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https://www.readbyqxmd.com/read/28376158/role-of-antigen-spread-and-distinctive-characteristics-of-immunotherapy-in-cancer-treatment
#1
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
#2
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...
April 4, 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
#3
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...
March 31, 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
#4
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...
March 31, 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
#5
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
#6
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
https://www.readbyqxmd.com/read/28239472/analyses-of-the-peripheral-immunome-following-multiple-administrations-of-avelumab-a-human-igg1-anti-pd-l1-monoclonal-antibody
#7
Renee N Donahue, Lauren M Lepone, Italia Grenga, Caroline Jochems, Massimo Fantini, Ravi A Madan, Christopher R Heery, James L Gulley, Jeffrey Schlom
BACKGROUND: Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28229344/variation-in-risk-and-outcomes-of-epstein-barr-virus-associated-breast-cancer-by-epidemiologic-characteristics-and-virus-detection-strategies-an-exploratory-study
#8
Sally L Glaser, Alison J Canchola, Theresa H M Keegan, Christina A Clarke, Teri A Longacre, Margaret L Gulley
PURPOSE: A relationship of Epstein-Barr virus (EBV) and breast cancer etiology and outcome may have clinical utility and potential to enhance understanding of tumor biology. Research to date has yielded variable results, likely reflecting differing virus detection assays and unaddressed epidemiologic heterogeneity across studies. METHODS: Applying our novel, five-target assay detection strategy in an exploratory study, we examined demographic, clinical, and tumor characteristics, and overall survival, associated with EBV positivity in breast adenocarcinomas from 59 non-Hispanic white and 68 Hispanic women sampled by age (<50, 50+) and stage (localized, regional/remote) and examined associations based on single assay targets...
April 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28220728/caring-for-older-adults-in-disasters-a-special-collection-of-papers-for-a-special-population
#9
Kelly Gulley, Kandra Strauss-Riggs, Craig Goolsby
No abstract text is available yet for this article.
February 2017: Disaster Medicine and Public Health Preparedness
https://www.readbyqxmd.com/read/28169299/corrigendum-greenland-subglacial-drainage-evolution-regulated-by-weakly-connected-regions-of-the-bed
#10
Matthew J Hoffman, Lauren C Andrews, Stephen F Price, Ginny A Catania, Thomas A Neumann, Martin P Lüthi, Jason Gulley, Claudia Ryser, Robert L Hawley, Blaine Morriss
No abstract text is available yet for this article.
February 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28129524/her2-testing-and-clinical-decision-making-in-gastroesophageal-adenocarcinoma-guideline-from-the-college-of-american-pathologists-american-society-for-clinical-pathology-and-the-american-society-of-clinical-oncology
#11
Angela N Bartley, Mary Kay Washington, Carol Colasacco, Christina B Ventura, Nofisat Ismaila, Al B Benson, Alfredo Carrato, Margaret L Gulley, Dhanpat Jain, Sanjay Kakar, Helen J Mackay, Catherine Streutker, Laura Tang, Megan Troxell, Jaffer A Ajani
Context ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA. Objectives To establish an evidence-based guideline for HER2 testing in patients with GEA, formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making...
February 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28093093/innovations-for-tomorrow-summary-of-the-2016-disaster-health-education-symposium
#12
Kelly Gulley, Kandra Strauss-Riggs, Thomas D Kirsch, Craig Goolsby
In an effort to enhance education, training, and learning in the disaster health community, the National Center for Disaster Medicine and Public Health (NCDMPH) gathered experts from around the nation in Bethesda, Maryland, on September 8, 2016, for the 2016 Disaster Health Education Symposium: Innovations for Tomorrow. This article summarizes key themes presented during the disaster health symposium including innovations in the following areas: training and education that saves lives, practice, teaching, sharing knowledge, and our communities...
January 17, 2017: Disaster Medicine and Public Health Preparedness
https://www.readbyqxmd.com/read/28077399/her2-testing-and-clinical-decision-making-in-gastroesophageal-adenocarcinoma-guideline-from-the-college-of-american-pathologists-american-society-for-clinical-pathology-and-american-society-of-clinical-oncology
#13
REVIEW
Angela N Bartley, Mary Kay Washington, Christina B Ventura, Nofisat Ismaila, Carol Colasacco, Al B Benson, Alfredo Carrato, Margaret L Gulley, Dhanpat Jain, Sanjay Kakar, Helen J Mackay, Catherine Streutker, Laura Tang, Megan Troxell, Jaffer A Ajani
CONTEXT: ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA. OBJECTIVES: To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making...
December 2016: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28038406/beta-hydroxy-beta-methylbutyrate-hmb-ameliorates-age-related-deficits-in-water-maze-performance-especially-in-male-rats
#14
Daniel G Kougias, Emily R Hankosky, Joshua M Gulley, Janice M Juraska
Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze...
