are ineffective against exon 17 mutations. However, the treatment efficacy of regorafenib for patients with GIST with exon 17 mutations is still unknown. Documented patients with GIST with exon 17 mutations were enrolled in this study. Patients received 160 mg of oral regorafenib daily on days 1-21 of a 28-day cycle. The primary end point of this trial was the clinical benefit rate (CBR; i.e., complete or partial response [PR], as well as stable disease [SD]) at 16 weeks. The secondary end points of this study included progression free survival (PFS), overall survival, and safety. Between June 2014 to May 2016, 18 patients were enrolled (15 of which were eligible for response evaluation). The CBR at 16 weeks was 93.3% (14 of 15; 6 PR and 8 SD). The median PFS was 22.1 months. The most common grade 3 toxicities were hand-and-foot skin reactions (10 of 18; 55.6%), followed by hypertension (5 of 18; 27.8%). Regorafenib significantly prolonged PFS in patients with advanced GIST harboring secondary mutations of exon 17. A phase III trial of regorafenib versus placebo is warranted. This trial is registered at ClinicalTrials.gov in November 2015, number NCT02606097.Key message: This phase II trial was conducted to assess the efficacy and safety of regorafenib in patients with GIST with exon 17 mutations. The results provide strong evidence that regorafenib significantly prolonged PFS in patients with advanced GIST harboring secondary mutations of exon 17.

  19. The Black Rock Forest Consortium: A narrative

    Science.gov (United States)

    Buzzetto-More, Nicole Antoinette

    The Black Rock Forest is a 3,785-acre wilderness area whose richly forested landscape represents the splendor of the Hudson Valley Region of New York State. Although originally intended to become the home of wealthy banker James Stillman, it was his son Ernest whose love of conservation caused him to embrace the then new and revolutionary practice of sustainable forestry and establish Black Rock in 1928. Due to Ernest Stillman's foresight, the property was protected from development and bequeathed to Harvard University following his death for the establishment of an experimental forest. The modern environmental movement in America began when the Black Rock Forest was threatened with development by Consolidated Edison, and the people of the surrounding community banded together, battling tirelessly for over 17 years to stop the degradation of this historic forest. The outcome of this crusade marked a hallmark win for the environment leaving an illustrious and inveterate legacy. The campaign resulted in the watershed legislation the National Environmental Policy Act, the formation of several environmental advocacy groups, the creation of the Council on Environmental Quality of the Executive Office of the President, as well as set a precedent for communities to initiate and win cases against major corporations in order to safeguard natural resources. In the midst of the controversy it became apparent that alternative futures for the Forest needed to be explored. As a result of a committee report and one man's vision, the idea emerged to create a consortium that would purchase and steward the Forest. With a formation that took nearly fifteen years, the Black Rock Forest Consortium was formed, a unique amalgamation of K--12 public and private schools, colleges and universities, and science and cultural centers that successfully collaborate to enhance scientific research, environmental conservation, and education. The Consortium works to bridge the gaps between learners

  20. Safety and pharmacokinetics of motesanib in combination with gemcitabine and erlotinib for the treatment of solid tumors: a phase 1b study

    Directory of Open Access Journals (Sweden)

    Sun Yu-Nien

    2011-07-01

    Full Text Available Abstract Background This phase 1b study assessed the maximum tolerated dose (MTD, safety, and pharmacokinetics of motesanib (a small-molecule antagonist of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit administered once daily (QD or twice daily (BID in combination with erlotinib and gemcitabine in patients with solid tumors. Methods Patients received weekly intravenous gemcitabine (1000 mg/m2 and erlotinib (100 mg QD alone (control cohort or in combination with motesanib (50 mg QD, 75 mg BID, 125 mg QD, or 100 mg QD; cohorts 1-4; or erlotinib (150 mg QD in combination with motesanib (100 or 125 mg QD; cohorts 5 and 6. Results Fifty-six patients were enrolled and received protocol-specified treatment. Dose-limiting toxicities occurred in 11 patients in cohorts 1 (n = 2, 2 (n = 4, 3 (n = 3, and 6 (n = 2. The MTD of motesanib in combination with gemcitabine and erlotinib was 100 mg QD. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Frequently occurring motesanib-related adverse events included diarrhea (n = 19, nausea (n = 18, vomiting (n = 13, and fatigue (n = 12, which were mostly of worst grade Conclusions Treatment with motesanib 100 mg QD plus erlotinib and gemcitabine was tolerable. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Trial Registration ClinicalTrials.gov NCT01235416

  1. A consortium approach to glass furnace modeling.

    Energy Technology Data Exchange (ETDEWEB)

    Chang, S.-L.; Golchert, B.; Petrick, M.

    1999-04-20

    Using computational fluid dynamics to model a glass furnace is a difficult task for any one glass company, laboratory, or university to accomplish. The task of building a computational model of the furnace requires knowledge and experience in modeling two dissimilar regimes (the combustion space and the liquid glass bath), along with the skill necessary to couple these two regimes. Also, a detailed set of experimental data is needed in order to evaluate the output of the code to ensure that the code is providing proper results. Since all these diverse skills are not present in any one research institution, a consortium was formed between Argonne National Laboratory, Purdue University, Mississippi State University, and five glass companies in order to marshal these skills into one three-year program. The objective of this program is to develop a fully coupled, validated simulation of a glass melting furnace that may be used by industry to optimize the performance of existing furnaces.

  2. Consortium for Petroleum & Natural Gas Stripper Wells

    Energy Technology Data Exchange (ETDEWEB)

    Joel L. Morrison; Sharon L. Elder

    2007-03-31

    The Pennsylvania State University, under contract to the U.S. Department of Energy (DOE), National Energy Technology Laboratory (NETL), established a national industry-driven Stripper Well Consortium (SWC) that is focused on improving the production performance of domestic petroleum and/or natural gas stripper wells. The SWC represents a partnership between U.S. petroleum and natural gas producers, trade associations, state funding agencies, academia, and the NETL. This document serves as the twelfth quarterly technical progress report for the SWC. Key activities for this reporting period included: (1) Drafting and releasing the 2007 Request for Proposals; (2) Securing a meeting facility, scheduling and drafting plans for the 2007 Spring Proposal Meeting; (3) Conducting elections and announcing representatives for the four 2007-2008 Executive Council seats; (4) 2005 Final Project Reports; (5) Personal Digital Assistant Workshops scheduled; and (6) Communications and outreach.

  3. Midwest Superconductivity Consortium: 1995 Progress report

    International Nuclear Information System (INIS)

    1996-01-01

    The mission of the Midwest Superconductivity Consortium, MISCON, is to advance the science and understanding of high Tc superconductivity. During the past year, 26 projects produced over 133 talks and 127 publications. Three Master's Degrees and 9 Doctor's of Philosophy Degrees were granted to students working on MISCON projects. Group activities and interactions involved 2 MISCON group meetings (held in January and July); the third MISCON Summer School held in July; 12 external speakers; 81 collaborations (with universities, industry, Federal laboratories, and foreign research centers); and 54 exchanges of samples and/or measurements. Research achievements this past year focused on understanding the effects of processing phenomena on structure-property interrelationships and the fundamental nature of transport properties in high-temp superconductors

  4. Perspectives of International Human Epigenome Consortium

    Directory of Open Access Journals (Sweden)

    Jae-Bum Bae

    2013-03-01

    Full Text Available As the International Human Epigenome Consortium (IHEC launched officially at the 2010 Washington meeting, a giant step toward the conquest of unexplored regions of the human genome has begun. IHEC aims at the production of 1,000 reference epigenomes to the international scientific community for next 7-10 years. Seven member institutions, including South Korea, Korea National Institute of Health (KNIH, will produce 25-200 reference epigenomes individually, and the produced data will be publically available by using a data center. Epigenome data will cover from whole genome bisulfite sequencing, histone modification, and chromatin access information to miRNA-seq. The final goal of IHEC is the production of reference maps of human epigenomes for key cellular status relevant to health and disease.

  5. ZATPAC: a model consortium evaluates teen programs.

    Science.gov (United States)

    Owen, Kathryn; Murphy, Dana; Parsons, Chris

    2009-09-01

    How do we advance the environmental literacy of young people, support the next generation of environmental stewards and increase the diversity of the leadership of zoos and aquariums? We believe it is through ongoing evaluation of zoo and aquarium teen programming and have founded a consortium to pursue those goals. The Zoo and Aquarium Teen Program Assessment Consortium (ZATPAC) is an initiative by six of the nation's leading zoos and aquariums to strengthen institutional evaluation capacity, model a collaborative approach toward assessing the impact of youth programs, and bring additional rigor to evaluation efforts within the field of informal science education. Since its beginning in 2004, ZATPAC has researched, developed, pilot-tested and implemented a pre-post program survey instrument designed to assess teens' knowledge of environmental issues, skills and abilities to take conservation actions, self-efficacy in environmental actions, and engagement in environmentally responsible behaviors. Findings from this survey indicate that teens who join zoo/aquarium programs are already actively engaged in many conservation behaviors. After participating in the programs, teens showed a statistically significant increase in their reported knowledge of conservation and environmental issues and their abilities to research, explain, and find resources to take action on conservation issues of personal concern. Teens also showed statistically significant increases pre-program to post-program for various conservation behaviors, including "I talk with my family and/or friends about things they can do to help the animals or the environment," "I save water...," "I save energy...," "When I am shopping I look for recycled products," and "I help with projects that restore wildlife habitat."

  6. A consortium approach to molecular genetic services. Scottish Molecular Genetics Consortium.

    OpenAIRE

    Brock, D J

    1990-01-01

    The four Scottish university medical genetics centres formed a consortium in 1985 to provide a DNA based service in prenatal diagnosis, carrier detection, and predictive testing for a range of Mendelian disorders. Each centre took sole responsibility for laboratory analyses of an assigned set of disorders, while families continued to be investigated and patients counselled within their own areas. DNA was extracted from relevant tissues in the centre most convenient to the family member and th...

  7. The MRI-Linear Accelerator Consortium: Evidence-Based Clinical Introduction of an Innovation in Radiation Oncology Connecting Researchers, Methodology, Data Collection, Quality Assurance, and Technical Development.

    Science.gov (United States)

    Kerkmeijer, Linda G W; Fuller, Clifton D; Verkooijen, Helena M; Verheij, Marcel; Choudhury, Ananya; Harrington, Kevin J; Schultz, Chris; Sahgal, Arjun; Frank, Steven J; Goldwein, Joel; Brown, Kevin J; Minsky, Bruce D; van Vulpen, Marco

    2016-01-01

    An international research consortium has been formed to facilitate evidence-based introduction of MR-guided radiotherapy (MR-linac) and to address how the MR-linac could be used to achieve an optimized radiation treatment approach to improve patients' survival, local, and regional tumor control and quality of life. The present paper describes the organizational structure of the clinical part of the MR-linac consortium. Furthermore, it elucidates why collaboration on this large project is necessary, and how a central data registry program will be implemented.

  8. A phase 1b dose expansion study of the pan-class I PI3K inhibitor buparlisib (BKM120) plus carboplatin and paclitaxel in PTEN deficient tumors and with dose intensified carboplatin and paclitaxel.

    Science.gov (United States)

    Smyth, Lillian M; Monson, Kelsey R; Jhaveri, Komal; Drilon, Alexander; Li, Bob T; Abida, Wassim; Iyer, Gopa; Gerecitano, John F; Gounder, Mrinal; Harding, James J; Voss, Martin H; Makker, Vicky; Ho, Alan L; Razavi, Pedram; Iasonos, Alexia; Bialer, Philip; Lacouture, Mario E; Teitcher, Jerrold B; Erinjeri, Joseph P; Katabi, Nora; Fury, Matthew G; Hyman, David M

    2017-12-01

    Purpose We previously reported the phase I dose escalation study of buparlisib, a pan-class 1A PI3K inhibitor, combined with platinum/taxane-based chemotherapy in patients with advanced solid tumors. The combination was well tolerated and promising preliminary efficacy was observed in PTEN deficient tumors. This phase I dose expansion study now evaluates buparlisib plus high dose carboplatin and paclitaxel in unselected patients with advanced solid tumors and buparlisib plus standard dose carboplatin and paclitaxel in patients with PTEN deficient tumors (ClinicalTrials.gov, NCT01297452). Methods There were two expansion cohorts: Cohort A received continuous buparlisib (100 mg/daily) orally plus high dose carboplatin AUC 6 and paclitaxel 200 mg/m2; Cohort B treated patients with PTEN deficient tumors only and they received the recommended phase II dose (RP2D) of continuous buparlisib (100 mg/daily) orally plus standard dose carboplatin AUC 5 and paclitaxel 175 mg/m2. Both cohorts received chemotherapy intravenously on day 1 of the 21-day cycle with pegfilgrastim support. Primary endpoint in Cohort A was to evaluate the safety and tolerability of chemotherapy dose intensification with buparlisib and in Cohort B was to describe preliminary efficacy of the combination among patients with tumors harboring a PTEN mutation or homozygous deletion. Results 14 subjects were enrolled, 7 in Cohort A and 7 in Cohort B. Dose reductions were required in 5 (71%) and 3 (43%) patients, in cohort A and B respectively. Grade 3 adverse events in Cohort A included lymphopenia (n = 5 [71%]), hyperglycemia (n = 2, [29%]), diarrhea (n = 2, [29%]) and rash (n = 2, [29%]) and in cohort B included lymphopenia (n = 5 [71%]), hyperglycemia (n = 4 [57%]) and neutropenia (n = 2 [29%]. The mean number of cycles on protocol was 6. The overall objective response rate was 14% (2 /14). No objective responses were observed in the PTEN deficient cohort. Four out of 6 patients with

  9. Establishing an International Soil Modelling Consortium

    Science.gov (United States)

    Vereecken, Harry; Schnepf, Andrea; Vanderborght, Jan

    2015-04-01

    -change-feedback processes, bridge basic soil science research and management, and facilitate the communication between science and society . To meet these challenges an international community effort is required, similar to initiatives in systems biology, hydrology, and climate and crop research. We therefore propose to establish an international soil modelling consortium with the aims of 1) bringing together leading experts in modelling soil processes within all major soil disciplines, 2) addressing major scientific gaps in describing key processes and their long term impacts with respect to the different functions and ecosystem services provided by soil, 3) intercomparing soil model performance based on standardized and harmonized data sets, 4) identifying interactions with other relevant platforms related to common data formats, protocols and ontologies, 5) developing new approaches to inverse modelling, calibration, and validation of soil models, 6) integrating soil modelling expertise and state of the art knowledge on soil processes in climate, land surface, ecological, crop and contaminant models, and 7) linking process models with new observation, measurement and data evaluation technologies for mapping and characterizing soil properties across scales. Our consortium will bring together modelers and experimental soil scientists at the forefront of new technologies and approaches to characterize soils. By addressing these aims, the consortium will contribute to improve the role of soil modeling as a knowledge dissemination instrument in addressing key global issues and stimulate the development of translational research activities. This presentation will provide a compelling case for this much-needed effort, with a focus on tangible benefits to the scientific and food security communities.

  10. SEEA SOUTHEAST CONSORTIUM FINAL TECHNICAL REPORT

    Energy Technology Data Exchange (ETDEWEB)

    Block, Timothy [Southeast Energy Efficiency Alliance; Ball, Kia [Southeast Energy Efficiency Alliance; Fournier, Ashley [Southeast Energy Efficiency Alliance

    2014-01-21

    In 2010 the Southeast Energy Efficiency Alliance (SEEA) received a $20 million Energy Efficiency and Conservation Block Grant (EECBG) under the U.S. Department of Energy’s Better Building Neighborhood Program (BBNP). This grant, funded by the American Recovery and Reinvestment Act, also included sub-grantees in 13 communities across the Southeast, known as the Southeast Consortium. The objective of this project was to establish a framework for energy efficiency retrofit programs to create models for replication across the Southeast and beyond. To achieve this goal, SEEA and its project partners focused on establishing infrastructure to develop and sustain the energy efficiency market in specific localities across the southeast. Activities included implementing minimum training standards and credentials for marketplace suppliers, educating and engaging homeowners on the benefits of energy efficiency through strategic marketing and outreach and addressing real or perceived financial barriers to investments in whole-home energy efficiency through a variety of financing mechanisms. The anticipated outcome of these activities would be best practice models for program design, marketing, financing, data collection and evaluation as well as increased market demand for energy efficiency retrofits and products. The Southeast Consortium’s programmatic impacts along with the impacts of the other BBNP grantees would further the progress towards the overall goal of energy efficiency market transformation. As the primary grantee SEEA served as the overall program administrator and provided common resources to the 13 Southeast Consortium sub-grantees including contracted services for contractor training, quality assurance testing, data collection, reporting and compliance. Sub-grantee programs were located in cities across eight states including Alabama, Florida, Georgia, Louisiana, North Carolina, South Carolina, Tennessee, Virginia and the U.S. Virgin Islands. Each sub

  11. Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors.

    Science.gov (United States)

    Haluska, Paul; Menefee, Michael; Plimack, Elizabeth R; Rosenberg, Jonathan; Northfelt, Donald; LaVallee, Theresa; Shi, Li; Yu, Xiang-Qing; Burke, Patricia; Huang, Jiaqi; Huang, Jaiqi; Viner, Jaye; McDevitt, Jennifer; LoRusso, Patricia

    2014-09-15

    This phase I, multicenter, open-label, single-arm, dose-escalation, and dose-expansion study evaluated the safety, tolerability, and antitumor activity of MEDI-573 in adults with advanced solid tumors refractory to standard therapy or for which no standard therapy exists. Patients received MEDI-573 in 1 of 5 cohorts (0.5, 1.5, 5, 10, or 15 mg/kg) dosed weekly or 1 of 2 cohorts (30 or 45 mg/kg) dosed every 3 weeks. Primary end points included the MEDI-573 safety profile, maximum tolerated dose (MTD), and optimal biologic dose (OBD). Secondary end points included MEDI-573 pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor activity. In total, 43 patients (20 with urothelial cancer) received MEDI-573. No dose-limiting toxicities were identified, and only 1 patient experienced hyperglycemia related to treatment. Elevations in levels of insulin and/or growth hormone were not observed. Adverse events observed in >10% of patients included fatigue, anorexia, nausea, diarrhea, and anemia. PK evaluation demonstrated that levels of MEDI-573 increased with dose at all dose levels tested. At doses >5 mg/kg, circulating levels of insulin-like growth factor (IGF)-I and IGFII were fully suppressed. Of 39 patients evaluable for response, none experienced partial or complete response and 13 had stable disease as best response. The MTD of MEDI-573 was not reached. The OBD was 5 mg/kg weekly or 30 or 45 mg/kg every 3 weeks. MEDI-573 showed preliminary antitumor activity in a heavily pretreated population and had a favorable tolerability profile, with no notable perturbations in metabolic homeostasis. ©2014 American Association for Cancer Research.

  12. Differential Toxicity in Patients with and without DNA Repair Mutations: Phase I Study of Carboplatin and Talazoparib in Advanced Solid Tumors.

    Science.gov (United States)

    Dhawan, Mallika S; Bartelink, Imke H; Aggarwal, Rahul Raj; Leng, Jim; Zhang, Jenna Z; Pawlowska, Nela; Terranova-Barberio, Manuela; Grabowsky, Jennifer A; Gewitz, Andrew; Chien, Amy J; Moasser, Mark; Kelley, Robin K; Maktabi, Tayeba; Thomas, Scott; Munster, Pamela N

    2017-11-01

    Purpose: The PARP inhibitor (PARPi) talazoparib may potentiate activity of chemotherapy and toxicity in cells vulnerable to DNA damage. Experimental Design: This phase I study evaluated the safety, tolerability, pharmacokinetics, and efficacy of talazoparib and carboplatin. Pharmacokinetic modeling explored associations between DNA vulnerability and hematologic toxicity. Results: Twenty-four patients (eight males; 16 females) with solid tumors were enrolled in four cohorts at 0.75 and 1 mg daily talazoparib and weekly carboplatin (AUC 1 and 1.5, every 2 weeks or every 3 weeks), including 14 patients (58%) with prior platinum treatment. Dose-limiting toxicities included grade 3 fatigue and grade 4 thrombocytopenia; the MTD was not reached. Grade 3/4 toxicities included fatigue (13%), neutropenia (63%), thrombocytopenia (29%), and anemia (38%). After cycle 2's dose, delays/reductions were required in all patients. One complete and two partial responses occurred in germline BRCA1/2 (gBRCA1/2) patients. Four patients showed stable disease beyond 4 months, three of which had known mutations in DNA repair pathways. Pharmacokinetic toxicity modeling suggests that after three cycles of carboplatin AUC 1.5 every 3 weeks and talazoparib 1 mg daily, neutrophil counts decreased 78% [confidence interval (CI), 87-68] from baseline in gBRCA carriers and 63% (CI, 72-55) in noncarriers ( P < 0.001). Pharmacokinetic toxicity modeling suggests an intermittent, pulse dosing schedule of PARP inhibition, differentiated by gBRCA mutation status, may improve the benefit/risk ratio of combination therapy. Conclusions: Carboplatin and talazoparib showed efficacy in DNA damage mutation carriers, but hematologic toxicity was more pronounced in gBRCA carriers. Carboplatin is best combined with intermittent talazoparib dosing differentiated by germline and somatic DNA damage mutation carriers. Clin Cancer Res; 23(21); 6400-10. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors.

    Science.gov (United States)

    Ricart, Alejandro D; Berlin, Jordan D; Papadopoulos, Kyriakos P; Syed, Samira; Drolet, Daniel W; Quaratino-Baker, Charlotte; Horan, Julie; Chick, Jon; Vermeulen, Wendy; Tolcher, Anthony W; Rowinsky, Eric K; Rothenberg, Mace L

    2008-12-01

    To evaluate the safety and describe the pharmacokinetic profile of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, in combination with cisplatin (CDDP) in adults with advanced solid tumors. CDDP was administered as a 2-h intravenous infusion followed by OSI-7904L intravenously over 30 min, both given every 3 weeks. Doses of each drug were escalated in separate cohorts of patients. Five dose levels of CDDP/OSI-7904L were explored: 60/6, 60/9, 60/12, 60/7.5, and 75/7.5 mg/m2. Pharmacokinetic samples, baseline plasma homocysteine, and genotype polymorphisms were evaluated. Twenty-seven patients were treated with 101 total courses of CDDP/OSI-7904L. Dose-limiting toxicity was observed in 2 patients in the CDDP/OSI-7904L 60/12 mg/m2 cohort. One patient experienced rash, stomatitis, dehydration, renal failure, hyperbilirubinemia, and fatal neutropenic sepsis, whereas the other patient experienced grade 3 nausea, vomiting, and ileus. Therefore, the CDDP/OSI-7904L 60/9 mg/m2 cohort was expanded, with 2 of 6 patients reporting significant fatigue. Other toxicities were mild or moderate. Intermediate dose levels of 60/7.5 and 75/7.5 mg/m2 were evaluated, and the latter was identified as the recommended dose for phase II studies. No major pharmacokinetic interactions between CDDP and OSI-7904L were observed. Three patients had partial responses (gastric adenocarcinoma and heavily pretreated breast cancer). There was no significant relationship between baseline homocysteine and toxicity. The recommended doses for CDDP and OSI-7904L administered once every 3 weeks are 75 and 7.5 mg/m2, respectively. Pharmacokinetic interaction between the agents was not apparent. Preliminary clinical activity was observed in breast and gastric cancer.

  14. Multi-University Southeast INIE Consortium

    International Nuclear Information System (INIS)

    Hawari, Ayman; Hertel, Nolan; Al-Sheikhly, Mohamed; Miller, Laurence; Bayoumi, Abdel-Moeze; Haghighat, Ali; Lewis, Kenneth

    2010-01-01

    The Multi-University Southeast INIE Consortium (MUSIC) was established in response to the US Department of Energy's (DOE) Innovations in Nuclear Infrastructure and Education (INIE) program. MUSIC was established as a consortium composed of academic members and national laboratory partners. The members of MUSIC are the nuclear engineering programs and research reactors of Georgia Institute of Technology (GIT), North Carolina State University (NCSU), University of Maryland (UMD), University of South Carolina (USC), and University of Tennessee (UTK). The University of Florida (UF), and South Carolina State University (SCSU) were added to the MUSIC membership in the second year. In addition, to ensure proper coordination between the academic community and the nation's premier research and development centers in the fields of nuclear science and engineering, MUSIC created strategic partnerships with Oak Ridge National Laboratory (ORNL) including the Spallation Neutron Source (SNS) project and the Joint Institute for Neutron Scattering (JINS), and the National Institute of Standards and Technology (NIST). A partnership was also created with the Armed Forces Radiobiology Research Institute (AFRRI) with the aim of utilizing their reactor in research if funding becomes available. Consequently, there are three university research reactors (URRs) within MUSIC, which are located at NCSU (1-MW PULSTAR), UMD (0.25-MW TRIGA) and UF (0.10-MW Argonaut), and the AFRRI reactor (1-MW TRIGA MARK F). The overall objectives of MUSIC are: (a) Demonstrate that University Research Reactors (URR) can be used as modern and innovative instruments of research in the basic and applied sciences, which include applications in fundamental physics, materials science and engineering, nondestructive examination, elemental analysis, and contributions to research in the health and medical sciences, (b) Establish a strong technical collaboration between the nuclear engineering faculty and the MUSIC URRs

  15. Consortium for Petroleum & Natural Gas Stripper Wells

    Energy Technology Data Exchange (ETDEWEB)

    Morrison, Joel [Pennsylvania State Univ., University Park, PA (United States)

    2011-12-01

    The United States has more oil and gas wells than any other country. As of December 31, 2004, there were more than half a million producing oil wells in the United States. That is more than three times the combined total for the next three leaders: China, Canada, and Russia. The Stripper Well Consortium (SWC) is a partnership that includes domestic oil and gas producers, service and supply companies, trade associations, academia, the Department of Energy’s Strategic Center for Natural Gas and Oil (SCNGO) at the National Energy Technology Laboratory (NETL), and the New York State Energy Research and Development Authority (NYSERDA). The Consortium was established in 2000. This report serves as a final technical report for the SWC activities conducted over the May 1, 2004 to December 1, 2011 timeframe. During this timeframe, the SWC worked with 173 members in 29 states and three international countries, to focus on the development of new technologies to benefit the U.S. stripper well industry. SWC worked with NETL to develop a nationwide request-for-proposal (RFP) process to solicit proposals from the U.S. stripper well industry to develop and/or deploy new technologies that would assist small producers in improving the production performance of their stripper well operations. SWC conducted eight rounds of funding. A total of 132 proposals were received. The proposals were compiled and distributed to an industry-driven SWC executive council and program sponsors for review. Applicants were required to make a formal technical presentation to the SWC membership, executive council, and program sponsors. After reviewing the proposals and listening to the presentations, the executive council made their funding recommendations to program sponsors. A total of 64 projects were selected for funding, of which 59 were fully completed. Penn State then worked with grant awardees to issue a subcontract for their approved work. SWC organized and hosted a total of 14 meetings

  16. Tumor vaccines

    International Nuclear Information System (INIS)

    Frank, M.; Ihan, A.

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regiments. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tumor vaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which immune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system, what makes them poorly immunogenic or even tolerogenic. Novel immunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor- specific T-lymphocyte transfer and tumor specific monoclonal antibodies). (author)

  17. Astroparticle Physics European Consortium Town Meeting Conference

    CERN Document Server

    2016-01-01

    The Astroparticle Physics European Consortium (APPEC) invites you to a town meeting at the Grand Amphithéatre de Sorbonne in Paris on the 6th and 7th April 2016 to discuss an update of the 2011 APPEC Astroparticle Physics roadmap, to be published in September 2016. In 2014 APPEC decided to launch an update of the 2011 Roadmap, transforming it to a “resource aware” roadmap. The intention was to gauge the financial impact of the beginnings of operation of the large global scale observatories put forward in the previous roadmap and to examine the possibilities of international coordination of future global initiatives. The APPEC Scientific Advisory Committee examined the field and prepared a set of recommendations. Based on these recommendations, the APPEC General Assembly drafted a set of “considerations” to be published by end of February 2016 and be debated in an open dialogue with the community, through the web page but primarily at the town meeting of 6-7 April. Based on this debate the final re...

  18. The nation's first consortium to address waste management issues

    International Nuclear Information System (INIS)

    Mikel, C.J.

    1991-01-01

    On July 26, 1989, the secretary of the Department of Energy (DOE), Admiral James Watkins, announced approval of the Waste-Management Education and Research Consortium (WERC). The consortium is composed of New Mexico State University (NMSU), the University of New Mexico, the New Mexico Institute of Mining and Technology, Los Alamos National Laboratory, and Sandia National Laboratories. This pilot program is expected to form a model for other regional and national programs. The WERC mission is to expand the national capability to address issues associated with the management of hazardous, radioactive, and solid waste. Research, technology transfer, and education/training are the three areas that have been identified to accomplish the objectives set by the consortium. The members of the consortium will reach out to the DOE facilities, other government agencies and facilities, and private institutions across the country. Their goal is to provide resources for solutions to waste management problems

  19. 78 FR 47674 - Genome in a Bottle Consortium-Progress and Planning Workshop

    Science.gov (United States)

    2013-08-06

    ... principal motivation for this consortium is to enable performance assessment of sequencing and science-based... progress of the consortium work, continue to get broad input from individual stakeholders to update or refine the consortium work plan, continue to broadly solicit consortium membership from interested...

  20. 77 FR 43237 - Genome in a Bottle Consortium-Work Plan Review Workshop

    Science.gov (United States)

    2012-07-24

    ... principal motivation for this consortium is to enable performance assessment of sequencing and science-based... National Institute of Standards and Technology Genome in a Bottle Consortium--Work Plan Review Workshop... stakeholders about the draft consortium work plan, broadly solicit consortium membership from interested...

  1. Biodeterioration studies of thermoplastics in nature using indigenous bacterial consortium

    Directory of Open Access Journals (Sweden)

    Mohd. Shahbaz Anwar

    2013-06-01

    Full Text Available Thermoplastics, poly vinyl chloride and low-density polyethylene were treated in the presence of indigenously developed bacterial consortium in laboratory and natural conditions. The consortium was developed using four bacteria, selected on the basis of utilization of PVC as primary carbon source, namely P. otitidis, B. aerius, B. cereus and A. pedis isolated from the plastic waste disposal sites in Northern India. The comparative in-vitro treatment studies as revealed by the spectral and thermal data, illustrated the relatively better biodegradation potential of developed consortium for PVC than the LDPE. Further, the progressive treatments of both the thermoplastics were conducted for three months under natural conditions. For this purpose, bioformulation of consortium was prepared and characterized for the viability up to 70 days of storage at 25±1ºC. The consortium treated polymer samples were monitored through SEM and FT-IR spectroscopy. Analytical data revealed the biodeterioration potential of the developed consortium for PVC and LDPE, which could help in disposing the plastic waste.

  2. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  3. Mammary tumors

    International Nuclear Information System (INIS)

    Weller, R.E.

    1988-10-01

    Mammary neoplasia is one of the more common malignancies affecting domestic species. Despite their importance, they are often over- diagnosed, undertreated and subject to several misconceptions propagated by veterinarians and pet owners alike. Mammary neoplasia is the most frequent tumor type encountered in the female accounting for almost half of all malignancies reported. The canine has the highest incidence of mammary tumors of all domestic species. In the dog, about 65 percent of mammary tumors are benign mixed tumors, and 25 percent are carcinomas. The rest are adenomas, myoepitheliomas, and malignant mixed tumors. The age distribution of mammary tumors closely follows the age distribution of most tumors in the dog. Mammary tumors are rare in dogs 2 years old, but incidence begins to increase sharply at approximately 6 years of age. Median age at diagnosis is about 10 years. No breed predilection has been consistently reported

  4. Global Consortium on Security Transformation : Fostering New ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Toward a Regional Security Architecture for the Horn of Africa - Phase II. The Horn of Africa region has endured decades of destruction and human suffering due to long and interrelated wars. View moreToward a Regional Security Architecture for the Horn of Africa - Phase II ...

  5. Germline mutations of BRCA1 gene exon 11 are not associated with platinum response neither with survival advantage in patients with primary ovarian cancer: understanding the clinical importance of one of the biggest human exons. A study of the Tumor Bank Ovarian Cancer (TOC) Consortium.

    Science.gov (United States)

    Dimitrova, Desislava; Ruscito, Ilary; Olek, Sven; Richter, Rolf; Hellwag, Alexander; Türbachova, Ivana; Woopen, Hannah; Baron, Udo; Braicu, Elena Ioana; Sehouli, Jalid

    2016-09-01

    Germline mutations in BRCA1 gene have been reported in up to 20 % of epithelial ovarian cancer (EOC) patients. Distinct clinical characteristics have been attributed to this special EOC population. We hypothesized that mutations in different BRCA1 gene exons may differently affect the clinical course of the disease. The aim of this study was to analyze, in a large cohort of primary EOCs, the clinical impact of mutations in BRCA1 gene exon 11, the largest exon of the gene sequence encoding the 60 % of BRCA1 protein. Two hundred sixty-three primary EOC patients, treated between 2000 and 2008 at Charité University Hospital of Berlin, were included. Patients' blood samples were obtained from the Tumor Ovarian Cancer (TOC) Network ( www.toc-network.de ). Direct sequencing of BRCA1 gene exon 11 was performed for each patient to detect mutations. Based on their BRCA1 exon 11 mutational status, patients were compared regarding clinico-pathological variables and survival. Mutations in BRCA1 exon 11 were found in 18 out of 263 patients (6.8 %). Further 10/263 (3.8 %) cases showed variants of uncertain significance (VUS). All exon 11 BRCA1-positive tumors (100 %) were Type 2 ovarian carcinomas (p = 0.05). Age at diagnosis was significantly younger in Type 2 exon 11 mutated patients (p = 0.01). On multivariate analysis, BRCA1 exon 11 mutational status was not found to be an independent predictive factor for optimal cytoreduction, platinum response, or survival. Mutations in BRCA1 gene exon 11 seem to predispose women to exclusively develop a Type 2 ovarian cancer at younger age. Exon 11 BRCA1-mutated EOC patients showed distinct clinico-pathological features but similar clinical outcome with respect to sporadic EOC patients.

