tbuckley/cabot-search huggingface dataset:
Randomized, double-blind, vector-controlled study of targeted immunotherapy in patients (pts) with hormone-refractory prostate cancer (HRPC)
Authors: P. W. Kantoff, L. M. Glode, S. I. Tannenbaum, D. L. Bilhartz, W. G. Pittman, T. J. Schuetz
Journal: Journal of Clinical Oncology (2006)

2501 Background: Therapeutic vaccines for prostate cancer have yielded encouraging data in uncontrolled Phase 1 and 2 studies. PROSTVAC-VF comprises 2 recombinant viral vectors each containing genes encoding the prostate-specific antigen (PSA) gene modified to optimize antigen presentation in HLA-A2+ pts and 3 T-cell costimulatory molecules (B7.1, LFA3, and ICAM-1 [TRICOM]). These vectors are administered in a heterologous prime-boost regimen with concurrent low-dose GM-CSF to enhance recruitment of antigen-presenting cells to the immunization site. Here we report results of a Phase 2 study in pts with metastatic HRPC. Methods: In this randomized, double-blind, controlled study, pts were randomized 2:1 to receive either PROSTVAC-VF plus GM-CSF or Control (empty vectors plus GM-CSF placebo) for 24 weeks. Eligible pts had rising PSA despite castrate testosterone levels and measurable, asymptomatic or non-narcotic-dependent metastases (positive bone scan or lymph node metastases on abdominal-pelvic CT scan). The primary endpoint is progression-free survival (PFS), with progression defined as appearance of new lesions on bone scan or RECIST-defined progression of nodal metastases. The planned sample size was 120 pts. The study was designed to detect a difference of 38% vs 12% PFS at Week 24 with a 2-sided α of 0.05 and 80% power. An independent Data Monitoring Committee evaluated safety data quarterly. Results: 125 pts were enrolled. Demographics are available for 122 pts (mean age, 73.3 years [range, 52–94]; ∼11% African American). Common adverse events (AEs) in 106 evaluable pts (blinded as of Jan 2006) included immunization site reactions (73%), fatigue (26%), fever (14%), and nausea (13%). The majority were of Grade 1/2 severity. Serious AEs attributed to immunization included 1 thrombotic thrombocytopenic purpura (TTP) event. Conclusions: A large, randomized, controlled study of therapeutic immunization with PROSTVAC-VF in 125 pts with metastatic HRPC has been completed. The therapy is well tolerated and findings are consistent with Phase 1 results, but also included a single case of TTP. Full efficacy data collection is ongoing. [Table: see text]
A phase 2 study of ARQ 501 in combination with gemcitabine in adult patients with treatment naïve, unresectable pancreatic adenocarcinoma
Authors: H. T. Khong, L. Dreisbach, H. L. Kindler, D. F. Trent, K. G. Jeziorski, I. Bonderenko, T. Popiela, D. M. Yagovane, G. Dombal
Journal: Journal of Clinical Oncology (2007)

