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https://www.readbyqxmd.com/read/29146441/combining-immunotherapies-for-the-treatment-of-prostate-cancer
#1
REVIEW
Jason M Redman, James L Gulley, Ravi A Madan
Sipuleucel-T, a therapeutic dendritic-cell vaccine, was Food and Drug Administration-approved for prostate cancer in 2010. No new immunotherapies for prostate cancer have been approved since. However, novel agents and combination approaches offer great promise for improving outcomes for prostate cancer patients. Here we review the latest developments in immunotherapy for prostate cancer. Sipuleucel-T has demonstrated a survival advantage of 4.1 months in metastatic castration-resistant prostate cancer. PSA-TRICOM (PROSTVAC), a prostate-specific antigen-targeted vaccine platform, showed evidence of clinical and immunologic efficacy in early-phase clinical trials, and results from a phase III trial in advanced disease are pending...
December 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29123964/a-novel-bifunctional-anti-pd-l1-tgf-%C3%AE-trap-fusion-protein-m7824-efficiently-reverts-mesenchymalization-of-human-lung-cancer-cells
#2
Justin M David, Charli Dominguez, Kristen K McCampbell, James L Gulley, Jeffrey Schlom, Claudia Palena
Mesenchymalization is a cellular and molecular program in which epithelial cells progressively lose their well-differentiated phenotype and adopt mesenchymal characteristics. Tumor mesenchymalization occurs during the progression of cancer to metastatic disease, and is also associated with resistance to multiple therapeutics, including killing by cytotoxic immune cells. Furthermore, tumor cells can evade immune destruction by upregulating the checkpoint molecule PD-L1, and emerging research has found higher PD-L1 expression in mesenchymalized tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29118215/adolescence-and-reward-making-sense-of-neural-and-behavioral-changes-amid-the-chaos
#3
Deena M Walker, Margaret R Bell, Cecilia Flores, Joshua M Gulley, Jari Willing, Matthew J Paul
Adolescence is a time of significant neural and behavioral change with remarkable development in social, emotional, and cognitive skills. It is also a time of increased exploration and risk-taking (e.g., drug use). Many of these changes are thought to be the result of increased reward-value coupled with an underdeveloped inhibitory control, and thus a hypersensitivity to reward. Perturbations during adolescence can alter the developmental trajectory of the brain, resulting in long-term alterations in reward-associated behaviors...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28855356/phase-i-study-of-a-poxviral-tricom-based-vaccine-directed-against-the-transcription-factor-brachyury
#4
Christopher R Heery, Claudia Palena, Sheri McMahon, Renee N Donahue, Lauren M Lepone, Italia Grenga, Ulrike Dirmeier, Lisa Cordes, Jenn Marté, William Dahut, Harpreet Singh, Ravi A Madan, Romaine I Fernando, Duane H Hamilton, Jeffrey Schlom, James L Gulley
Purpose: The transcription factor brachyury has been shown in preclinical studies to be a driver of the epithelial-to-mesenchymal transition (EMT) and resistance to therapy of human tumor cells. This study describes the characterization of a Modified Vaccinia Ankara (MVA) vector-based vaccine expressing the transgenes for brachyury and three human costimulatory molecules (B7.1, ICAM-1, and LFA-3, designated TRICOM) and a phase I study with this vaccine.Experimental Design: Human dendritic cells (DC) were infected with MVA-brachyury-TRICOM to define their ability to activate brachyury-specific T cells...
November 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28837181/avelumab-for-the-treatment-of-metastatic-merkel-cell-carcinoma
#5
REVIEW
L M Cordes, J L Gulley
Avelumab is a promising new therapeutic agent for patients with metastatic Merkel cell carcinoma, a rare and aggressive type of neuroendocrine tumor of the skin. Until the recent approval of avelumab (Bavencio), no therapies were approved by the U.S. Food and Drug Administration for the treatment of metastatic Merkel cell carcinoma. In a recent trial, avelumab, an anti-programmed death ligand-1 antibody, demonstrated an objective response in 28 of 88 patients (31.8% [95.9% CI, 21.9-43.1]) with advanced, chemotherapy-refractory Merkel cell carcinoma...