  6. 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

    received selinexor (3 to 85 mg/m(2)) in 21- or 28-day cycles. Pre- and post-treatment levels of XPO1 mRNA in patient-derived leukocytes were determined by reverse transcriptase quantitative polymerase chain reaction, and tumor biopsies were examined by immunohistochemistry for changes in markers consistent...... with XPO1 inhibition. Antitumor response was assessed according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. RESULTS: The most common treatment-related adverse events included fatigue (70%), nausea (70%), anorexia (66%), and vomiting (49%), which were generally grade 1 or 2......-dependent elevations in XPO1 mRNA in leukocytes were demonstrated up to a dose level of 28 mg/m(2) before plateauing, and paired tumor biopsies showed nuclear accumulation of key tumor-suppressor proteins, reduction of cell proliferation, and induction of apoptosis. Among 157 patients evaluable for response, one...

  7. The National Astronomy Consortium (NAC) - Overview

    Science.gov (United States)

    Sheth, Kartik; Mills, Elisabeth A. C.; Hooper, Eric; National Astronomy Consortium

    2015-01-01

    The National Astronomy Consortium (NAC; see https://sites.google.com/site/nraonac/) is a growing national partnership between majority and minority universities and institutions with the goal of increasing the numbers of under-represented minorities and students who might otherwise be overlooked by the traditional academic pipeline into STEM, or related, careers. The NAC model is based on the successful 'Posse Foundation' model for undergraduate success and incorporates all its major components: pre-training of cohorts to prepare them for the research experience, joint weekly cohort activities throughout the research summer, peer- and multiple mentoring, weekly discussion of various aspects of professional and career development, continued engagement of students in science after return to home institution and lifelong mentoring. The mentors also form a cohort, exchanging information and learning from each other. With its partner institutions, the NAC aims to build a complete pipeline from undergraduate through career for the next generation of scientists and engineers. Our annual goal is to create two to three cohorts of four to five students at each site (currently NRAO-Charlottesville, NRAO-Socorro and U. Wisconsin - Madison). Recruitment occurs in the fall semester with seminars and colloquia in partnership with faculty at the minority serving institutions and the GRAD-MAP program at the University of Maryland. In this talk we describe in detail all the components of the NAC and report on our progress. We are keen to interact and partner with new universities and institutions and encourage them to contact the NAC at nac4stem@googlegroups.com.

  8. Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib - findings from an investigator initiated phase 2 study

    DEFF Research Database (Denmark)

    Niemann, Carsten U; Herman, Sarah E M; Maric, Irina

    2016-01-01

    PURPOSE: Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress...... the chemoattraction of CLL cells. CONCLUSIONS: In conjunction with inhibition of BCR signaling, these changes in the tumor microenvironment likely contribute to the anti-tumor activity of ibrutinib and may impact the efficacy of immunotherapeutic strategies in patients with CLL....

  9. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  10. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  11. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  12. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study

    Directory of Open Access Journals (Sweden)

    Marincek Nicolas

    2013-01-01

    Full Text Available Abstract Background We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. Methods In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Results Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle, 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1–4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1–158 months, 34 (range: 1–118 months and 29 (range: 1–113 months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59 vs. intermediate dose, p = 0.03 and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79 vs. low dose, p = 0.03. Conclusions Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211.

  13. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.

    Science.gov (United States)

    Marincek, Nicolas; Jörg, Ann-Catherine; Brunner, Philippe; Schindler, Christian; Koller, Michael T; Rochlitz, Christoph; Müller-Brand, Jan; Maecke, Helmut R; Briel, Matthias; Walter, Martin A

    2013-01-15

    We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors. In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols. Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03). Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).

  14. Antioxidant activity of the probiotic consortium in vitro

    Directory of Open Access Journals (Sweden)

    Saule Saduakhasova

    2014-01-01

    Full Text Available Introduction: Available evidence suggests that probiotics have different biological functions that depend on several mechanisms, such as antioxidant and DNA-protective activities. The probiotic consortium includes bacterial cultures such as Streptococcus thermophilus, Lactococcus lactis, Lactobacillus plantarum, and other bacterial cultures isolated from traditional Kazakh dairy products (ayran, kumys, shubat, and healthy clinical material. The aim of this study was to investigate the total antioxidant activity of the consortium of probiotic bacteria and to determine the activity of superoxide dismutase, glutathione reductase, and DNA-protective action. Material and methods: In vitro comet assay was used to determine the antigenotoxicity of the probiotic consortium. Total antioxidant activity was determined using a method of analysis with Trolox as the equivalent. The analysis method of superoxide dismutase activity assesses the inhibition rate of the nitroblue tetrazolium reduction to formazan by superoxide dismutase. Determination of glutathione reductase activity is based on the measurement of the NADPH oxidation speed. Results: A significantly high level of the total antioxidant activity of the probiotic consortium intact cells (15.3 mM/ml was observed whereas the activity index of  lysate  was 11.1 mM/ml. The superoxide dismutase activity of probiotic consortium lysate was evaluated, with values that peaked at 0.24 U/mg protein. The superoxide dismutase activity of the consortium was lower in comparison to L.fernentum E-3 and L.fernentum E-18 cultures with values of 0.85 U/mg and 0.76 U/mg protein, respectively. SOD activity of probiotic consortium whole cells was not observed, which is typical for lactic acid bacteria. Glutathione reductase plays an important role in the optimal protection from oxidative stress. Glutathione reductase activity of the studied probiotic consortium was low; moreover, the activity of the lysate was two times

  15. Intraoperative stereotactic injection of Indigo Carmine dye to mark ill-defined tumor margins: a prospective phase I-II study.

    Science.gov (United States)

    Margetis, Konstantinos; Rajappa, Prajwal; Tsiouris, Apostolos John; Greenfield, Jeffrey P; Schwartz, Theodore H

    2015-01-01

    A critical goal in neurosurgical oncology is maximizing the extent of tumor resection while minimizing the risk to normal white matter tracts. Frameless stereotaxy and white matter mapping are indispensable tools in this effort, but deep tumor margins may not be accurately defined because of the "brain shift" at the end of the operation. The authors investigated the safety and efficacy of a technique for marking the deep margins of intraaxial tumors with stereotactic injection of Indigo Carmine dye. Investigational New Drug study approval for a prospective study in adult patients with gliomas was obtained from the FDA (Investigational New Drug no. 112680). At surgery, 1-3 stereotactic injections of 0.01 ml of Indigo Carmine dye were performed through the initial bur holes into the deep tumor margins before elevation of the bone flap. White light microscopic resection was conducted in standard fashion by using frameless stereotactic navigation until the injected margins were identified. The resection of the injected tumor margins and the extent of resection of the whole tumor volume were determined by using postoperative volumetric MRI. In total 17 injections were performed in 10 enrolled patients (6 male, 4 female), whose mean age was 49 years. For all patients, the injection points were identified intraoperatively and tumor was resected at these points. The staining pattern was reproducible; it was a sphere of stained tissue approximately 5 mm in diameter. A halo of stained tissue and a backflow of dye through the needle tract were also noted, but these were clearly distinct from the staining pattern of the injection point, which was vividly colored and demarcated. Postoperative MR images verified the resection of all injection points. The mean extent of resection of the tumor as a whole was 97.1%. For 1 patient, a brain abscess developed on postoperative Day 16 and needed additional surgical treatment. Stereotactic injection of Indigo Carmine dye can be used to

  16. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  17. Histone acetylation and histone deacetylase activity of magnesium valproate in tumor and peripheral blood of patients with cervical cancer. A phase I study

    Science.gov (United States)

    Chavez-Blanco, Alma; Segura-Pacheco, Blanca; Perez-Cardenas, Enrique; Taja-Chayeb, Lucia; Cetina, Lucely; Candelaria, Myrna; Cantu, David; Gonzalez-Fierro, Aurora; Garcia-Lopez, Patricia; Zambrano, Pilar; Perez-Plasencia, Carlos; Cabrera, Gustavo; Trejo-Becerril, Catalina; Angeles, Enrique; Duenas-Gonzalez, Alfonso

    2005-01-01

    Background The development of cancer has been associated with epigenetic alterations such as aberrant histone deacetylase (HDAC) activity. It was recently reported that valproic acid is an effective inhibitor of histone deacetylases and as such induces tumor cell differentiation, apoptosis, or growth arrest. Methods Twelve newly diagnosed patients with cervical cancer were treated with magnesium valproate after a baseline tumor biopsy and blood sampling at the following dose levels (four patients each): 20 mg/kg; 30 mg/kg, or 40 mg/kg for 5 days via oral route. At day 6, tumor and blood sampling were repeated and the study protocol ended. Tumor acetylation of H3 and H4 histones and HDAC activity were evaluated by Western blot and colorimetric HDAC assay respectively. Blood levels of valproic acid were determined at day 6 once the steady-state was reached. Toxicity of treatment was evaluated at the end of study period. Results All patients completed the study medication. Mean daily dose for all patients was 1,890 mg. Corresponding means for the doses 20-, 30-, and 40-mg/kg were 1245, 2000, and 2425 mg, respectively. Depressed level of consciousness grade 2 was registered in nine patients. Ten patients were evaluated for H3 and H4 acetylation and HDAC activity. After treatment, we observed hyperacetylation of H3 and H4 in the tumors of nine and seven patients, respectively, whereas six patients demonstrated hyperacetylation of both histones. Serum levels of valproic acid ranged from 73.6–170.49 μg/mL. Tumor deacetylase activity decreased in eight patients (80%), whereas two had either no change or a mild increase. There was a statistically significant difference between pre and post-treatment values of HDAC activity (mean, 0.36 vs. 0.21, two-tailed t test p valproate at a dose between 20 and 40 mg/kg inhibits deacetylase activity and hyperacetylates histones in tumor tissues. PMID:16001982

  18. Targeting thapsigargin towards tumors

    DEFF Research Database (Denmark)

    Christensen, Søren Brøgger; Doan, Thi Quynh Nhu; Paulsen, Eleonora Sandholdt

    2015-01-01

    substrates for either prostate specific antigen (PSA) or prostate specific membrane antigen (PSMA) prodrugs were created, which selectively affect prostate cancer cells or neovascular tissue in tumors. One of the prodrug is currently tested in clinical phase II. The prodrug under clinical trial has been...

  19. CCCT - NCTN Steering Committees - Pediatric and Adolescent Tumor

    Science.gov (United States)

    The Pediatric and Adolescent Solid Tumor Steering Committee addresses the design, prioritization and evaluation of concepts for large phase 2 and phase 3 clinical trials in extracranial solid tumors of children and youth.

  20. A phase I study of continuous oral dosing of OSI-906, a dual inhibitor of insulin-like growth factor-1 and insulin receptors, in patients with advanced solid tumors.

    Science.gov (United States)

    Puzanov, Igor; Lindsay, Colin R; Goff, Laura; Sosman, Jeff; Gilbert, Jill; Berlin, Jordan; Poondru, Srinivasu; Simantov, Ronit; Gedrich, Rich; Stephens, Andrew; Chan, Emily; Evans, T R Jeffry

    2015-02-15

    OSI-906 is a potent inhibitor of insulin-like growth factor-1 receptor (IGF1R) and insulin receptor (IR). The purpose of this study was to determine the MTD, safety, pharmacokinetics, pharmacodynamics, and preliminary activity of OSI-906 in patients with advanced solid tumors. This was a nonrandomized, open-label, phase I, dose-escalation study in patients with advanced solid tumors. The study also included a diabetic expansion cohort and a biomarker expansion cohort of patients with colorectal cancer. Patients were treated with OSI-906 by once- or twice-daily continuous dosing schedules. Of 95 patients enrolled in the study, 86 received at least one dose of OSI-906. Dose-limiting toxicities included QTc prolongation, grade 2 abdominal pain and nausea, hyperglycemia, and elevation of aspartate aminotransferase and alanine aminotransferase (all grade 3). The MTDs were established to be 400 mg once daily and 150 mg twice daily. The recommended phase II dose was determined as 150 mg twice daily. OSI-906 was rapidly absorbed with a half-life of 5 hours, and steady-state plasma concentrations were achieved by day 8. Pharmacodynamic effects on IGF1R and IR phosphorylation were levels observed and correlated with plasma concentrations of OSI-906. Thirty-one patients had stable disease as their best response. One patient with melanoma had a radiographic partial response and underwent resection, during which only melanocytic debris but no viable tumor tissue was identified. At the established MTD, OSI-906 was well tolerated and antitumor activity was observed. These results support further evaluation of OSI-906 in solid tumors. ©2014 American Association for Cancer Research.

  1. Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study.

    Science.gov (United States)

    Pestrin, Marta; Bessi, Silvia; Puglisi, Fabio; Minisini, Alessandro M; Masci, Giovanna; Battelli, Nicola; Ravaioli, Alberto; Gianni, Lorenzo; Di Marsico, Roberta; Tondini, Carlo; Gori, Stefania; Coombes, Charles R; Stebbing, Justin; Biganzoli, Laura; Buyse, Marc; Di Leo, Angelo

    2012-07-01

    This multicenter phase II trial was designed to evaluate the activity of lapatinib in metastatic breast cancer patients with HER2-negative primary tumors and HER2-positive circulating tumor cells (CTCs). In this study MBC patients with HER2-negative primary tumors and HER2-positive CTCs previously treated with at least a first-line therapy for metastatic disease received lapatinib 1500 mg/day. The CellSearch System® was used for CTCs isolation and bio-characterization. HER2 status was assessed on CTCs by immunofluorescence. A case was defined as CTCs positive if ≥2 CTC/7.5 ml of blood were isolated and HER2-positive if ≥50% of CTCs were HER2-positive. 139 HER2-negative patients were screened, 96 patients were positive for CTCs (mean number of CTCs: 85; median number of CTCs: 19; range 2-1637). Seven of the 96 patients (7%) had ≥50% HER2-positive CTCs and were eligible for treatment with lapatinib. No objective tumor responses occurred in this population. In one patient, disease stabilization lasting 254 days (8.5 months) was observed. From the findings of this study, we concluded that a subset of patients with a HER2-negative primary tumor presents HER2-positive CTCs during disease progression, although the HER2 shift rate seems to be lower than previously reported. Despite the lack of objective response, the durable disease stabilization observed in one patient cannot rule out the hypothesis that lapatinib may have some activity in this patient population. However, considering that only 1/139 screened patients may potentially have derived benefit from this approach, future trials designed according to the presented strategy cannot be recommended.

  2. Tumor vaccines:

    OpenAIRE

    Frank, Mojca; Ihan, Alojz

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tol...

  3. 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,

  4. 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

  5. [Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma].

    Science.gov (United States)

    Schuler-Thurner, B; Bartz-Schmidt, K-U; Bornfeld, N; Cursiefen, C; Fuisting, B; Grisanti, S; Heindl, L M; Holbach, L; Keserü, M; Knorr, H; Koch, K; Kruse, F; Meiller, R; Metz, C; Meyer-ter-Vehn, T; Much, M; Reinsberg, M; Schliep, S; Seitz, B; Schuler, G; Süsskind, D; Viestenz, A; Wagenfeld, L; Zeschnigk, M

    2015-12-01

    Uveal melanomas are the most common malignant tumors of the eye. With modern molecular biological diagnostic methods, such as chromosome 3 typing and gene expression analysis, these tumors can be categorized into highly aggressive (monosomy 3, class II) and less aggressive forms. This molecular biological stratification is primarily important for determining the risk of these tumors as no therapy is currently available that is able to prevent or delay metastases. A randomized study of patients with a poor prognosis (monosomy 3) is currently being carried out in order to determine whether a cancer vaccine prepared from autologous (patient's own) dendritic cells and uveal melanoma RNA can prevent or delay progression and further metastases of this extremely aggressive form of cancer. Inclusion in the uveal melanoma study, which hopes to provide a potential therapeutic option for patients, is only possible if patients are referred to an institution that is able to manufacture and provide this vaccination before the patient is operated on or treated with radiation. Untreated tumor material is necessary for producing the vaccine on an individualized patient basis.

  6. Phase I and pharmacologic study of oral ZD9331, a novel nonpolyglutamated thymidylate synthase inhibitor, in adult patients with solid tumors.

    NARCIS (Netherlands)

    Jonge, M.J.A. de; Punt, C.J.A.; Sparreboom, A.; Planting, A.S.T.; Peters, M.E.W.J.; Schraaf, J. van de; Jackman, A.; Smith, R.J.H.; Mulder, P.H.M. de; Verweij, J.

    2002-01-01

    PURPOSE: To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors. PATIENTS AND METHODS: Patients were treated with oral ZD9331 given once

  7. Phase I and pharmacologic study of oral ZD9331, a novel nonpolyglutamated thymidylate synthase inhibitor, in adult patients with solid tumors

    NARCIS (Netherlands)

    de Jonge, Maja J. A.; Punt, Cornelis J. A.; Sparreboom, Alex; Planting, André S. T.; Peters, M. E. W. J.; van de Schraaf, Jacqueline; Jackman, Ann; Smith, Rob; de Mulder, Pieter H. M.; Verweij, Jaap

    2002-01-01

    To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors. Patients were treated with oral ZD9331 given once daily (od) or twice daily (bid)

  8. Histone acetylation and histone deacetylase activity of magnesium valproate in tumor and peripheral blood of patients with cervical cancer. A phase I study

    Directory of Open Access Journals (Sweden)

    Cabrera Gustavo

    2005-07-01

    Full Text Available Abstract Background The development of cancer has been associated with epigenetic alterations such as aberrant histone deacetylase (HDAC activity. It was recently reported that valproic acid is an effective inhibitor of histone deacetylases and as such induces tumor cell differentiation, apoptosis, or growth arrest. Methods Twelve newly diagnosed patients with cervical cancer were treated with magnesium valproate after a baseline tumor biopsy and blood sampling at the following dose levels (four patients each: 20 mg/kg; 30 mg/kg, or 40 mg/kg for 5 days via oral route. At day 6, tumor and blood sampling were repeated and the study protocol ended. Tumor acetylation of H3 and H4 histones and HDAC activity were evaluated by Western blot and colorimetric HDAC assay respectively. Blood levels of valproic acid were determined at day 6 once the steady-state was reached. Toxicity of treatment was evaluated at the end of study period. Results All patients completed the study medication. Mean daily dose for all patients was 1,890 mg. Corresponding means for the doses 20-, 30-, and 40-mg/kg were 1245, 2000, and 2425 mg, respectively. Depressed level of consciousness grade 2 was registered in nine patients. Ten patients were evaluated for H3 and H4 acetylation and HDAC activity. After treatment, we observed hyperacetylation of H3 and H4 in the tumors of nine and seven patients, respectively, whereas six patients demonstrated hyperacetylation of both histones. Serum levels of valproic acid ranged from 73.6–170.49 μg/mL. Tumor deacetylase activity decreased in eight patients (80%, whereas two had either no change or a mild increase. There was a statistically significant difference between pre and post-treatment values of HDAC activity (mean, 0.36 vs. 0.21, two-tailed t test p Conclusion Magnesium valproate at a dose between 20 and 40 mg/kg inhibits deacetylase activity and hyperacetylates histones in tumor tissues.

  9. Phase 2 study of treatment selection based on tumor thymidylate synthase expression in previously untreated patients with metastatic colorectal cancer: A trial of the ECOG-ACRIN Cancer Research Group (E4203).

    Science.gov (United States)

    Meropol, Neal J; Feng, Yang; Grem, Jean L; Mulcahy, Mary F; Catalano, Paul J; Kauh, John S; Hall, Michael J; Saltzman, Joel N; George, Thomas J; Zangmeister, Jeffrey; Chiorean, Elena G; Cheema, Puneet S; O'Dwyer, Peter J; Benson, Al B

    2018-02-15

    The authors hypothesized that patients with metastatic colorectal cancer (mCRC) who had tumors with low thymidylate synthase (TS-L) expression would have a higher response rate to combined 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab (FOLFOX/Bev) than those with high TS (TS-H) expression and that combined irinotecan and oxaliplatin (IROX) plus bevacizumab (IROX/Bev) would be more effective than FOLFOX/Bev in those with TS-H tumors. TS protein expression was determined in mCRC tissue. Patients who had TS-L tumors received FOLFOX/Bev, and those who had TS-H tumors were randomly assigned to receive either FOLFOX/Bev or IROX/Bev. The primary endpoint was the response rate (complete plus partial responses). In total, 211 of 247 patients (70% TS-H) were registered to the treatment phase. Efficacy analyses included eligible patients who had started treatment (N = 186). The response rates for patients who received IROX/Bev (TS-H), FOLFOX/Bev (TS-H), and FOLFOX/Bev (TS-L) were 33%, 38%, and 49%, respectively (P = nonsignificant). The median progression-free survival (PFS) was 10 months (95% confidence interval [CI], 9-12 months; 10 months in the IROX/Bev TS-H group, 9 months in the FOLFOX/Bev TS-H group, and 13 months in the FOLFOX/Bev TS-L group). The TS-L group had improved PFS compared with the TS-H group that received FOLFOX/Bev (hazard ratio, 1.6; 95% CI, 1.0%-2.4%; P = .04; Cox regression). The median overall survival (OS) was 22 months (95% CI, 20 29 months; 18 months in the IROX/Bev TS-H group, 21 months in the FOLFOX/Bev TS-H group, and 32 months in the TS-L group). OS comparisons for the 2 TS-H arms and for the FOLFOX/Bev TS-H versus TS-L arms were not significantly different. TS expression was prognostic: Patients with TS-L tumors who received FOLFOX/Bev had a longer PFS than those with TS-H tumors, along with a trend toward longer OS. Patients with TS-H tumors did not benefit more from IROX/Bev than from FOLFOX/Bev. Cancer 2018

  10. Augmentation of a Microbial Consortium for Enhanced Polylactide (PLA) Degradation.

    Science.gov (United States)

    Nair, Nimisha R; Sekhar, Vini C; Nampoothiri, K Madhavan

    2016-03-01

    Bioplastics are eco-friendly and derived from renewable biomass sources. Innovation in recycling methods will tackle some of the critical issues facing the acceptance of bioplastics. Polylactic acid (PLA) is the commonly used and well-studied bioplastic that is presumed to be biodegradable. Considering their demand and use in near future, exploration for microbes capable of bioplastic degradation has high potential. Four PLA degrading strains were isolated and identified as Penicillium chrysogenum, Cladosporium sphaerospermum, Serratia marcescens and Rhodotorula mucilaginosa. A consortium of above strains degraded 44 % (w/w) PLA in 30 days time in laboratory conditions. Subsequently, the microbial consortium employed effectively for PLA composting.

  11. Midwest Superconductivity Consortium - Final Progress Report October 2001

    Energy Technology Data Exchange (ETDEWEB)

    Bement, Arden L.

    2001-10-23

    The basic mission of the Consortium was to advance the science and understanding of high-T{sub c} superconductivity and to promote the development of new materials and improved processing technology. Focused group efforts were the key element of the research program. One program area is the understanding of the layered structures involved in candidate materials and the factors that control their formation, stability and relationship superconductor properties. The other program area had a focus upon factors that limit or control the transport properties such as weak links, flux lattice behavior, and interfaces. Interactions among Consortium d with industrial armiates were an integral part of the program.

  12. Tumoral tracers

    International Nuclear Information System (INIS)

    Camargo, E.E.

    1979-01-01

    Direct tumor tracers are subdivided in the following categories:metabolite tracers, antitumoral tracers, radioactive proteins and cations. Use of 67 Ga-citrate as a clinically important tumoral tracer is emphasized and gallium-67 whole-body scintigraphy is discussed in detail. (M.A.) [pt

  13. Carcinoid Tumors

    Science.gov (United States)

    ... spread to other parts of the body. Doctors don't know what causes the mutations that can lead to carcinoid tumors. But they know that carcinoid tumors develop in neuroendocrine cells. Neuroendocrine cells are found in various organs throughout the body. They perform some nerve cell ...

  14. Animal tumors

    International Nuclear Information System (INIS)

    Gillette, E.L.

    1983-01-01

    There are few trained veterinary radiation oncologists and the expense of facilities has limited the extent to which this modality is used. In recent years, a few cobalt teletherapy units and megavoltage x-ray units have been employed in larger veterinary institutions. In addition, some radiation oncologists of human medical institutions are interested and willing to cooperate with veterinarians in the treatment of animal tumors. Carefully designed studies of the response of animal tumors to new modalities serve two valuable purposes. First, these studies may lead to improved tumor control in companion animals. Second, these studies may have important implications to the improvement of therapy of human tumors. Much remains to be learned of animal tumor biology so that appropriate model systems can be described for such studies. Many of the latter studies can be sponsored by agencies interested in the improvement of cancer management

  15. Biodegradation of diesel fuel by a microbial consortium in the presence of 1-alkoxymethyl-2-methyl-5-hydroxypyridinium chloride homologues

    DEFF Research Database (Denmark)

    Chrzanowski, L; Stasiewicz, M; Owsianiak, Mikolaj

    2009-01-01

    hypothesize that in the presence of diesel fuel low-water-soluble ionic liquids may become more toxic to hydrocarbon-degrading microorganisms. In this study the influence of 1-alkoxymethyl-2-methyl-5-hydroxypyridinium chloride homologues (side-chain length from C-3 to C-18) on biodegradation of diesel fuel...... by a bacterial consortium was investigated. Whereas test performed for the consortium cultivated on disodium succinate showed that toxicity of the investigated ionic liquids decreased with increase in side-chain length, only higher homologues (C-8-C-18) caused a decrease in diesel fuel biodegradation....... As a result of exposure to toxic compounds also modification in cell surface hydrophobicity was observed (MATH). Disulphine blue active substances method was employed to determine partitioning index of ionic liquids between water and diesel fuel phase, which varied from 1.1 to 51% for C-3 and C-18 homologues...

  16. Computational Astrophysics Consortium 3 - Supernovae, Gamma-Ray Bursts and Nucleosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Woosley, Stan [Univ. of California, Santa Cruz, CA (United States)

    2014-08-29

    Final project report for UCSC's participation in the Computational Astrophysics Consortium - Supernovae, Gamma-Ray Bursts and Nucleosynthesis. As an appendix, the report of the entire Consortium is also appended.

  17. 24 CFR 943.124 - What elements must a consortium agreement contain?

    Science.gov (United States)

    2010-04-01

    ... HOUSING AND URBAN DEVELOPMENT PUBLIC HOUSING AGENCY CONSORTIA AND JOINT VENTURES Consortia § 943.124 What... existence of the consortium and the terms under which a PHA may join or withdraw from the consortium before...

  18. Three-Dimensional Radiation Therapy to the Primary Tumor With Concurrent Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer: Results of a Multicenter Phase 2 Study From PPRA-RTOG, China.

    Science.gov (United States)

    Su, ShengFa; Li, Tao; Lu, Bing; Wang, XiaoHu; Li, JianCheng; Chen, Ming; Lu, You; Bai, YuJu; Hu, YinXiang; Ouyang, WeiWei; Ma, Zhu; Li, QingSong; Li, HuiQin; Wang, Yu

    2015-11-15

    The aim of this prospective multi-institutional phase 2 study was to investigate disease control, survival outcomes, and toxicity after thoracic three-dimensional radiation therapy (3D-RT) with concurrent chemotherapy for newly diagnosed stage IV non-small cell lung cancer (NSCLC). Eligible patients were 18 to 80 years of age, had a Karnofsky performance status (KPS) score ≥70%, and newly diagnosed stage IV NSCLC with limited metastatic disease (defined as involving ≤3 organs). Patients received platinum-doublet chemotherapy with concurrent irradiation to the primary tumor. Primary endpoints were overall survival (OS) and acute toxicity. From May 2008 to May 2012, 198 eligible patients were enrolled from 7 cancer centers. Most patients died with distant metastasis; only 10% died with isolated primary recurrence. Median OS time was 13.0 months (95% confidence interval [CI]: 11.7-14.3); OS rates were 53.5% at 1 year, 15.8% at 2 years, and 9.2% at 3 years. Median progression-free survival (PFS) time was 9.0 months (95% CI: 7.7-10.3); corresponding PFS rates were 30.8%, 8.2%, and 6.1%. The 1-year, 2-year, and 3-year local (primary tumor) control rates were 78.8%, 57.7%, and 55.4%. Multivariate analysis showed that delivery of ≥63 Gy to the primary tumor (P=.014), having a primary tumor volume acute toxicities were hematologic: leukopenia (37.9%), thrombocytopenia (10.1%), and anemia (6.9%). No patients experienced grade 4 or 5 radiation-related toxicity; 2.5% had acute grade 3 pneumonitis, and 6.6% had acute grade 3 radiation esophagitis. Thoracic 3D-RT to the primary tumor with concurrent chemotherapy led to satisfactory survival outcomes with acceptable toxicity. Radiation dose, primary tumor volume, and PFS after treatment all predicted survival in these patients with limited-metastasis NSCLC. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Three-Dimensional Radiation Therapy to the Primary Tumor With Concurrent Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer: Results of a Multicenter Phase 2 Study From PPRA-RTOG, China

    Energy Technology Data Exchange (ETDEWEB)

    Su, ShengFa [Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, and Guizhou Cancer Hospital, Guiyang (China); Teaching and Research Section of Oncology, Guizhou Medical University, Guiyang (China); Li, Tao [Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu (China); Lu, Bing, E-mail: lbgymaaaa@163.com [Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, and Guizhou Cancer Hospital, Guiyang (China); Teaching and Research Section of Oncology, Guizhou Medical University, Guiyang (China); Wang, XiaoHu, E-mail: xhwanggansu@163.com [Department of Radiation Oncology, Gansu Cancer Hospital, Lanzhou (China); Li, JianCheng [Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Fuzhou (China); Chen, Ming [Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou (China); Lu, You [Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu (China); Bai, YuJu [Department of Oncology, Affiliated Hospital of Zunyi Medical College, Zunyi (China); Hu, YinXiang; Ouyang, WeiWei; Ma, Zhu; Li, QingSong; Li, HuiQin; Wang, Yu [Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, and Guizhou Cancer Hospital, Guiyang (China); Teaching and Research Section of Oncology, Guizhou Medical University, Guiyang (China)

    2015-11-15

    Purpose: The aim of this prospective multi-institutional phase 2 study was to investigate disease control, survival outcomes, and toxicity after thoracic three-dimensional radiation therapy (3D-RT) with concurrent chemotherapy for newly diagnosed stage IV non-small cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 18 to 80 years of age, had a Karnofsky performance status (KPS) score ≥70%, and newly diagnosed stage IV NSCLC with limited metastatic disease (defined as involving ≤3 organs). Patients received platinum-doublet chemotherapy with concurrent irradiation to the primary tumor. Primary endpoints were overall survival (OS) and acute toxicity. Results: From May 2008 to May 2012, 198 eligible patients were enrolled from 7 cancer centers. Most patients died with distant metastasis; only 10% died with isolated primary recurrence. Median OS time was 13.0 months (95% confidence interval [CI]: 11.7-14.3); OS rates were 53.5% at 1 year, 15.8% at 2 years, and 9.2% at 3 years. Median progression-free survival (PFS) time was 9.0 months (95% CI: 7.7-10.3); corresponding PFS rates were 30.8%, 8.2%, and 6.1%. The 1-year, 2-year, and 3-year local (primary tumor) control rates were 78.8%, 57.7%, and 55.4%. Multivariate analysis showed that delivery of ≥63 Gy to the primary tumor (P=.014), having a primary tumor volume <134 cm{sup 3} (P=.008), and having a stable or higher KPS score after treatment (P=.01) were independent predictors of better OS. The most common severe (grades 3-4) acute toxicities were hematologic: leukopenia (37.9%), thrombocytopenia (10.1%), and anemia (6.9%). No patients experienced grade 4 or 5 radiation-related toxicity; 2.5% had acute grade 3 pneumonitis, and 6.6% had acute grade 3 radiation esophagitis. Conclusions: Thoracic 3D-RT to the primary tumor with concurrent chemotherapy led to satisfactory survival outcomes with acceptable toxicity. Radiation dose, primary tumor volume, and PFS after treatment all

  20. Towards efficient crude oil degradation by a mixed bacterial consortium

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, K.S.M.; Thahira-Rahman, J.; Banat, I.M. [University of Ulster, Coleraine, Northern Ireland (United Kingdom). School of Biological and Environmental Studies; Lakshmanaperumalsamy, P. [Bharathiar Univ., Tamilnadu (India). Dept. of Environmental Sciences

    2002-12-01

    A laboratory study was undertaken to assess the optimal conditions for biodegradation of Bombay High (BH) crude oil. Among 130 oil degrading bacterial cultures isolated from oil contaminated soil samples, Micrococcus sp. GS2-22, Corynebacterium sp. GS5-66, Flavobacterium sp. DS5-73, Bacillus sp. DS6-86 and Pseudomonas sp. DS10-129 were selected for the study based on the efficiency of crude oil utilisation. A mixed bacterial consortium prepared using the above strains was also used. Individual bacterial cultures showed less growth and degradation than did the mixed bacterial consortium. At 1% crude oil concentration, the mixed bacterial consortium degraded a maximum of 78% of BH crude oil. This was followed by 66% by Pseudomonas sp. DS10-129, 59% by Bacillus sp. DS6-86, 49% by Micrococcus sp. GS2-22, 43% by Corynebacterium sp. GS5-66 and 41% by Flavobacterium sp. DS5-73. The percentage of degradation by the mixed bacterial consortium decreased from 78% to 52% as the concentration of crude oil was increased from 1% to 10%. Temperature of 30{sup o}C and pH 7.5 were found to be optima for maximum biodegradation. (Author)

  1. Rio Grande Basin Consortium: Mission, goals, and activities

    Science.gov (United States)

    Deborah A. Potter; Deborah M. Finch

    1996-01-01

    The Rio Grande Basin Consortium (RGBC) serves as a networking group and clearinghouse for scientific information pertaining to the Rio Grande Basin. Its membership consists of natural and social scientists from New Mexico’s three research universities, administrators, and resource managers from federal, state, and local governmental agencies, members of community and...