15017 Background: ARQ 501 is a DNA damage checkpoint pathway activator whose effect is to induce selective cell death in cancer cells, independent of the tumor cell’s p53 status. Current evidence implicates a rapid and sustained increase of the pro-apoptotic protein E2F-1 by ARQ 501 as the mechanism of action. Cancer cells are selectively affected due to their pre-existing DNA damage. Induction of E2F-1 in combination with gemcitabine demonstrated potent anti-tumor activity in xenografts of human pancreatic cancer (PACA-2). A recommended phase 2 dose of 400 mg/m 2 of ARQ 501 and 800 mg/m 2 gemcitabine was identified. Methods: A Phase 2 study in adult patients with treatment naïve, non-resectable adenocarcinoma of the pancreas was initiated to assess the effect of ARQ 501 and gemcitabine on ORR in approximately 66 patients. Cycles consisting of weekly ARQ 501 (400mg/m 2 ) and gemcitabine (800 mg/m 2 were repeated every 4 weeks until progression, unacceptable toxicity, or another discontinuation criterion was met. Results: 73 patients were enrolled, with 58 treated to date with at least one infusion. Data is available for 27 patients (16M/11F, median age, 63 years). Of these 27, 5 did not reach a post baseline assessment (3 deaths, 2 PD prior to week 8), 20 are evaluable for response at eight weeks (1 PR, 12 SD of 8–24+ weeks), 7 PD) and 2 have yet to be assessed but are active. Tumor regressions have been observed in 6/20 patients assessed to date. This includes 1 PR, 4 MR (14.3% - 24%) and 1 patient with significant reduction (29.6%) in pancreatic lesions although new superficial liver lesions were observed. Adverse events (N=235) the most common being: anemia (54, 22%), hemolysis (17, 7%), fatigue (15, 6%), edema (7, 3%), and nausea (5, 2%). Conclusions: ARQ 501 has been administered to 58 patients with treatment-naïve, non-resectable adenocarcinoma of the pancreas. Enrollment is complete and early efficacy data is encouraging. A high proportion of patients (13/20) have achieved a minimum SD at the first tumor evaluation. In addition, objective tumor regressions has been observed in this study, providing preliminary confirmation of the utility of induction of E2F-1 in combination with gemcitabine. [Table: see text]
The Outcome of Patients (pts) with Acute Promyelocytic Leukemia (APL) Who Fail Both All–Trans-retinoic Acid (ATRA) and Arsenic Trioxide (ATO).
Authors: Ravin Jain Garg, Hagop Kantarjian, Meetu Agrawal, Farhad Ravandi, Gautam Borthakur, Steven M. Kornblau, Alessandra Ferrajoli, Guillermo Garcia-Manero, Susan O'Brien, Jorge Cortes
Journal: Blood (2009)
A Meta-Analysis of Nodular Sclerosis Hodgkin Lymphoma Identifies Risk Loci at 6p21.32
Authors: Wendy Cozen, Dalin Li, Timothy Best, David J. Van Den Berg, Andrew Skol, Victoria K. Cortessis, Thomas M Mack, Sally L. Glaser, Fred Schumacher, Lawrence Weiss, Bharat N. Nathwani, Amie Hwang, Smita Bhatia, Louise C Strong, Leslie L. Robison, David V Conti, Kenan Onel
Journal: Blood (2010)
Anti-Tumor Cytotoxicity of γδ T Cells Expanded from Blood Cells of Myeloma and Leukemia Patients Against Self Tumor Cells — Enhancement of the Anti-Tumor Cytotoxicity by Type I IFN, Dendritic Cells, and Activated αβ T Cells.
Authors: Anri Saito, Miwako Narita, Norihiro Watanabe, Nozomi Tochiki, Noriyuki Satoh, Toshio Yano, Jun Takizawa, Tatsuo Furukawa, Ken Toba, Yoshifusa Aizawa, Masuhiro Takahashi
Journal: Blood (2007)
Elevated Serum Hepcidin in Patients with AML Prior to and After Allogeneic Hematopoietic Cell Transplantation Does Not Correlate with Transfusional Body Iron, HFE Genotype or Graft Versus Host Disease and May Protect From Excessive Parenchymal Iron Loading.
