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Steven Rosenberg

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https://www.readbyqxmd.com/read/28431923/sources-of-racial-disparities-in-hiv-prevalence-in-men-who-have-sex-with-men-in-atlanta-ga-usa-a-modelling-study
#1
Steven M Goodreau, Eli S Rosenberg, Samuel M Jenness, Nicole Luisi, Sarah E Stansfield, Gregorio A Millett, Patrick S Sullivan
BACKGROUND: In the USA, men who have sex men (MSM) are at high risk for HIV, and black MSM have a substantially higher prevalence of infection than white MSM. We created a simulation model to assess the strength of existing hypotheses and data that account for these disparities. METHODS: We built a dynamic, stochastic, agent-based network model of black and white MSM aged 18-39 years in Atlanta, GA, USA, that incorporated race-specific individual and dyadic-level prevention and risk behaviours, network attributes, and care patterns...
April 18, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28416490/preclinical-characterization-of-bet-family-bromodomain-inhibitor-abbv-075-suggests-combination-therapeutic-strategies
#2
Mai H Bui, Xiaoyu Lin, Daniel H Albert, Leiming Li, Lloyd T Lam, Emily J Faivre, Scott Warder, Xiaoli Huang, Denise Wilcox, Cherrie K Donawho, George S Sheppard, Le Wang, Steve Fidanze, John K Pratt, Dachun Liu, Lisa Hasvold, Tamar Uziel, Xin Lu, Fred Kohlhapp, Guowei Fang, Steven W Elmore, Saul H Rosenberg, Keith F McDaniel, Warren M Kati, Yu Shen
ABBV-075 is a potent and selective BET family bromodomain inhibitor that recently entered Phase I clinical trials. Comprehensive preclinical characterization of ABBV-075 demonstrated broad activity across cell lines and tumor models representing a variety of hematological malignancies and solid tumor indications. In most cancer cell lines derived from solid tumors, ABBV-075 triggers prominent G1 cell cycle arrest without extensive apoptosis. In this study, we show that ABBV-075 efficiently triggers apoptosis in acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) cells...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28408606/landscape-of-immunogenic-tumor-antigens-in-successful-immunotherapy-of-virally-induced-epithelial-cancer
#3
Sanja Stevanović, Anna Pasetto, Sarah R Helman, Jared J Gartner, Todd D Prickett, Bryan Howie, Harlan S Robins, Paul F Robbins, Christopher A Klebanoff, Steven A Rosenberg, Christian S Hinrichs
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus-associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens...
April 14, 2017: Science
https://www.readbyqxmd.com/read/28395880/treatment-of-metastatic-uveal-melanoma-with-adoptive-transfer-of-tumour-infiltrating-lymphocytes-a-single-centre-two-stage-single-arm-phase-2-study
#4
Smita S Chandran, Robert P T Somerville, James C Yang, Richard M Sherry, Christopher A Klebanoff, Stephanie L Goff, John R Wunderlich, David N Danforth, Daniel Zlott, Biman C Paria, Arvind C Sabesan, Abhishek K Srivastava, Liqiang Xi, Trinh H Pham, Mark Raffeld, Donald E White, Mary Ann Toomey, Steven A Rosenberg, Udai S Kammula
BACKGROUND: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma...
April 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28377481/characterization-of-an-immunogenic-mutation-in-a-patient-with-metastatic-triple-negative-breast-cancer
#5
Yasmine Assadipour, Nikolaos Zacharakis, Jessica S Crystal, Todd D Prickett, Jared J Gartner, Robert P T Somerville, Hui Xu, Mary A Black, Li Jia, Harshini Chinnasamy, Isaac Kriley, Lily Lu, John R Wunderlich, Zhili Zheng, Yong-Chen Lu, Paul F Robbins, Steven A Rosenberg, Stephanie L Goff, Steven A Feldman
The administration of autologous tumor infiltrating lymphocytes (TIL) can mediate durable tumor regressions in patients with melanoma likely based on the recognition of immunogenic somatic mutations expressed by the cancer. There is limited data regarding the immunogenicity of mutations in breast cancer. We sought to identify immunogenic non-synonymous mutations in a patient with triple-negative breast cancer (TNBC) in order to identify and isolate mutation-reactive TIL for possible use in adoptive cell transfer...