  2. International Arid Lands Consortium's contributions to Madrean Archipelago stewardship

    Science.gov (United States)

    Peter F. Ffolliott; Jeffery O. Dawson; Itshack Moshe; Timothy E. Fulbright; E. Carter Johnson; Paul Verburg; Muhannad Shatanawi; Donald F. Caccamise; Jim P. M. Chamie

    2005-01-01

    The International Arid Lands Consortium (IALC) was established in 1990 to promote research, education, and training activities related to the development, management, and reclamation of arid and semiarid lands worldwide. Building on a decade of experience, the IALC continues to increase the knowledge base for managers by funding research, development, and demonstration...

  3. The Consortium for Advancing Renewable Energy Technology (CARET)

    Science.gov (United States)

    Gordon, E. M.; Henderson, D. O.; Buffinger, D. R.; Fuller, C. W.; Uribe, R. M.

    1998-01-01

    The Consortium for Advancing Renewable Energy (CARET) is a research and education program which uses the theme of renewable energy to build a minority scientist pipeline. CARET is also a consortium of four universities and NASA Lewis Research Center working together to promote science education and research to minority students using the theme of renewable energy. The consortium membership includes the HBCUs (Historically Black Colleges and Universities), Fisk, Wilberforce and Central State Universities as well as Kent State University and NASA Lewis Research Center. The various stages of this pipeline provide participating students experiences with a different emphasis. Some emphasize building enthusiasm for the classroom study of science and technology while others emphasize the nature of research in these disciplines. Still others focus on relating a practical application to science and technology. And, of great importance to the success of the program are the interfaces between the various stages. Successfully managing these transitions is a requirement for producing trained scientists, engineers and technologists. Presentations describing the CARET program have been given at this year's HBCU Research Conference at the Ohio Aerospace Institute and as a seminar in the Solar Circle Seminar series of the Photovoltaic and Space Environments Branch at NASA Lewis Research Center. In this report, we will describe the many positive achievements toward the fulfillment of the goals and outcomes of our program. We will begin with a description of the interactions among the consortium members and end with a description of the activities of each of the member institutions .

  4. The Worker Rights Consortium Makes Strides toward Legitimacy.

    Science.gov (United States)

    Van der Werf, Martin

    2000-01-01

    Discusses the rapid growth of the Workers Rights Consortium, a student-originated group with 44 member institutions which opposes sweatshop labor conditions especially in the apparel industry. Notes disagreements about the number of administrators on the board of directors and about the role of industry representives. Compares this group with the…

  5. Effects of the Consortium of Pseudomonas, Bacillus and ...

    African Journals Online (AJOL)

    Johnny

    degrading bacteria were used for the study and analysis was for a period of three weeks at one week interval. The values of ... concluded that the consortium of these bacteria can be used for the decontamination of polycyclic aromatic ... The saturated and aromatic hydrocarbons are transformed into oxygenated products by.

  6. An Appraisal of the Consortium of Tanzania University and ...

    African Journals Online (AJOL)

    wemafr

    Abstract. This study investigated factors constraining effective growth of the Consortium of Tanzania. University and Research Libraries (COTUL). A mixed research design was employed to gain a deeper insight into the subject matter. Data was collected using interviews, questionnaires and observations. Fifty-eight (58) ...

  7. Asian Consortium for Computational Materials Science (ACCMS-1)

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science; Volume 26; Issue 1. Issue front cover thumbnail. Volume 26, Issue 1. January 2003, pages 1-205. Proceedings of the first conference of the “Asian Consortium for Computational Materials Science (ACCMS-1)”, Bangalore, 2001. pp 1-2. Foreword · G P Das V Kumar S ...

  8. Academic Library Consortium in Jordan: An Evaluation Study

    Science.gov (United States)

    Ahmed, Mustafa H.; Suleiman, Raid Jameel

    2013-01-01

    Purpose: Due to the current financial and managerial difficulties that are encountered by libraries in public universities in Jordan and the geographical diffusion of these academic institutions, the idea of establishing a consortium was proposed by the Council of Higher Education to combine these libraries. This article reviews the reality of…

  9. Effects of the Consortium of Pseudomonas , Bacillus and ...

    African Journals Online (AJOL)

    The effect of the consortium of Pseudomonas, Bacillus and Micrococcus spp on polycyclic aromatic hydrocarbons in crude oil was carried out using standard microbiological methods. Spectrophotometer, gas chromatography and viable count which determined the optical density, the polycyclic aromatic hydrocarbons and ...

  10. A Novel Methylotrophic Bacterial Consortium for Treatment of Industrial Effluents.

    Science.gov (United States)

    Hingurao, Krushi; Nerurkar, Anuradha

    2018-01-01

    Considering the importance of methylotrophs in industrial wastewater treatment, focus of the present study was on utilization of a methylotrophic bacterial consortium as a microbial seed for biotreatment of a variety of industrial effluents. For this purpose, a mixed bacterial methylotrophic AC (Ankleshwar CETP) consortium comprising of Bordetella petrii AC1, Bacillus licheniformis AC4, Salmonella subterranea AC5, and Pseudomonas stutzeri AC8 was used. The AC consortium showed efficient biotreatment of four industrial effluents procured from fertilizer, chemical and pesticide industries, and common effluent treatment plant by lowering their chemical oxygen demand (COD) of 950-2000 mg/l to below detection limit in 60-96 h in 6-l batch reactor and 9-15 days in 6-l continuous reactor. The operating variables of wastewater treatment, viz. COD, BOD, pH, MLSS, MLVSS, SVI, and F/M ratio of these effluents, were also maintained in the permissible range in both batch and continuous reactors. Therefore, formation of the AC consortium has led to the development of an efficient microbial seed capable of treating a variety of industrial effluents containing pollutants generated from their respective industries.

  11. Effects of the Consortium of Pseudomonas, Bacillus and ...

    African Journals Online (AJOL)

    BSN

    Abstract. The effect of the consortium of Pseudomonas, Bacillus and Micrococcus spp on polycyclic aromatic hydrocarbons in crude oil was carried out using standard microbiological methods. Spectrophotometer, gas chromatography and viable count which determined the optical density, the polycyclic aromatic ...

  12. Effects of the Consortium of Pseudomonas, Bacillus and ...

    African Journals Online (AJOL)

    The effect of the consortium of Pseudomonas, Bacillus and Micrococcus spp on polycyclic aromatic hydrocarbons in crude oil was carried out using standard microbiological methods. Spectrophotometer, gas chromatography and viable count which determined the optical density, the polycyclic aromatic hydrocarbons and ...

  13. Preface of the Proceedings of the Doctoral Consortium

    NARCIS (Netherlands)

    Vinciarelli, A.; Pelachaud, C.; Cowie, R.; Nijholt, Antinus

    2009-01-01

    This volume collects the contributions presented at the ACII 2009 Doctoral Consortium, the event aimed at gathering PhD students with the goal of sharing ideas about the theories behind affective computing; its development; and its application. Published papers have been selected out a large number

  14. Characterization of an autotrophic bioreactor microbial consortium degrading thiocyanate.

    Science.gov (United States)

    Watts, Mathew Paul; Spurr, Liam Patrick; Gan, Han Ming; Moreau, John William

    2017-07-01

    Thiocyanate (SCN - ) forms as a by-product of cyanidation during gold ore processing and can be degraded by a variety of microorganisms utilizing it as an energy, nitrogen, sulphur and/or carbon source. In complex consortia inhabiting bioreactor systems, a range of metabolisms are sustained by SCN - degradation; however, despite the addition or presence of labile carbon sources in most bioreactor designs to date, autotrophic bacteria have been found to dominate key metabolic functions. In this study, we cultured an autotrophic SCN - -degrading consortium directly from gold mine tailings. In a batch-mode bioreactor experiment, this consortium degraded 22 mM SCN - , accumulating ammonium (NH 4 + ) and sulphate (SO 4 2- ) as the major end products. The consortium consisted of a diverse microbial community comprised of chemolithoautotrophic members, and despite the absence of an added organic carbon substrate, a significant population of heterotrophic bacteria. The role of eukaryotes in bioreactor systems is often poorly understood; however, we found their 18S rRNA genes to be most closely related to sequences from bacterivorous Amoebozoa. Through combined chemical and phylogenetic analyses, we were able to infer roles for key microbial consortium members during SCN - biodegradation. This study provides a basis for understanding the behaviour of a SCN - degrading bioreactor under autotrophic conditions, an anticipated approach to remediating SCN - at contemporary gold mines.

  15. Characteristics of a bioflocculant produced by a consortium of ...

    African Journals Online (AJOL)

    The characteristics of a bioflocculant produced by a consortium of 2 bacteria belonging to the genera Cobetia and Bacillus was investigated. The extracellular bioflocculant was composed of 66% uronic acid and 31% protein and showed an optimum flocculation (90% flocculating activity) of kaolin suspension at a dosage of ...

  16. Institutional Support : Consortium for Economic and Social Research ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The Consortium pour la recherche économique et sociale (CRES) is an association of a multidisciplinary team of researchers based in Dakar, Sénégal. Its activities are organized under five departments: growth, poverty and equity; local development, regional integration and globalization; human resources economics; the ...

  17. First-in-Class ERK1/2 Inhibitor Ulixertinib (BVD-523) in Patients with MAPK Mutant Advanced Solid Tumors: Results of a Phase I Dose-Escalation and Expansion Study.

    Science.gov (United States)

    Sullivan, Ryan J; Infante, Jeffrey R; Janku, Filip; Wong, Deborah Jean Lee; Sosman, Jeffrey A; Keedy, Vicki; Patel, Manish R; Shapiro, Geoffrey I; Mier, James W; Tolcher, Anthony W; Wang-Gillam, Andrea; Sznol, Mario; Flaherty, Keith; Buchbinder, Elizabeth; Carvajal, Richard D; Varghese, Anna M; Lacouture, Mario E; Ribas, Antoni; Patel, Sapna P; DeCrescenzo, Gary A; Emery, Caroline M; Groover, Anna L; Saha, Saurabh; Varterasian, Mary; Welsch, Dean J; Hyman, David M; Li, Bob T

    2018-02-01

    Ulixertinib (BVD-523) is an ERK1/2 kinase inhibitor with potent preclinical activity in BRAF- and RAS-mutant cell lines. In this multicenter phase I trial (NCT01781429), 135 patients were enrolled to an accelerated 3 + 3 dose-escalation cohort and six distinct dose-expansion cohorts. Dose escalation included 27 patients, dosed from 10 to 900 mg twice daily and established the recommended phase II dose (RP2D) of 600 mg twice daily. Ulixertinib exposure was dose proportional to the RP2D, which provided near-complete inhibition of ERK activity in whole blood. In the 108-patient expansion cohort, 32% of patients required dose reduction. The most common treatment-related adverse events were diarrhea (48%), fatigue (42%), nausea (41%), and dermatitis acneiform (31%). Partial responses were seen in 3 of 18 (17%) patients dosed at or above maximum tolerated dose and in 11 of 81 (14%) evaluable patients in dose expansion. Responses occurred in patients with NRAS -, BRAF V600-, and non-V600 BRAF -mutant solid tumors. Significance: Here, we describe the first-in-human dose-escalation study of an ERK1/2 inhibitor for the treatment of patients with advanced solid tumors. Ulixertinib has an acceptable safety profile with favorable pharmacokinetics and has shown early evidence of clinical activity in NRAS - and BRAF V600- and non-V600-mutant solid-tumor malignancies. Cancer Discov; 8(2); 184-95. ©2017 AACR. See related commentary by Smalley and Smalley, p. 140 This article is highlighted in the In This Issue feature, p. 127 . ©2017 American Association for Cancer Research.

  18. India Ink Incorporated Multifunctional Phase-transition Nanodroplets for Photoacoustic/Ultrasound Dual-modality Imaging and Photoacoustic Effect Based Tumor Therapy

    OpenAIRE

    Jian, Jia; Liu, Chengbo; Gong, Yuping; Su, Lei; Zhang, Bin; Wang, Zhigang; wang, Dong; Zhou, Yu; Xu, Fenfen; Li, Pan; Zheng, Yuanyi; Song, Liang; Zhou, Xiyuan

    2014-01-01

    The in vivo applications of gas-core microbubbles have been limited by gas diffusion, rapid body clearance, and poor vascular permeability. To overcome these limitations, using a modified three-step emulsion process, we have developed a first-of-its-kind India ink incorporated optically-triggerable phase-transition perfluorocarbon nanodroplets (INDs) that can provide not only three types of contrast mechanisms—conventional/thermoelastic photoacoustic, phase-transition/nonlinear photoacoustic,...

  19. Radiology of neuroendocrine tumors

    International Nuclear Information System (INIS)

    Hako, R.; Hakova, H.; Gulova, I.

    2011-01-01

    Neuroendocrine tumors arise in the bronchopulmonary or gastrointestinal tract, but they can arise in almost any organ. The tumors have varied malignant potential depending on the site of their origin. Metastases may be present at the time of diagnosis, which often occurs at a late stage of the disease. Most NETs have nonspecific imaging characteristics. Imaging plays a pivotal role in the localization and staging of neuroendocrine tumors and in monitoring the treatment response. Imaging should involve multi-phase computed tomography, contrast material-enhanced magnetic resonance imaging, contrast-enhanced ultrasonography and other one. Hepatic metastatic disease in particular lends itself to a wide range of interventional treatment options. Transcatheter arterial embolization may be used alone or in combination with chemo embolization. Ablative techniques, hepatic cryotherapy and percutaneous ethanol injection may then be undertaken. A multidisciplinary approach to treatment and follow-up is important. (author)

  20. 25 CFR 1000.310 - What information must the Tribe's/Consortium's response contain?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false What information must the Tribe's/Consortium's response... INDIAN SELF-DETERMINATION AND EDUCATION ACT Reassumption § 1000.310 What information must the Tribe's/Consortium's response contain? (a) The Tribe's/Consortium's response must indicate the specific measures that...

  1. A Phase III, Double-Blind, Placebo-Controlled Prospective Randomized Clinical Trial of d-Threo-Methylphenidate HCl in Brain Tumor Patients Receiving Radiation Therapy

    International Nuclear Information System (INIS)

    Butler, Jerome M.; Case, L. Douglas; Atkins, James; Frizzell, Bart; Sanders, George; Griffin, Patricia; Lesser, Glenn; McMullen, Kevin; McQuellon, Richard; Naughton, Michelle; Rapp, Stephen; Stieber, Volker; Shaw, Edward G.

    2007-01-01

    Purpose: The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT. Methods and Materials: Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administered as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam. Results: The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms. Conclusions: Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL

  2. Tumor Markers

    Science.gov (United States)

    ... only a small number of people will test positive for the disease who do not have it—in other words, it will result in very few false-positive results. Although tumor markers are extremely useful in ...

  3. Tumor Grade

    Science.gov (United States)

    ... Peer Review and Funding Outcomes Step 4: Award Negotiation & Issuance Manage Your Award Grants Management Contacts Monitoring ... may require immediate or more aggressive treatment. The importance of tumor grade in planning treatment and determining ...

  4. A contrast enhancement and scanning techniques for CT angiography of head and neck. One phase injection method for simultaneous imaging of vessels and tumor

    International Nuclear Information System (INIS)

    Morita, Yasuhiko; Indo, Hiroko; Noikura, Takenori

    1999-01-01

    We report on a method of CT-Angiography useful for examining lesion of the head and neck using three-dimensional images and measured CT value. This study focused on some of the important blood vessels in the head and neck. The aim of this method was to obtain high-contrast enhancement for both vessels and tumors at same time. A total amount of 100 ml nonionic contrast media (Omnipaque 240, 240 mg iodine per milliliter, Daiichi seiyaku, Tokyo, Japan) was injected intravenously with a flow of 1.5 ml/sec. Spiral scans, 24 rotations with 24 seconds, were started at a time when remaining amount of contrast media had become 30 to 20 ml. All CT scans were performed using double speed spiral scan technique with a slice thickness of 2 to 3 mm and table speeds from 3 to 5 mm/rotation. The patients populations consisted of 9 men and 6 women who ranged in age from 37 to 85 years. Sixteen CT-angiography were performed according to this method. Mean CT values of major blood vessels were measured in order to find out threshold at the level of submandibular gland in 13 examinations for 12 subjects. Important vessels like the common, internal, and the external artery, internal and external jugular vein were clearly visible in all subjects. Three dimensional images of these vessels could also be reconstructed for 15 of the subjects. Mean CT values were 211 Hounsfield units (HU) and 209 HU for the right and left internal carotid artery, respectively, and 204 HU and 206 HU for the right and left external carotid artery, respectively. Mean CT values for right and left internal jugular vein were 195 HU and 194 HU respectively. Measured CT values at each important blood vessels showed this method could yields acceptable enhancements. Good enhancement effect of tumor and blood vessels in the same scan seems to be mutually incompatible. One very important trade-off is the early enhancement effect at blood vessels versus the late enhancement effect at tumors. The other important trade

  5. Vaccination with autologous dendritic cells pulsed with multiple tumor antigens for treatment of patients with malignant melanoma: results from a phase I/II trial

    DEFF Research Database (Denmark)

    Trepiakas, Redas; Berntsen, Annika; Hadrup, Sine Reker

    2010-01-01

    Dendritic cells are regarded as the most effective antigen presenting cells and coordinators of the immune response and therefore suitable as vaccine basis. Here we present results from a clinical study in which patients with malignant melanoma (MM) with verified progressive disease received...... vaccination with autologous monocyte-derived mature dendritic cells (DC) pulsed with p53, survivin and telomerase-derived peptides (HLA-A2+ patients) or with autologous/allogeneic tumor lysate (HLA-A2(-) patients) in combination with low-dose interleukin (IL)-2 and interferon (IFN)-alpha2b....

  6. Aggressive simultaneous radiochemotherapy with cisplatin and paclitaxel in combination with accelerated hyperfractionated radiotherapy in locally advanced head and neck tumors. Results of a phase I-II trial

    Energy Technology Data Exchange (ETDEWEB)

    Kuhnt, T.; Pigorsch, S.; Pelz, T.; Haensgen, G.; Dunst, J. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Becker, A. [Dept. of Radiotherapy, Martin Luther Univ., Halle (Germany); Dept. of Radiotherapy, Municipial Hospital, Dessau (Germany); Bloching, M.; Passmann, M. [Dept. of Head and Neck Surgery, Martin Luther Univ., Halle (Germany); Lotterer, E. [Dept. of Internal Medicine I, Martin Luther Univ., Halle (Germany)

    2003-10-01

    We have tested a very aggressive combination protocol with cisplatin and escalated paclitaxel in combination with accelerated hyperfractionated radiotherapy to assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), overall toxicity, and response rate. Patients and Methods: The trial recruited 24 patients (21 males, three females, mean age 57 years) treated at our department from 1998 through 2001. Irradiation was administered in daily doses of 2 Gy up to 30 Gy followed by 1.4 Gy twice daily up to 70.6 Gy to the primary tumor and involved nodes and 51 Gy to the clinically negative regional nodes. The chemotherapy schedule included cisplatin in a fixed dose of 20 mg/m{sup 2} on days 1-5 and 29-33 and paclitaxel at increasing dose levels of 20, 25, 30 mg/m{sup 2} twice weekly over the whole treatment time. Patients were recruited in cohorts of three to six, and the MTD was reached if two out of six patients in one cohort developed DLT. DLT was defined as any grade 4 toxicity or any grade 3 toxicity requiring treatment interruption or unplanned hospitalization or any grade 3 neurotoxicity. We recruited mainly patients with large tumors for this protocol; all patients were stage IV, and the mean tumor volume (primary + metastases) amounted to 72 {+-} 61 cm{sup 3}. The mean follow-up was 30 months (range 4-39 months). Results: One early death (peritonitis and sepsis a t day 10) occurred, and 23 patients were evaluable for acute toxicity and response. The MTD of paclitaxel was reached at the third dose level (30 mg/m{sup 2} paclitaxel twice weekly). The DLT was severe mucositis grade 3 (n = 1) and skin erythema grade 4 (n = 2). After determining the MTD, another 14 patients were treated at the recommended dose level of paclitaxel with 25 mg/m{sup 2} twice weekly. In summary, 13/23 patients (57%) developed grade 3 and 10/23 (43%) grade 2 mucositis. Two patients (9%) had grade 4, five (22%) grade 3, and 16 (69%) grade 2 dermatitis. One patient died at day 30

  7. Tumor Types: Understanding Brain Tumors

    Science.gov (United States)

    Search Menu Facebook Twitter YouTube Flickr Instagram LinkedIn Brain Tumor Information | News & Blog Our Mission Our History Mission Leadership & Staff Financials Careers News & Blog Contact Us Donate Now Our Impact Our Impact Recent News News & ...

  8. Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group.

    NARCIS (Netherlands)

    Stupp, R.; Tosoni, A.; Bromberg, J.E.; Hau, P.; Campone, M.; Gijtenbeek, J.M.M.; Frenay, M.; Breimer, L.; Wiesinger, H.; Allgeier, A.; Bent, M.J. van den; Bogdahn, U.; Graaf, W.T.A. van der; Yun, H.J.; Gorlia, T.; Lacombe, D.; Brandes, A.A.

    2011-01-01

    BACKGROUND: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models. PATIENTS AND METHODS: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II

  9. Verification and Validation Process for Progressive Damage and Failure Analysis Methods in the NASA Advanced Composites Consortium

    Science.gov (United States)

    Wanthal, Steven; Schaefer, Joseph; Justusson, Brian; Hyder, Imran; Engelstad, Stephen; Rose, Cheryl

    2017-01-01

    The Advanced Composites Consortium is a US Government/Industry partnership supporting technologies to enable timeline and cost reduction in the development of certified composite aerospace structures. A key component of the consortium's approach is the development and validation of improved progressive damage and failure analysis methods for composite structures. These methods will enable increased use of simulations in design trade studies and detailed design development, and thereby enable more targeted physical test programs to validate designs. To accomplish this goal with confidence, a rigorous verification and validation process was developed. The process was used to evaluate analysis methods and associated implementation requirements to ensure calculation accuracy and to gage predictability for composite failure modes of interest. This paper introduces the verification and validation process developed by the consortium during the Phase I effort of the Advanced Composites Project. Specific structural failure modes of interest are first identified, and a subset of standard composite test articles are proposed to interrogate a progressive damage analysis method's ability to predict each failure mode of interest. Test articles are designed to capture the underlying composite material constitutive response as well as the interaction of failure modes representing typical failure patterns observed in aerospace structures.

  10. A Global Approach to Rare Diseases Research and Orphan Products Development: The International Rare Diseases Research Consortium (IRDiRC).

    Science.gov (United States)

    Cutillo, Christine M; Austin, Christopher P; Groft, Stephen C

    2017-01-01

    Rare diseases present unique challenges to researchers due to the global distribution of patients, complexity and low prevalence of each disease, and limited availability of data. They are also overwhelming and costly for patients, their families, communities, and society. As such, global integration of rare diseases research is necessary to accelerate the understanding, diagnosis, and treatment of rare disorders. The International Rare Diseases Research Consortium (IRDiRC) was born out of that need for a coordinated international community. IRDiRC was launched in 2011 to facilitate cooperation and collaboration on a global scale among the many stakeholders active in rare diseases research to stimulate better coordination, and thereby maximize output of rare diseases research efforts around the world. Members include funders, academic researchers, companies, and patient advocacy organizations all of whom share the common goals and principles of IRDiRC. The overarching objectives of the Consortium are to contribute to the development of 200 new therapies and a means to diagnose most rare diseases, by 2020. As IRDiRC approaches the end of its fifth year, these initial objectives have been largely achieved and new partners from across the globe are joining. This presents the Consortium with the exciting opportunity to set new and even more ambitious goals for the next phase with the ultimate goal of improved health through faster and better diagnostic capabilities and novel therapies for people living with rare diseases and conditions throughout the world.

  11. Impact of primary metastatic bone disease in germ cell tumors

    DEFF Research Database (Denmark)

    Oing, C; Oechsle, K; Necchi, A

    2017-01-01

    Background: Bone metastases (BM) are rare in germ cell tumor (GCT) patients. Systematic data on risk factors, treatment and outcome are largely lacking. Patients and methods: A database created by an international consortium including 123 GCT patients with BM at primary diagnosis was retrospectiv......Background: Bone metastases (BM) are rare in germ cell tumor (GCT) patients. Systematic data on risk factors, treatment and outcome are largely lacking. Patients and methods: A database created by an international consortium including 123 GCT patients with BM at primary diagnosis...... prognosticators in univariate analysis were a mediastinal primary (PFS; HR 1.92; 95%CI, 1.05-3.50; OS; HR 2.16; 95%CI, 1.14-4.09) and the presence of liver and/or brain metastases (PFS; HR 1.89; 95%CI, 1.13-3.17; OS; HR 1.91; 95%CI, 0.024) Seminomatous histology was the strongest predictor for favorable PFS...

  12. Mediastinal tumors

    International Nuclear Information System (INIS)

    Canizares, Claudio; Araujo, Ivan; Rodriguez, Amparo; Robles, Wilson; Simba, Catalina

    2005-01-01

    In our practice the mediastinal tumors are infrequent. The mediastinum is the portion of the thoracic cavity that contains numerous organs and structures which makes a crossroad for the diagnostic process. Within which congenital cysts, inflammatory and benign tumors, malignant neoplasms may develop. In the superior compartment are found: thymoma and thymic cysts, germ cell tumors, thyroid lesions, parathyroid adenomas, malignant lymphomas, paragangliomas, hemangiomas, lipomas, and inflammatory lesions such as fibrosing mediastinitis. In the middle portion: pericardial cysts, bronchial cysts, malignant lymphomas. In the posterior region: neurogenic tumors such as Shawnomas, neurofibromas, ganglioneuroblastomas, neuroblastomas, paragangliomas, and gastro enteric cysts. We describe two cases. One of a female patient with a prominent tumor in the anterior compartment of the mediastinum, detected by the x-ray films. Initially a cardiac lesion was excluded by echographic, angiographic studies. The biopsy exhibited a prominent fibrosis that suggested fibrosing mediastinitis (sclerosing). Whoever the immunohistochemical phenotype was positive for lambda chains, determining the diagnosis of lymphoma. The other case is of a young male with a thymoma associated to a pure red cell aplasia, which was the initial clinical symptom. Computerized tomography and thyroid scintigraphy was used. (The author)

  13. Mapping Project Connections Over Time in a Heliophysics Education Consortium

    Science.gov (United States)

    Davis, H. B.; Young, C. A.; Mayo, L.

    2017-12-01

    To evaluate the goal of the synergies created among the 20+ projects in the Science Mission Directorate Heliophysics Consortium, participants were asked to identify connections before and after the first and second years. Social network analysis shows the changes in the number and nature of the connections. Further data collection and analysis focused on the nature of the connections, how they were developed, and if and how they are sustained. The nature and extent of connections was examined in relationship to the consortium structures and activities. What kinds of community-building activities are effective? Which activities and communication is valued by the projects? When a collaboration is established, does it use the community tools or move off line? These and other questions will be discussed.

  14. Growing Rhizomatically: Disability Studies, the Art Gallery and the Consortium

    Directory of Open Access Journals (Sweden)

    Kristin Anne Lindgren

    2014-03-01

    Full Text Available In this essay, we propose that the Deleuzoguattarian rhizome offers a map and metaphor for the field of disability studies, especially as it develops outside the boundaries of a defined program or curriculum. As an example of rhizomatic growth, we discuss a series of events in the Philadelphia area in fall 2012 that focused on disability studies and disability arts and culture, including an art exhibition entitled What Can A Body Do? and a scholarly residency sponsored by the Greater Philadelphia Women’s Studies Consortium. We suggest that the art gallery offers a generative space for the growth of disability studies, disability aesthetics, and new models of access, and we emphasize the importance of cross-institutional collaboration in the development of disability studies not only as a field but as a field of energy. Keywords: rhizome, Deleuze and Guattari, art gallery, contemporary art, curator, access, audio description, multisensory, collaboration, consortium, disability aesthetics, What Can A Body Do?

  15. University-industry consortium: maximizing the use of limited resources for instructor training

    International Nuclear Information System (INIS)

    Norton, R.E.; Williams, T.M.

    1987-01-01

    This proposed development effort would accomplish three major objectives, as follows: 1. To identify and verify, through job analysis, the critical professional tasks that must be performed by electric utility instructors. 2. To adapt and revise existing instructor training modules to make them self-contained and highly specific to the professional knowledge and skills needed by electric utility instructors. 3. To develop new instructor training modules, if needed, to meet utility instructor training needs that are not addressed by any existing materials. It is anticipated that approximately twenty (20) modules will be needed to address all of the critical instructor tasks identified during the job analysis phase. The National Center for Research in Vocational Education proposes that it would be very cost-effective and time-efficient to cooperatively undertake the development of the needed instructor training modules with a consortium of about to ten interested electric utility companies

  16. Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    But-Hadzic, Jasna, E-mail: jbut@onko-i.si [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Anderluh, Franc [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Brecelj, Erik; Edhemovic, Ibrahim [Division of Surgery, Institute of Oncology, Ljubljana (Slovenia); Secerov-Ermenc, Ajra; Hudej, Rihard; Jeromen, Ana [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Kozelj, Miran; Krebs, Bojan [Division of Surgery, University Medical Centre Maribor, Maribor (Slovenia); Oblak, Irena [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia); Omejc, Mirko [Division of Surgery, University Medical Centre Lubljana, Ljubljana (Slovenia); Vogrin, Andrej [Division of Diagnostics, Institute of Oncology, Ljubljana (Slovenia); Velenik, Vaneja [Division of Radiotherapy, Institute of Oncology, Ljubljana (Slovenia)

    2016-12-01

    Background and Purpose: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Methods and Materials: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m{sup 2}/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Results: Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Conclusions: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.

  17. A Phase II Study of Preradiotherapy Chemotherapy Followed by Hyperfractionated Radiotherapy for Newly Diagnosed High-Risk Medulloblastoma/Primitive Neuroectodermal Tumor: A Report From the Children's Oncology Group (CCG 9931)

    International Nuclear Information System (INIS)

    Allen, Jeffrey; Donahue, Bernadine; Mehta, Minesh; Miller, Douglas C.; Rorke, Lucy B.; Jakacki, Regina; Robertson, Patricia; Sposto, Richard; Holmes, Emi; Vezina, Gilbert; Muraszko, Karin; Puccetti, Diane; Prados, Michael; Chan, K.-W.

    2009-01-01

    Purpose: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT). Methods and Materials: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm 2 postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) with a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions. Results: The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% ± 5% and 52% ± 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage. Conclusions: The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design.

  18. Imaging of brain tumors

    International Nuclear Information System (INIS)

    Gaensler, E.H.L.

    1995-01-01

    The contents are diagnostic approaches, general features of tumors -hydrocephalus, edema, attenuation and/or intensity value, hemorrhage, fat, contrast enhancement, intra-axial supratentorial tumors - tumors of glial origin, oligodendrogliomas, ependymomas, subependymomas, subependymal giant cell astrocytomas, choroid plexus papilloma; midline tumors - colloid cysts, craniopharyngiomas; pineal region tumors and miscellaneous tumors i.e. primary intracerebral lymphoma, primitive neuroectodermal tumors, hemangioblastomas; extraaxial tumors - meningiomas; nerve sheath tumors -schwannomas, epidermoids, dermoids, lipomas, arachnoid cysts; metastatic tumors (8 refs.)

  19. Tumor markers in colorectal cancer

    OpenAIRE

    Fernandes, Luís César [UNIFESP; Matos, Delcio [UNIFESP

    2002-01-01

    Colorectal cancer is a clinical entity of a persistent relevance in clinical practice and its early diagnosis is a determinant factor to obtain better therapeutic results. Tumor markers are helpful means for a better approach to individuals with such neoplasm. In the present review, the authors analyze the phases in which surgical-clinical treatment markers must be used: diagnosis, determination of tumor stage, establishment of prognosis and detection of recurrence. Current and future markers...

  20. A phase I, first in man study of OSI-7836 in patients with advanced refractory solid tumors: IND.147, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group.

    Science.gov (United States)

    Goss, G; Siu, L L; Gauthier, I; Chen, E X; Oza, A M; Goel, R; Maroun, J; Powers, J; Walsh, W; Maclean, M; Drolet, D W; Rusk, J; Seymour, L K

    2006-11-01

    To determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, tolerability, toxicity profile, dose-limiting toxicities (DLTs), anti-tumor activity and pharmacokinetics of OSI-7836 given IV on day 1 and day 8 every 3 weeks in patients with advanced incurable cancer. Twenty-seven previously treated patients with advanced or metastatic solid tumors were enrolled in this phase I study conducted by the National Cancer Institute of Canada Clinical Trial Group (NCIC CTG). OSI-7836 was administered IV on day 1 and day 8 every 3 weeks. The dose was initially escalated from 100 to 600 mg/m2 and finally de-escalated to 200 mg/m2 in seven cohorts of patients. Patients were evaluated every other cycle of treatment for radiological response. Pharmacokinetics were performed on day 1 and day 8 of cycle 1 for all patients. Twenty-six patients were evaluable for toxicity. All patients experienced reversible Grade 3 lymphopenia beginning at cycle 1. The maximal delivered dose was 600 mg/m2. MTD was reached at 400 mg/m2. DLTs included fever, fatigue, rash, herpes simplex infection, nausea and vomiting. The RP2D was 200 mg/m2. No objective responses were seen in 21 evaluable patients. Pharmacokinetics were dose proportional, with a mean half-life of 46.0 min and a clearance of 34 l/(h.m2). OSI-7836 given at 200 mg/m2 on day 1 and day 8 every 3 weekly is associated with manageable toxicity and is recommended for further study. While no objective responses were seen, the significant treatment related lymphopenia suggests that hematologic malignancies may warrant further investigation.