Authors: Ann-Kathrin Eisfeld, Mark Westerman, Rainer Krahl, Sabine Leiblein, Uwe Gerd Liebert, Marianne Hehme, Dietger Niederwieser, Haifa Kathrin Al-Ali
Journal: Blood (2009)
GW26-e3901 Prevalence and risk factors of hypertension among pre- and post-menopausal women: a cross-sectional study in a rural area of northeast China
Authors: Ying Zhou, Xinghu Zhou, Xiaofan Guo, Guozhe Sun, Zhao Li, Liqiang Zheng, Hongmei Yang, Shasha Yu, Wenna Li, Lu Zhou, Yingxian Sun
Journal: Journal of the American College of Cardiology (2015)
Abstract A08: Imaging in cancer immunology: Phenotyping of multiple immune cell subsets in-situ in FFPE tissue sections
Authors: James R. Mansfield, Clifford C. Hoyt, Edward Stack, Steven H. Lin, Michael Feldman, Carlo Bifulco, Bernard A. Fox
Journal: Cancer Research (2016)

Abstract There has been a rapid grown in the field of tumor immunobiology in recent years as a result of recent successes in cancer immunotherapies, and it is becoming clear that immune cells play many sometimes conflicting roles in the tumor microenvironment. However, obtaining phenotypic information about the various immune cells that play these roles in and around the tumor has been a challenge. Existing methods can either deliver phenotypic information on homogenous samples (e.g., flow cytometry or PCR) or morphologic information on single immunomarkers (standard IHC). We present here a methodology for delivering quantitative per-cell marker expression and phenotyping, analogous to that obtained from flow cytometry, but from cells imaged in situ in FFPE tissue sections. This methodology combines: the sequential multi-marker labeling of up to 6 antigens using antibodies all of the same species in a single section; automated multispectral imaging (MSI) to remove the typically problematic FFPE tissue autofluorescence and correct cross-talk between fluorescent channels; and an automated image analysis that can quantitate the per-cell marker expression, determine the cellular phenotype, count these cells separately in the tumor compartment and in the stroma and provide high-resolution images of their distributions. We present here several examples of this new methodology in breast, lung and head and neck cancers. Each application example will show 6-plex multiplexed staining, per-cell quantitation of each marker and multi-marker cellular phenotyping from multispectral images of standard clinical biopsy sections, as well as methods to explore the spatial distributions of the phenotyped cells in and around the tumor. Citation Format: James R. Mansfield, Clifford C. Hoyt, Edward Stack, Steven H. Lin, Michael Feldman, Carlo Bifulco, Bernard A. Fox. Imaging in cancer immunology: Phenotyping of multiple immune cell subsets in-situ in FFPE tissue sections. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A08.
A health care navigation tool assesses asthma self-management and health literacy
Authors: Luzmercy Perez, Knashawn H. Morales, Heather Klusaritz, Xiaoyan Han, Jingru Huang, Marisa Rogers, Ian M. Bennett, Cynthia S. Rand, Grace Ndicu, Andrea J. Apter
Journal: Journal of Allergy and Clinical Immunology (2016)
INR and Vitamin K Dependent Coagulation Factor Fluctuation during Warfarin Initiation and Stable Therapy in Patients Dosed with the Fiix-Prothrombin Time or the Quick Prothrombin Time. the Fiix Trial
Authors: Brynja R. Gudmundsdottir, Petur I. Jonsson, Pall T. Onundarson
Journal: Blood (2014)
Dopaminergic Enhancement of Striatal Response to Reward in Major Depression
Authors: Roee Admon, Roselinde H. Kaiser, Daniel G. Dillon, Miranda Beltzer, Franziska Goer, David P. Olson, Gordana Vitaliano, Diego A. Pizzagalli
Journal: American Journal of Psychiatry (2016)

Major depressive disorder is characterized by reduced reward-related striatal activation and dysfunctional reward learning, putatively reflecting decreased dopaminergic signaling. The goal of this study was to test whether a pharmacological challenge designed to facilitate dopaminergic transmission can enhance striatal responses to reward and improve reward learning in depressed individuals.In a double-blind placebo-controlled design, 46 unmedicated depressed participants and 43 healthy control participants were randomly assigned to receive either placebo or a single low dose (50 mg) of the D2/D3 receptor antagonist amisulpride, which is believed to increase dopamine signaling through presynaptic autoreceptor blockade. To investigate the effects of increased dopaminergic transmission on reward-related striatal function and behavior, a monetary incentive delay task (in conjunction with functional MRI) and a probabilistic reward learning task were administered at absorption peaks of amisulpride.Depressed participants selected previously rewarded stimuli less frequently than did control participants, indicating reduced reward learning, but this effect was not modulated by amisulpride. Relative to depressed participants receiving placebo (and control participants receiving amisulpride), depressed participants receiving amisulpride exhibited increased striatal activation and potentiated corticostriatal functional connectivity between the nucleus accumbens and the midcingulate cortex in response to monetary rewards. Stronger corticostriatal connectivity in response to rewards predicted better reward learning among depressed individuals receiving amisulpride as well as among control participants receiving placebo.Acute enhancement of dopaminergic transmission potentiated reward-related striatal activation and corticostriatal functional connectivity in depressed individuals but had no behavioral effects. Taken together, the results suggest that targeted pharmacological treatments may normalize neural correlates of reward processing in depression; despite such acute effects on neural function, behavioral modification may require more chronic exposure. This is consistent with previous reports that antidepressant effects of amisulpride in depression emerged after sustained administration.