April 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28358128/corrigendum-rare-variants-of-large-effect-in-brca2-and-chek2-affect-risk-of-lung-cancer
#6
Yufei Wang, James D McKay, Thorunn Rafnar, Zhaoming Wang, Maria N Timofeeva, Peter Broderick, Xuchen Zong, Marina Laplana, Yongyue Wei, Younghun Han, Amy Lloyd, Manon Delahaye-Sourdeix, Daniel Chubb, Valerie Gaborieau, William Wheeler, Nilanjan Chatterjee, Gudmar Thorleifsson, Patrick Sulem, Geoffrey Liu, Rudolf Kaaks, Marc Henrion, Ben Kinnersley, Maxime Vallée, Florence Le Calvez-Kelm, Victoria L Stevens, Susan M Gapstur, Wei V Chen, David Zaridze, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Hans E Krokan, Maiken Elvestad Gabrielsen, Frank Skorpen, Lars Vatten, Inger Njølstad, Chu Chen, Gary Goodman, Simone Benhamou, Tonu Vooder, Kristjan Välk, Mari Nelis, Andres Metspalu, Marcin Lener, Jan Lubiński, Mattias Johansson, Paolo Vineis, Antonio Agudo, Francoise Clavel-Chapelon, H Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Kay-Tee Khaw, Mikael Johansson, Elisabete Weiderpass, Anne Tjønneland, Elio Riboli, Mark Lathrop, Ghislaine Scelo, Demetrius Albanes, Neil E Caporaso, Yuanqing Ye, Jian Gu, Xifeng Wu, Margaret R Spitz, Hendrik Dienemann, Albert Rosenberger, Li Su, Athena Matakidou, Timothy Eisen, Kari Stefansson, Angela Risch, Stephen J Chanock, David C Christiani, Rayjean J Hung, Paul Brennan, Maria Teresa Landi, Richard S Houlston, Christopher I Amos
No abstract text is available yet for this article.
March 30, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28356272/choline-and-its-metabolites-are-differently-associated-with-cardiometabolic-risk-factors-history-of-cardiovascular-disease-and-mri-documented-cerebrovascular-disease-in-older-adults
#7
Annie J Roe, Shucha Zhang, Rafeeque A Bhadelia, Elizabeth J Johnson, Alice H Lichtenstein, Gail T Rogers, Irwin H Rosenberg, Caren E Smith, Steven H Zeisel, Tammy M Scott
Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism.Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovascular disease, and cerebrovascular pathology.Design: A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain (n = 296; mean ± SD age: 73 ± 8.1 y) was assessed...
March 29, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28291388/lymphoma-remissions-caused-by-anti-cd19-chimeric-antigen-receptor-t-cells-are-associated-with-high-serum-interleukin-15-levels
#8
James N Kochenderfer, Robert P T Somerville, Tangying Lu, Victoria Shi, Adrian Bot, John Rossi, Allen Xue, Stephanie L Goff, James C Yang, Richard M Sherry, Christopher A Klebanoff, Udai S Kammula, Marika Sherman, Arianne Perez, Constance M Yuan, Tatyana Feldman, Jonathan W Friedberg, Mark J Roschewski, Steven A Feldman, Lori McIntyre, Mary Ann Toomey, Steven A Rosenberg
Purpose T cells genetically modified to express chimeric antigen receptors (CARs) targeting CD19 (CAR-19) have potent activity against acute lymphoblastic leukemia, but fewer results supporting treatment of lymphoma with CAR-19 T cells have been published. Patients with lymphoma that is chemotherapy refractory or relapsed after autologous stem-cell transplantation have a grim prognosis, and new treatments for these patients are clearly needed. Chemotherapy administered before adoptive T-cell transfer has been shown to enhance the antimalignancy activity of adoptively transferred T cells...