  1. Pituitary Tumors

    Science.gov (United States)

    ... nursing, or cause a man to lose his sex drive or lower his sperm count. Pituitary tumors often go undiagnosed because their symptoms resemble those of so many other more common diseases. × Definition The pituitary is a small, bean-sized gland ...

  2. Nephrogenic tumors

    International Nuclear Information System (INIS)

    Wiesbauer, P.

    2008-01-01

    Nephroblastomas are the most common malignant renal tumors in childhood. According to the guidelines of the SIOP (Societe Internationale d'Oncologie Pediatrique) and GPOH (Gesellschaft fuer Paediatrische Onkologie und Haematologie) pre-operative chemotherapy can be started without histological confirmation and thus initial imaging studies, in particular ultrasound, play an outstanding role for diagnostic purposes

  3. SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors

    Directory of Open Access Journals (Sweden)

    Christine S. Higham

    2017-01-01

    Full Text Available Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1- associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST has been reported. Methods. We evaluated the objective response (OR rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%. Results. 34 NF1 (median age 33 years and 14 sporadic (median age 40 years MPNST patients enrolled. Five of 28 (17.9% evaluable NF1 MPNST patients had a partial response (PR, as did 4 of 9 (44.4% patients with sporadic MPNST. Stable disease (SD was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

  4. Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial.

    Science.gov (United States)

    Komatsu, Yoshito; Doi, Toshihiko; Sawaki, Akira; Kanda, Tatsuo; Yamada, Yasuhide; Kuss, Iris; Demetri, George D; Nishida, Toshirou

    2015-10-01

    The randomized, double-blind, placebo-controlled GRID trial tested the oral multikinase inhibitor regorafenib in 199 patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib, and showed a significant improvement in progression-free survival (PFS) versus placebo [hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.19-0.39; p regorafenib 160 mg once daily with matching placebo, in combination with best supportive care. The primary study endpoint was progression-free survival (PFS); safety was evaluated through the incidence of adverse events (AEs). Seventeen Japanese patients were randomized to regorafenib (n = 12) or placebo (n = 5). Patient demographics were consistent with those of the overall study population. PFS was significantly longer with regorafenib than placebo (HR 0.08; 95 % CI 0.02-0.45; p = 0.000164). Centrally assessed disease control rates were 58 % and 20 % in the regorafenib and placebo groups, respectively (p = 0.080796). Treatment-related adverse events (AEs) were reported in all regorafenib-treated patients and 60 % of placebo recipients; the most frequent AE was hand-foot skin reaction (HFSR) (92 % versus 20 %, respectively). Regorafenib showed efficacy and a manageable safety profile in Japanese patients with advanced GIST, consistent with the overall GRID study population. AEs, such as HFSR and maculopapular rash, were observed more frequently in Japanese patients. Although dose modification was frequently reported, only one patient with hepatic failure discontinued regorafenib because of AEs.

  5. COSMIC: A Regimen of Intensity Modulated Radiation Therapy Plus Dose-Escalated, Raster-Scanned Carbon Ion Boost for Malignant Salivary Gland Tumors: Results of the Prospective Phase 2 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, Alexandra D., E-mail: alexdjensen@gmx.de [Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany); Nikoghosyan, Anna V.; Lossner, Karen [Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany); Haberer, Thomas; Jäkel, Oliver [Heidelberg Ion Beam Therapy Centre, Heidelberg (Germany); Münter, Marc W.; Debus, Jürgen [Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany)

    2015-09-01

    Purpose: To investigate the effect of intensity modulated radiation therapy (IMRT) and dose-escalated carbon ion (C12) therapy in adenoid cystic carcinoma (ACC) and other malignant salivary gland tumors (MSGTs) of the head and neck. Patients and Methods: COSMIC (combined treatment of malignant salivary gland tumors with intensity modulated radiation therapy and carbon ions) is a prospective phase 2 trial of 24 Gy(RBE) C12 followed by 50 Gy IMRT in patients with pathologically confirmed MSGT. The primary endpoint is mucositis Common Terminology Criteria grade 3; the secondary endpoints are locoregional control (LC), progression-free survival (PFS), overall survival (OS), and toxicity. Toxicity was scored according to the Common Terminology Criteria for Adverse Events version 3; treatment response was scored according to Response Evaluation Criteria in Solid Tumors 1.1. Results: Between July 2010 and August 2011, 54 patients were accrued, and 53 were available for evaluation. The median follow-up time was 42 months; patients with microscopically incomplete resections (R1, n=20), gross residual disease (R2, n=17), and inoperable disease (n=16) were included. Eighty-nine percent of patients had ACC, and 57% had T4 tumors. The most common primary sites were paranasal sinus (34%), submandibular gland, and palate. At the completion of radiation therapy, 26% of patients experienced grade 3 mucositis, and 20 patients reported adverse events of the ear (38%). The most common observed late effects were grade 1 xerostomia (49%), hearing impairment (25%, 2% ipsilateral hearing loss), and adverse events of the eye (20%), but no visual impairment or loss of vision. Grade 1 central nervous system necrosis occurred in 6%, and 1 grade 4 ICA hemorrhage without neurologic sequelae. The best response was 54% (complete response/partial remission). At 3 years, the LC, PFS, and OS were 81.9%, 57.9%, and 78.4%, respectively. No difference was found regarding resection status. The

  6. The effect of different dosing regimens of motesanib on the gallbladder: a randomized phase 1b study in patients with advanced solid tumors

    International Nuclear Information System (INIS)

    Rosen, Lee S; Hei, Yong-jiang; Hsu, Cheng-Pang; Tebbutt, Niall C; Lipton, Lara; Price, Timothy J; Belman, Neil D; Boccia, Ralph V; Hurwitz, Herbert I; Stephenson Jr, Joe J; Wirth, Lori J; McCoy, Sheryl

    2013-01-01

    Gallbladder toxicity, including cholecystitis, has been reported with motesanib, an orally administered small-molecule antagonist of VEGFRs 1, 2 and 3; PDGFR; and Kit. We assessed effects of motesanib on gallbladder size and function. Patients with advanced metastatic solid tumors ineligible for or progressing on standard-of-care therapies with no history of cholecystitis or biliary disease were randomized 2:1:1 to receive motesanib 125 mg once daily (Arm A); 75 mg twice daily (BID), 14-days-on/7-days-off (Arm B); or 75 mg BID, 5-days-on/2-days-off (Arm C). Primary endpoints were mean change from baseline in gallbladder size (volume by ultrasound; independent review) and function (ejection fraction by CCK-HIDA; investigator assessment). Forty-nine patients received ≥1 dose of motesanib (Arms A/B/C, n = 25/12/12). Across all patients, gallbladder volume increased by a mean 22.2 cc (from 38.6 cc at baseline) and ejection fraction decreased by a mean 19.2% (from 61.3% at baseline) during treatment. Changes were similar across arms and appeared reversible after treatment discontinuation. Three patients had cholecystitis (grades 1, 2, 3, n = 1 each) that resolved after treatment discontinuation, one patient developed grade 3 acute cholecystitis requiring cholecystectomy, and two patients had other notable grade 1 gallbladder disorders (gallbladder wall thickening, gallbladder dysfunction) (all in Arm A). Two patients developed de novo gallstones during treatment. Twelve patients had right upper quadrant pain (Arms A/B/C, n = 8/1/3). The incidence of biliary “sludge” in Arms A/B/C was 39%/36%/27%. Motesanib treatment was associated with increased gallbladder volume, decreased ejection fraction, biliary sludge, gallstone formation, and infrequent cholecystitis. ClinicalTrials.gov http://clinicaltrials.gov/ct2/show/NCT00448786?term

  7. A phase 1, open label, dose escalation study to investigate the safety, tolerability, and pharmacokinetics of MG1102 (apolipoprotein(a) Kringle V) in patients with solid tumors.

    Science.gov (United States)

    Kim, Gun Min; Reid, Tony; Shin, Sang Joon; Rha, Sun Young; Ahn, Joong Bae; Lee, Sung Sil; Chung, Hyun Cheol

    2017-12-01

    Purpose MG1102 is a potent inhibitor of angiogenesis in both in vitro and in vivo models. The purpose of the study was to investigate the safety and tolerability, pharmacokinetic (PK) profile, and preliminary antitumor efficacy of MG1102. Methods Patients with refractory solid tumors were eligible. Each patient received 1 dose of MG1102 followed by a 6-day rest period, during which they underwent PK assessments and safety monitoring. If the initial dose was tolerated, the patient continued with the 21-day treatment of MG1102 (5 days on, 2 days off for 3 weeks). Dose escalation was planned in 6 cohorts (6, 12, 24, 48, 96, and 192 mg/m 2 ). Primary objectives included safety and maximum tolerated dose (MTD) assessment. Secondary objectives included assessment of PK, pharmacodynamics, and efficacy. Results A total of 16 patients were enrolled and 12 (75%) completed the study. The most common cancer type was colorectal cancer (n = 10). There was no dose limiting toxicity and the MTD was not reached at 192 mg/m 2 . The most frequent treatment-emergent adverse events were gastrointestinal disorders, including nausea (30.8%), abdominal pain (23.1%), constipation (23.1%), and dyspepsia (23.1%). The PK of MG1102 was slightly less than dose proportional from Cohorts 3 to 6. Among 13 response-evaluable patients, 1 unconfirmed partial response (PR) was seen (in the 48 mg/m 2 cohort) and 4 patients had stable disease. Conclusions The safety profile of MG1102 was generally manageable and the toxicities resolved quickly. Potential antitumor activity was observed with 1 unconfirmed PR (60% size reduction).

  8. Geodesy and the UNAVCO Consortium: Three Decades of Innovations

    Science.gov (United States)

    Rowan, L. R.; Miller, M. M.; Meertens, C. M.; Mattioli, G. S.

    2015-12-01

    UNAVCO, a non-profit, university consortium that supports geoscience research using geodesy, began with the ingenious recognition that the nascent Global Positioning System constellation (GPS) could be used to investigate earth processes. The consortium purchased one of the first commercially available GPS receivers, Texas Instrument's TI-4100 NAVSTAR Navigator, in 1984 to measure plate deformation. This early work was highlighted in a technology magazine, GPSWorld, in 1990. Over a 30-year period, UNAVCO and the community have helped advance instrument design for mobility, flexibility, efficiency and interoperability, so research could proceed with higher precision and under ever challenging conditions. Other innovations have been made in data collection, processing, analysis, management and archiving. These innovations in tools, methods and data have had broader impacts as they have found greater utility beyond research for timing, precise positioning, safety, communication, navigation, surveying, engineering and recreation. Innovations in research have expanded the utility of geodetic tools beyond the solid earth science through creative analysis of the data and the methods. For example, GPS sounding of the atmosphere is now used for atmospheric and space sciences. GPS reflectrometry, another critical advance, supports soil science, snow science and ecological research. Some research advances have had broader impacts for society by driving innovations in hazards risk reduction, hazards response, resource management, land use planning, surveying, engineering and other uses. Furthermore, the geodetic data is vital for the design of space missions, testing and advancing communications, and testing and dealing with interference and GPS jamming. We will discuss three decades (and counting) of advances by the National Science Foundation's premiere geodetic facility, consortium and some of the many geoscience principal investigators that have driven innovations in

  9. The IRIS consortium: international cooperation in advanced reactor development

    International Nuclear Information System (INIS)

    Carelli, M.; Petrovic, B.; Miller, K.; Lombardi, C.; Ricotti, M.E.

    2005-01-01

    Besides its many outstanding technical innovations in the design and safety, the most innovative feature of the International Reactor Innovative and Secure (IRIS), is perhaps the international cooperation which carries on its development. IRIS is designed by an international consortium which currently numbers 21 organizations from ten countries across four continents. It includes reactor, fuel and fuel cycle vendors, component manufacturers, laboratories, academia, architect engineers and power producers. The defining organizational characteristics of IRIS is that while Westinghouse has overall lead and responsibility, this lead is of the type of 'primus inter pares' (first among equals) rather than the traditional owner versus suppliers/contractors relationship. All members of the IRIS consortium contribute and expect to have a return, should IRIS be successfully deployed, commensurate to their investment. The nature of such return will be tailored to the type of each organization, because it will of course be of a different nature for say a component manufacturer, university, or architect engineer. One fundamental tenet of the consortium is that all members, regardless of their amount of contribution, have equal access to all information developed within the project. Technical work is thus being coordinated by integrated subgroups and the whole team meets twice a year to perform an overall review of the work, discuss policy and strategy and plan future activities. Personnel from consortium members have performed internships, mostly at Westinghouse locations in Pittsburgh, Pennsylvania, and Windsor, Connecticut, but also at other members, as it has been the case for several graduate students. In fact, more than one hundred students at the various universities have been working on IRIS, most of them conducting graduate theses at the master or doctoral level. The IRIS experience has proved very helpful to the students in successfully landing their employment choice

  10. Protein Interaction Data Curation - The International Molecular Exchange Consortium (IMEx)

    Science.gov (United States)

    Orchard, Sandra; Kerrien, Samuel; Abbani, Sara; Aranda, Bruno; Bhate, Jignesh; Bidwell, Shelby; Bridge, Alan; Briganti, Leonardo; Brinkman, Fiona S. L.; Cesareni, Gianni; Chatr-aryamontri, Andrew; Chautard, Emilie; Chen, Carol; Dumousseau, Marine; Goll, Johannes; Hancock, Robert E. W.; Hannick, Linda I.; Jurisica, Igor; Khadake, Jyoti; Lynn, David J.; Mahadevan, Usha; Perfetto, Livia; Raghunath, Arathi; Ricard-Blum, Sylvie; Roechert, Bernd; Salwinski, Lukasz; Stümpflen, Volker; Tyers, Mike; Uetz, Peter; Xenarios, Ioannis; Hermjakob, Henning

    2013-01-01

    The IMEx consortium is an international collaboration between major public interaction data providers to share curation effort and make a non-redundant set of protein interactions available in a single search interface on a common website (www.imexconsortium.org). Common curation rules have been developed and a central registry is used to manage the selection of articles to enter into the dataset. The advantages of such a service to the user, quality control measures adopted and data distribution practices are discussed. PMID:22453911

  11. Fully automated synthesis of ¹¹C-acetate as tumor PET tracer by simple modified solid-phase extraction purification.

    Science.gov (United States)

    Tang, Xiaolan; Tang, Ganghua; Nie, Dahong

    2013-12-01

    Automated synthesis of (11)C-acetate ((11)C-AC) as the most commonly used radioactive fatty acid tracer is performed by a simple, rapid, and modified solid-phase extraction (SPE) purification. Automated synthesis of (11)C-AC was implemented by carboxylation reaction of MeMgBr on a polyethylene Teflon loop ring with (11)C-CO2, followed by acidic hydrolysis with acid and SCX cartridge, and purification on SCX, AG11A8 and C18 SPE cartridges using a commercially available (11)C-tracer synthesizer. Quality control test and animals positron emission tomography (PET) imaging were also carried out. A high and reproducible decay-uncorrected radiochemical yield of (41.0 ± 4.6)% (n=10) was obtained from (11)C-CO2 within the whole synthesis time about 8 min. The radiochemical purity of (11)C-AC was over 95% by high-performance liquid chromatography (HPLC) analysis. Quality control test and PET imaging showed that (11)C-AC injection produced by the simple SPE procedure was safe and efficient, and was in agreement with the current Chinese radiopharmaceutical quality control guidelines. The novel, simple, and rapid method is readily adapted to the fully automated synthesis of (11)C-AC on several existing commercial synthesis module. The method can be used routinely to produce (11)C-AC for preclinical and clinical studies with PET imaging. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  13. Brain Tumor Symptoms

    Science.gov (United States)

    ... Brain Anatomy Brain Tumor Symptoms Headaches Seizures Memory Depression Mood Swings & Cognitive Changes Fatigue Other Symptoms Diagnosis Types of Tumors Risk Factors Brain Tumor Statistics Brain Tumor Dictionary Webinars Anytime Learning About Us ...

  14. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  15. An open label phase II study evaluating first-line EGFR tyrosine kinase inhibitor erlotinib in non-small cell lung cancer patients with tumors showing high EGFR gene copy number.

    Science.gov (United States)

    Szutowicz-Zielińska, Ewa; Konopa, Krzysztof; Kowalczyk, Anna; Suszko-Każarnowicz, Małgorzata; Duchnowska, Renata; Szczęsna, Aleksandra; Ratajska, Magdalena; Sowa, Aleksander; Limon, Janusz; Biernat, Wojciech; Burzykowski, Tomasz; Jassem, Jacek; Dziadziuszko, Rafał

    2017-03-07

    First-line treatment with epidermal growth factor receptor (EGFR) inhibitors in NSCLC is effective in patients with activating EGFR mutations. The activity of erlotinib in patients harboring high EGFR gene copy number has been considered debatable. A multicenter, open-label, single-arm phase II clinical trial was performed to test the efficacy of erlotinib in the first-line treatment of NSCLC patients harboring high EGFR gene copy number defined as ≥4 copies in ≥40% of cells. Between December 2007 and April 2011, tumor samples from 149 subjects were screened for EGFR gene copy number by fluorescence in-situ hybridization (FISH), Out of 49 patients with positive EGFR FISH test, 45 were treated with erlotinib. Median PFS in the intent-to-treat population was 3.3 months (95%CI: 1.8-3.9 months), and median overall survival was 7.9 months (95% CI: 5.1-12.6 months). Toxicity profile of erlotinib was consistent with its known safety profile. The trial was stopped prematurely at 63% of originally planned sample size due to accumulating evidence that EGFR gene copy number should not be used to select NSCLC patients to first-line therapy with EGFR TKI. Data on erlotinib efficacy according to EGFR, KRAS and BRAF mutations are additionally presented. This trial argues against using high gene copy number for selection of NSCLC patients to first-line therapy with EGFR TKIs. The study adds to the discussion on efficacy of other targeted agents in patients with target gene amplified tumors.

  16. Neurofibromatosis Type 2 (NF2) Natural History Consortium

    National Research Council Canada - National Science Library

    Slattery, William H., III

    2005-01-01

    .... We will standardize the volumetric analysis of intracranial and spinal tumors, assess the patients' audiological, neurological, and ophthalmological functioning, and analyze molecular and clinical...

  17. Neurofibromatosis Type 2 (NF2) Natural History Consortium

    National Research Council Canada - National Science Library

    Slattery, William H

    2006-01-01

    .... We will standardize the volumetric analysis of intracranial and spinal tumors, assess the patients audiological, neurological, and ophthalmological functioning, and analyze molecular and clinical...

  18. Decolorization and biodegradation of reactive dyes and dye wastewater by a developed bacterial consortium.

    Science.gov (United States)

    Saratale, R G; Saratale, G D; Chang, J S; Govindwar, S P

    2010-11-01

    A bacterial consortium (consortium GR) consisting of Proteus vulgaris NCIM-2027 and Micrococcus glutamicus NCIM-2168 could rapidly decolorize and degrade commonly-used sulfonated reactive dye Green HE4BD and many other reactive dyes. Consortium GR shows markedly higher decolorization activity than that of the individual strains. The preferable physicochemical parameters were identified to achieve higher dye degradation and decolorization efficiency. The supplementation of cheap co-substrates (e.g., extracts of agricultural wastes) could enhance the decolorization performance of consortium GR. Extent of mineralization was determined with TOC and COD measurements, showing nearly complete mineralization of Green HE4BD by consortium GR (up to 90% TOC and COD reduction) within 24 h. Oxidoreductive enzymes seemed to be involved in fast decolorization/degradation process with the evidence of enzymes induction in the bacterial consortium. Phytotoxicity and microbial toxicity studies confirm that the biodegraded products of Green HE4BD by consortium GR are non-toxic. Consortium GR also shows significant biodegradation and decolorization activities for mixture of reactive dyes as well as the effluent from actual dye manufacturing industry. This confers the possibility of applying consortium GR for the treatment of industrial wastewaters containing dye pollutants.

  19. Evaluating robustness of a diesel-degrading bacterial consortium isolated from contaminated soil

    DEFF Research Database (Denmark)

    Sydow, Mateusz; Owsianiak, Mikolaj; Szczepaniak, Zuzanna

    2016-01-01

    kinetics on individual hydrocarbons. However, despite this low resistance, structural and functional resilience were high, as verified by re-exposing the hydrocarbon-perturbed consortium to diesel fuel. The high resilience is either due to the short exposure time, insufficient for permanent changes...... in consortium structure and function, or the ability of some consortium members to be maintained during exposure on degradation intermediates produced by other members. Thus, the consortium is expected to cope with short-term exposures to narrow carbon feeds, while maintaining its structural and functional...... integrity, which remains an advantage over biodegradation approaches using single species cultures....

  20. Contrast-enhanced ultrasonography depicts small tumor vessels for the evaluation of pancreatic tumors

    International Nuclear Information System (INIS)

    Okamoto, Yuko; Kawamoto, Hirofumi; Takaki, Akinobu; Ishida, Etsuji; Ogawa, Tsuneyoshi; Kuwaki, Kenji; Kobayashi, Yoshiyuki; Sakaguchi, Kohsaku; Shiratori, Yasushi

    2007-01-01

    Objective: The aim of this study is to evaluate the efficacy of contrast-enhanced ultrasonography for the diagnosis of pancreatic tumors. Materials and methods: Contrast-enhanced ultrasonography with Levovist was performed on 62 consecutive patients (53 with pancreatic cancer, 4 with islet cell tumor, 3 with inflammatory pancreatic tumor, and 2 with metastatic tumor). The vascular and perfusion image phases of the tumors were evaluated and compared with the findings of contrast-enhanced computed tomography. Results: Contrast-enhanced ultrasonography showed tumor vessels around and/or in the tumor at the vascular image phase in 79% of pancreatic cancer patients (42/53). At the perfusion image phase, 96% of pancreatic cancers (51/53) were classified as hypo-enhancement type. However, tiny spotty or irregular heterogeneous enhanced lesions were found in 84% of hypo-enhanced pancreatic cancer patients (43/51). The presence of small vessels at the vascular image phase was closely correlated with the presence of these intratumor regional enhanced lesions at the perfusion image phase (κ coefficient = 0.42). The sensitivity of contrast-enhanced ultrasonography (100%) for pancreatic cancer was superior to that of contrast-enhanced computed tomography (91%), but no significant difference was observed between the two (McNemar test: p = 0.063). Conclusion: Contrast-enhanced ultrasonography with Levovist successfully visualizes fine vessels and enhancement in pancreatic tumors, and is useful for evaluating pancreatic tumors

  1. Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium

    Science.gov (United States)

    Poole, Elizabeth M.; Trabert, Britton; White, Emily; Arslan, Alan A.; Patel, Alpa V.; Setiawan, V. Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A.; Buring, Julie; Butler, Lesley M.; Chamosa, Saioa; Clendenen, Tess V.; Dossus, Laure; Fortner, Renee; Gapstur, Susan M.; Gaudet, Mia M.; Gram, Inger T.; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V.; Lee, I-Min; Lundin, Eva; Merritt, Melissa A.; Onland-Moret, N. Charlotte; Peters, Ulrike; Poynter, Jenny N.; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P.; Schairer, Catherine; Schouten, Leo J.; Sjöholm, Louise K.; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A.; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P.; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S.

    2016-01-01

    Purpose An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Patients and Methods Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Results Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. Conclusion The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. PMID:27325851

  2. Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.

    Science.gov (United States)

    Wentzensen, Nicolas; Poole, Elizabeth M; Trabert, Britton; White, Emily; Arslan, Alan A; Patel, Alpa V; Setiawan, V Wendy; Visvanathan, Kala; Weiderpass, Elisabete; Adami, Hans-Olov; Black, Amanda; Bernstein, Leslie; Brinton, Louise A; Buring, Julie; Butler, Lesley M; Chamosa, Saioa; Clendenen, Tess V; Dossus, Laure; Fortner, Renee; Gapstur, Susan M; Gaudet, Mia M; Gram, Inger T; Hartge, Patricia; Hoffman-Bolton, Judith; Idahl, Annika; Jones, Michael; Kaaks, Rudolf; Kirsh, Victoria; Koh, Woon-Puay; Lacey, James V; Lee, I-Min; Lundin, Eva; Merritt, Melissa A; Onland-Moret, N Charlotte; Peters, Ulrike; Poynter, Jenny N; Rinaldi, Sabina; Robien, Kim; Rohan, Thomas; Sandler, Dale P; Schairer, Catherine; Schouten, Leo J; Sjöholm, Louise K; Sieri, Sabina; Swerdlow, Anthony; Tjonneland, Anna; Travis, Ruth; Trichopoulou, Antonia; van den Brandt, Piet A; Wilkens, Lynne; Wolk, Alicja; Yang, Hannah P; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S

    2016-08-20

    An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype. © 2016 by American Society of Clinical Oncology.

  3. Inner-City Energy and Environmental Education Consortium

    Energy Technology Data Exchange (ETDEWEB)

    1993-06-11

    The numbers of individuals with adequate education and training to participate effectively in the highly technical aspects of environmental site cleanup are insufficient to meet the increasing demands of industry and government. Young people are particularly sensitive to these issues and want to become better equipped to solve the problems which will confront them during their lives. Educational institutions, on the other hand, have been slow in offering courses and curricula which will allow students to fulfill these interests. This has been in part due to the lack of federal funding to support new academic programs. This Consortium has been organized to initiate focused educational effort to reach inner-city youth with interesting and useful energy and environmental programs which can lead to well-paying and satisfying careers. Successful Consortium programs can be replicated in other parts of the nation. This report describes a pilot program in Washington, DC, Philadelphia, and Baltimore with the goal to attract and retain inner-city youth to pursue careers in energy-related scientific and technical areas, environmental restoration, and waste management.

  4. Multiple Syntrophic Interactions in a Terephthalate-Degrading Methanogenic Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Lykidis, Athanasios; Chen, Chia-Lung; Tringe, Susannah G.; McHardy, Alice C.; Copeland, Alex 5; Kyrpides, Nikos C.; Hugenholtz, Philip; Liu, Wen-Tso

    2010-08-05

    Terephthalate (TA) is one of the top 50 chemicals produced worldwide. Its production results in a TA-containing wastewater that is treated by anaerobic processes through a poorly understood methanogenic syntrophy. Using metagenomics, we characterized the methanogenic consortium tinside a hyper-mesophilic (i.e., between mesophilic and thermophilic), TA-degrading bioreactor. We identified genes belonging to dominant Pelotomaculum species presumably involved in TA degradation through decarboxylation, dearomatization, and modified ?-oxidation to H{sub 2}/CO{sub 2} and acetate. These intermediates are converted to CH{sub 4}/CO{sub 2} by three novel hyper-mesophilic methanogens. Additional secondary syntrophic interactions were predicted in Thermotogae, Syntrophus and candidate phyla OP5 and WWE1 populations. The OP5 encodes genes capable of anaerobic autotrophic butyrate production and Thermotogae, Syntrophus and WWE1 have the genetic potential to oxidize butyrate to COsub 2}/H{sub 2} and acetate. These observations suggest that the TA-degrading consortium consists of additional syntrophic interactions beyond the standard H{sub 2}-producing syntroph ? methanogen partnership that may serve to improve community stability.

  5. A programmable Escherichia coli consortium via tunable symbiosis.

    Directory of Open Access Journals (Sweden)

    Alissa Kerner

    Full Text Available Synthetic microbial consortia that can mimic natural systems have the potential to become a powerful biotechnology for various applications. One highly desirable feature of these consortia is that they can be precisely regulated. In this work we designed a programmable, symbiotic circuit that enables continuous tuning of the growth rate and composition of a synthetic consortium. We implemented our general design through the cross-feeding of tryptophan and tyrosine by two E. coli auxotrophs. By regulating the expression of genes related to the export or production of these amino acids, we were able to tune the metabolite exchanges and achieve a wide range of growth rates and strain ratios. In addition, by inverting the relationship of growth/ratio vs. inducer concentrations, we were able to "program" the co-culture for pre-specified attributes with the proper addition of inducing chemicals. This programmable proof-of-concept circuit or its variants can be applied to more complex systems where precise tuning of the consortium would facilitate the optimization of specific objectives, such as increasing the overall efficiency of microbial production of biofuels or pharmaceuticals.

  6. Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort.

    Science.gov (United States)

    Masciari, Serena; Dillon, Deborah A; Rath, Michelle; Robson, Mark; Weitzel, Jeffrey N; Balmana, Judith; Gruber, Stephen B; Ford, James M; Euhus, David; Lebensohn, Alexandra; Telli, Melinda; Pochebit, Stephen M; Lypas, Georgios; Garber, Judy E

    2012-06-01

    Breast cancer is the most common tumor in women with Li-Fraumeni Syndrome (LFS), an inherited cancer syndrome associated with germline mutations in the TP53 tumor suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohistochemistry and FISH in small series. We seek to complement the existing small literature with this report of a histopathologic analysis of breast cancers from women with documented LFS. Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39 germline TP53 mutation carriers were assembled from investigators in the LFS consortium. Central histology review was performed on 93% of the specimens by a single breast pathologist from a major university hospital. Histology, grade, and hormone receptor status were assessed by immunohistochemistry; HER-2 status was defined by immunohistochemistry and/or FISH. The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other histologies were observed. The median age at diagnosis was 32 years (range 22-46). Of the invasive cancers, 84% were positive for ER and/or PR; and 81% were high grade. Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53% were positive for both ER and HER2+; other ER/PR/HER2 combinations were observed. The DCIS were positive for ER and HER2 in 27% of the cases. This report of the phenotype of breast cancers from women with LFS nearly doubles the literature on this topic. Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive. These findings suggest that modern treatments may result in improved outcomes for women with LFS-associated breast cancer.

  7. There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a pediatric oncology group phase III trial comparing conventional vs. hyperfractionated radiotherapy

    International Nuclear Information System (INIS)

    Mandell, Lynda R.; Kadota, Richard; Freeman, Carolyn; Douglass, Edwin C.; Fontanesi, James; Cohen, Michael E.; Kovnar, Edward; Burger, Peter; Sanford, Robert A.; Kepner, James; Friedman, Henry; Kun, Larry E.

    1999-01-01

    Purpose: In June 1992, POG began accrual to a phase III study, POG-9239, designed to compare the time to disease progression, overall survival, and toxicities observed in children with newly diagnosed brainstem tumor treated with 100 mg/m 2 of infusional cisplatin and randomized to either conventional vs. hyperfractionated radiotherapy. Methods and Materials: Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the pons. Histologic confirmation of diagnosis was not mandatory, provided that the clinical and MRI scan findings were typical for a diffusely infiltrating pontine lesion. Treatment consisted of a six-week course of local field radiotherapy with either once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy (arm 1) or a twice a day regimen of 117 cGy per fraction to a total dose of 7020 cGy (the second of the three hyperfractionated dose escalation levels of POG-8495) (arm 2). Because of previously reported poor results with conventional radiotherapy alone, cisplatin was included as a potential radiosensitizer in an attempt to improve progression-free and ultimate survival rates. Based on results of the phase I cisplatin dose escalation trial, POG-9139, 100 mg/m 2 was chosen for this trial and was delivered by continuous infusion over a 120-hour period, beginning on the first day of radiotherapy and repeated during weeks 3 and 5. One hundred thirty eligible patients were treated on protocol, 66 on arm 1 and 64 on arm 2. Results: The results we report are from time of diagnosis through October 1997. For patients treated on arm 1, the median time to disease progression (defined as time to off study) was 6 months (range 2-15 months) and the median time to death 8.5 months (range 3-24 months); survival at 1 year was 30.9% and at 2 years, 7.1%. For patients treated on arm 2, the corresponding values were 5 months (range 1-12 months) and 8 months (range 1-23 months), with 1- and 2-year

  8. Safety, Biodistribution, and Radiation Dosimetry of68Ga-OPS202 (68Ga-NODAGA-JR11) in Patients with Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Phase I Imaging Study.

    Science.gov (United States)

    Nicolas, Guillaume P; Beykan, Seval; Bouterfa, Hakim; Kaufmann, Jens; Bauman, Andreas; Lassmann, Michael; Reubi, Jean Claude; Rivier, Jean E F; Maecke, Helmut R; Fani, Melpomeni; Wild, Damian

    2017-10-12

    Preclinical and preliminary clinical evidence indicates that radiolabeled somatostatin receptor (sst) antagonists perform better than agonists in terms of detecting neuroendocrine tumors (NETs). This prospective phase I/II study is the first to evaluate an sst antagonist, 68 Ga-OPS202 ( 68 Ga-NODAGA-JR11; NODAGA=1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid and JR11=Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH 2 )) for PET imaging. Here, we report results of the phase I component of the study. Methods: Patients received two single intravenous injections of 150 MBq 68 Ga-OPS202 three to 4 weeks apart (15 µg peptide at visit 1 and 50 µg at visit 2). At visit 1, a dynamic PET/CT scan was performed over the kidney during the first 30 min post-injection and static whole-body scans at 0.5, 1, 2, and 4 h p.i; at visit 2, a static whole-body scan was performed at 1 h. Blood samples and urine were collected at regular intervals to determine 68 Ga-OPS202 pharmacokinetics. Safety, biodistribution, radiation dosimetry, and the most appropriate imaging time-point for 68 Ga-OPS202 were assessed. Results: Twelve patients with well-differentiated gastroenteropancreatic (GEP) NETs took part in the study. 68 Ga-OPS202 rapidly cleared from the blood; the mean residence time in the blood was 2.4 ± 1.1 min/L. The organs with the highest mean dose coefficients were the urinary bladder wall, kidneys, and spleen. The calculated effective dose was 2.4E-02 ± 0.2E-02 mSv/MBq, corresponding to 3.6 mSv for a reference activity of 150 MBq. Based on total numbers of detected malignant lesions, the optimal time window for the scan was between 1 and 2 h. For malignant liver lesions, the time point at which most patients had the highest mean tumor contrast was 1 h. 68 Ga-OPS202 was well tolerated; adverse events were grade 1 or 2 and there were no signals of concern for laboratory blood or urinalysis tests. Conclusion: 68 Ga-OPS202 shows favorable biodistribution and imaging

  9. Creating a multi-center rare disease consortium – the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)

    Science.gov (United States)

    Cheng, Katherine; Gupta, Sandeep K.; Kantor, Susanna; Kuhl, Jonathan T.; Aceves, Seema S.; Bonis, Peter A.; Capocelli, Kelley E.; Carpenter, Christina; Chehade, Mirna; Collins, Margaret H.; Dellon, Evan S.; Falk, Gary W.; Gopal-Srivastava, Rashmi; Gonsalves, Nirmala; Hirano, Ikuo; King, Eileen C.; Leung, John; Krischer, Jeffrey P.; Mukkada, Vincent A.; Schoepfer, Alain; Spergel, Jonathan M.; Straumann, Alex; Yang, Guang-Yu; Furuta, Glenn T.; Rothenberg, Marc E.