March 1, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/27991518/greenland-subglacial-drainage-evolution-regulated-by-weakly-connected-regions-of-the-bed
#15
Matthew J Hoffman, Lauren C Andrews, Stephen A Price, Ginny A Catania, Thomas A Neumann, Martin P Lüthi, Jason Gulley, Claudia Ryser, Robert L Hawley, Blaine Morriss
Penetration of surface meltwater to the bed of the Greenland Ice Sheet each summer causes an initial increase in ice speed due to elevated basal water pressure, followed by slowdown in late summer that continues into fall and winter. While this seasonal pattern is commonly explained by an evolution of the subglacial drainage system from an inefficient distributed to efficient channelized configuration, mounting evidence indicates that subglacial channels are unable to explain important aspects of hydrodynamic coupling in late summer and fall...
December 19, 2016: Nature Communications
https://www.readbyqxmd.com/read/27751359/karyotypic-abnormalities-associated-with-epstein-barr-virus-status-in-classical-hodgkin-lymphoma
#16
Nathan D Montgomery, Wilborn B Coward, Steven Johnson, Ji Yuan, Margaret L Gulley, Stephanie P Mathews, Kathleen Kaiser-Rogers, Kathleen W Rao, Warren G Sanger, Jennifer N Sanmann, Yuri Fedoriw
Classical Hodgkin lymphoma (CHL) is morphologically characterized by scattered malignant Hodgkin/Reed-Sternberg (HRS) cells that are far outnumbered by surrounding reactive hematolymphoid cells. Approximately half of all cases of CHL are associated with infection by Epstein-Barr virus (EBV), an oncogenic herpesvirus that expresses a number of proteins thought to contribute to transformation. While a small number of published studies have attempted to identify recurrent cytogenetic abnormalities in CHL, no large case series have explored karyotypic differences between EBV-positive and EBV-negative tumors...
September 2016: Cancer Genetics
https://www.readbyqxmd.com/read/27739389/understanding-comorbidity-among-internalizing-problems-integrating-latent-structural-models-of-psychopathology-and-risk-mechanisms
#17
Benjamin L Hankin, Hannah R Snyder, Lauren D Gulley, Tina H Schweizer, Patricia Bijttebier, Sabine Nelis, Gim Toh, Michael W Vasey
It is well known that comorbidity is the rule, not the exception, for categorically defined psychiatric disorders, and this is also the case for internalizing disorders of depression and anxiety. This theoretical review paper addresses the ubiquity of comorbidity among internalizing disorders. Our central thesis is that progress in understanding this co-occurrence can be made by employing latent dimensional structural models that organize psychopathology as well as vulnerabilities and risk mechanisms and by connecting the multiple levels of risk and psychopathology outcomes together...
November 2016: Development and Psychopathology
https://www.readbyqxmd.com/read/27702645/timing-of-amphetamine-exposure-in-relation-to-puberty-onset-determines-its-effects-on-anhedonia-exploratory-behavior-and-dopamine-d1-receptor-expression-in-young-adulthood
#18
Shuo Kang, Mariah M Wu, Roberto Galvez, Joshua M Gulley
Non-medical use of amphetamine (AMPH) among adolescents is prevalent, which is problematic given the potential consequences of developmental drug exposure on brain function and behavior. Previously we found in adult male rats that AMPH exposure starting before puberty induces a persistent decrease in dopamine D1 receptor (D1R) function in the medial prefrontal cortex (mPFC). Here we investigated if this dysfunction was associated with changes in D1R expression in the mPFC and nucleus accumbens (NAc). We also determined if starting drug exposure well before or near the onset of puberty would influence AMPH-induced changes in D1R expression and behavior...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27623471/evaluating-elevated-hemoglobin
#19
LETTER
Brandi N Reeves, Margaret L Gulley
No abstract text is available yet for this article.
September 13, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27622067/tarp-vaccination-is-associated-with-slowing-in-psa-velocity-and-decreasing-tumor-growth-rates-in-patients-with-stage-d0-prostate-cancer
#20
Lauren V Wood, Antonio Fojo, Brenda D Roberson, Meghan S B Hughes, William Dahut, James L Gulley, Ravi A Madan, Philip M Arlen, Marianna Sabatino, David F Stroncek, Luciano Castiello, Jane B Trepel, Min-Jung Lee, Howard L Parnes, Seth M Steinberg, Masaki Terabe, Julia Wilkerson, Ira Pastan, Jay A Berzofsky
T-cell receptor alternate reading frame protein (TARP) is a 58-residue protein over-expressed in prostate and breast cancer. We investigated TARP peptide vaccination's impact on the rise in PSA (expressed as Slope Log(PSA) or PSA Doubling Time (PSADT)), validated tumor growth measures, and tumor growth rate in men with Stage D0 prostate cancer. HLA-A*0201 positive men were randomized to receive epitope-enhanced (29-37-9V) and wild-type (27-35) TARP peptides administered as a Montanide/GM-CSF peptide emulsion or as an autologous peptide-pulsed dendritic cell vaccine every 3 weeks for a total of five vaccinations with an optional 6th dose of vaccine at 36 weeks based on immune response or PSADT criteria with a booster dose of vaccine for all patients at 48 and 96 weeks...
August 2016: Oncoimmunology
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