July 2017: Drugs of Today
https://www.readbyqxmd.com/read/28725428/highlights-of-the-31st-annual-meeting-of-the-society-for-immunotherapy-of-cancer-sitc-2016
#6
REVIEW
James L Gulley, Elizabeth A Repasky, Laura S Wood, Lisa H Butterfield
Therapeutic efforts to engage the immune system against cancer have yielded exciting breakthroughs and a growing list of approved immune-based agents across a variety of disease states. Despite the early successes and durable responses associated with treatments such as immune checkpoint inhibition, there is still progress to be made in the field of cancer immunotherapy. The 31st annual meeting of the Society for Immunotherapy of Cancer (SITC 2016), which took place November 11-13, 2016 in National Harbor, Maryland, showcased the latest advancements in basic, translational, and clinical research focused on cancer immunology and immunotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28716068/highlights-of-the-31st-annual-meeting-of-the-society-for-immunotherapy-of-cancer-sitc-2016
#7
REVIEW
James L Gulley, Elizabeth A Repasky, Laura S Wood, Lisa H Butterfield
Therapeutic efforts to engage the immune system against cancer have yielded exciting breakthroughs and a growing list of approved immune-based agents across a variety of disease states. Despite the early successes and durable responses associated with treatments such as immune checkpoint inhibition, there is still progress to be made in the field of cancer immunotherapy. The 31st annual meeting of the Society for Immunotherapy of Cancer (SITC 2016), which took place November 11-13, 2016 in National Harbor, Maryland, showcased the latest advancements in basic, translational, and clinical research focused on cancer immunology and immunotherapy...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28663235/immunotherapy-of-prostate-cancer-facts-and-hopes
#8
REVIEW
Marijo Bilusic, Ravi A Madan, James L Gulley
In the last few years, immunotherapy has become an important cancer treatment modality, and although the principles of immunotherapy have evolved over many decades, the FDA approvals of sipuleucel-T and ipilimumab began a new wave in immuno-oncology. Despite the current enthusiasm, it is unlikely that any of the immunotherapeutics alone can dramatically change prostate cancer outcomes, but combination strategies are more promising and provide a reason for optimism. Several completed and ongoing studies have shown that the combination of cancer vaccines or checkpoint inhibitors with different immunotherapeutic agents, hormonal therapy (enzalutamide), radiotherapy (radium 223), DNA-damaging agents (olaparib), or chemotherapy (docetaxel) can enhance immune responses and induce more dramatic, long-lasting clinical responses without significant toxicity...
November 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28653584/immunotherapy-biomarkers-2016-overcoming-the-barriers
#9
James L Gulley, Jay A Berzofsky, Marcus O Butler, Alessandra Cesano, Bernard A Fox, Sacha Gnjatic, Sylvia Janetzki, Shyam Kalavar, Vaios Karanikas, Samir N Khleif, Ilan Kirsch, Peter P Lee, Cristina Maccalli, Holden Maecker, Jeffrey Schlom, Barbara Seliger, Janet Siebert, David F Stroncek, Magdalena Thurin, Jianda Yuan, Lisa H Butterfield
This report summarizes the symposium, 'Immunotherapy Biomarkers 2016: Overcoming the Barriers', which was held on April 1, 2016 at the National Institutes of Health in Bethesda, Maryland. The symposium, cosponsored by the Society for Immunotherapy of Cancer (SITC) and the National Cancer Institute (NCI), focused on emerging immunotherapy biomarkers, new technologies, current hurdles to further progress, and recommendations for advancing the field of biomarker development.
March 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28644303/prostate-cancer-immunotherapy-the-path-forward
#10
Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: To provide an overview of current strategies being investigated in the development of immunotherapy in prostate cancer. RECENT FINDINGS: Development of immunotherapy in prostate cancer actually began in 2010 with FDA approval of sipuleucel-T. Given that immune checkpoint inhibitor trials have either been negative at the phase III level or underwhelming in smaller studies, it is likely that combination strategies will be required to further maximize the impact immune-based therapies on the clinical course of the disease...
September 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28534538/prostate-cancer-better-vistas-ahead-potential-and-pitfalls-of-immunotherapy
#11
Ravi A Madan, James L Gulley
No abstract text is available yet for this article.