    2017-01-01

     Eosinophilic gastrointestinal disorders (EGIDs) affect various segments of the gastrointestinal tract. Since these disorders are rare, collaboration is essential to enroll subjects in clinical studies and study the broader population. The Rare Diseases Clinical Research Network (RDCRN), a program of the National Center for Advancing Translational Sciences (NCATS), funded the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in 2014 to advance the field of EGIDs. CEGIR facilitates collaboration among various centers, subspecialties, patients, professional organizations and patient-advocacy groups and includes 14 clinical sites. It has successfully initiated two large multi-center clinical studies looking to refine EGID diagnoses and management. Several pilot studies are underway that focus on various aspects of EGIDs including novel therapeutic interventions, diagnostic and monitoring methods, and the role of the microbiome in pathogenesis. CEGIR currently nurtures five physician-scholars through a career training development program and has published more than 40 manuscripts since its inception. This review focuses on CEGIR’s operating model and progress and how it facilitates a framework for exchange of ideas and stimulates research and innovation. This consortium provides a model for progress on other potential clinical areas. PMID:29333363

  10. Modified response evaluation criteria in solid tumors and European Association for The Study of the Liver criteria using delayed-phase imaging at an early time point predict survival in patients with unresectable intrahepatic cholangiocarcinoma following yttrium-90 radioembolization.

    Science.gov (United States)

    Camacho, Juan C; Kokabi, Nima; Xing, Minzhi; Prajapati, Hasmukh J; El-Rayes, Bassel; Kim, Hyun S

    2014-02-01

    To investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) refractory to standard chemotherapy after yttrium-90 ((90)Y) radioembolization therapy. In an institutional review board-approved prospective correlative study, 21 consecutive patients with ICC refractory to standard chemotherapy underwent (90)Y radioembolization therapy. Target and overall Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) treatment responses were assessed. The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies. Conventional definitions for complete and partial response were applied; these responses comprised objective response. Restaging imaging was obtained at 1- and 3-month intervals until patient death. Survival analyses by Kaplan-Meier and log-rank proportional models including application of the landmark method to avoid lead-time bias were performed from the day of treatment. Significance was set at P 90)Y therapy was 16.3 months (95% confidence interval, 7.2-25.4 mo). Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders (P 90)Y radioembolization therapy for ICC predicted OS. RECIST did not correlate with survival. © 2014 Published by SIR on behalf of SIR.

  11. Consortium de recherche pour le développement de l'agriculture en ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Research Consortium for the Development of Agriculture in Haiti. Even before it was hit by a devastating earthquake in January 2010, Haiti's children suffered some of the worst rates of undernutrition in Latin America and the Caribbean. View moreResearch Consortium for the Development of Agriculture in Haiti ...

  12. Renaissance Educational Consortium Ensuring Individualized Progress in Technology and Science (RECEIPTS)

    Science.gov (United States)

    Caddell, Esther Harte; And Others

    1975-01-01

    Describes the rationale for, development of, and activities of the Renaissance Educational Consortium Ensuring Individualized Progress in Technology and Science (RECEIPTS). The effort is designed to build a consortium of community resources with a focus on science and technology in order to combat the problems of low academic motivation and…

  13. The creation of the SAVE consortium – Saving Asia's Vultures from ...

    African Journals Online (AJOL)

    This article describes the background to this problem, caused mainly by the veterinary drug diclofenac, and the establishment and structure of the SAVE consortium created to help coordinate the necessary conservation response. The lessons learnt in Asia and the working model of such a consortium are presented, which ...

  14. Northeast Artificial Intelligence Consortium Annual Report. 1988 Artificial Intelligence Applications to Speech Recognition. Volume 8

    Science.gov (United States)

    1989-10-01

    1988 Artificial Intelligence Applications to Speech Recognition Syracuse University Harvey E. Rhody, Thomas R. Ridley, John A. ,les DTIC S ELECTE FEB...Include Security Oiewftction) NORTHEAST ARTIFICIAL INTELLIGENCE CONSORTIUM ANNUAL REPORT - 1988 Artificial Intelligence Applications to Speech...Intelligence Consortium 1988 Annual Report Volume 8 Artificial Intelligence Applications to Speech Recognition Harvey E. Rhody Thomas R. Ridley John A

  15. The Activities of the European Consortium on Nuclear Data Development and Analysis for Fusion

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, U., E-mail: ulrich.fischer@kit.edu [Karlsruhe Institute of Technology, Institute for Neutron Physic and Reactor Technology, 76344 Eggenstein-Leopoldshafen (Germany); Avrigeanu, M.; Avrigeanu, V. [Horia Hulubei National Institute of Physics and Nuclear Engineering (IFIN-HH), RO-077125 Magurele (Romania); Cabellos, O. [Departamento de Ingenieria Nuclear, Universidad Politecnica de Madrid, 28006 Madrid (Spain); Kodeli, I. [Jozef Stefan Institute (JSI), Jamova 39, 1000 Ljubljana (Slovenia); Koning, A. [Nuclear Research and Consultancy Group (NRG), Westerduinweg 3, 1755 LE Petten (Netherlands); Konobeyev, A.Yu. [Karlsruhe Institute of Technology, Institute for Neutron Physic and Reactor Technology, 76344 Eggenstein-Leopoldshafen (Germany); Leeb, H. [Technische Universitaet Wien, Atominstitut, Wiedner Hauptstrasse 8–10, 1040 Wien (Austria); Rochman, D. [Nuclear Research and Consultancy Group (NRG), Westerduinweg 3, 1755 LE Petten (Netherlands); Pereslavtsev, P. [Karlsruhe Institute of Technology, Institute for Neutron Physic and Reactor Technology, 76344 Eggenstein-Leopoldshafen (Germany); Sauvan, P. [Universidad Nacional de Educacion a Distancia, C. Juan del Rosal, 12, 28040 Madrid (Spain); Sublet, J.-C. [Euratom/CCFE Fusion Association, Culham Science Centre, OX14 3DB (United Kingdom); Trkov, A. [Jozef Stefan Institute (JSI), Jamova 39, 1000 Ljubljana (Slovenia); Dupont, E. [OECD Nuclear Energy Agency, Paris (France); Leichtle, D.; Izquierdo, J. [Fusion for Energy, Barcelona (Spain)

    2014-06-15

    This paper presents an overview of the activities of the European Consortium on Nuclear Data Development and Analysis for Fusion. The Consortium combines available European expertise to provide services for the generation, maintenance, and validation of nuclear data evaluations and data files relevant for ITER, IFMIF and DEMO, as well as codes and software tools required for related nuclear calculations.

  16. The fungal consortium of Andromeda polifolia in bog habitats

    Directory of Open Access Journals (Sweden)

    N.V. Filippova

    2015-09-01

    Full Text Available (1 Andromeda polifolia (bog rosemary is a common plant species in northern circumboreal peatlands. While not a major peat-forming species in most peatlands, it is characterised by a substantial woody below-ground biomass component that contributes directly to the accumulation of organic matter below the moss surface, as well as sclerophyllous leaf litter that contributes to the accumulation of organic matter above the moss surface. Rather little is known about the fungal communities associated with this plant species. Hence, we investigated the fungal consortium of A. polifolia in three distinct vegetation communities of ombrotrophic bogs near Khanty-Mansiysk, West Siberia, Russia, in 2012 and 2013. These vegetation communities were forested bog (Tr = treed, Sphagnum-dominated lawn (Ln, and Eriophorum-Sphagnum-dominated hummock (Er. (2 In total, 37 fungal taxa, belonging to five classes and 16 families, were identified and described morphologically. Seven fungal species were previously known from Andromeda as host. Others are reported for the first time, thus considerably expanding the fungal consortium of this dwarf shrub. Most taxa were saprobic on fallen leaves of A. polifolia found amongst Sphagnum in the bog. Two taxa were parasitic on living plant tissues and one taxon was saprobic on dead twigs. Three taxa, recorded only on A. polifolia leaves and on no other plant species or materials, may be host-specific to this dwarf shrub. (3 A quantitative analysis of the frequency of occurrence of all taxa showed that one taxon (Coccomyces duplicarioides was very abundant, 64 % of the taxa occurred frequently, and 32 % of the taxa occurred infrequently. The mean Shannon diversity index of the community was 2.4. (4 There were no statistical differences in the fungal community composition of A. polifolia in the three vegetation communities investigated in this study. Redundancy analysis suggested that some fungal taxa were positively, and others

  17. STRUCTURE OF CONSORTIUM DESTRUCTIVE COMPONENTS IN THE INDUSTRIAL AREA OF KRIVYI RIG BASIN

    Directory of Open Access Journals (Sweden)

    V. V. Kachinskaya

    2014-07-01

    Full Text Available Тhe structural organization and a biological variety of ground mesofauna on consortium level of the organization of ecosystems are considered. The analysis of indicators of the structural organization and a biodiversity of ground mesofauna in consortium Ulmus and Populus in the conditions of territories of industrial mining – metallurgical complex of Krivyi Rig Basin is carried out. It is established that taxonomical structure of ground mesofauna is characterized by insignificant number and quantity of taxonomical groups. Prevalence in morfo-ecological structure of hortobiontes and herpetobiontes testifies about faunae considerable attachment to consortium determinants and influences of a steppe climate on its structure. Prevalence of phytophages and polyphages in trophic structure is caused by combination of determinants specificity of consortium and zone source of fauna formations. The structural organization of ground mesofauna in consortium Ulmus and Populus in the conditions of industrial sites is characterized simplified taxonomical structure with a low biodiversity at all levels. It was suggested that structural and functional organization of destructive components of the block consortium of Ulmus and Populus in the conditions of industrial sites are simplified and determined by biogeochemical patterns of pedogenic and leaf litter layer of consortium and type of anthropogenic impact. Management and sustainable use of consortium under technogenic pressure should be based on the effects of extreme and critical components in the evolution of consortium. These critical points are the type of leading man-made factors and pedogenic and leaf litter biogeochemical conditions of consortium determinants, which results in inhibition of development and simplification of the structural and functional organization of destructive components of the block. The elaboration of measures to restore and maintain that structural and functional organization

  18. Mineralization of linear alkylbenzene sulfonate by a four-member aerobic bacterial consortium

    International Nuclear Information System (INIS)

    Jimenez, L.; Breen, A.; Thomas, N.; Sayler, G.S.; Federle, T.W.

    1991-01-01

    A bacterial consortium capable of linear alkylbenzene sulfonate (LAS) mineralization under aerobic conditions was isolated from a chemostat inoculated with activated sludge. The consortium, designated KJB, consisted of four members, all of which were gram-negative, rod-shaped bacteria that grew in pairs and short chains. Three isolates had biochemical properties characteristic of Pseudomonas spp.; the fourth showed characteristics of the Aeromonas spp. Cell suspensions were grown together in minimal medium with [ 14 C]LAS as the only carbon source. After 13 days of incubation, more than 25% of the [ 14 C]LAS was mineralized to 14 CO 2 by the consortium. Pure bacterial cultures and combinations lacking any one member of the KJB bacterial consortium did not mineralize LAS. Three isolates carried out primary biodegradation of the surfactant, and one did not. This study shows that the four bacteria complemented each other and synergistically mineralized LAS, indicating catabolic cooperation among the four consortium members

  19. CREAT A CONSORTIUM AND DEVELOP PREMIUM CARBON PRODUCTS FROM COAL

    Energy Technology Data Exchange (ETDEWEB)

    John M. Andresen

    2003-08-01

    The Consortium for Premium Carbon Products from Coal, with funding from the U.S. Department of Energy's National Energy Technology Laboratory and matching funds from industry and academic institutions continued to excel in developing innovative technologies to use coal and coal-derived feedstocks to produce premium carbon product. During Budget Period 5, eleven projects were supported and sub-contracted were awarded to seven organizations. The CPCPC held two meetings and one tutorial at various locations during the year. Budget Period 5 was a time of growth for CPCPC in terms of number of proposals and funding requested from members, projects funded and participation during meetings. Although the membership was stable during the first part of Budget Period 5 an increase in new members was registered during the last months of the performance period.

  20. A marine microbial consortium apparently mediating anaerobic oxidation of methane

    DEFF Research Database (Denmark)

    Boetius, A.; Ravenschlag, K.; Schubert, CJ

    2000-01-01

    microorganisms mediating this reaction have not yet been isolated, and the pathway of anaerobic oxidation of methane is insufficiently understood. Recent data suggest that certain archaea reverse the process of methanogenesis by interaction with sulphate-reducing bacteria(5-7). Here we provide microscopic...... evidence for a structured consortium of archaea and sulphate-reducing bacteria, which we identified by fluorescence in situ hybridization using specific 16S rRNA-targeted oligonucleotide probes. In this example of a structured archaeal-bacterial symbiosis, the archaea grow in dense aggregates of about 100...... cells and are surrounded by sulphate-reducing bacteria. These aggregates were abundant in gas-hydrate-rich sediments with extremely high rates of methane-based sulphate reduction, and apparently mediate anaerobic oxidation of methane....

  1. Caspian Pipeline Consortium, Bellwether of Russia's Investment climate?

    International Nuclear Information System (INIS)

    Dellecker, A.

    2008-01-01

    The Caspian Pipeline Consortium (CPC), a shipper-owned oil pipeline carrying Caspian oil to Russia's Black Sea port of Novorossyisk, remains to this day the only oil export pipeline on Russian territory that is not under the control of the state company Transneft. Completed in 2001, the CPC was, from the start, the product of a fragile balance of power between states eager to maintain control of hydrocarbon flows and private companies able to finance the necessary infrastructure. Despite its economic success, the future of the CPC currently hinges on a share-holding dispute pitting Russia against private shareholders. This essay places the CPC dossier in the broader context of Russia's investment climate and argues that the dispute's dynamic is an important bellwether of the Russian energy policy. (author)

  2. Collaboration in a Wireless Grid Innovation Testbed by Virtual Consortium

    Science.gov (United States)

    Treglia, Joseph; Ramnarine-Rieks, Angela; McKnight, Lee

    This paper describes the formation of the Wireless Grid Innovation Testbed (WGiT) coordinated by a virtual consortium involving academic and non-academic entities. Syracuse University and Virginia Tech are primary university partners with several other academic, government, and corporate partners. Objectives include: 1) coordinating knowledge sharing, 2) defining key parameters for wireless grids network applications, 3) dynamically connecting wired and wireless devices, content and users, 4) linking to VT-CORNET, Virginia Tech Cognitive Radio Network Testbed, 5) forming ad hoc networks or grids of mobile and fixed devices without a dedicated server, 6) deepening understanding of wireless grid application, device, network, user and market behavior through academic, trade and popular publications including online media, 7) identifying policy that may enable evaluated innovations to enter US and international markets and 8) implementation and evaluation of the international virtual collaborative process.

  3. Consortium for Algal Biofuel Commercialization (CAB-COMM) Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Mayfield, Stephen P. [Univ. of California, San Diego, CA (United States)

    2015-12-04

    The Consortium for Algal Biofuel Commercialization (CAB-Comm) was established in 2010 to conduct research to enable commercial viability of alternative liquid fuels produced from algal biomass. The main objective of CAB-Comm was to dramatically improve the viability of algae as a source of liquid fuels to meet US energy needs, by addressing several significant barriers to economic viability. To achieve this goal, CAB-Comm took a diverse set of approaches on three key aspects of the algal biofuels value chain: crop protection; nutrient utilization and recycling; and the development of genetic tools. These projects have been undertaken as collaboration between six academic institutions and two industrial partners: University of California, San Diego; Scripps Institution of Oceanography; University of Nebraska, Lincoln; Rutgers University; University of California, Davis; Johns Hopkins University; Sapphire Energy; and Life Technologies.

  4. Assessment of microalgae and nitrifiers activity in a consortium in a continuous operation and the effect of oxygen depletion

    Directory of Open Access Journals (Sweden)

    Gustavo Vargas

    2016-09-01

    Conclusions: The consortium it can be obtained in a single continuous operation, and has a high capacity for nitrogen removal with low oxygen content. The consortium could prove to be a more economical method compared to traditional.

  5. On the Need to Establish an International Soil Modeling Consortium

    Science.gov (United States)

    Vereecken, H.; Vanderborght, J.; Schnepf, A.

    2014-12-01

    Soil is one of the most critical life-supporting compartments of the Biosphere. Soil provides numerous ecosystem services such as a habitat for biodiversity, water and nutrients, as well as producing food, feed, fiber and energy. To feed the rapidly growing world population in 2050, agricultural food production must be doubled using the same land resources footprint. At the same time, soil resources are threatened due to improper management and climate change. Despite the many important functions of soil, many fundamental knowledge gaps remain, regarding the role of soil biota and biodiversity on ecosystem services, the structure and dynamics of soil communities, the interplay between hydrologic and biotic processes, the quantification of soil biogeochemical processes and soil structural processes, the resilience and recovery of soils from stress, as well as the prediction of soil development and the evolution of soils in the landscape, to name a few. Soil models have long played an important role in quantifying and predicting soil processes and related ecosystem services. However, a new generation of soil models based on a whole systems approach comprising all physical, mechanical, chemical and biological processes is now required to address these critical knowledge gaps and thus contribute to the preservation of ecosystem services, improve our understanding of climate-change-feedback processes, bridge basic soil science research and management, and facilitate the communication between science and society. To meet these challenges an international community effort is required, similar to initiatives in systems biology, hydrology, and climate and crop research. Our consortium will bring together modelers and experimental soil scientists at the forefront of new technologies and approaches to characterize soils. By addressing these aims, the consortium will contribute to improve the role of soil modeling as a knowledge dissemination instrument in addressing key

  6. Phase 2 Trial of Accelerated, Hypofractionated Whole-Breast Irradiation of 39 Gy in 13 Fractions Followed by a Tumor Bed Boost Sequentially Delivering 9 Gy in 3 Fractions in Early-Stage Breast Cancer

    International Nuclear Information System (INIS)

    Kim, Ja Young; Jung, So-Youn; Lee, Seeyoun; Kang, Han-Sung; Lee, Eun Sook; Park, In Hae; Lee, Keun Seok; Ro, Jungsil; Lee, Nam Kwon; Shin, Kyung Hwan

    2013-01-01

    Purpose: To report a phase 2 trial of accelerated, hypofractionated whole-breast irradiation (AH-WBI) delivered as a daily dose of 3 Gy to the whole breast followed by a tumor bed boost. Methods and Materials: Two hundred seventy-six patients diagnosed with breast cancer (pT1-2 and pN0-1a) who had undergone breast-conserving surgery in which the operative margins were negative were treated with AH-WBI delivered as 39 Gy in 13 fractions of 3 Gy to the whole breast once daily over 5 consecutive working days, and 9 Gy in 3 sequential fractions of 3 Gy to a lumpectomy cavity, all within 3.2 weeks. Results: After a median follow-up period of 57 months (range: 27-75 months), the rate of 5-year locoregional recurrence was 1.4% (n=4), whereas that of disease-free survival was 97.4%. No grade 3 skin toxicity was reported during the follow-up period. Qualitative physician cosmetic assessments of good or excellent were noted in 82% of the patients at 2 months after the completion of AH-WBI. The global cosmetic outcome did not worsen over time, and a good or excellent cosmetic outcome was reported in 82% of the patients at 3 years. The mean pretreatment percentage breast retraction assessment was 12.00 (95% confidence interval [CI]: 11.14-12.86). The mean value of percentage breast retraction assessment increased to 13.99 (95% CI: 12.17-15.96) after 1 year and decreased to 13.54 (95% CI: 11.84-15.46) after 3 years but was not significant (P>.05). Conclusions: AH-WBI consisting of 39 Gy in 13 fractions followed by a tumor bed boost sequentially delivering 9 Gy in 3 fractions can be delivered with excellent disease control and tolerable skin toxicity in patients with early-stage breast cancer after breast-conserving surgery

  7. Phase 2 Trial of Accelerated, Hypofractionated Whole-Breast Irradiation of 39 Gy in 13 Fractions Followed by a Tumor Bed Boost Sequentially Delivering 9 Gy in 3 Fractions in Early-Stage Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ja Young [Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Jung, So-Youn; Lee, Seeyoun; Kang, Han-Sung; Lee, Eun Sook; Park, In Hae; Lee, Keun Seok; Ro, Jungsil [Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Lee, Nam Kwon [Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Korea University Medical Center, Collage of Medicine, Seoul (Korea, Republic of); Shin, Kyung Hwan, E-mail: radiat@ncc.re.kr [Proton Therapy Center, Research Institute and Hospital, National Cancer Center, Goyang (Korea, Republic of); Department of Radiation Oncology, Korea University Medical Center, Collage of Medicine, Seoul (Korea, Republic of)

    2013-12-01

    Purpose: To report a phase 2 trial of accelerated, hypofractionated whole-breast irradiation (AH-WBI) delivered as a daily dose of 3 Gy to the whole breast followed by a tumor bed boost. Methods and Materials: Two hundred seventy-six patients diagnosed with breast cancer (pT1-2 and pN0-1a) who had undergone breast-conserving surgery in which the operative margins were negative were treated with AH-WBI delivered as 39 Gy in 13 fractions of 3 Gy to the whole breast once daily over 5 consecutive working days, and 9 Gy in 3 sequential fractions of 3 Gy to a lumpectomy cavity, all within 3.2 weeks. Results: After a median follow-up period of 57 months (range: 27-75 months), the rate of 5-year locoregional recurrence was 1.4% (n=4), whereas that of disease-free survival was 97.4%. No grade 3 skin toxicity was reported during the follow-up period. Qualitative physician cosmetic assessments of good or excellent were noted in 82% of the patients at 2 months after the completion of AH-WBI. The global cosmetic outcome did not worsen over time, and a good or excellent cosmetic outcome was reported in 82% of the patients at 3 years. The mean pretreatment percentage breast retraction assessment was 12.00 (95% confidence interval [CI]: 11.14-12.86). The mean value of percentage breast retraction assessment increased to 13.99 (95% CI: 12.17-15.96) after 1 year and decreased to 13.54 (95% CI: 11.84-15.46) after 3 years but was not significant (P>.05). Conclusions: AH-WBI consisting of 39 Gy in 13 fractions followed by a tumor bed boost sequentially delivering 9 Gy in 3 fractions can be delivered with excellent disease control and tolerable skin toxicity in patients with early-stage breast cancer after breast-conserving surgery.

  8. STRUCTURE OF CONSORTIUM DESTRUCTIVE COMPONENTS IN THE INDUSTRIAL AREA OF KRIVYI RIG BASIN

    Directory of Open Access Journals (Sweden)

    Kachinskaya V.V.

    2014-08-01

    Full Text Available Тhe structural organization and a biological variety of ground mesofauna on consortium level of the organization of ecosystems are considered. The analysis of indicators of the structural organization and a biodiversity of ground mesofauna in consortium Ulmus and Populus in the conditions of territories of industrial mining – metallurgical complex of Krivyi Rig Basin is carried out. It is established that taxonomical structure of ground mesofauna is characterized by insignificant number and quantity of taxonomical groups. Prevalence in morfo-ecological structure of hortobiontes and herpetobiontes testifies about faunae considerable attachment to consortium determinants and influences of a steppe climate on its structure. Prevalence of phytophages and polyphages in trophic structure is caused by combination of determinants specificity of consortium and zone source of fauna formations. The structural organization of ground mesofauna in consortium Ulmus and Populus in the conditions of industrial sites is characterized simplified taxonomical structure with a low biodiversity at all levels. It was suggested that structural and functional organization of destructive components of the block consortium of Ulmus and Populus in the conditions of industrial sites are simplified and determined by biogeochemical patterns of pedogenic and leaf litter layer of consortium and type of anthropogenic impact. Management and sustainable use of consortium under technogenic pressure should be based on the effects of extreme and critical components in the evolution of consortium. These critical points are the type of leading man-made factors and pedogenic and leaf litter biogeochemical conditions of consortium determinants, which results in inhibition of development and simplification of the structural and functional organization of destructive components of the block. The elaboration of measures to restore and maintain that structural and functional organization

  9. Humin as an electron donor for enhancement of multiple microbial reduction reactions with different redox potentials in a consortium.

    Science.gov (United States)

    Zhang, Dongdong; Zhang, Chunfang; Xiao, Zhixing; Suzuki, Daisuke; Katayama, Arata

    2015-02-01

    A solid-phase humin, acting as an electron donor, was able to enhance multiple reductive biotransformations, including dechlorination of pentachlorophenol (PCP), dissimilatory reduction of amorphous Fe (III) oxide (FeOOH), and reduction of nitrate, in a consortium. Humin that was chemically reduced by NaBH4 served as an electron donor for these microbial reducing reactions, with electron donating capacities of 0.013 mmol e(-)/g for PCP dechlorination, 0.15 mmol e(-)/g for iron reduction, and 0.30 mmol e(-)/g for nitrate reduction. Two pairs of oxidation and reduction peaks within the humin were detected by cyclic voltammetry analysis. 16S rRNA gene sequencing-based microbial community analysis of the consortium incubated with different terminal electron acceptors, suggested that Dehalobacter sp., Bacteroides sp., and Sulfurospirillum sp. were involved in the PCP dechlorination, dissimilatory iron reduction, and nitrate reduction, respectively. These findings suggested that humin functioned as a versatile redox mediator, donating electrons for multiple respiration reactions with different redox potentials. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  10. Direct Ethanol Production from Breadfruit Starch (Artocarpus communis Forst. by Engineered Simultaneous Saccharification and Fermentation (ESSF using Microbes Consortium

    Directory of Open Access Journals (Sweden)

    Iftachul Farida

    2015-02-01

    Full Text Available Breadfruit (Artocarpus communis Forst. is one of sources for ethanol production, which has high starch content (89%. Ethanol production from breadfruit starch was conducted by Simultaneous Saccharification and Fermentation (SSF technology using microbes consortium. The aim of the research was to examine a method to produce ethanol by SSF technology using microbes consortium at high yield and efficiency. The main research consisted of two treatments, namely normal SSF and enginereed SSF. The results showed that normal SSF using aeration and agitation during cultivation could produce ethanol at 11.15 ± 0.18 g/L, with the yield of product (Yp/s 0.34 g ethanol/g substrate; and yield of biomass (Yx/s 0.29 g cell/g substrate, respectively. A better result was obtained using engineered SSF in which aeration was stopped after biomass condition has reached the end of the exponential phase. The ethanol produced was 12.75 ± 0.04 g/L, with the yields of product (Yp/s 0.41 g ethanol/g substrate, and the yield of cell (Yx/s 0.09 g cell/g substrate.

  11. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  12. Tumors and Pregnancy

    Science.gov (United States)

    Tumors during pregnancy are rare, but they can happen. Tumors can be either benign or malignant. Benign tumors aren't cancer. Malignant ones are. The most common cancers in pregnancy are breast cancer, cervical cancer, lymphoma, and melanoma. ...

  13. DCB - Tumor Metastasis Research

    Science.gov (United States)

    Tumor metastasis research examines the mechanisms that allow cancer cells to leave the primary tumor and spread to another part of the body. Learn about recent tumor metastasis research studies supported by the Division of Cancer Biology.

  14. Childhood Brain Tumors

    Science.gov (United States)

    Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

  15. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  16. Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naïve advanced or metastatic esophagogastric cancer.

    Science.gov (United States)

    Moehler, Markus; Mahlberg, Rolf; Heinemann, Volker; Obermannová, Radka; Kubala, Eugen; Melichar, Bohuslav; Weinmann, Arndt; Scigalla, Paul; Tesařová, Marietta; Janda, Petr; Hédouin-Biville, Fabienne; Mansoor, Wasat

    2017-03-01

    This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS). Patients aged ≥18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m 2 followed by oxaliplatin 130 mg/m 2 (maximum 8 cycles) and then S-1 [20 mg/m 2 (cohort 1) or 25 mg/m 2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2-14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer. DLT was reported for two of the five patients in cohort 2, defining 20 mg/m 2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naïve advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m 2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. The promising activity of EOS (S-1 dose level, 25 mg/m 2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer.

  17. Phase I-II study of two consecutive courses of high-dose epipodophyllotoxin, ifosfamide, and carboplatin with autologous bone marrow transplantation for treatment of adult patients with solid tumors.

    Science.gov (United States)

    Lotz, J P; Machover, D; Malassagne, B; Hingh, B; Donsimoni, R; Gumus, Y; Gerota, J; Lam, Y; Tulliez, M; Marsiglia, H

    1991-10-01

    We describe a phase I-II study of two consecutive 5-day courses of a three-drug regimen of ifosfamide (IFM), carboplatin (CBDCA), and either etoposide (VP-16) (regimen 1) or teniposide (VM-26) (regimen 2) in high doses together with autologous bone marrow transplantation (ABMT), for previously treated patients with ovarian carcinoma (OC), germ cell tumors (GCT), gestational trophoblastic disease (GTD), or oat cell carcinoma (OCC). Forty-four patients entered the study. Two patients with OC received regimen 1, and 22 were given regimen 2. Sixteen patients with GCT, two with GTD, and two with OCC were treated with regimen 1. Six patients (13%) died of toxicity. Nephropathy and esophagitis were the dose-limiting toxic effects. The maximum-tolerated doses (MTDs) were 1,500 and 200 mg/m2/d for 5 days for IFM and CBDCA, respectively, in combination with VP-16 250 mg/m2/d for 5 days (regimen 1), and 150, 1,500, and 200 mg/m2/d for 5 days for VM-26, IFM, and CBDCA, respectively (regimen 2). The response rate of patients with OC was 78% (complete response [CR], 14%). For patients previously resistant to chemotherapy, the response rate was 70%. There were no long-term disease-free survivors among patients with OC. The response rate of patients with GCT was 60% (CR, 33%). All responders with GCT were resistant to previous chemotherapy. Unmaintained CRs lasted 2, 6, 8+, 27+, and 37+ months. Of the two patients with GTD, one with previous resistance to chemotherapy attained a CR of 18+ months. One patient with OCC attained a CR lasting 6 months. The regimen possesses great antitumor activity. It produced CRs of long duration in a number of patients with GCT and GTD who were previously resistant to chemotherapy.

  18. Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial.

    Science.gov (United States)

    Chung, Vincent; Mansfield, Aaron S; Braiteh, Fadi; Richards, Donald; Durivage, Henry; Ungerleider, Richard S; Johnson, Francis; Kovach, John S

    2017-07-01

    Purpose: To determine the MTD and to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors. Experimental Design: LB-100 was administered intravenously daily for 3 days in 21-day cycles in a 3 + 3 dose escalation design. Results: There were 29 patient entries over 7 dose escalations. One patient stopped treatment after one dose because of an acute infection and was reenrolled after recovery; each course was analyzed as a separate patient entry. Two patients had dose-limiting toxicity (reversible increases in serum creatinine or calculated serum creatinine clearance) at the 3.1 mg/m 2 level. Probable or possible study drug-related grade 3 adverse events occurred in 6 (20.7%) patients [anemia ( n = 2), decreased creatinine clearance, dyspnea, hyponatremia, and lymphopenia]. Ten (50%) of 20 response-evaluable patients had stable disease for four or more cycles. One patient with pancreatic adenocarcinoma had a partial response noted after 10 cycles, which was maintained for five additional cycles. The other patients achieving stable disease had one of the following: fibrosarcoma, chondrosarcoma, thymoma, atypical carcinoid of lung, or ovarian, testicular, breast ( n = 2), and prostate cancer. The recommended phase II dose of LB-100 is 2.33 mg/m 2 daily for 3 days every 3 weeks. Conclusions: The safety, tolerability, preliminary evidence of antitumor activity, and novel mechanism of action of LB-100 support its continued development alone and in combination with other therapies. Clin Cancer Res; 23(13); 3277-84. ©2016 AACR . ©2016 American Association for Cancer Research.

  19. NASA Systems Engineering Research Consortium: Defining the Path to Elegance in Systems

    Science.gov (United States)

    Watson, Michael D.; Farrington, Phillip A.

    2016-01-01

    The NASA Systems Engineering Research Consortium was formed at the end of 2010 to study the approaches to producing elegant systems on a consistent basis. This has been a transformative study looking at the engineering and organizational basis of systems engineering. The consortium has engaged in a variety of research topics to determine the path to elegant systems. In the second year of the consortium, a systems engineering framework emerged which structured the approach to systems engineering and guided our research. This led in the third year to set of systems engineering postulates that the consortium is continuing to refine. The consortium has conducted several research projects that have contributed significantly to the understanding of systems engineering. The consortium has surveyed the application of the NASA 17 systems engineering processes, explored the physics and statistics of systems integration, and considered organizational aspects of systems engineering discipline integration. The systems integration methods have included system energy analysis, Akaike Information Criteria (AIC), State Variable Analysis, Multidisciplinary Coupling Analysis (MCA), Multidisciplinary Design Optimization (MDO), System Cost Modeling, System Robustness, and Value Modeling. Organizational studies have included the variability of processes in change evaluations, margin management within the organization, information theory of board structures, social categorization of unintended consequences, and initial looks at applying cognitive science to systems engineering. Consortium members have also studied the bidirectional influence of policy and law with systems engineering.