GW26-e2453 Beneficial Effect of Lycopene on Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress in Neonatal Mouse Cardiomyocytes
Authors: Jiqian Xu, Houxiang Hu, Bin Chen, Rongchuan Yue, Zhou Zhou, Lei Xu, Shuang Zhang, Chunyan Tan, Zhengping Yu
Journal: Journal of the American College of Cardiology (2015)
The Local Edge Machine: inference of dynamic models of gene regulation
Authors: Kevin A. McGoff, Xin Guo, Anastasia Deckard, Christina M. Kelliher, Adam R. Leman, Lauren J. Francey, John B. Hogenesch, Steven B. Haase, John L. Harer
Journal: Genome biology (2016)

We present a novel approach, the Local Edge Machine, for the inference of regulatory interactions directly from time-series gene expression data. We demonstrate its performance, robustness, and scalability on in silico datasets with varying behaviors, sizes, and degrees of complexity. Moreover, we demonstrate its ability to incorporate biological prior information and make informative predictions on a well-characterized in vivo system using data from budding yeast that have been synchronized in the cell cycle. Finally, we use an atlas of transcription data in a mammalian circadian system to illustrate how the method can be used for discovery in the context of large complex networks.
Chemical Genomics Reveals JAK STAT Activation As a Mechanism of Resistance to HDAC Inhibitors in B Cell Lymphomas
Authors: Matthew S. McKinney, Anne W Beaven, Andrea Moffitt, Jason Landon Smith, Eric Lock, Dereje Jima, Jane Healy, Guojie Li, Adrienne Greenough, Cassandra L Love, Xiao Yi Yang, David Dunson, Herbert Kim Lyerly, Leon Bernal-Mizrachi, Randy D. Gascoyne, Sandeep S. Dave
Journal: Blood (2014)
Activity of cediranib (AZD2171) in patients (pts) with previously untreated metastatic renal cell cancer (RCC). A phase II trial of the PMH Consortium
Authors: S. S. Sridhar, M. J. Mackenzie, S. J. Hotte, S. D. Mukherjee, C. Kollmannsberger, M. A. Haider, E. X. Chen, L. Wang, R. Srinivasan, S. P. Ivy, M. J. Moore
Journal: Journal of Clinical Oncology (2008)

5047 Background: Cediranib (AZD2171) is an oral highly potent, selective pan-VEGFR tyrosine kinase inhibitor expected to show activity in metastatic RCC, where other agents of its class, sorafenib and sunitinib already have FDA approval. Methods: Pts with advanced untreated RCC were enrolled in this multicenter, open-label phase II study. Eligibility criteria included measurable disease, ECOG performance status of 0–2, and adequate organ function. All pts received a starting dose of 45 mg orally daily, titrated according to tolerance. The primary endpoint was RECIST-defined objective response (OR). Pts underwent radiographic staging at baseline and every 8wks and were treated until progressive disease or unacceptable toxicity. Secondary endpoints were median and 6mo PFS, MS, OS, safety, tolerability and PK evaluation. Exploratory endpoints included changes in DCE-MRI parameters, and correlative markers. Results: Forty-three patients have now been enrolled. Median age was 62 (range 44–83); PS 0:1 (21:22); and 34 pts (79%) were male. 32 patients are evaluable for response, 4 are inevaluable, and 7 are too early. Partial response was observed in 12/32 (38%) pts (95% CI: 21–56%), stable disease in 15/32 (47%) pts (95%CI: 29–65%), and progressive disease in 5/32 (16%) pts (95%CI: 5–33%). Overall tumor control rate was 27/32 or 84% (95% CI: 67–95%). Median PFS was 8.7 months (95%CI: 5.1-not reached). 6-month progression free proportion was 63% (95%CI 42–77%). Treatment-related grade 3 or greater AEs included hypertension (13pts), fatigue (11pts), joint pain (5pts), abdominal pain (2pts) and dyspnea (5pts). Currently 19pts remain on study. Conclusions: Cediranib has substantial antitumor activity, with tumor control rates of 84% in pts with previously untreated advanced RCC. The real question will relate to ideal sequencing of these new targeted agents and determining the best imaging modality to measure their effect. Contracts: N01CM17107, N01CM62203 No significant financial relationships to disclose.