August 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28514440/extreme-hydrothermal-conditions-at-an-active-plate-bounding-fault
#12
Rupert Sutherland, John Townend, Virginia Toy, Phaedra Upton, Jamie Coussens, Michael Allen, Laura-May Baratin, Nicolas Barth, Leeza Becroft, Carolin Boese, Austin Boles, Carolyn Boulton, Neil G R Broderick, Lucie Janku-Capova, Brett M Carpenter, Bernard Célérier, Calum Chamberlain, Alan Cooper, Ashley Coutts, Simon Cox, Lisa Craw, Mai-Linh Doan, Jennifer Eccles, Dan Faulkner, Jason Grieve, Julia Grochowski, Anton Gulley, Arthur Hartog, Jamie Howarth, Katrina Jacobs, Tamara Jeppson, Naoki Kato, Steven Keys, Martina Kirilova, Yusuke Kometani, Rob Langridge, Weiren Lin, Timothy Little, Adrienn Lukacs, Deirdre Mallyon, Elisabetta Mariani, Cécile Massiot, Loren Mathewson, Ben Melosh, Catriona Menzies, Jo Moore, Luiz Morales, Chance Morgan, Hiroshi Mori, Andre Niemeijer, Osamu Nishikawa, David Prior, Katrina Sauer, Martha Savage, Anja Schleicher, Douglas R Schmitt, Norio Shigematsu, Sam Taylor-Offord, Damon Teagle, Harold Tobin, Robert Valdez, Konrad Weaver, Thomas Wiersberg, Jack Williams, Nick Woodman, Martin Zimmer
Temperature and fluid pressure conditions control rock deformation and mineralization on geological faults, and hence the distribution of earthquakes. Typical intraplate continental crust has hydrostatic fluid pressure and a near-surface thermal gradient of 31 ± 15 degrees Celsius per kilometre. At temperatures above 300-450 degrees Celsius, usually found at depths greater than 10-15 kilometres, the intra-crystalline plasticity of quartz and feldspar relieves stress by aseismic creep and earthquakes are infrequent...
June 1, 2017: Nature
https://www.readbyqxmd.com/read/28477372/adcc-employing-an-nk-cell-line-hank-expressing-the-high-affinity-cd16-allele-with-avelumab-an-anti-pd-l1-antibody
#13
Caroline Jochems, James W Hodge, Massimo Fantini, Kwong Y Tsang, Amanda J Vandeveer, James L Gulley, Jeffrey Schlom
NK-92 cells, and their derivative, designated aNK, were obtained from a patient with non-Hodgkin lymphoma. Prior clinical studies employing adoptively transferred irradiated aNK cells have provided evidence of clinical benefit and an acceptable safety profile. aNK cells have now been engineered to express IL-2 and the high affinity (ha) CD16 allele (designated haNK). Avelumab is a human IgG1 anti-PD-L1 monoclonal antibody, which has shown evidence of clinical activity in a range of human tumors. Prior in vitro studies have shown that avelumab has the ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) of human tumor cells when combined with NK cells...
August 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28447902/reporting-results-of-molecular-tests-a-retrospective-examination-of-braf-mutation-reporting
#14
Amanda L Treece, Margaret L Gulley, Patricia Vasalos, Cherie Paquette, Neal I Lindeman, Lawrence J Jennings, Angela N Bartley
CONTEXT: - With enormous growth in the field of molecular pathology, the reporting of results gleaned from this testing is essential to guide patient care. OBJECTIVE: - To examine molecular reports from laboratories participating in proficiency testing for required elements to convey molecular laboratory test results to clinicians and patients. DESIGN: - Molecular laboratories participating in the College of American Pathologists (CAP) proficiency testing program for BRAF mutation analysis were solicited to submit examples of final reports from 2 separate proficiency testing reporting cycles...
May 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28376158/role-of-antigen-spread-and-distinctive-characteristics-of-immunotherapy-in-cancer-treatment
#15
REVIEW
James L Gulley, Ravi A Madan, Russell Pachynski, Peter Mulders, Nadeem A Sheikh, James Trager, Charles G Drake
Immunotherapy is an important breakthrough in cancer. US Food and Drug Administration-approved immunotherapies for cancer treatment (including, but not limited to, sipuleucel-T, ipilimumab, nivolumab, pembrolizumab, and atezolizumab) substantially improve overall survival across multiple malignancies. One mechanism of action of these treatments is to induce an immune response against antigen-bearing tumor cells; the resultant cell death releases secondary (nontargeted) tumor antigens. Secondary antigens prime subsequent immune responses (antigen spread)...