  20. Hormonal component of tumor photodynamic therapy response

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush

    2008-02-01

    The involvement of adrenal glucocorticoid hormones in the response of the treatment of solid tumors by photodynamic therapy (PDT) comes from the induction of acute phase response by this modality. This adrenal gland activity is orchestrated through the engagement of the hypothalamic-pituitary-adrenal hormonal axis incited by stress signals emanating from the PDT-treated tumor. Glucocorticoid hormone activity engendered within the context of PDT-induced acute phase response performs multiple important functions; among other involvements they beget acute phase reactant production, systemic neutrophil mobilization, and control the production of inflammation-modulating and immunoregulatory proteins.

  1. HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium.

    Science.gov (United States)

    Pillai, Rathi N; Behera, Madhusmita; Berry, Lynne D; Rossi, Mike R; Kris, Mark G; Johnson, Bruce E; Bunn, Paul A; Ramalingam, Suresh S; Khuri, Fadlo R

    2017-11-01

    Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC). Patients with advanced-stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories to examine 10 oncogenic drivers. The LCMC database was queried for patients with HER2 mutations to access demographic data, treatment history, and vital status. An exploratory analysis was performed to evaluate the survival of patients with HER2 mutations who were treated with HER2-directed therapies. A total of 920 patients were tested for HER2 mutations; 24 patients (3%) harbored exon 20 insertion mutations (95% confidence interval, 2%-4%). One patient had a concurrent mesenchymal-epithelial transition factor (MET) amplification. The median age of the patients was 62 years, with a slight predominance of females over males (14 females vs 10 males). The majority of the patients were never-smokers (71%) and presented with advanced disease at the time of diagnosis. The median survival for patients who received HER2-targeted therapies (12 patients) was 2.1 years compared with 1.4 years for those who did not (12 patients) (P = .48). Patients with HER2 mutations were found to have inferior survival compared with the rest of the LCMC cohort with other mutations: the median survival was 3.5 years in the LCMC population receiving targeted therapy and 2.4 years for patients not receiving targeted therapy. HER2 mutations were detected in 3% of patients with lung adenocarcinoma in the LCMC. HER2-directed therapies should be investigated in this subgroup of patients. Cancer 2017;123:4099-4105. © 2017 American Cancer Society. © 2017 American Cancer Society.

  2. ISPRS STUDENT CONSORTIUM: THE NETWORK OF YOUTH IN GEOINFORMATION SOCIETY

    Directory of Open Access Journals (Sweden)

    C. O. Kivilcim

    2012-07-01

    Full Text Available The ISPRS Student Consortium (SC initiative started at the 20th ISPRS Congress in Istanbul, 2004.After four years of volunteer activity, an official structure for volunteers was needed. With the implementation of the SC Statutes in the ISPRS Beijing Congress in 2008, the first ISPRS Student Consortium Board Members were elected. Since this day, SC volunteers and supporters have continued to contribute through numerous activities in order to promote the Society and connect young people with a similar interest in the profession. So far, promotional activities have taken place in various places in Europe, North and Central America, Asia and Australia. SC members have not only participated in the events, but also organized activities, taken responsibilities and represented youth in ISPRS midterm symposiums and ISPRS Centenary Celebrations as well as other related events. Summer schools, as the main SC event, are organized with the help of ISPRS TC VI/5 and are focused on the needs and interests of scientific communities around the world. The SC community has been constantly growing with almost 750 members over 85 countries at present, registered through our self-developed website. The organization also publishes its own Newsletter four times per year, with the intention to transmit the messages and news from ISPRS and the SC. The Newsletter is a perfect platform for presenting useful technical, educational and informational material prepared by members and distributed freely among the supporters. Throughout time, the SC has received guiding, motivational and administrative support from WG VI/5 as well as TC VI and the ISPRS Council. Activities have been financially supported by foundations, commercial enterprises and academic organizations and many SC members have received grants to present their work in different scientific events. In addition, the SC has started and established permanent connections and signed agreements for better networking with

  3. Biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by a prospective consortium and its most effective isolate Serratia marcescens

    Energy Technology Data Exchange (ETDEWEB)

    Young, D.M.; Ogden, K.L. [Univ. of Arizona, Tucson, AZ (United States). Dept. of Chemical and Environmental Engineering; Unkefer, P.J. [Los Alamos National Lab., NM (United States). Chemical Science and Technology Div.

    1997-03-05

    The biotransformation of hexahydro-1,3,5-trinitro-1,3,5 triazine (RDX) has been observed in liquid culture by a consortium of bacteria found in horse manure. Five types of bacteria were found to predominate in the consortium and were isolated. The most effective of these isolates at transforming RDX was Serratia marcescens. The biotransformation of RDX by all of these bacteria was found to occur only in the anoxic stationary phase. The process of bacterial growth and RDX biotransformation was quantified for the purpose of developing a predictive type model. Cell growth was assumed to follow Monod kinetics. All of the aerobic and anoxid growth parameters were determined: {mu}{sub max}, K{sub s}, and Y{sub x/s}. RDX was found to competitively inhibit cell growth in both atmospheres. Degradation of RDX by Serratia marcescens was found to proceed through the stepwise reduction of the three nitro groups to nitroso groups. Each of these reductions was found to be first order in both component and cell concentrations. The degradation rate constant for the first step in this reduction process by the consortium was 0.022 L/g cells {center_dot} h compared to 0.033 L/g cells {center_dot} h for the most efficient isolate.

  4. Relationship Between Mammographic Density and Breast Cancer Death in the Breast Cancer Surveillance Consortium

    Science.gov (United States)

    2012-01-01

    Background Women with elevated mammographic density have an increased risk of developing breast cancer. However, among women diagnosed with breast cancer, it is unclear whether higher density portends reduced survival, independent of other factors. Methods We evaluated relationships between mammographic density and risk of death from breast cancer and all causes within the US Breast Cancer Surveillance Consortium. We studied 9232 women diagnosed with primary invasive breast carcinoma during 1996–2005, with a mean follow-up of 6.6 years. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS) density classification. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression; women with scattered fibroglandular densities (BI-RADS 2) were the referent group. All statistical tests were two-sided. Results A total of 1795 women died, of whom 889 died of breast cancer. In multivariable analyses (adjusted for site, age at and year of diagnosis, American Joint Committee on Cancer stage, body mass index, mode of detection, treatment, and income), high density (BI-RADS 4) was not related to risk of death from breast cancer (HR = 0.92, 95% CI = 0.71 to 1.19) or death from all causes (HR = 0.83, 95% CI = 0.68 to 1.02). Analyses stratified by stage and other prognostic factors yielded similar results, except for an increased risk of breast cancer death among women with low density (BI-RADS 1) who were either obese (HR = 2.02, 95% CI = 1.37 to 2.97) or had tumors of at least 2.0cm (HR = 1.55, 95% CI = 1.14 to 2.09). Conclusions High mammographic breast density was not associated with risk of death from breast cancer or death from any cause after accounting for other patient and tumor characteristics. Thus, risk factors for the development of breast cancer may not necessarily be the same as factors influencing the risk of death after breast cancer has developed. PMID:22911616

  5. Worldwide Consortium for the Grid (W2COG) Research Initiative Phase 1

    Science.gov (United States)

    2006-03-31

    all IPv6 capable devices. o IPSec VPNs implemented in hosts or routers can be used to provide confidentiality where a lower grade of security is...35 These Overlay Networks are intended to be created by tunnelling , which is one way of creating a Virtual Private Network ( VPN ). VPNs ...interconnection over IPv4 networks using secure tunnels . Initially, it is expected that the built-in IPSec features in all IPv6 compliant devices will

  6. The Municipal Solid-State Street Lighting Consortium Public Outdoor Lighting Inventory: Phase I: Survey Results

    Energy Technology Data Exchange (ETDEWEB)

    Kinzey, Bruce R.; Smalley, Edward; Haefer, R.

    2014-09-30

    This document presents the results of a voluntary web-based inventory survey of public street and area lighting across the U.S. undertaken during the latter half of 2013.This survey attempts to access information about the national inventory in a “bottoms-up” manner, going directly to owners and operators. Adding to previous “top down” estimates, it is intended to improve understanding of the role of public outdoor lighting in national energy use.

  7. Rejection versus escape: the tumor MHC dilemma.

    Science.gov (United States)

    Garrido, Federico; Ruiz-Cabello, Francisco; Aptsiauri, Natalia

    2017-02-01

    Most tumor cells derive from MHC-I-positive normal counterparts and remain positive at early stages of tumor development. T lymphocytes can infiltrate tumor tissue, recognize and destroy MHC class I (MHC-I)-positive cancer cells ("permissive" phase I). Later, MHC-I-negative tumor cell variants resistant to T-cell killing emerge. During this process, tumors first acquire a heterogeneous MHC-I expression pattern and finally become uniformly MHC-I-negative. This stage (phase II) represents a "non-permissive" encapsulated structure with tumor nodes surrounded by fibrous tissue containing different elements including leukocytes, macrophages, fibroblasts, etc. Molecular mechanisms responsible for total or partial MHC-I downregulation play a crucial role in determining and predicting the antigen-presenting capacity of cancer cells. MHC-I downregulation caused by reversible ("soft") lesions can be upregulated by TH1-type cytokines released into the tumor microenvironment in response to different types of immunotherapy. In contrast, when the molecular mechanism of the tumor MHC-I loss is irreversible ("hard") due to a genetic defect in the gene/s coding for MHC-I heavy chains (chromosome 6) or beta-2-microglobulin (B2M) (chromosome 15), malignant cells are unable to upregulate MHC-I, remain undetectable by cytotoxic T-cells, and continue to grow and metastasize. Based on the tumor MHC-I molecular analysis, it might be possible to define MHC-I phenotypes present in cancer patients in order to distinguish between non-responders, partial/short-term responders, and likely durable responders. This highlights the need for designing strategies to enhance tumor MHC-I expression that would allow CTL-mediated tumor rejection.

  8. Bioaugmentation of an acetate-oxidising anaerobic consortium in up-flow sludge blanket reactor subjected to high ammonia loads

    DEFF Research Database (Denmark)

    Fotidis, Ioannis; Karakashev, Dimitar Borisov; Angelidaki, Irini

    . in association with Methanoculleus spp. strain MAB1), is an acetate oxidising methanogenic consortium that can produce methane (CH4) at high ammonia levels. In the current study the bioaugmentation of the SAO culture in a mesophilic up-flow anaerobic sludge blanket (UASB) reactor subjected to high ammonia loads...... was tested. The co-cultivation in fed-batch of a fast-growing hydrogenotrophic methanogen (i.e. Methanoculleus bourgensis) with the SAO culture was also investigated. Results obtained clearly demonstrated that bioaugmentation of SAO culture in a UASB reactor was not possible most probably due to the slow...... growth of the culture. The incubation period (duration of lag+exponential phase) of SAO culture was reduced more than 30% when it was cocultivated with Methanoculleus bourgensis, in fed-batch reactors. Therefore, the bioaugmentation of the SAO culture along with Methanoculleus bourgensis in a UASB...

  9. Consortium analysis of 7 candidate SNPs for ovarian cancer

    DEFF Research Database (Denmark)

    Ramus, S.J.; Vierkant, R.A.; Johnatty, S.E.

    2008-01-01

    . A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result......The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H...... (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin...

  10. Phosphorus mobilizing consortium Mammoth P™ enhances plant growth

    Science.gov (United States)

    Bell, Colin; Mancini, Lauren M.; Lee, Melanie N.; Conant, Richard T.; Wallenstein, Matthew D.

    2016-01-01

    Phosphorus (P) is a critical nutrient used to maximize plant growth and yield. Current agriculture management practices commonly experience low plant P use efficiency due to natural chemical sorption and transformations when P fertilizer is applied to soils. A perplexing challenge facing agriculture production is finding sustainable solutions to deliver P more efficiently to plants. Using prescribed applications of specific soil microbial assemblages to mobilize soil bound—P to improve crop nutrient uptake and productivity has rarely been employed. We investigated whether inoculation of soils with a bacterial consortium developed to mobilize soil P, named Mammoth PTM, could increase plant productivity. In turf, herbs, and fruits, the combination of conventional inorganic fertilizer combined with Mammoth PTM increased productivity up to twofold compared to the fertilizer treatments without the Mammoth PTM inoculant. Jalapeño plants were found to bloom more rapidly when treated with either Mammoth P. In wheat trials, we found that Mammoth PTM by itself was able to deliver yields equivalent to those achieved with conventional inorganic fertilizer applications and improved productivity more than another biostimulant product. Results from this study indicate the substantial potential of Mammoth PTM to enhance plant growth and crop productivity. PMID:27326379

  11. The End of Life Nursing Education Nursing Consortium project.

    Science.gov (United States)

    Ferrell, Betty; Malloy, Pam; Virani, Rose

    2015-04-01

    In 2000, the City of Hope Medical Center and the American Association of Colleges of Nursing (AACN) developed the End-of-Life Nursing Education Consortium (ELNEC)-Core curriculum to educate nurses and other healthcare professionals on end of life care, so that attention to the dying could be improved and their unique needs addressed. Since its inception, over 19,500 nurses and other professionals have attended the ELNEC train-the-trainer courses. Upon course completion, the participants, often nurse educators, returned to their schools, healthcare systems, and communities and introduced the ELNEC content into nursing curricula, annual competencies, and new employee orientation. In 2005, the national ELNEC Project Team concluded that an international curriculum should be developed. The first ELNEC International course was launched in 2006 in Salzburg, Austria. Since that time, trainers have come from 85 countries world-wide, and the curriculum has been translated into eight languages. In 2015, three international courses will be presented: in Beijing, China, Kipkaren, Kenya, and Salzburg, Austria.

  12. Dedicated Beamline Facilities for Catalytic Research. Synchrotron Catalysis Consortium (SCC)

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jingguang [Columbia Univ., New York, NY; Frenkel, Anatoly [Yeshiva Univ., New York, NY (United States); Rodriguez, Jose [Brookhaven National Lab. (BNL), Upton, NY (United States); Adzic, Radoslav [Brookhaven National Lab. (BNL), Upton, NY (United States); Bare, Simon R. [UOP LLC, Des Plaines, IL (United States); Hulbert, Steve L. [Brookhaven National Lab. (BNL), Upton, NY (United States); Karim, Ayman [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mullins, David R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Overbury, Steve [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-03-04

    Synchrotron spectroscopies offer unique advantages over conventional techniques, including higher detection sensitivity and molecular specificity, faster detection rate, and more in-depth information regarding the structural, electronic and catalytic properties under in-situ reaction conditions. Despite these advantages, synchrotron techniques are often underutilized or unexplored by the catalysis community due to various perceived and real barriers, which will be addressed in the current proposal. Since its establishment in 2005, the Synchrotron Catalysis Consortium (SCC) has coordinated significant efforts to promote the utilization of cutting-edge catalytic research under in-situ conditions. The purpose of the current renewal proposal is aimed to provide assistance, and to develop new sciences/techniques, for the catalysis community through the following concerted efforts: Coordinating the implementation of a suite of beamlines for catalysis studies at the new NSLS-II synchrotron source; Providing assistance and coordination for catalysis users at an SSRL catalysis beamline during the initial period of NSLS to NSLS II transition; Designing in-situ reactors for a variety of catalytic and electrocatalytic studies; Assisting experimental set-up and data analysis by a dedicated research scientist; Offering training courses and help sessions by the PIs and co-PIs.

  13. The Climate Change Consortium of Wales (C3W)

    Science.gov (United States)

    Hendry, K. R.; Reis, J.; Hall, I. R.

    2011-12-01

    In response to the complexity and multidisciplinary nature of climate change research, the Climate Change Consortium of Wales (C3W) was formed in 2009 by the Welsh universities of Aberystwyth, Bangor, Cardiff and Swansea. Initially funded by Welsh Government, through the Higher Education Funding Council for Wales, the Countryside Council for Wales and the universities, C3W aims to bring together climate change researchers from a wide range of disciplines to explore scientific and sociological drivers, impacts and implications at local, national and international scale. The specific aims are to i) improve our fundamental understanding of the causes, nature, timing and consequences of climate change on Planet Earth's environment and on humanity, and ii) to reconfigure climate research in Wales as a recognisable centre of excellence on the world stage. In addition to improving the infrastructure for climate change research, we aim to improve communication, networking, collaborative research, and multidisciplinary data assimilation within and between the Welsh universities, and other UK and international institutions. Furthermore, C3W aims to apply its research by actively contributing towards national policy development, business development and formal and informal education activities within and beyond Wales.

  14. Brain Vascular Malformation Consortium: Overview, Progress and Future Directions.

    Science.gov (United States)

    Akers, Amy L; Ball, Karen L; Clancy, Marianne; Comi, Anne M; Faughnan, Marie E; Gopal-Srivastava, Rashmi; Jacobs, Thomas P; Kim, Helen; Krischer, Jeffrey; Marchuk, Douglas A; McCulloch, Charles E; Morrison, Leslie; Moses, Marsha; Moy, Claudia S; Pawlikowska, Ludmilla; Young, William L

    2013-04-01

    Brain vascular malformations are resource-intensive to manage effectively, are associated with serious neurological morbidity, lack specific medical therapies, and have no validated biomarkers for disease severity and progression. Investigators have tended to work in "research silos" with suboptimal cross-communication. We present here a paradigm for interdisciplinary collaboration to facilitate rare disease research. The Brain Vascular Malformation Consortium (BVMC) is a multidisciplinary, inter-institutional group of investigators, one of 17 consortia in the Office of Rare Disease Research Rare Disease Clinical Research Network (RDCRN). The diseases under study are: familial Cerebral Cavernous Malformations type 1, common Hispanic mutation (CCM1-CHM); Sturge-Weber Syndrome (SWS); and brain arteriovenous malformation in hereditary hemorrhagic telangiectasia (HHT). Each project is developing biomarkers for disease progression and severity, and has established scalable, relational databases for observational and longitudinal studies that are stored centrally by the RDCRN Data Management and Coordinating Center. Patient Support Organizations (PSOs) are a key RDCRN component in the recruitment and support of participants. The BVMC PSOs include Angioma Alliance, Sturge Weber Foundation , and HHT Foundation International . Our networks of clinical centers of excellence in SWS and HHT, as well as our PSOs, have enhanced BVMC patient recruitment. The BVMC provides unique and valuable resources to the clinical neurovascular community, and recently reported findings are reviewed. Future planned studies will apply successful approaches and insights across the three projects to leverage the combined resources of the BVMC and RDCRN in advancing new biomarkers and treatment strategies for patients with vascular malformations.

  15. The Global Cancer Genomics Consortium: interfacing genomics and cancer medicine.

    Science.gov (United States)

    2012-08-01

    The Global Cancer Genomics Consortium (GCGC) is an international collaborative platform that amalgamates cancer biologists, cutting-edge genomics, and high-throughput expertise with medical oncologists and surgical oncologists; they address the most important translational questions that are central to cancer research and treatment. The annual GCGC symposium was held at the Advanced Centre for Treatment Research and Education in Cancer, Mumbai, India, from November 9 to 11, 2011. The symposium showcased international next-generation sequencing efforts that explore cancer-specific transcriptomic changes, single-nucleotide polymorphism, and copy number variations in various types of cancers, as well as the structural genomics approach to develop new therapeutic targets and chemical probes. From the spectrum of studies presented at the symposium, it is evident that the translation of emerging cancer genomics knowledge into clinical applications can only be achieved through the integration of multidisciplinary expertise. In summary, the GCGC symposium provided practical knowledge on structural and cancer genomics approaches, as well as an exclusive platform for focused cancer genomics endeavors. ©2012 AACR.

  16. Malignant phyllodes breast tumor

    OpenAIRE

    Lisa R. Shah-Patel, MD

    2017-01-01

    Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  17. Malignant phyllodes breast tumor

    Directory of Open Access Journals (Sweden)

    Lisa R. Shah-Patel, MD

    2017-12-01

    Full Text Available Malignant phyllodes tumor is a rare tumor of the breast occurring in females usually between the ages of 35 and 55 years. It is often difficult to distinguish benign from malignant phyllodes tumors from other benign entities such as fibroadenomas. This case presentation demonstrates a woman with malignant phyllodes tumor treated with mastectomy with abdominal skin flap reconstruction.

  18. Liver Tumors (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Liver Tumors KidsHealth / For Parents / Liver Tumors What's in this article? Types of Tumors ... Cancerous) Tumors Symptoms Diagnosis Treatment Coping Print The liver is the body's largest solid organ. Lying next ...

  19. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  20. Supratentorial tumors; Supratentorielle Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.; Dillmann, K.; Roth, C.; Backens, M.; Reith, W. [Universitaetsklinikum Saarland, Homburg (Germany). Klinik fuer Diagnostische und Interventionelle Neuroradiologie

    2007-06-15

    Magnetic resonance imaging is a routine diagnostic measure for a suspected intracerebral mass. Computed tomography is usually also indicated. Further diagnostic procedures as well as the interpretation of the findings vary depending on the tumor location. This contribution discusses the symptoms and diagnostics for supratentorial tumors separated in relation to their intra- or extracranial location. Supratentorial tumors include astrocytoma, differentiated by their circumscribed and diffuse growth, ganglioglioma, ependyoma, neurocytoma, primitive neuroectodermal tumors (PNET), oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNET), meningoangiomatosis, pineal tumors, hamartoma, lymphoma, craniopharyngeoma and metastases. The supratentorial extracranial tumors include the choroid plexus, colloid cysts, meningeoma, infantile myofibromatosis and lipoma. The most common subforms, especially of astrocytoma, will also be presented. (orig.)

  1. Strategic Design of Synthetic Consortium with embedded Wastewater Treatment Potential: Deciphering the Competence of Isolates from Diverse Microbiome

    Directory of Open Access Journals (Sweden)

    Shikha eDahiya

    2016-05-01

    Full Text Available Microorganisms plays vital role in efficient biological treatment. Supplementation of external microorganisms with high degradation rates can enhance the process efficiency significantly. Potential strains were isolated from long term wastewater treating reactors and identified using phylogenetic analysis of 16S rRNA gene fragments with the nearest neighbours extracted during BLAST search. Later the study was designed in two phases which revealed interesting findings. Phase I evaluates the potential of isolated strains viz., Pseudomonas otitidis, Bacillus firmus, Bacillus subtilis and Bacillus circulans for their individual ability in terms of COD and nutrients removal. Bacillus circulans showed highest carbon (COD removal (70%; 0.56 kg CODR/m3-day, while maximum nutrients removal (nitrate, 81%; phosphates, 90% was observed with Bacillus subtilis. B. firmus showed maximum volatile fatty acid (VFA production. Based on Phase I results, four synthetic consortia were designed in phase II with diverse combination of isolates and evaluated for its remediation efficiencies. Consortium 4 (P. otitidis, B. subtilis and B. firmus illustrated higher treatment potential [COD, 86%; SDR (cum: 0.64 kg CODR/m3-day; Nitrates, 87%; Phosphates, 97%]. The exploitation of such explicit consortia can overcome the inefficiencies pre-existing with the biological wastewater treatment plants by acting as prospective candidates for bio-augmenting the native microflora. This communication illustrated development of the efficient consortia using lab isolated strains to improve the performance of wastewater treatment.

  2. Formulation of bacterial consortium as whole cell biocatalyst for degradation of oil compounds

    Science.gov (United States)

    Yetti, Elvi; A'la, Amalia; Luthfiyah, Nailul; Wijaya, Hans; Thontowi, Ahmad; Yopi

    2017-11-01

    In this research, weaim to investigateformulation of bacterial consortium as whole cell biocatalyst for degradation of oil compounds. We constructed microbial consortium from 4 (four) selected marine oil bacteria to become 15 (twelve) combination culture. Those bacteria were from collection of Laboratory of Biocatalyst and Fermentation, Research Center for Biotechnology, Indonesian Institutes of Sciences and designated as Labrenzia sp. MBTDCMFRIMab26, Labrenzia aggregata strasin HQB397, Novosphingobium pentaromativorans strain PQ-3 16S, and Novosphingobium pentaromativorans strain US6-1. The mixture or bacteria consortia, denoted as F1, F2, …F15 consisted of 1, 2, 3 and 4 bacterial strains, respectively. The strains were selected based on the criteria that they were able to display good growth in crude oil containing media. Five bacterialformulationsshowed good potentialas candidates for microbial consortium. We will optimize these consortium with carrier matrix choosed from biomass materials and also carry out oil content analysis.

  3. Rationale and design of the multiethnic Pharmacogenomics in Childhood Asthma consortium

    DEFF Research Database (Denmark)

    Farzan, Niloufar; Vijverberg, Susanne J; Andiappan, Anand K

    2017-01-01

    corticosteroid users. Among patients from 13 studies with available data on asthma exacerbations, a third reported exacerbations despite inhaled corticosteroid use. In the future pharmacogenomics studies within the consortium, the pharmacogenomics analyses will be performed separately in each center...

  4. Aerospace Workforce Development: The Nebraska Proposal; and Native Connections: A Multi-Consortium Workforce Development Proposal

    Science.gov (United States)

    Bowen, Brent; Vlasek, Karisa; Russell, Valerie; Teasdale, Jean; Downing, David R.; deSilva, Shan; Higginbotham, Jack; Duke, Edward; Westenkow, Dwayne; Johnson, Paul

    2004-01-01

    This report contains two sections, each of which describes a proposal for a program at the University of Nebraska. The sections are entitled: 1) Aerospace Workforce Development Augmentation Competition; 2) Native Connections: A Multi-Consortium Workforce Development Proposal.

  5. 2000 Puget Sound LiDAR Consortium (PSLC) Topographic LiDAR: Kitsap Peninsula, Washington

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TerraPoint surveyed and created this data for the Puget Sound LiDAR Consortium under contract. The area surveyed is approximately 1,146 square miles and covers part...

  6. 2015 Puget Sound LiDAR Consortium (PSLC) LiDAR: WA DNR Lands (P2)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — In June 2014, WSI, a Quantum Spatial Inc. (QSI) company, was contracted by the Puget Sound LiDAR Consortium (PSLC) to collect Light Detection and Ranging (LiDAR)...

  7. 2014 Puget Sound LiDAR Consortium (PSLC) Topographic LiDAR: Willapa Valley (Delivery 1)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — In January, 2014 WSI, a Quantum Spatial (QSI) company, was contracted by the Puget Sound LiDAR Consortium (PSLC) to collect Light Detection and Ranging (LiDAR) data...

  8. Numerate Intends to Join ATOM Consortium to Rapidly Accelerate Preclinical Drug Development | FNLCR

    Science.gov (United States)

    SAN FRANCISCO – Computational drug design company Numerate has signed a letter of intent to join an open consortium of scientists staffed from two U.S. national laboratories, industry, and academia working to transform drug discovery and developmen

  9. 2013 Puget Sound LiDAR Consortium (PSLC) Topographic LiDAR: Saddle Mountain

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — In October 2013, WSI, a Quantum Spatial Company (QSI), was contracted by the Puget Sound LiDAR Consortium (PSLC) to collect Light Detection and Ranging (LiDAR) data...

  10. 2015 Puget Sound LiDAR Consortium (PSLC) LiDAR: WA DNR Lands (P1)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — In June 2014, WSI, a Quantum Spatial Inc. (QSI) company, was contracted by the Puget Sound LiDAR Consortium (PSLC) to collect Light Detection and Ranging (LiDAR)...

  11. Novel fungal consortium pretreatment of waste oat straw to enhance economic and efficient biohydrogen production

    Directory of Open Access Journals (Sweden)

    Lirong Zhou

    2016-12-01

    Full Text Available Bio-pretreatment using a fungal consortium to enhance the efficiency of lignocellulosic biohydrogen production was explored.  A fungal consortium comprised of T. viride and P. chrysosporium as microbial inoculum was compared with untreated and single-species-inoculated samples. Fungal bio-pretreatment was carried out at atmospheric conditions with limited external energy input.  The effectiveness of the pretreatment is evaluated according to its lignin removal and digestibility. Enhancement of biohydrogen production is observed through scanning electron microscopy (SEM analysis. Fungal consortium pretreatment effectively degraded oat straw lignin (by >47% in 7 days leading to decomposition of cell-wall structure as revealed in SEM images, increasing biohydrogen yield. The hydrogen produced from the fungal consortium pretreated straw increased by 165% 6 days later, and was more than produced from either a single fungi species of T. viride or P. chrysosponium pretreated straw (94% and 106%, respectively. No inhibitory effect on hydrogen production was observed.

  12. 2003 Puget Sound LiDAR Consortium (PSLC) Topographic LiDAR: Snohomish County, Washington

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — TerraPoint surveyed and created this data for the Puget Sound LiDAR Consortium under contract. The area surveyed is approximately 167 square miles and covers a...

  13. The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM)

    Science.gov (United States)

    The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM) was formed to promote international, multidisciplinary collaborations to advance our understanding of the etiology and outcomes of kidney cancer.

  14. 2011 Puget Sound LiDAR Consortium (PSLC) Topographic LiDAR: Quinault River Basin

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Watershed Sciences, Inc. (WSI) collected Light Detection and Ranging (LiDAR) data on the Quinault River Basin survey area for the Puget Sound LiDAR Consortium and...

  15. 2009 Puget Sound LiDAR Consortium (PSLC) Topographic LiDAR: Lewis County, Washington

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Watershed Sciences, Inc. (WSI) collected Light Detection and Ranging (LiDAR) data for the Lewis County survey area for the Puget Sound LiDAR Consortium. This data...

  16. Federal Laboratory Consortium Recognizes Unituxin Collaborators with Excellence in Technology Transfer Awards | Poster

    Science.gov (United States)

    The Federal Laboratory Consortium (FLC) presented an Excellence in Technology Transfer award to the group that collaborated to bring Unituxin (dinutuximab, also known as ch14.18), an immunotherapy for neuroblastoma, to licensure.

  17. Report of the 4th Workshop for Technology Transfer for Intelligent Compaction Consortium.

    Science.gov (United States)

    2016-03-01

    On October 2728, 2015, the Kentucky Transportation Cabinet (KYTC) hosted the 4th workshop for : the Technology Transfer for Intelligent Compaction Consortium (TTICC), a Transportation Pooled Fund : (TPF5(233)) initiative designed to identify, s...

  18. Four-dimensional treatment planning and fluoroscopic real-time tumor tracking radiotherapy for moving tumor

    International Nuclear Information System (INIS)

    Shirato, Hiroki; Shimizu, Shinichi; Kitamura, Kei; Nishioka, Takeshi; Kagei, Kenji; Hashimoto, Seiko; Aoyama, Hidefumi; Kunieda, Tatsuya; Shinohara, Nobuo; Dosaka-Akita, Hirotoshi; Miyasaka, Kazuo

    2000-01-01

    Purpose: To achieve precise three-dimensional (3D) conformal radiotherapy for mobile tumors, a new radiotherapy system and its treatment planning system were developed and used for clinical practice. Methods and Materials: We developed a linear accelerator synchronized with a fluoroscopic real-time tumor tracking system by which 3D coordinates of a 2.0-mm gold marker in the tumor can be determined every 0.03 second. The 3D relationships between the marker and the tumor at different respiratory phases are evaluated using CT image at each respiratory phase, whereby the optimum phase can be selected to synchronize with irradiation (4D treatment planning). The linac is triggered to irradiate the tumor only when the marker is located within the region of the planned coordinates relative to the isocenter. Results: The coordinates of the marker were detected with an accuracy of ± 1 mm during radiotherapy in the phantom experiment. The time delay between recognition of the marker position and the start or stop of megavoltage X-ray irradiation was 0.03 second. Fourteen patients with various tumors were treated by conformal radiotherapy with a 'tight' planning target volume (PTV) margin. They were surviving without relapse or complications with a median follow-up of 6 months. Conclusion: Fluoroscopic real-time tumor tracking radiotherapy following 4D treatment planning was developed and shown to be feasible to improve the accuracy of the radiotherapy for mobile tumors

  19. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P

    2015-01-01

    BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were...... carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...

  20. [Wilms tumor in hemihypertrophy].

    Science.gov (United States)

    Sauer, O; Wemmer, U

    1977-04-07

    The case of a 4-year-old boy with Wilms' tumor and hemihypertrophy is described. Wilms' tumors are frequently associated with congenital malformations of the urinary tract, with aniridia and hemihypertrophy. Hemihypertrophy is a relatively rare malformation (1:14000) in the common population, but in patients with Wilms' tumors its frequency is about 1:49. Besides Wilms' tumors tumors of the adrenal cortex and hepatoblastomas are frequently observed together with hemihypertrophy.

  1. The Pharmaceutical Industry Beamline of Pharmaceutical Consortium for Protein Structure Analysis

    CERN Document Server

    Nishijima, K

    2002-01-01

    The Pharmaceutical Industry Beamline was constructed by the Pharmaceutical Consortium for Protein Structure Analysis which was established in April 2001. The consortium is composed of 22 pharmaceutical companies affiliating with the Japan Pharmaceutical Manufacturers Association. The beamline is the first exclusive on that is owned by pharmaceutical enterprises at SPring-8. The specification and equipments of the Pharmaceutical Industry Beamline is almost same as that of RIKEN Structural Genomics Beamline I and II. (author)

  2. Northeast Artificial Intelligence Consortium Annual Report. Volume 2. 1988 Discussing, Using, and Recognizing Plans (NLP)

    Science.gov (United States)

    1989-10-01

    Encontro Portugues de Inteligencia Artificial (EPIA), Oporto, Portugal, September 1985. [15] N. J. Nilsson. Principles Of Artificial Intelligence. Tioga...FI1 F COPY () RADC-TR-89-259, Vol II (of twelve) Interim Report October 1969 AD-A218 154 NORTHEAST ARTIFICIAL INTELLIGENCE CONSORTIUM ANNUAL...7a. NAME OF MONITORING ORGANIZATION Northeast Artificial Of p0ilcabe) Intelligence Consortium (NAIC) Rome_____ Air___ Development____Center

  3. Highly migratory shark fisheries research by the National Shark Research Consortium (NSRC), 2002-2007

    OpenAIRE

    Hueter, Robert E.; Cailliet, Gregor M.; Ebert, David A.; Musick, John A.; Burgess, George H.