A novel strategy based on genomics and specific PCR reveals how a multidrug-resistant Mycobacterium tuberculosis strain became prevalent in Equatorial Guinea 15 years after its emergence
Authors: L. Pérez-Lago, S. Izco, M. Herranz, G. Tudó, M. Carcelén, I. Comas, O. Sierra, J. González-Martín, M.J. Ruiz-Serrano, J. Eyene, E. Bouza, D. García de Viedma
Journal: Clinical Microbiology and Infection (2016)
Genome-Wide Association Study Identifies PNPLA3 I148M Variant Associated with Elevated Transaminase Levels after Induction Therapy in Pediatric ALL Patients
Authors: Christian A. Fernandez, Colton Smith, Wenjian Yang, Chengcheng Liu, Laura B. Ramsey, Seth E. Karol, Ching-Hon Pui, William E. Evans, Sima Jeha, Mary V. Relling
Journal: Blood (2015)
Stimulation of T Cells by Lenalidomide Involves Putative Lenalidomide Binding Proteins CD3-Epsilon-Associated Protein and GDP-Mannose Pyrophosphorylase a
Authors: Ani ta K Gandhi, Audrey Rogovitz, Antonia Lopez-Girona, Derek Mendy, Lisa Morrison, Weilin Xie, Peter H Schafer
Journal: Blood (2008)
Characterization of Anti-Human GPVI Autoantibodies Mediating Persistent Target Immnunodepletion over a 15-Year Period.
Authors: Hiroshi Takayama, Yoshitaka Hosaka, Kazuyuki Nakayama, Kamon Shirakawa, Tetsushi Kawahara, Katsuki Naitoh, Mikihiko Shinozaki, Motoyasu Honda, Toru Yamakawa, Shoji Furusako
Journal: Blood (2005)
Thrombin Induces Apoptosis in Human and Rat Podocytes in a Protease Activated Receptor (PAR)-Dependent Manner
Authors: Ruchika Sharma, Amanda P Waller, Adam Guess, Shipra Agrawal, Berend Isermann, William E. Smoyer, Marvin T. Nieman, Bryce A. Kerlin
Journal: Blood (2014)
Codanin-1 Binds to Key Erythroid Genes and Its Knockdown Coupled with Ectopic Mutant Expression Recapitulates the Congenital Dyserythropoietic Anemia Type I (CDA I) Phenotype
Authors: Linette Bosques, Caroline Tang, Diane Krause, Sherman M. Weissman, Patrick G Gallagher, Mitchell J. Weiss, Hannah Tamary, Gary M. Kupfer
Journal: Blood (2014)
Short‐duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial
Authors: Eric Lawitz, Fred Poordad, Julio A. Gutierrez, Jennifer T. Wells, Carmen E. Landaverde, Barbara Evans, Anita Howe, Hsueh‐Cheng Huang, Jerry Jing Li, Peggy Hwang, Frank J. Dutko, Michael Robertson, Janice Wahl, Eliav Barr, Barbara Haber
Journal: Hepatology (2016)

Direct‐acting antiviral agents (DAAs) represent the standard of care for patients with hepatitis C virus (HCV) infection. Combining DAAs with different mechanisms may allow for shorter treatment durations that are effective across multiple genotypes. The aim of the C‐SWIFT study was to identify the minimum effective treatment duration across multiple genotypes. C‐SWIFT was an open‐label, single‐center trial in treatment‐naïve patients with chronic HCV genotype (GT)1 or 3 infection. All patients received elbasvir (EBR) 50 mg/grazoprevir (GZR) 100 mg with sofosbuvir (SOF) 400 mg for 4‐12 weeks. Patients with GT1 infection who failed therapy were eligible for retreatment with EBR/GZR+SOF and ribavirin for 12 weeks. The primary efficacy endpoint was sustained virological response [SVR]12 (SVR of HCV RNA &lt;15 IU/mL 12 weeks after the end of therapy). Rates of SVR12 were 32% (10 of 31) and 87% (26 of 30) in patients without cirrhosis with GT1 infection treated for 4 and 6 weeks and 80% (16 of 20) and 81% (17 of 21) in GT1‐infected patients with cirrhosis treated for 6 and 8 weeks. Among GT3‐infected