April 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28375787/avelumab-an-anti-programmed-death-ligand-1-antibody-in-patients-with-refractory-metastatic-urothelial-carcinoma-results-from-a-multicenter-phase-ib-study
#16
MULTICENTER STUDY
Andrea B Apolo, Jeffrey R Infante, Ani Balmanoukian, Manish R Patel, Ding Wang, Karen Kelly, Anthony E Mega, Carolyn D Britten, Alain Ravaud, Alain C Mita, Howard Safran, Thomas E Stinchcombe, Marko Srdanov, Arnold B Gelb, Michael Schlichting, Kevin Chin, James L Gulley
Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1...
July 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28373007/avelumab-for-metastatic-or-locally-advanced-previously-treated-solid-tumours-javelin-solid-tumor-a-phase-1a-multicohort-dose-escalation-trial
#17
Christopher R Heery, Geraldine O'Sullivan-Coyne, Ravi A Madan, Lisa Cordes, Arun Rajan, Myrna Rauckhorst, Elizabeth Lamping, Israel Oyelakin, Jennifer L Marté, Lauren M Lepone, Renee N Donahue, Italia Grenga, Jean-Marie Cuillerot, Berend Neuteboom, Anja von Heydebreck, Kevin Chin, Jeffrey Schlom, James L Gulley
BACKGROUND: Avelumab (MSB0010718C) is a human IgG1 monoclonal antibody that binds to PD-L1, inhibiting its binding to PD-1, which inactivates T cells. We aimed to establish the safety and pharmacokinetics of avelumab in patients with solid tumours while assessing biological correlatives for future development. METHODS: This open-label, single-centre, phase 1a, dose-escalation trial (part of the JAVELIN Solid Tumor trial) assessed four doses of avelumab (1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg), with dose-level cohort expansions to provide additional safety, pharmacokinetics, and target occupancy data...
May 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28373005/avelumab-for-patients-with-previously-treated-metastatic-or-recurrent-non-small-cell-lung-cancer-javelin-solid-tumor-dose-expansion-cohort-of-a-multicentre-open-label-phase-1b-trial
#18
MULTICENTER STUDY
James L Gulley, Arun Rajan, David R Spigel, Nicholas Iannotti, Jason Chandler, Deborah J L Wong, Joseph Leach, W Jeff Edenfield, Ding Wang, Hans Juergen Grote, Anja von Heydebreck, Kevin Chin, Jean-Marie Cuillerot, Karen Kelly
BACKGROUND: Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). METHODS: In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA...
May 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28352946/new-price-new-hope-an-examination-of-the-effects-of-doubling-the-ticket-price-in-uk-lotto
#19
David Forrest, O David Gulley
The UK Lotto game was introduced in November 1994 with a standard 6/49 format and an entry fee of £1 per ticket. After several years, revenue began to fall despite extensive publicity and a variety of inducements. By 2013, nominal weekly revenue was less than half the 1995 level. In October 2013, the operator doubled the price of a ticket to £2 and made a number of changes to the pay-out structure of smaller prizes. The intent of the changes was to reverse the long downward trend in game revenue by encouraging higher jackpots and offering more pay-out opportunities for each ticket...
March 28, 2017: Journal of Gambling Studies
https://www.readbyqxmd.com/read/28325688/current-and-emerging-molecular-tests-for-human-papillomavirus-related-neoplasia-in-the-genomic-era
#20
REVIEW
Sixto M Leal, Margaret L Gulley
Laboratory tests have a key role in preventing human papillomavirus (HPV)-driven carcinomas and in guiding therapeutic interventions. An understanding of the virology, immunology, and carcinogenesis of HPV is essential for choosing appropriate diagnostic test modalities and developing new and even more effective cancer prevention strategies. HPV infects basal epithelial cells on multiple surfaces and induces carcinoma primarily in the cervix and the oropharynx. HPV types are stratified as high risk or low risk based on their carcinogenic potential...
May 2017: Journal of Molecular Diagnostics: JMD
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