    2007-01-01

    The National Shark Research Consortium (NSRC) includes the Center for Shark Research at Mote Marine Laboratory, the Pacific Shark Research Center at Moss Landing Marine Laboratories, the Shark Research Program at the Virginia Institute of Marine Science, and the Florida Program for Shark Research at the University of Florida. The consortium objectives include shark-related research in the Gulf of Mexico and along the Atlantic and Pacific coasts of the U.S., education and scientific cooperation.

  4. Brain Immune Interactions as the Basis of Gulf War Illness: Gulf War Illness Consortium (GWIC)

    Science.gov (United States)

    2015-10-01

    priming of glial responses that cause a chronic activation loop of stronger and longer proinflammatory signaling effects between the immune system and the...AWARD NUMBER: W81XWH-13-2-0072 TITLE: Brain Immune Interactions as the Basis of Gulf War Illness: Gulf War Illness Consortium (GWIC) PRINCIPAL...4. TITLE AND SUBTITLE Brain Immune Interactions as the Basis of Gulf War Illness: Gulf War Illness Consortium (GWIC) 5a. CONTRACT NUMBER 5b. GRANT

  5. Potential Bacterial Consortium to Increase the Effectiveness of Beer Wastewater Treatment

    OpenAIRE

    Putu Nia Anggraeni; Ida Bagus Wayan Gunam; Retno Kawuri

    2014-01-01

    The main objective of this research is to determine the effectiveness of microbial consortia in beer wastewater treatment. The research was initiated with the isolation of soil microbial consortium that has been contaminated by beer waste water, followed by the selection of the best potential microbial beer wastewater treatment. At the end, the selection of the best microbial consortium was tested in beer wastewater treatment based on pollutant parameters namely biochemical oxygen demand (BOD...

  6. Washoe Tribe Nevada Inter-Tribal Energy Consortium Energy Organization Enhancement Project Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jennifer [Washoe Tribe of NV and Ca

    2014-11-06

    The Washoe Tribe of Nevada and California was awarded funding from the Department of Energy to complete the Nevada Inter-Tribal Energy Consortium Energy Organization Enhancement Project. The main goal of the project was to enhance the capacity of the Nevada Inter-Tribal Energy Consortium (NITEC) to effectively assist tribes within Nevada to technically manage tribal energy resources and implement tribal energy projects.

  7. Tumors and tumor-like lesions

    International Nuclear Information System (INIS)

    Koesling, S.; Stoevesandt, D.; Knipping, S.

    2007-01-01

    Tumors and tumor-like lesions are rare diseases in the paranasal sinuses. There is a great variety of histological types, but only a small number of morphological patterns on imaging. Histology is an important point in therapeutic planning. In most cases it is obtained by sampling, which is not as difficult in the sinonasal area as in other regions of the body. The main task of imaging is an exact estimation of the extent and spread of a lesion. This article discusses the possibilities and limitations of CT and MRI in the assessment of the dignity and spread of paranasal tumors and tumor-like lesions in consideration of necessary therapeutic information. Additionally, an overview of features on imaging of different paranasal tumors and tumor-like lesions is given. (orig.)

  8. Biodegradation mechanisms and kinetics of azo dye 4BS by a microbial consortium.

    Science.gov (United States)

    He, Fang; Hu, Wenrong; Li, Yuezhong

    2004-10-01

    A microbial consortium consisting of a white-rot fungus 8-4* and a Pseudomonas 1-10 was isolated from wastewater treatment facilities of a local dyeing house by enrichment, using azo dye Direct Fast Scarlet 4BS as the sole source of carbon and energy, which had a high capacity for rapid decolorization of 4BS. To elucidate the decolorization mechanisms, decolorization of 4BS was compared between individual strains and the microbial consortium under different treatment processes. The microbial consortium showed a significant improvement on dye decolorization rates under either static or shaking culture, which might be attributed to the synergetic reaction of single strains. From the curve of COD values and the UV-visible spectra of 4BS solutions before and after decolorization cultivation with the microbial consortium, it was found that 4BS could be mineralized completely, and the results had been used for presuming the degrading pathway of 4BS. This study also examined the kinetics of 4BS decolorization by immobilized microbial consortium. The results demonstrated that the optimal decolorization activity was observed in pH range between four and 9, temperature range between 20 and 40 degrees C and the maximal specific decolorization rate occurred at 1,000 mg l(-1) of 4BS. The proliferation and distribution of microbial consortium were also microscopically observed, which further confirmed the decolorization mechanisms of 4BS.

  9. Prebiotics Mediate Microbial Interactions in a Consortium of the Infant Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Daniel A. Medina

    2017-10-01

    Full Text Available Composition of the gut microbiome is influenced by diet. Milk or formula oligosaccharides act as prebiotics, bioactives that promote the growth of beneficial gut microbes. The influence of prebiotics on microbial interactions is not well understood. Here we investigated the transformation of prebiotics by a consortium of four representative species of the infant gut microbiome, and how their interactions changed with dietary substrates. First, we optimized a culture medium resembling certain infant gut parameters. A consortium containing Bifidobacterium longum subsp. infantis, Bacteroides vulgatus, Escherichia coli and Lactobacillus acidophilus was grown on fructooligosaccharides (FOS or 2′-fucosyllactose (2FL in mono- or co-culture. While Bi. infantis and Ba. vulgatus dominated growth on 2FL, their combined growth was reduced. Besides, interaction coefficients indicated strong competition, especially on FOS. While FOS was rapidly consumed by the consortium, B. infantis was the only microbe displaying significant consumption of 2FL. Acid production by the consortium resembled the metabolism of microorganisms dominating growth in each substrate. Finally, the consortium was tested in a bioreactor, observing similar predominance but more pronounced acid production and substrate consumption. This study indicates that the chemical nature of prebiotics modulate microbial interactions in a consortium of infant gut species.

  10. Results From the John Glenn Biomedical Engineering Consortium. A Success Story for NASA and Northeast Ohio

    Science.gov (United States)

    Nall, Marsha M.; Barna, Gerald J.

    2009-01-01

    The John Glenn Biomedical Engineering Consortium was established by NASA in 2002 to formulate and implement an integrated, interdisciplinary research program to address risks faced by astronauts during long-duration space missions. The consortium is comprised of a preeminent team of Northeast Ohio institutions that include Case Western Reserve University, the Cleveland Clinic, University Hospitals Case Medical Center, The National Center for Space Exploration Research, and the NASA Glenn Research Center. The John Glenn Biomedical Engineering Consortium research is focused on fluid physics and sensor technology that addresses the critical risks to crew health, safety, and performance. Effectively utilizing the unique skills, capabilities and facilities of the consortium members is also of prime importance. Research efforts were initiated with a general call for proposals to the consortium members. The top proposals were selected for funding through a rigorous, peer review process. The review included participation from NASA's Johnson Space Center, which has programmatic responsibility for NASA's Human Research Program. The projects range in scope from delivery of prototype hardware to applied research that enables future development of advanced technology devices. All of the projects selected for funding have been completed and the results are summarized. Because of the success of the consortium, the member institutions have extended the original agreement to continue this highly effective research collaboration through 2011.

  11. The Consortium for Advanced Simulation of Light Water Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Ronaldo Szilard; Hongbin Zhang; Doug Kothe; Paul Turinsky

    2011-10-01

    The Consortium for Advanced Simulation of Light Water Reactors (CASL) is a DOE Energy Innovation Hub for modeling and simulation of nuclear reactors. It brings together an exceptionally capable team from national labs, industry and academia that will apply existing modeling and simulation capabilities and develop advanced capabilities to create a usable environment for predictive simulation of light water reactors (LWRs). This environment, designated as the Virtual Environment for Reactor Applications (VERA), will incorporate science-based models, state-of-the-art numerical methods, modern computational science and engineering practices, and uncertainty quantification (UQ) and validation against data from operating pressurized water reactors (PWRs). It will couple state-of-the-art fuel performance, neutronics, thermal-hydraulics (T-H), and structural models with existing tools for systems and safety analysis and will be designed for implementation on both today's leadership-class computers and the advanced architecture platforms now under development by the DOE. CASL focuses on a set of challenge problems such as CRUD induced power shift and localized corrosion, grid-to-rod fretting fuel failures, pellet clad interaction, fuel assembly distortion, etc. that encompass the key phenomena limiting the performance of PWRs. It is expected that much of the capability developed will be applicable to other types of reactors. CASL's mission is to develop and apply modeling and simulation capabilities to address three critical areas of performance for nuclear power plants: (1) reduce capital and operating costs per unit energy by enabling power uprates and plant lifetime extension, (2) reduce nuclear waste volume generated by enabling higher fuel burnup, and (3) enhance nuclear safety by enabling high-fidelity predictive capability for component performance.

  12. Computerized comprehensive data analysis of Lung Imaging Database Consortium (LIDC)

    International Nuclear Information System (INIS)

    Tan Jun; Pu Jiantao; Zheng Bin; Wang Xingwei; Leader, Joseph K.

    2010-01-01

    Purpose: Lung Image Database Consortium (LIDC) is the largest public CT image database of lung nodules. In this study, the authors present a comprehensive and the most updated analysis of this dynamically growing database under the help of a computerized tool, aiming to assist researchers to optimally use this database for lung cancer related investigations. Methods: The authors developed a computer scheme to automatically match the nodule outlines marked manually by radiologists on CT images. A large variety of characteristics regarding the annotated nodules in the database including volume, spiculation level, elongation, interobserver variability, as well as the intersection of delineated nodule voxels and overlapping ratio between the same nodules marked by different radiologists are automatically calculated and summarized. The scheme was applied to analyze all 157 examinations with complete annotation data currently available in LIDC dataset. Results: The scheme summarizes the statistical distributions of the abovementioned geometric and diagnosis features. Among the 391 nodules, (1) 365 (93.35%) have principal axis length ≤20 mm; (2) 120, 75, 76, and 120 were marked by one, two, three, and four radiologists, respectively; and (3) 122 (32.48%) have the maximum volume overlapping ratios ≥80% for the delineations of two radiologists, while 198 (50.64%) have the maximum volume overlapping ratios <60%. The results also showed that 72.89% of the nodules were assessed with malignancy score between 2 and 4, and only 7.93% of these nodules were considered as severely malignant (malignancy ≥4). Conclusions: This study demonstrates that LIDC contains examinations covering a diverse distribution of nodule characteristics and it can be a useful resource to assess the performance of the nodule detection and/or segmentation schemes.

  13. Thirty Years of Innovation in Seismology with the IRIS Consortium

    Science.gov (United States)

    Sumy, D. F.; Woodward, R.; Aderhold, K.; Ahern, T. K.; Anderson, K. R.; Busby, R.; Detrick, R. S.; Evers, B.; Frassetto, A.; Hafner, K.; Simpson, D. W.; Sweet, J. R.; Taber, J.

    2015-12-01

    The United States academic seismology community, through the National Science Foundation (NSF)-funded Incorporated Research Institutions for Seismology (IRIS) Consortium, has promoted and encouraged a rich environment of innovation and experimentation in areas such as seismic instrumentation, data processing and analysis, teaching and curriculum development, and academic science. As the science continually evolves, IRIS helps drive the market for new research tools that enable science by establishing a variety of standards and goals. This has often involved working directly with manufacturers to better define the technology required, co-funding key development work or early production prototypes, and purchasing initial production runs. IRIS activities have helped establish de-facto international standards and impacted the commercial sector in areas such as seismic instrumentation, open-access data management, and professional development. Key institutional practices, conducted and refined over IRIS' thirty-year history of operations, have focused on open-access data availability, full retention of maximum-bandwidth, continuous data, and direct community access to state-of-the-art seismological instrumentation and software. These practices have helped to cultivate and support a thriving commercial ecosystem, and have been a key element in the professional development of multiple generations of seismologists who now work in both industry and academia. Looking toward the future, IRIS is increasing its engagement with industry to better enable bi-directional exchange of techniques and technology, and enhancing the development of tomorrow's workforce. In this presentation, we will illustrate how IRIS has promoted innovations grown out of the academic community and spurred technological advances in both academia and industry.

  14. Prostate Cancer Clinical Consortium Clinical Research Site: Targeted Therapies

    Science.gov (United States)

    2017-10-01

    relevance to targeted therapies. Our overarching goal is to more effectively bring novel agents and new biomarker driven trials directly to patients...direct relevance to targeted therapies. Our overarching goal is to more effectively bring novel agents and new biomarker driven trials directly to...al: Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device . PLoS One 7:e35976, 2012 21

  15. Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor.

    Directory of Open Access Journals (Sweden)

    Neil L Spector

    Full Text Available The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER in human tumors.Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor.In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers.Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor concentrations that maximally

  16. Hepatic tumors in children.

    Science.gov (United States)

    Stocker, J T

    2001-02-01

    Although they account for only 1% to 4% of solid tumors in children, hepatic tumors and pseudotumors offer a diagnostic challenge to the clinician seeing only an occasional case. Metastatic lesions such as neuroblastoma, Wilms' tumor, and lymphoma are the most common neoplasm seen in the liver, but 10 distinct primary tumors and pseudotumors of the liver occur with some regularity, and a few others may be seen rarely, including leiomyosarcoma, rhabdoid tumor, and endodermal sinus tumor. Five of these neoplasms--hepatoblastoma, infantile hemangio-endothelioma, mesenchymal hamartoma, undifferentiated embryonal sarcoma, and embryonal rhabdomyosarcoma of the biliary tree--occur only in children and are the major focus of the article.

  17. ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate for operable malignant gastrointestinal stromal tumor: monitoring with 18F-FDG PET and correlation with genotype and GLUT4 expression.

    Science.gov (United States)

    Van den Abbeele, Annick D; Gatsonis, Constantine; de Vries, Daniel J; Melenevsky, Yulia; Szot-Barnes, Agnieszka; Yap, Jeffrey T; Godwin, Andrew K; Rink, Lori; Huang, Min; Blevins, Meridith; Sicks, Jorean; Eisenberg, Burton; Siegel, Barry A

    2012-04-01

    We investigated the correlation between metabolic response by (18)F-FDG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib mesylate therapy. (18)F-FDG PET was performed at baseline, 1-7 d, and 4 or 8 wk after imatinib mesylate initiation. Best objective response was defined by version 1.0 of the Response Evaluation Criteria in Solid Tumors (RECIST). Mutational analysis and tumor GLUT4 expression by immunohistochemistry were done on tissue obtained at baseline or surgery. (18)F-FDG PET showed high baseline tumor glycolytic activity (mean SUV(max), 14.2; range, 1.3-53.2), decreasing after 1 wk of imatinib mesylate (mean, 5.5; range, -0.5-47.7, P imatinib mesylate initiation, metabolic response by (18)F-FDG PET was documented earlier (1-7 d) and was of much greater magnitude (36/44) than that documented by RECIST (2/39). Immunohistochemistry data suggest that GLUT4 may play a role in (18)F-FDG uptake in gastrointestinal stromal tumor, GLUT4 levels decrease after imatinib mesylate therapy in most patients with PMR, and the biologic action of imatinib mesylate interacts with glycolysis and GLUT4 expression. A greater than 85% metabolic response was observed as early as days 1-7 in patients with exon 11 mutations.

  18. [Brain tumor immunotherapy: Illusion or hope?

    Science.gov (United States)

    Migliorini, Denis; Dutoit, Valérie; Walker, Paul R; Dietrich, Pierre-Yves

    2017-05-01

    Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials. Indeed, the tumor bed is hostile to anti-tumor immune responses due to many escape mechanisms, and this is particularly true in the context of brain tumors, a master in eliciting immunosuppressive cells and molecules. The goal of this review is to describe the hopes and challenges of brain tumors immunotherapy and to propose an inventory of the current clinical research with specific focus on the therapies targeting the tumor microenvironment. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  19. Microbial hydrogen production from sewage sludge bioaugmented with a constructed microbial consortium

    Energy Technology Data Exchange (ETDEWEB)

    Kotay, Shireen Meher; Das, Debabrata [Department of Biotechnology, Indian Institute of Technology, Kharagpur 721302 (India)

    2010-10-15

    A constructed microbial consortium was formulated from three facultative H{sub 2}-producing anaerobic bacteria, Enterobacter cloacae IIT-BT 08, Citrobacter freundii IIT-BT L139 and Bacillus coagulans IIT-BT S1. This consortium was tested as the seed culture for H{sub 2} production. In the initial studies with defined medium (MYG), E. cloacae produced more H{sub 2} than the other two strains and it also was found to be the dominant member when consortium was used. On the other hand, B. coagulans as a pure culture gave better H{sub 2} yield (37.16 ml H{sub 2}/g COD{sub consumed}) than the other two strains using sewage sludge as substrate. The pretreatment of sludge included sterilization (15% v/v), dilution and supplementation with 0.5% w/v glucose, which was found to be essential to screen out the H{sub 2} consuming bacteria and ameliorate the H{sub 2} production. Considering (1:1:1) defined consortium as inoculum, COD reduction was higher and yield of H{sub 2} was recorded to be 41.23 ml H{sub 2}/g COD{sub reduced}. Microbial profiling of the spent sludge showed that B. coagulans was the dominant member in the constructed consortium contributing towards H{sub 2} production. Increase in H{sub 2} yield indicated that in consortium, the substrate utilization was significantly higher. The H{sub 2} yield from pretreated sludge (35.54 ml H{sub 2}/g sludge) was comparatively higher than that reported in literature (8.1-16.9 ml H{sub 2}/g sludge). Employing formulated microbial consortium for biohydrogen production is a successful attempt to augment the H{sub 2} yield from sewage sludge. (author)

  20. The Consortium of Advanced Residential Buildings (CARB) - A Building America Energy Efficient Housing Partnership

    Energy Technology Data Exchange (ETDEWEB)

    Robb Aldrich; Lois Arena; Dianne Griffiths; Srikanth Puttagunta; David Springer

    2010-12-31

    This final report summarizes the work conducted by the Consortium of Advanced Residential Buildings (CARB) (http://www.carb-swa.com/), one of the 'Building America Energy Efficient Housing Partnership' Industry Teams, for the period January 1, 2008 to December 31, 2010. The Building America Program (BAP) is part of the Department of Energy (DOE), Energy Efficiency and Renewable Energy, Building Technologies Program (BTP). The long term goal of the BAP is to develop cost effective, production ready systems in five major climate zones that will result in zero energy homes (ZEH) that produce as much energy as they use on an annual basis by 2020. CARB is led by Steven Winter Associates, Inc. with Davis Energy Group, Inc. (DEG), MaGrann Associates, and Johnson Research, LLC as team members. In partnership with our numerous builders and industry partners, work was performed in three primary areas - advanced systems research, prototype home development, and technical support for communities of high performance homes. Our advanced systems research work focuses on developing a better understanding of the installed performance of advanced technology systems when integrated in a whole-house scenario. Technology systems researched included: - High-R Wall Assemblies - Non-Ducted Air-Source Heat Pumps - Low-Load HVAC Systems - Solar Thermal Water Heating - Ventilation Systems - Cold-Climate Ground and Air Source Heat Pumps - Hot/Dry Climate Air-to-Water Heat Pump - Condensing Boilers - Evaporative condensers - Water Heating CARB continued to support several prototype home projects in the design and specification phase. These projects are located in all five program climate regions and most are targeting greater than 50% source energy savings over the Building America Benchmark home. CARB provided technical support and developed builder project case studies to be included in near-term Joule Milestone reports for the following community scale projects: - SBER Overlook at

  1. The Human Toxome Collaboratorium: A Shared Environment for Multi-Omic Computational Collaboration within a Consortium.

    Science.gov (United States)

    Fasani, Rick A; Livi, Carolina B; Choudhury, Dipanwita R; Kleensang, Andre; Bouhifd, Mounir; Pendse, Salil N; McMullen, Patrick D; Andersen, Melvin E; Hartung, Thomas; Rosenberg, Michael

    2015-01-01

    The Human Toxome Project is part of a long-term vision to modernize toxicity testing for the 21st century. In the initial phase of the project, a consortium of six academic, commercial, and government organizations has partnered to map pathways of toxicity, using endocrine disruption as a model hazard. Experimental data is generated at multiple sites, and analyzed using a range of computational tools. While effectively gathering, managing, and analyzing the data for high-content experiments is a challenge in its own right, doing so for a growing number of -omics technologies, with larger data sets, across multiple institutions complicates the process. Interestingly, one of the most difficult, ongoing challenges has been the computational collaboration between the geographically separate institutions. Existing solutions cannot handle the growing heterogeneous data, provide a computational environment for consistent analysis, accommodate different workflows, and adapt to the constantly evolving methods and goals of a research project. To meet the needs of the project, we have created and managed The Human Toxome Collaboratorium, a shared computational environment hosted on third-party cloud services. The Collaboratorium provides a familiar virtual desktop, with a mix of commercial, open-source, and custom-built applications. It shares some of the challenges of traditional information technology, but with unique and unexpected constraints that emerge from the cloud. Here we describe the problems we faced, the current architecture of the solution, an example of its use, the major lessons we learned, and the future potential of the concept. In particular, the Collaboratorium represents a novel distribution method that could increase the reproducibility and reusability of results from similar large, multi-omic studies.

  2. The Human Toxome Collaboratorium: a shared environment for multi-omic computational collaboration within a consortium

    Directory of Open Access Journals (Sweden)

    Rick A Fasani

    2016-02-01

    Full Text Available The Human Toxome Project is part of a long-term vision to modernize toxicity testing for the 21st century. In the initial phase of the project, a consortium of six academic, commercial, and government organizations has partnered to map pathways of toxicity, using endocrine disruption as a model hazard. Experimental data is generated at multiple sites, and analyzed using a range of computational tools. While effectively gathering, managing, and analyzing the data for high-content experiments is a challenge in its own right, doing so for a growing number of -omics technologies, with larger data sets, across multiple institutions complicates the process. Interestingly, one of the most difficult, ongoing challenges has been the computational collaboration between the geographically separate institutions. Existing solutions cannot handle the growing heterogeneous data, provide a computational environment for consistent analysis, accommodate different workflows, and adapt to the constantly evolving methods and goals of a research project. To meet the needs of the project, we have created and managed The Human Toxome Collaboratorium, a shared computational environment hosted on third-party cloud services. The Collaboratorium provides a familiar virtual desktop, with a mix of commercial, open-source, and custom-built applications. It shares some of the challenges of traditional information technology, but with unique and unexpected constraints that emerge from the cloud. Here we describe the problems we faced, the current architecture of the solution, an example of its use, the major lessons we learned, and the future potential of the concept. In particular, the Collaboratorium represents a novel distribution method that could increase the reproducibility and reusability of results from similar large, multi-omic studies.

  3. Conversion of Crude Oil to Methane by a Microbial Consortium Enriched From Oil Reservoir Production Waters

    Directory of Open Access Journals (Sweden)

    Carolina eBerdugo-Clavijo

    2014-05-01

    Full Text Available The methanogenic biodegradation of crude oil is an important process occurring in petroleum reservoirs and other oil-containing environments such as contaminated aquifers. In this process, syntrophic bacteria degrade hydrocarbon substrates to products such as acetate, and/or H2 and CO2 that are then used by methanogens to produce methane in a thermodynamically dependent manner. We enriched a methanogenic crude oil-degrading consortium from production waters sampled from a low temperature heavy oil reservoir. Alkylsuccinates indicative of fumarate addition to C5 and C6 n-alkanes were identified in the culture (above levels found in controls, corresponding to the detection of an alkyl succinate synthase gene (assA in the culture. In addition, the enrichment culture was tested for its ability to produce methane from residual oil in a sandstone-packed column system simulating a mature field. Methane production rates of up 5.8 μmol CH4/g of oil/day were measured in the column system. Amounts of produced methane were in relatively good agreement with hydrocarbon loss showing depletion of more than 50% of saturate and aromatic hydrocarbons. Microbial community analysis revealed that the enrichment culture was dominated by members of the genus Smithella, Methanosaeta, and Methanoculleus. However, a shift in microbial community occurred following incubation of the enrichment in the sandstone columns. Here, Methanobacterium sp. were most abundant, as were bacterial members of the genus Pseudomonas and other known biofilm forming organisms. Our findings show that microorganisms enriched from petroleum reservoir waters can bioconvert crude oil components to methane both planktonically and in sandstone-packed columns as test systems. Further, the results suggest that different organisms may contribute to oil biodegradation within different phases (e.g., planktonic versus sessile within a subsurface crude oil reservoir.

  4. Feasibility of electric property tomography of pelvic tumors at 3T

    NARCIS (Netherlands)

    Balidemaj, Edmond; van Lier, Astrid L H M W; Crezee, Hans; Nederveen, Aart J.; Stalpers, Lukas J A; Van Den Berg, Cornelis A.T.

    2015-01-01

    Purpose Investigation of the validity of the "transceive phase assumption" for Electric Property Tomography of pelvic tumors at 3T. The acquired electric conductivities of pelvic tumors are beneficial for improved specific absorption rate determination in hyperthermia treatment planning. Methods

  5. Feasibility of electric property tomography of pelvic tumors at 3T

    NARCIS (Netherlands)

    Balidemaj, Edmond; van Lier, Astrid L. H. M. W.; Crezee, Hans; Nederveen, Aart J.; Stalpers, Lukas J. A.; van den Berg, Cornelis A. T.

    2015-01-01

    Investigation of the validity of the "transceive phase assumption" for Electric Property Tomography of pelvic tumors at 3T. The acquired electric conductivities of pelvic tumors are beneficial for improved specific absorption rate determination in hyperthermia treatment planning. Electromagnetic

  6. Brain and Spinal Tumors

    Science.gov (United States)

    ... vessels. Also under investigation are ways to improve drug delivery to the tumor and to prevent the side- ... vessels. Also under investigation are ways to improve drug delivery to the tumor and to prevent the side- ...

  7. The anti-tumor effect of the quinoline-3-carboxamide tasquinimod: blockade of recruitment of CD11b+ Ly6Chi cells to tumor tissue reduces tumor growth

    International Nuclear Information System (INIS)

    Deronic, Adnan; Leanderson, Tomas; Ivars, Fredrik

    2016-01-01

    Previous work has demonstrated immunomodulatory, anti-tumor, anti-metastatic and anti-angiogenic effects of the small molecule quinoline-3-carboxamide tasquinimod in pre-clinical cancer models. To better understand the anti-tumor effects of tasquinimod in transplantable tumor models, we have evaluated the impact of the compound both on recruitment of myeloid cells to tumor tissue and on tumor-induced myeloid cell expansion as these cells are known to promote tumor development. Mice bearing subcutaneous 4 T1 mammary carcinoma tumors were treated with tasquinimod in the drinking water. A BrdU-based flow cytometry assay was utilized to assess the impact of short-term tasquinimod treatment on myeloid cell recruitment to tumors. Additionally, long-term treatment was performed to study the anti-tumor effect of tasquinimod as well as its effects on splenic myeloid cells and their progenitors. Myeloid cell populations were also immune-depleted by in vivo antibody treatment. Short-term tasquinimod treatment did not influence the proliferation of splenic Ly6C hi and Ly6G hi cells, but instead reduced the influx of Ly6C hi cells to the tumor. Treatment with tasquinimod for various periods of time after tumor inoculation revealed that the anti-tumor effect of this compound mainly operated during the first few days of tumor growth. Similar to tasquinimod treatment, antibody-mediated depletion of Ly6C hi cells within that same time frame, caused reduced tumor growth, thereby confirming a significant role for these cells in tumor development. Additionally, long-term tasquinimod treatment reduced the splenomegaly and expansion of splenic myeloid cells during a later phase of tumor development. In this phase, tasquinimod normalized the tumor-induced alterations in myeloerythroid progenitor cells in the spleen but had only limited impact on the same populations in the bone marrow. Our results indicate that tasquinimod treatment reduces tumor growth by operating early after tumor

  8. Augmented reality in a tumor resection model.

    Science.gov (United States)

    Chauvet, Pauline; Collins, Toby; Debize, Clement; Novais-Gameiro, Lorraine; Pereira, Bruno; Bartoli, Adrien; Canis, Michel; Bourdel, Nicolas

    2018-03-01

    Augmented Reality (AR) guidance is a technology that allows a surgeon to see sub-surface structures, by overlaying pre-operative imaging data on a live laparoscopic video. Our objectives were to evaluate a state-of-the-art AR guidance system in a tumor surgical resection model, comparing the accuracy of the resection with and without the system. Our system has three phases. Phase 1: using the MRI images, the kidney's and pseudotumor's surfaces are segmented to construct a 3D model. Phase 2: the intra-operative 3D model of the kidney is computed. Phase 3: the pre-operative and intra-operative models are registered, and the laparoscopic view is augmented with the pre-operative data. We performed a prospective experimental study on ex vivo porcine kidneys. Alginate was injected into the parenchyma to create pseudotumors measuring 4-10 mm. The kidneys were then analyzed by MRI. Next, the kidneys were placed into pelvictrainers, and the pseudotumors were laparoscopically resected. The AR guidance system allows the surgeon to see tumors and margins using classical laparoscopic instruments, and a classical screen. The resection margins were measured microscopically to evaluate the accuracy of resection. Ninety tumors were segmented: 28 were used to optimize the AR software, and 62 were used to randomly compare surgical resection: 29 tumors were resected using AR and 33 without AR. The analysis of our pathological results showed 4 failures (tumor with positive margins) (13.8%) in the AR group, and 10 (30.3%) in the Non-AR group. There was no complete miss in the AR group, while there were 4 complete misses in the non-AR group. In total, 14 (42.4%) tumors were completely missed or had a positive margin in the non-AR group. Our AR system enhances the accuracy of surgical resection, particularly for small tumors. Crucial information such as resection margins and vascularization could also be displayed.

  9. Aggressive malignant phyllodes tumor

    OpenAIRE

    Nathan Roberts; Dianne M. Runk

    2015-01-01

    Introduction: Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3–0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10–30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumo...

  10. JV Task 120 - Coal Ash Resources Research Consortium Research

    Energy Technology Data Exchange (ETDEWEB)

    Debra Pflughoeft-Hassett; Loreal Heebink; David Hassett; Bruce Dockter; Kurt Eylands; Tera Buckley; Erick Zacher

    2009-03-28

    The Coal Ash Resources Research Consortium{reg_sign} (CARRC{reg_sign}, pronounced 'cars') is the core coal combustion product (CCP) research group at the Energy & Environmental Research Center (EERC). CARRC focuses on performing fundamental and applied scientific and engineering research emphasizing the environmentally safe, economical use of CCPs. CARRC member organizations, which include utilities and marketers, are key to developing industry-driven research in the area of CCP utilization and ensuring its successful application. The U.S. Department of Energy is a partner in CARRC through the EERC Jointly Sponsored Research Program, which provides matching funds for industrial member contributions and facilitates an increased level of effort in CARRC. CARRC tasks were designed to provide information on CCP performance, including environmental performance, engineering performance, favorable economics, and improved life cycle of products and projects. CARRC technical research tasks are developed based on member input and prioritization. CARRC special projects are developed with members and nonmembers to provide similar information and to support activities, including the assembly and interpretation of data, support for standards development and technology transfer, and facilitating product development and testing. CARRC activities from 2007 to 2009 included a range of research tasks, with primary work performed in laboratory tasks developed to answer specific questions or evaluate important fundamental properties of CCPs. The tasks were included in four categories: (1) Environmental Evaluations of CCPs; (2) Evaluation of Impacts on CCPs from Emission Controls; (3) Construction and Product-Related Activities; and (4) Technology Transfer and Maintenance Tasks. All tasks are designed to work toward achieving the CARRC overall goal and supporting objectives. The various tasks are coordinated in order to provide broad and useful technical data for CARRC members

  11. Innovations in Nuclear Infrastructure and Education From the SW Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Reece, Warren

    2011-03-22

    This report describes the final expenditures for the INIE project during FY 08/09. (There were no expenditures during FY09/10 or during FY10/11.) To see the list of accomplishments done using the INIE funds, please see the reports included here. The last of the FY 07/08 funds were brought forward and used to complete two distance education modules teaching reactor experiments. These modules and parts from the modules are still being used and are being disseminated off-campus as a part of our distance education effort. The second largest expenditure was sending students to the ANS to present student papers on work that they had done the previous year underwritten by INIE funds. The remaining expenditures were IDC charges and minor travel expenses to give students a tour of a medical facility. Once again we wish to express of sincere appreciation of the INIE program and hope that the return on investment is appreciated by the DOE. Although INIE has come to a close, looking back at all the Consortium has accomplished is astounding. And, as was hoped, these funds have proved to be a springboard for continuing work, particularly at Texas A&M. With the resurgence of nuclear power, the utilities have realized that the nuclear workforce in the near future will be too small for the task of bringing dozens of new plants on line and have turned their attention to the URRs to help feed the workforce pipeline. The distance education modules developed at the A&M are soon to be broadcast throughout the country to help train a new generation of nuclear workers. Our students at the Nuclear Science Center at being snapped up by the nuclear power plants after graduating. Our research projects at A&M have all ended with new data, new ways of looking at old problems, and produced a covey of good students. I want to say 'Thanks' with utmost sincerity because without the INIE funds our efforts would yield a small fraction of the accomplishments you see in this report.