patients without cirrhosis, SVR12 was 93% (14 of 15) and 100% (14 of 14) after 8 and 12 weeks. SVR12 in GT3‐infected patients with cirrhosis was 83% (10 of 12) after 12 weeks of treatment. Twenty‐three GT1‐infected patients who relapsed following initial treatment completed retreatment; all achieved SVR12. In the initial treatment phase, there was one serious adverse event of pneumonia, which led to treatment discontinuation, and during retreatment, 1 patient discontinued ribavirin because of pruritus. Conclusion : Data from this study support the use of 8‐week treatment regimens that maintain high efficacy, even for patients with HCV GT3 infection. Retreatment of patients who failed short‐duration therapy was achieved through extended treatment duration and addition of ribavirin. (H epatology 2017;65:439‐450).
QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS
Authors: Darcy B. Wilson, Peter C. Nowell
Journal: The Journal of Experimental Medicine (1970)

Studies were designed to provide some explanation for the unexpectedly large proportion (2%) of parental rat strain peripheral blood lymphocytes that are reactive in the mixed lymphocyte interaction (MLI) to a strong homologous transplantation isoantigen(s) present on cells from an F1 donor. The possibilities considered involve nonspecific activation and multispecific reactivity on the part of the responding cells. The essential findings of this study were: (a) In 3-way mixed cultures, lymphocytes obtained from tolerant animals were not "recruited" to proliferate in the presence of cells from normal, isologous donors which were in the process of responding to F1 cells bearing the tolerance-inducing antigens. With the use of chromosome markers and normal and tolerant parental strain donors of different sexes, the responsive cells were identified and proved to be derived from the normal and not the tolerant donor. (b) The magnitude of the proliferative response is increased additively when potentially reactive cells are exposed to two antigen systems simultaneously. On the other hand, doubling the "gene-dosage" of the genetic determinants of the H isoantigens employed had no effect on the responding cells. (c) A state of induced immunologic tolerance to one H isoantigen system did not alter the response capacity of cells from such a donor to an alternative antigen system. (d) Mixed cultures of heterologous cells from human and rat donors displayed a proliferative response which was less than that of homologous mixed cultures from human or rat donors. Prior sensitization of rat donors with human cells, however, greatly increased the mitotic activity of rat lymphocytes stimulated with human cells. These results suggest that the large number of responsive cells in the MLI do not include a significant number recruited or activated in some nonspecific manner. Rather, they appear to be fully specific in their response capacities so that a given lymphocyte does not react to a multiplicity of different antigens. The degree of proliferation depends on the number of different antigen systems presented to the responding population and not on the number of genetic determinants or "gene dosage" of a given isoantigen system. Finally, on a cell-for-cell basis, the peripheral blood lymphocyte population contains more cells reactive to histocompatibility isoantigens within the species than to heterologous antigens of a different species.