March 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28275546/cognitive-behavioral-therapy-increases-amygdala-connectivity-with-the-cognitive-control-network-in-both-mdd-and-ptsd
#9
Haochang Shou, Zhen Yang, Theodore D Satterthwaite, Philip A Cook, Steven E Bruce, Russell T Shinohara, Benjamin Rosenberg, Yvette I Sheline
BACKGROUND: Both major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are characterized by alterations in intrinsic functional connectivity. Here we investigated changes in intrinsic functional connectivity across these disorders as a function of cognitive behavioral therapy (CBT), an effective treatment in both disorders. METHODS: 53 unmedicated right-handed participants were included in a longitudinal study. Patients were diagnosed with PTSD (n = 18) and MDD (n = 17) with a structured diagnostic interview and treated with 12 sessions of manualized CBT over a 12-week period...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28249900/light-elevation-enhances-immune-eradication-of-colon-cancer-metastases
#10
Guilin Qiao, Jianzhong Qin, Nicholas Kunda, Jed F Calata, Dolores L Mahmud, Peter Gann, Yang-Xin Fu, Steven A Rosenberg, Bellur S Prabhakar, Ajay V Maker
The majority of patients with colon cancer will develop advanced disease, with the liver being the most common site of metastatic disease. Patients with increased numbers of tumor-infiltrating lymphocytes in primary colon tumors and liver metastases have improved outcomes. However, the molecular factors that could empower antitumor immune responses in this setting remain to be elucidated. We reported that the immunostimulatory cytokine LIGHT (TNFSF14) in the microenvironment of colon cancer metastases associates with improved patient survival, and here we demonstrate in an immunocompetent murine model that colon tumors expressing LIGHT stimulate lymphocyte proliferation and tumor cell-specific antitumor immune responses...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28224927/an-age-and-sex-specific-gene-expression-score-is-associated-with-revascularization-and-coronary-artery-disease-insights-from-the-prospective-multicenter-imaging-study-for-evaluation-of-chest-pain-promise-trial
#11
Deepak Voora, Adrian Coles, Kerry L Lee, Udo Hoffmann, James A Wingrove, Brian Rhees, Lin Huang, Susan E Daniels, Mark Monane, Steven Rosenberg, Svati H Shah, William E Kraus, Geoffrey S Ginsburg, Pamela S Douglas
BACKGROUND: Identifying predictors of coronary artery disease (CAD)-related procedures and events remains a priority. METHODS: We measured an age- and sex-specific gene expression score (ASGES) previously validated to detect obstructive CAD (oCAD) in symptomatic nondiabetic patients in the PROMISE trial. The outcomes were oCAD (≥70% stenosis in ≥1 vessel or ≥50% left main stenosis on CT angiography [CTA]) and a composite endpoint of death, myocardial infarction, revascularization, or unstable angina...
February 2017: American Heart Journal
https://www.readbyqxmd.com/read/28198830/-final-common-pathway-of-human-cancer-immunotherapy-targeting-random-somatic-mutations
#12
REVIEW
Eric Tran, Paul F Robbins, Steven A Rosenberg
Effective clinical cancer immunotherapies, such as administration of the cytokine IL-2, adoptive cell transfer (ACT) and the recent success of blockade of the checkpoint modulators CTLA-4 and PD-1, have been developed without clear identification of the immunogenic targets expressed by human cancers in vivo. Immunotherapy of patients with cancer through the use of ACT with autologous lymphocytes has provided an opportunity to directly investigate the antigen recognition of lymphocytes that mediate cancer regression in humans...
February 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28144760/routine-computer-tomography-imaging-for-the-detection-of-recurrences-in-high-risk-melanoma-patients
#13
Tristen S Park, Giao Q Phan, James C Yang, Udai Kammula, Marybeth S Hughes, Kasia Trebska-McGowan, Kathleen E Morton, Donald E White, Steven A Rosenberg, Richard M Sherry
BACKGROUND: The use of routine CT imaging for surveillance in asymptomatic patients with cutaneous melanoma is controversial. We report our experience using a surveillance strategy that included CT imaging for a cohort of patients with high-risk melanoma. METHODS: A total of 466 patients with high-risk cutaneous melanoma enrolled in adjuvant immunotherapy trials were followed for tumor progression by physical examination, labs, and CT imaging as defined by protocol...
April 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28093487/a-pilot-trial-of-the-combination-of-vemurafenib-with-adoptive-cell-therapy-in-patients-with-metastatic-melanoma
#14
Drew C Deniger, Mei Li M Kwong, Anna Pasetto, Mark E Dudley, John R Wunderlich, Michelle M Langhan, Chyi-Chia Richard Lee, Steven A Rosenberg
PURPOSE: This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAF(V600) mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma. EXPERIMENTAL DESIGN: A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration...
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28060881/individual-hiv-risk-versus-population-impact-of-risk-compensation-after-hiv-preexposure-prophylaxis-initiation-among-men-who-have-sex-with-men
#15
Samuel M Jenness, Akshay Sharma, Steven M Goodreau, Eli S Rosenberg, Kevin M Weiss, Karen W Hoover, Dawn K Smith, Patrick Sullivan
OBJECTIVES: Risk compensation (RC) could reduce or offset the biological prevention benefits of HIV preexposure prophylaxis (PrEP) among those at substantial risk of infection, including men who have sex with men (MSM). We investigated the potential extent and causal mechanisms through which RC could impact HIV transmission at the population and individual levels. METHODS: Using a stochastic network-based mathematical model of HIV transmission dynamics among MSM in the United States, we simulated RC as a reduction in the probability of condom use after initiating PrEP, with heterogeneity by PrEP adherence profiles and partnership type in which RC occurred...