  12. Innovations in Nuclear Infrastructure and Education From the SW Consortium

    International Nuclear Information System (INIS)

    Reece, Warren

    2011-01-01

    This report describes the final expenditures for the INIE project during FY 08/09. (There were no expenditures during FY09/10 or during FY10/11.) To see the list of accomplishments done using the INIE funds, please see the reports included here. The last of the FY 07/08 funds were brought forward and used to complete two distance education modules teaching reactor experiments. These modules and parts from the modules are still being used and are being disseminated off-campus as a part of our distance education effort. The second largest expenditure was sending students to the ANS to present student papers on work that they had done the previous year underwritten by INIE funds. The remaining expenditures were IDC charges and minor travel expenses to give students a tour of a medical facility. Once again we wish to express of sincere appreciation of the INIE program and hope that the return on investment is appreciated by the DOE. Although INIE has come to a close, looking back at all the Consortium has accomplished is astounding. And, as was hoped, these funds have proved to be a springboard for continuing work, particularly at Texas A and M. With the resurgence of nuclear power, the utilities have realized that the nuclear workforce in the near future will be too small for the task of bringing dozens of new plants on line and have turned their attention to the URRs to help feed the workforce pipeline. The distance education modules developed at the A and M are soon to be broadcast throughout the country to help train a new generation of nuclear workers. Our students at the Nuclear Science Center at being snapped up by the nuclear power plants after graduating. Our research projects at A and M have all ended with new data, new ways of looking at old problems, and produced a covey of good students. I want to say 'Thanks' with utmost sincerity because without the INIE funds our efforts would yield a small fraction of the accomplishments you see in this report.

  13. Open Geospatial Consortium standards supporting Lake Maggiore Early Warning System

    Science.gov (United States)

    Cannata, Massimiliano; Antonovic, Milan; Molinari, Monia; Pozzoni, Maurizio

    2013-04-01

    management to OGC services with internally implemented software (GeoShield [7]). The presentation illustrates the case study focusing on selected technical solution and strength, weakness and opportunities that the authors identified in the conduction of this experimentation. References: [1] http://www.ti.ch [2] http://www.pcilocarno.ch [3] http://www.supsi.ch/ist [4] Klopfer, M., Simonis, I. (Eds.), SANY - An Open Service Architecture for Sensor Networks, SANY Consortium, 2009. [5] http://www.tridec-online.eu [6] http://istgeo.ist.supsi.ch/software/istsos [7] http://sites.google.com/site/geoshieldproject

  14. Rapid maturation of effector T cells in tumors, but not lymphoid organs, during tumor regression.

    Directory of Open Access Journals (Sweden)

    Lyse A Norian

    2007-09-01

    Full Text Available Increasing the efficacy of adoptively transferred, tumor antigen specific T cells is a major goal of immunotherapy. Clearly, a more thorough understanding of the effector phase of T cell responses, within the tumor site itself, would be beneficial. To examine this issue, we adoptively transferred tumor antigen-specific effector T cells into tumor-bearing mice, then performed kinetic evaluations of their phenotype, function, and survival in tumors, draining lymph nodes (dLNs, and spleens during regression of murine fibrosarcomas. Effector function in tumors was quantitated through the use of a novel intratumoral cytolytic assay. This approach revealed dynamic changes in the phenotype, cytolytic capacity, and viability of tumor infiltrating effector T cells during the course of tumor regression. Over a period of days, T cells within tumors rapidly transitioned from a CD25(hi/CD27(hi to a CD25(low/CD27(low phenotype and displayed an increase in cytolytic capacity, indicative of effector maturation. Simultaneously, however, the viability of maturing T cells within tumors diminished. In contrast, transferred T cells trafficking through lymphoid organs were much more static, as they maintained a stable phenotype, robust cytolytic activity, and high viability. Therefore, there exists a marked phenotypic and functional divergence between tumor-infiltrating effector T cells and their counterparts in lymphoid organs. Our results indicate that the population of tumor-infiltrating T cells is unique in experiencing rapid effector maturation post-transfer, and suggest that strategies aimed at prolonging the survival of CD25(low/CD27(low full effectors, which displayed the highest levels of intratumoral cytolytic activity, should enhance the efficacy of T cell based tumor immunotherapies.

  15. 25 CFR 1000.21 - When does a Tribe/Consortium have a “material audit exception”?

    Science.gov (United States)

    2010-04-01

    ...-Governance Eligibility § 1000.21 When does a Tribe/Consortium have a “material audit exception”? A Tribe/Consortium has a material audit exception if any of the audits that it submitted under § 1000.17(c... 25 Indians 2 2010-04-01 2010-04-01 false When does a Tribe/Consortium have a âmaterial audit...

  16. The Historically Black Colleges and Universities/Minority Institutions Environmental Technology Consortium annual report, 1991--1992

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1992-12-31

    The member institutions of the Consortium continue to play a significant role in increasing the number of African Americans who enter the environmental professions through the implementation of the Consortium`s RETT Plan for Research, Education, and Technology Transfer. The four major program areas identified in the RETT Plan are as follows: (1) minority outreach and precollege education; (2) undergraduate education and postsecondary training; (3) graduate and postgraduate education and research; and (4) technology transfer.

  17. Multiple Primary Tumors

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It ... KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous .... layer of the colon. The tumor cells are strongly positive to chromagranin and AE1/AE3. Features are those of carcinoid tumor of the colon. She was ...

  18. Granular Cell Tumor

    African Journals Online (AJOL)

    Necrosis within the tumor was absent, no mitosis was. Granular cell tumors are seldom diagnosed identified in the section and the edges of the accurately clinically. The lesion in this case was sample were tumor free (Figure 2). mistaken for a sebaceous cyst and following ulceration resembled carcinoma of the vulvar.

  19. Malignant tumors of childhood

    International Nuclear Information System (INIS)

    Brooks, B.J.

    1986-01-01

    This book contains 34 papers about malignant tumors. some of the titles are: Invasive Cogenital Mesoblastic Nephroma, Leukemia Update, Unusual Perinatal Neoplasms, Lymphoma Update, Gonadal Germ Cell Tumors in Children, Nutritional Status and Cancer of Childhood, and Chemotherapy of Brain tumors in Children

  20. Soft tissue mixed tumor

    Directory of Open Access Journals (Sweden)

    Eiichi Hiraishi

    2009-12-01

    Full Text Available Mixed tumors are relatively common in the skin and salivary glands, but extremely rare in soft tissues, often resulting in diagnostic problems. The occurrence of these tumors in the hand is especially limited. In this article we report the clinical, radiological, and histological features of a mixed tumor of the hypothenar region of the right hand.

  1. Multiple Primary Tumors

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It ... KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous .... layer of the colon. The tumor cells are strongly positive to chromagranin and AE1/AE3. Features are those of carcinoid tumor of the colon. She was ...

  2. Radionuclide Therapy for Neuroendocrine Tumors.

    Science.gov (United States)

    Cives, Mauro; Strosberg, Jonathan

    2017-02-01

    Peptide receptor radionuclide therapy (PRRT) is a form of systemic radiotherapy that allows targeted delivery of radionuclides to tumor cells expressing high levels of somatostatin receptors. The two radiopeptides most commonly used for PRRT, 90 Y-DOTATOC and 177 Lu-DOTATATE, have been successfully employed for more than a decade for the treatment of advanced neuroendocrine tumors (NETs). Recently, the phase III, randomized NETTER-1 trial has compared 177 Lu-DOTATATE versus high-dose octreotide LAR in patients with progressive, metastatic midgut NETs, demonstrating exceptional tolerability and efficacy. This review summarizes recent developments in the field of radionuclide therapy for gastroenteropancreatic and lung NETs and considers possible strategies to further enhance its clinical efficacy.

  3. Zinc bioaccumulation by microbial consortium isolated from nickel smelter sludge disposal site

    Directory of Open Access Journals (Sweden)

    Kvasnová Simona

    2017-06-01

    Full Text Available Heavy metal pollution is one of the most important environmental issues of today. Bioremediation by microorganisms is one of technologies extensively used for pollution treatment. In this study, we investigated the heavy metal resistance and zinc bioaccumulation by microbial consortium isolated from nickel sludge disposal site near Sereď (Slovakia. The composition of consortium was analyzed based on MALDI-TOF MS of cultivable bacteria and we have shown that the consortium was dominated by bacteria of genus Arthrobacter. While consortium showed very good growth in the zinc presence, it was able to remove only 15 % of zinc from liquid media. Selected members of consortia have shown lower growth rates in the zinc presence but selected isolates have shown much higher bioaccumulation abilities compared to whole consortium (up to 90 % of zinc removal for NH1 strain. Bioremediation is frequently accelerated through injection of native microbiota into a contaminated area. Based on data obtained in this study, we can conclude that careful selection of native microbiota could lead to the identification of bacteria with increased bioaccumulation abilities.

  4. Development of a consortium for water security and safety: Planning for an early warning system

    Science.gov (United States)

    Clark, R.M.; Adam, N.R.; Atluri, V.; Halem, M.; Vowinkel, E.F.; ,

    2004-01-01

    The events of September 11, 2001 have raised concerns over the safety and security of the Nation's critical infrastructure including water and waste water systems. In June 2002, the U.S. EPA's Region II Office (New York City), in response to concerns over water security, in collaboration with Rutgers University agreed to establish a Regional Drinking Water Security and Safety Consortium (RDWSSC). Members of the consortium include: Rutgers University's Center for Information Management, Integration and Connectivity (CIMIC), American Water (AW), the Passaic Valley Water Commission (PVWC), the North Jersey District Water Supply Commission (NJDWSC), the N.J. Department of Environmental Protection, the U.S. Geological Survey (USGS), and the U.S. Environmental Protection Agencies, Region II Office. In December of 2002 the consortium members signed a memorandum of understanding (MOU) to pursue activities to enhance regional water security. Development of an early warning system for source and distributed water was identified as being of primary importance by the consortium. In this context, an early warning system (EWS) is an integrated system of monitoring stations located at strategic points in a water utilities source waters or in its distribution system, designed to warn against contaminants that might threaten the health and welfare of drinking water consumers. This paper will discuss the consortium's progress in achieving these important objectives.

  5. Decolorization of azo dyes (Direct Blue 151 and Direct Red 31 by moderately alkaliphilic bacterial consortium

    Directory of Open Access Journals (Sweden)

    Sylvine Lalnunhlimi

    2016-03-01

    Full Text Available Abstract Removal of synthetic dyes is one of the main challenges before releasing the wastes discharged by textile industries. Biodegradation of azo dyes by alkaliphilic bacterial consortium is one of the environmental-friendly methods used for the removal of dyes from textile effluents. Hence, this study presents isolation of a bacterial consortium from soil samples of saline environment and its use for the decolorization of azo dyes, Direct Blue 151 (DB 151 and Direct Red 31 (DR 31. The decolorization of azo dyes was studied at various concentrations (100–300 mg/L. The bacterial consortium, when subjected to an application of 200 mg/L of the dyes, decolorized DB 151 and DR 31 by 97.57% and 95.25% respectively, within 5 days. The growth of the bacterial consortium was optimized with pH, temperature, and carbon and nitrogen sources; and decolorization of azo dyes was analyzed. In this study, the decolorization efficiency of mixed dyes was improved with yeast extract and sucrose, which were used as nitrogen and carbon sources, respectively. Such an alkaliphilic bacterial consortium can be used in the removal of azo dyes from contaminated saline environment.

  6. Perception Is Reality: quality metrics in pancreas surgery - a Central Pancreas Consortium (CPC) analysis of 1399 patients.

    Science.gov (United States)

    Abbott, Daniel E; Martin, Grace; Kooby, David A; Merchant, Nipun B; Squires, Malcolm H; Maithel, Shishir K; Weber, Sharon M; Winslow, Emily R; Cho, Clifford S; Bentrem, David J; Kim, Hong Jin; Scoggins, Charles R; Martin, Robert C; Parikh, Alexander A; Hawkins, William G; Ahmad, Syed A

    2016-05-01

    Several groups have defined pancreatic surgery quality metrics that identify centers delivering quality care. Although these metrics are perceived to be associated with good outcomes, their relationship with actual outcomes has not been established. A national cadre of pancreatic surgeons was surveyed regarding perceived quality metrics, which were evaluated against the Central Pancreas Consortium (CPC) database to determine actual performance and relationships with long-term outcomes. The most important metrics were perceived to be participation in clinical trials, appropriate clinical staging, perioperative mortality, and documentation of receipt of adjuvant therapy. Subsequent analysis of 1399 patients in the CPC dataset demonstrated that a R0 retroperitoneal and neck margin was obtained in 79% (n = 1109) and 91.4% (n = 1278) of cases, respectively. 74% of patients (n = 1041) had >10 lymph nodes harvested, and LN positivity was 65% (n = 903). 76% (n = 960) of eligible patients (surgery first approach) received adjuvant therapy within 60 days of surgery. Multivariate analysis demonstrated margin status, identification of >10 lymph nodes, nodal status, tumor grade and delivery of adjuvant therapy within 60 days to be associated with improved overall survival. These analyses demonstrate that systematic monitoring of surgeons' perceived quality metrics provides critical prognostic information, which is associated with patient survival. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  7. Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor a inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Doyle, Mittie; Landewé, Robert; Matteson, Eric L.; Gaylis, Norman; Wollenhaupt, Jürgen; Murphy, Frederick T.; Xu, Stephen; Zhou, Yiying; Hsia, Elizabeth C.

    2015-01-01

    Introduction: The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor-alpha (TNF)-inhibitor(s). Methods: Patients enrolled into this multicenter, randomized, double-blind, placebo-controlled study of active

  8. In vitro inhibition of enterobacteria-reactive CD4+Tumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    Mangano, K.; Sardesai, N.; D'Alcamo, M.

    2008-01-01

    VGX-1027 is an isozaxoline compound that has recently been found to primarily target the function of murine macrophages but not of T cells, inhibiting secretion of tumor necrosis factor (TNF)-alpha in response to different Toll-like receptor agonists in vitro and in vivo. The well-defined role of...

  9. Cholecystokinin expression in tumors

    DEFF Research Database (Denmark)

    Rehfeld, Jens F

    2016-01-01

    Cholecystokinin (CCK) is a classic gut hormone. CCK is also a complex system of peptides expressed in several molecular forms in enteroendocrine I cells, in cerebral and peripheral neurons, in cardiac myocytes and spermatozoa. CCK gene expression has now been found at protein or peptide level...... in different neuroendocrine tumors; cerebral gliomas and astrocytomas and specific pediatric tumors. Tumor hypersecretion of CCK was recently reported in a patient with a metastatic islet cell tumor and hypercholecystokininemia resulting in a novel tumor syndrome, the cholecystokininoma syndrome. This review...

  10. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  11. Tumor-Penetrating Peptides

    Science.gov (United States)

    Teesalu, Tambet; Sugahara, Kazuki N.; Ruoslahti, Erkki

    2013-01-01

    Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC), contains the integrin-binding RGD motif. RGD mediates tumor-homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR) motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular “zip code” of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies, and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is present in the

  12. PET and endocrine tumors

    International Nuclear Information System (INIS)

    Rigo, P.; Belhocine, T.; Hustinx, R.; Foidart-Willems, J.

    2000-01-01

    The authors review the main indications of PET examination, and specifically of 18 FDG, in the assessment of endocrine tumors: of the thyroid, of the parathyroid, of the adrenal and of the pituitary glands. Neuroendocrine tumors, gastro-entero-pancreatic or carcinoid tumors are also under the scope. Usually, the most differentiated tumors show only poor uptake of the FDG as they have a weak metabolic and proliferative activity. In the assessment of endocrine tumors, FDG-PET should be used only after most specific nuclear examinations been performed. (author)

  13. Contributing Factors of Temozolomide Resistance in MCF-7 Tumor Xenograft Models

    OpenAIRE

    Kato, Yoshinori; Okollie, Baasil; Raman, Venu; Vesuna, Farhad; Zhao, Ming; Baker, Sharyn D.; Bhujwalla, Zaver M.; Artemov, Dmitri

    2007-01-01

    Vasculature mediated drug resistance in tumors was studied in female SCID mice bearing wild type MCF-7 and adriamycin resistant MCF-7/ADR xenograft using temozolomide (TMZ). A strong tumor growth inhibitory effect of TMZ treatment was observed in MCF-7 tumors during the initial treatment phase with subsequent relapse, but not in MCF-7/ADR tumors. Non-invasive MRI measurements of tumor vascular volume and vascular permeability-surface area product (PS) demonstrated significant reduction of PS ...

  14. Ecofriendly degradation, decolorization and detoxification of textile effluent by a developed bacterial consortium.

    Science.gov (United States)

    Phugare, Swapnil S; Kalyani, Dayanand C; Surwase, Shripad N; Jadhav, Jyoti P

    2011-07-01

    Present study illustrates the effectual decolorization and degradation of the textile effluent using a developed bacterial consortium SDS, consisted of bacterial species Providencia sp. SDS and Pseudomonas aeuroginosa strain BCH, originally isolated from dye contaminated soil. The intensive metabolic activity of the consortium SDS led to complete decolorization of textile effluent within 20 h at pH 7 and temperature 30°C. Significant induction in the activities of veratryl alcohol oxidase, laccase, azoreductase and DCIP reductase were observed during decolorization, which indicates their involvement in decolorization and degradation process. The decolorization and biodegradation was monitored using UV-vis spectroscopy, IR spectroscopy, HPLC and HPTLC analysis. Toxicological analysis of effluent before and after treatment was performed using classical Allium cepa test. Investigations of various toxicological parameters viz, oxidative stress response, cytotoxicity, genotoxicity and phytotoxicity, collectively concludes that, the toxicity of effluent reduces significantly after treatment with consortium SDS. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Call for participation in the neurogenetics consortium within the Human Variome Project.

    Science.gov (United States)

    Haworth, Andrea; Bertram, Lars; Carrera, Paola; Elson, Joanna L; Braastad, Corey D; Cox, Diane W; Cruts, Marc; den Dunnen, Johann T; Farrer, Matthew J; Fink, John K; Hamed, Sherifa A; Houlden, Henry; Johnson, Dennis R; Nuytemans, Karen; Palau, Francesc; Rayan, Dipa L Raja; Robinson, Peter N; Salas, Antonio; Schüle, Birgitt; Sweeney, Mary G; Woods, Michael O; Amigo, Jorge; Cotton, Richard G H; Sobrido, Maria-Jesus

    2011-08-01

    The rate of DNA variation discovery has accelerated the need to collate, store and interpret the data in a standardised coherent way and is becoming a critical step in maximising the impact of discovery on the understanding and treatment of human disease. This particularly applies to the field of neurology as neurological function is impaired in many human disorders. Furthermore, the field of neurogenetics has been proven to show remarkably complex genotype-to-phenotype relationships. To facilitate the collection of DNA sequence variation pertaining to neurogenetic disorders, we have initiated the "Neurogenetics Consortium" under the umbrella of the Human Variome Project. The Consortium's founding group consisted of basic researchers, clinicians, informaticians and database creators. This report outlines the strategic aims established at the preliminary meetings of the Neurogenetics Consortium and calls for the involvement of the wider neurogenetic community in enabling the development of this important resource.

  16. Engineered bidirectional communication mediates a consensus in a microbial biofilm consortium.

    Science.gov (United States)

    Brenner, Katie; Karig, David K; Weiss, Ron; Arnold, Frances H

    2007-10-30

    Microbial consortia form when multiple species colocalize and communally generate a function that none is capable of alone. Consortia abound in nature, and their cooperative metabolic activities influence everything from biodiversity in the global food chain to human weight gain. Here, we present an engineered consortium in which the microbial members communicate with each other and exhibit a "consensus" gene expression response. Two colocalized populations of Escherichia coli converse bidirectionally by exchanging acyl-homoserine lactone signals. The consortium generates the gene-expression response if and only if both populations are present at sufficient cell densities. Because neither population can respond without the other's signal, this consensus function can be considered a logical AND gate in which the inputs are cell populations. The microbial consensus consortium operates in diverse growth modes, including in a biofilm, where it sustains its response for several days.

  17. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... markers . Most malignant germ cell tumors release tumor markers. The following tumor markers are used to detect extracranial germ cell tumors: ... testicular germ cell tumors, blood levels of the tumor markers help show if the tumor is a seminoma ...

  18. A consortium approach for disaster relief and technology research and development: Fire station earth

    Science.gov (United States)

    Ling, Douglas C.

    1992-06-01

    A new paradigm is proposed for alleviating the chronic problem of inadequate response to natural and man-made disasters. Fundamental flaws and weaknesses in the current disaster mitigation system point to the need for an international consortium involving governments, academia, industry, and businesses. Recent changes in social and political framework offer a unique opportunity of rethink and reform the existing disaster response mechanism. Benefits of a collaborative consortium approach may include commercial incentives, improved cost effectiveness, coherence in research and development efforts, conduciveness for long-term planning, and improved deployment of technology for disaster mitigation.

  19. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Pearce, C L; Near, A M; Van Den Berg, D J

    2009-01-01

    The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had...... been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P... and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted....

  20. Oak woodlands and forests fire consortium: A regional view of fire science sharing

    Science.gov (United States)

    Grabner, Keith W.; Stambaugh, Michael C.; Marschall, Joseph M.; Abadir, Erin R.

    2013-01-01

    The Joint Fire Science Program established 14 regional fire science knowledge exchange consortia to improve the delivery of fire science information and communication among fire managers and researchers. Consortia were developed regionally to ensure that fire science information is tailored to meet regional needs. In this paper, emphasis was placed on the Oak Woodlands and Forests Fire Consortium to provide an inside view of how one regional consortium is organized and its experiences in sharing fire science through various social media, conference, and workshop-based fire science events.

  1. Social Behavior in Medulloblastoma: Functional Analysis of Tumor-Supporting

    Science.gov (United States)

    2013-07-01

    used MADM to probe into early phases of gliomagenesis, and surprisingly found the lack of overpopulation of mutant NSCs. Among NSC-derived cell types...focus is on brain tumors. Several Berlin-based research groups have specialized on investigating the impact of parenchymal interactions of brain tumor

  2. The clinical factors associated with benign renal tumors

    International Nuclear Information System (INIS)

    Yamashita, Ryo; Nakamura, Masafumi; Matsuzaki, Masato; Matsui, Takashi; Yamaguchi, Raizo; Niwakawa, Masashi; Tobisu, Kenichi; Asakura, Koiku; Ito, Ichiro

    2009-01-01

    In this study, we sought to define the incidence of benign renal tumors in our institute and to clarify the clinical factors associated with benign renal tumors, in order to assist in forming preoperative differential diagnoses. From October 2002 to July 2007, we performed 157 nephrectomies in patients preoperatively diagnosed with renal cell carcinoma. We chose 81 tumors, all of which were less than 5 cm, for further study. We reviewed double-phase helical CT imaging retrospectively, specifically focusing on attenuation patterns and homogeneity. We also compared clinical factors, including age, sex and tumor size, between the benign and malignant renal tumors. The patient's median age was 67 years (mean age, 63 years), and the median tumor diameter was 3.0 cm (mean, 3.2 cm). Benign renal tumors were found in 10 (12%) of the 81 tumors; these included seven cases of oncocytoma and three cases of angiomyolipoma with minimal fat. Several factors were significant clinical determinants of differentiation between benign and malignant renal tumors: homogeneity in CT, female gender, and small tumor size all predominated in cases of benign tumors. Attenuation pattern in CT, however, was not a significant factor (p=0.344). When a patient, especially a female, presents with a small and homogeneous renal tumor, careful consideration should be given to the possibility of a benign process, which needs further consideration before performing excessive surgery. (author)

  3. B-lymfocytdepletring og andre biologiske behandlingsmuligheder ved Graves' oftalmopatiTumor necrosis factor-alpha binding capacity and anti-infliximab antibodies measured by fluid-phase radioimmunoassays as predictors of clinical efficacy of infliximab in Crohn's disease

    DEFF Research Database (Denmark)

    El, Fassi D.; Hegedus, L.; Nielsen, Claus Henrik

    2008-01-01

    The current medical treatment options for Graves' ophthalmopathy (GO) are unsatisfactory. Recent treatment of GO patients with the B-lymphocyte depleting monoclonal antibody rituximab or with the anti-tumor necrosis factor-alpha agents etanercept and infliximab has shown promising results. We...... discuss the use of these and other biological agents targeting B lymphocytes, T-lymphocyte interaction with antigen-presenting cells, or cytokines in the future treatment of GO Udgivelsesdato: 2008/6/9...

  4. Contrast-enhanced helical CT of the pancreas. Optimal timing of imaging for pancreatic tumor evaluation

    International Nuclear Information System (INIS)

    Koide, Kazuki; Sekiguchi, Ryuzo

    2001-01-01

    We performed three-phase helical CT in patients suspected pancreatic tumors and investigated the optimal timing of imaging for evaluation of the pancreatic mass. The pancreatic-phase was superior in detecting pancreatic tumors, including islet cell tumors that may show strong enhancement. However, portal vein-phase imaging was also superior in 16.7% of our patients. Taking into account examination for hepatic metastasis, helical CT of any pancreatic tumor should include images obtained in the pancreatic and portal vein phases. (author)

  5. From Franchise Network to Consortium: The Evolution and Operation of a New Kind of Further and Higher Education Partnership

    Science.gov (United States)

    Bridge, Freda; Fisher, Roy; Webb, Keith

    2003-01-01

    The Consortium for Post-Compulsory Education and Training (CPCET) is a single subject consortium of further education and higher education providers of professional development relating to in-service teacher training for the whole of the post-compulsory sector. Involving more than 30 partners spread across the North of England, CPCET evolved from…

  6. 77 FR 71831 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-3D PDF Consortium...

    Science.gov (United States)

    2012-12-04

    ... Production Act of 1993--3D PDF Consortium, Inc. Notice is hereby given that, on November 8, 2012, pursuant to Section 6(a) of the National Cooperative Research and Production Act of 1993, 15 U.S.C. Sec. 4301 et seq. (``the Act''), 3D Consortium, Inc. (``3D PDF'') has filed written notifications simultaneously with the...

  7. 78 FR 72713 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-3D PDF Consortium...

    Science.gov (United States)

    2013-12-03

    ... Production Act of 1993--3D PDF Consortium, Inc. Notice is hereby given that, on October 31, 2013, pursuant to Section 6(a) of the National Cooperative Research and Production Act of 1993, 15 U.S.C. 4301 et seq. (``the Act''), 3D PDF Consortium, Inc. (``3D PDF'') has filed written notifications simultaneously with...

  8. 77 FR 38831 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-3D PDF Consortium...

    Science.gov (United States)

    2012-06-29

    ... Production Act of 1993--3D PDF Consortium, Inc. Notice is hereby given that, on June 4, 2012, pursuant to Section 6(a) of the National Cooperative Research and Production Act of 1993, 15 U.S.C. 4301 et seq. (``the Act''), 3D PDF Consortium, Inc. (``3D PDF'') has filed written notifications simultaneously with...

  9. 25 CFR 1000.394 - What audit requirements must a self-governance Tribe/Consortium follow?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false What audit requirements must a self-governance Tribe... INDIAN SELF-DETERMINATION AND EDUCATION ACT Miscellaneous Provisions § 1000.394 What audit requirements must a self-governance Tribe/Consortium follow? The Tribe/Consortium must provide to the designated...

  10. Enhanced bio-decolorization of azo dyes by co-immobilized quinone-reducing consortium and anthraquinone

    DEFF Research Database (Denmark)

    Su, YY; Zhang, Yifeng; Wang, J

    2009-01-01

    In the present study, the accelerating effect of co-immobilized anthraquinone and quinone-reducing consortium was investigated in the bio-decolorization process. The anthraquinone and quinone-reducing consortium were co-immobilized by entrapment in calcium alginate. The co-immobilized beads...

  11. Tumor detection with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Packer, S.

    1984-01-01

    The most common primary ocular tumor in adults is malignant melanoma of the choroid. Metastatic tumors to the choroid occur with the same frequency. The radioactive phosphorous uptake test is used most often as a nuclear diagnostic test. The test does not differentiate melanomas from metastases, and it is necessary to perform surgery for proper placement of a detection device within a distance of 1-2 mm of the tumor. These deficiencies leave ophthalmologists with a pressing need for a gamma-emitting radiopharmaceutical that would facilitate noninvasive identification of choroidal melanoma. This need is made more urgent by the fact that recently, radiation therapy has been used to treat these tumors rather than enucleation. Eyes then harbor irradiated melanoma whose status is unknown. The tumor rarely decreases in size more than 25% to 50%. There is thus a need for a specific diagnostic test to assess the nature of the tumor and the effectiveness of therapy

  12. [Immune system and tumors].

    Science.gov (United States)

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

  13. Imaging of pancreatic tumors

    International Nuclear Information System (INIS)

    Brambs, Hans-Juergen; Juchems, Markus

    2010-01-01

    Ductal adenocarcinoma is the most frequent solid tumor of the pancreas. This tumor has distinct features including early obstruction of the pancreatic duct, diminished enhancement after administration of contrast material due to desmoplastic growth, high propensity to infiltrate adjacent structures and to metastasize into the liver and the peritoneum. Hormone active endocrine tumors cause specific clinical symptoms. Imaging is aimed at localization of these hypervascular tumors. Non hormone active tumors are most frequently malignant and demonstrate very varying features. Cystic pancreatic tumors are increasingly detected by means of cross sectional imaging. Exact classification can be achieved with knowledge of the macropathology and considering clinical presentation as well as age and gender of the patients. (orig.)

  14. Central nervous system tumors

    International Nuclear Information System (INIS)

    Curran, W.J. Jr.

    1991-01-01

    Intrinsic tumors of the central nervous system (CNS) pose a particularly challenging problem to practicing oncologists. These tumors rarely metastasize outside the CNS, yet even histologically benign tumors can be life-threatening due to their local invasiveness and strategic location. The surrounding normal tissues of the nervous system is often incapable of full functional regeneration, therefore prohibiting aggressive attempts to use either complete surgical resection or high doses of irradiation. Despite these limitations, notable achievements have recently been recorded in the management of these tumors

  15. Aggressive malignant phyllodes tumor.

    Science.gov (United States)

    Roberts, Nathan; Runk, Dianne M

    2015-01-01

    Originally described in 1838 by Muller, phyllodes tumor is a rare fibroepithelial neoplasm which represents roughly 0.3-0.9% of all breast cancers. Phyllodes tumor are divided into benign, borderline and malignant histologic categories. Malignant phyllodes tumor represent anywhere from 10-30% of all phyllodes tumors. This group has both the potential to recur locally and metastasize, however not all malignant phyllodes behave this way. The challenge lays in predicting which tumor will recur locally or metastasize. Distinguishing this subset of malignant phyllodes tumor is paramount. We present a case of malignant phyllodes which presented with metastatic disease. What is fascinating about this case is not only the initial presentation but also the aggressiveness of this variation of phyllodes tumor. The patient initially presented with a large mass which encompassed her whole right breast. On surgical pathology the mass measured roughly 31cm in diameter and weighed over 10kg. Within 5 weeks from surgery the patient had suffered brain metastases and also 6 local recurrent tumors. The patient passed roughly 11 weeks after her first visit to our office. Despite biopsy proven malignant phyllodes tumor, it was near impossible to predict such a rapid course of disease progression in our patient. Our case illustrates the unpredictable nature of this disease in general and it possibly sheds light on a variant of the disease which had undergone an aggressive transformation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. TUMORES ANEXIALES Y EMBARAZO

    OpenAIRE

    Tapia M.,Mauricio; Orellana H.,Ricardo; Cisterna C.,Patricio; Gazitúa P.,Raimundo; Sepúlveda A.,Rodrigo

    2005-01-01

    Objetivo: Evaluar la frecuencia de tumores anexiales en el embarazo, la histología tumoral y los resultados perinatales. Pacientes y método: Análisis retrospectivo de 33 pacientes con diagnóstico de tumor anexial y embarazo atendidas en el Servicio de Obstetricia del Hospital San Juan de Dios entre febrero de 2001 a julio de 2004. Resultados: La asociación tumor anexial y embarazo fue 1 en 424 embarazos. El tipo histológico más frecuente fue el cistoadenoma seroso (19,2%). La cirugía no alter...

  17. Management of CNS tumors

    International Nuclear Information System (INIS)

    Griem, M.L.

    1987-01-01

    The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered

  18. The Historically Black Colleges and Universities/Minority Institutions Environmental Technology Consortium annual report draft, 1995--1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-07-01

    The HBCU/MI ET Consortium was established in January 1990, through a memorandum of Understanding (MOU) among its member institutions. This group of research-oriented Historically Black Colleges and Universities and Minority Institutions (HBCUs/MIs) agreed to work together to initiate or revise educational programs, develop research partnerships with public and private sector organizations, and promote technology development and transfer to address the nation`s critical environmental problems. While the Consortium`s Research, Education and Technology Transfer (RETT) Plan is the cornerstone of its overall program efforts, the initial programmatic activities of the Consortium focused on environmental education at all levels with the objective of addressing the underrepresentation of minorities in the environmental professions. This 1996 Annual Report provides an update on the activities of the Consortium with a focus on environmental curriculum development for the Technical Qualifications Program (TQP) and Education for Sustainability.

  19. Adenomatoid odontogenic tumor, an uncommon tumor

    Directory of Open Access Journals (Sweden)

    K Vasudevan

    2012-01-01

    Full Text Available Here we report a case of adenomatoid odontogenic tumor (AOT in the maxilla in a young girl aged 14 years and its surgical management. We also review the literature and variations in the nomenclature and classifications of this interesting tumor. The review of literature gives an interesting picture regarding terminologies in the past and dilemma in classifying this tumor. The introduction of the name adenomatoid odontogenic tumour has resulted in the simpler and fruitful surgical management like enucleation and curettage with no reports of recurrences. In the past, similar lesion with the terminology like adeno ameloblastoma has resulted in unnecessary mutilating surgery. The conflicting views whether the lesion is being neoplasm or an anomalous hamartomatous growth is also being discussed.

  20. Consortium for Nanomaterials for Aerospace Commerce and Technology (CONTACT)

    Science.gov (United States)

    2013-02-01

    magnetic fields. 9. We have identified and revealed the magneto - elastic coupling in frustrated Co3V2O8 through optical measurements in high magnetic...p. 391. 25. “ Magneto - elastic Coupling in Magnetically Frustrated Co3V2O8,” J. L. Musfeldt, L. I. Vergara, J. Cao, L. C. Tung, Y. J. Wang, F. Yen, Y...orders in the complex phase diagram of Mn1-xFexWO4 through elastic neutron scattering experiments and revealed the important role of magnetic