2017: PloS One
https://www.readbyqxmd.com/read/28042904/the-polyanalgesic-consensus-conference-pacc-recommendations-on-intrathecal-drug-infusion-systems-best-practices-and-guidelines
#16
REVIEW
Timothy R Deer, Jason E Pope, Salim M Hayek, Anjum Bux, Eric Buchser, Sam Eldabe, Jose A De Andrés, Michael Erdek, Dennis Patin, Jay S Grider, Daniel M Doleys, Marilyn S Jacobs, Tony L Yaksh, Lawrence Poree, Mark S Wallace, Joshua Prager, Richard Rauck, Oscar DeLeon, Sudhir Diwan, Steven M Falowski, Helena M Gazelka, Philip Kim, Michael Leong, Robert M Levy, Gladstone McDowell, Porter McRoberts, Ramana Naidu, Samir Narouze, Christophe Perruchoud, Steven M Rosen, William S Rosenberg, Michael Saulino, Peter Staats, Lisa J Stearns, Dean Willis, Elliot Krames, Marc Huntoon, Nagy Mekhail
INTRODUCTION: Pain treatment is best performed when a patient-centric, safety-based philosophy is used to determine an algorithmic process to guide care. Since 2007, the International Neuromodulation Society has organized a group of experts to evaluate evidence and create a Polyanalgesic Consensus Conference (PACC) to guide practice. METHODS: The current PACC update was designed to address the deficiencies and innovations emerging since the previous PACC publication of 2012...
February 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/28028540/ocean-heat-drives-rapid-basal-melt-of-the-totten-ice-shelf
#17
Stephen Rich Rintoul, Alessandro Silvano, Beatriz Pena-Molino, Esmee van Wijk, Mark Rosenberg, Jamin Stevens Greenbaum, Donald D Blankenship
Mass loss from the West Antarctic ice shelves and glaciers has been linked to basal melt by ocean heat flux. The Totten Ice Shelf in East Antarctica, which buttresses a marine-based ice sheet with a volume equivalent to at least 3.5 m of global sea-level rise, also experiences rapid basal melt, but the role of ocean forcing was not known because of a lack of observations near the ice shelf. Observations from the Totten calving front confirm that (0.22 ± 0.07) × 10(6) m(3) s(-1) of warm water enters the cavity through a newly discovered deep channel...
December 2016: Science Advances
https://www.readbyqxmd.com/read/27978720/competitive-1-2-c-atom-shifts-in-the-strained-carbene-spiro-3-3-hept-1-ylidene-explained-by-distinct-ring-puckered-conformers
#18
Murray G Rosenberg, Theodor Schrievers, Udo H Brinker
Spiro[3.3]hept-1-ylidene is a markedly strained carbene reaction intermediate that was generated by high-vacuum flash pyrolysis (HVFP) of the corresponding p-tosylhydrazone sodium salt. Five hydrocarbons were produced from the Bamford-Stevens reactant in 82% overall yield. The carbene undergoes two [1,2]-sigmatropic rearrangements via competing 1,2-C atom shifts. Ring-contraction yields cyclopropylidenecyclobutane, while ring-expansion affords bicyclo[3.2.0]hept-1(5)-ene. The ring contraction is regiospecific despite the formation of some 1-methylenespiro[2...
December 16, 2016: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/27965307/dual-specific-chimeric-antigen-receptor-t-cells-and-an-indirect-vaccine-eradicate-a-variety-of-large-solid-tumors-in-an-immunocompetent-self-antigen-setting
#19
Clare Y Slaney, Bianca von Scheidt, Alexander J Davenport, Paul Beavis, Jennifer A Westwood, Sherly Mardiana, David Tscharke, Sarah Ellis, H Miles Prince, Joseph A Trapani, Ricky W Johnstone, Mark J Smyth, Michele W L Teng, Aesha Ali, Zhiya Yu, Steven A Rosenberg, Nicholas P Restifo, Paul J Neeson, Phillip K Darcy, Michael H Kershaw
PURPOSE: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. EXPERIMENTAL DESIGN: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100)...
December 13, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27959684/t-cell-transfer-therapy-targeting-mutant-kras-in-cancer
#20
Eric Tran, Paul F Robbins, Yong-Chen Lu, Todd D Prickett, Jared J Gartner, Li Jia, Anna Pasetto, Zhili Zheng, Satyajit Ray, Eric M Groh, Isaac R Kriley, Steven A Rosenberg
We identified a polyclonal CD8+ T-cell response against mutant KRAS G12D in tumor-infiltrating lymphocytes obtained from a patient with metastatic colorectal cancer. We observed objective regression of all seven lung metastases after the infusion of approximately 1.11×10(11) HLA-C*08:02-restricted tumor-infiltrating lymphocytes that were composed of four different T-cell clonotypes that specifically targeted KRAS G12D. However, one of these lesions had progressed on evaluation 9 months after therapy. The lesion was resected and found to have lost the chromosome 6 haplotype encoding the HLA-C*08:02 class I major histocompatibility complex (MHC) molecule...
December 8, 2016: New England Journal of Medicine
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