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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
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
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...
October 1, 2016: Neuroscience
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
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
Kathleen E Fenerty, Les R Folio, Nicholas J Patronas, Jennifer L Marté, James L Gulley, Christopher R Heery
BACKGROUND: The Response Evaluation Criteria in Solid Tumors (RECIST) are the current standard for evaluating disease progression or therapy response in patients with solid tumors. RECIST 1.1 calls for axial, longest-diameter (or perpendicular short axis of lymph nodes) measurements of a maximum of five tumors, which limits clinicians' ability to adequately measure disease burden, especially in patients with irregularly shaped tumors. This is especially problematic in chordoma, a disease for which RECIST does not always adequately capture disease burden because chordoma tumors are typically irregularly shaped and slow-growing...
2016: BMC Cancer
Christopher R Heery, Ravi A Madan, Mark N Stein, Walter M Stadler, Robert S DiPaola, Myrna Rauckhorst, Seth M Steinberg, Jennifer L Marté, Clara C Chen, Italia Grenga, Renee N Donahue, Caroline Jochems, William L Dahut, Jeffrey Schlom, James L Gulley
PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine...
July 28, 2016: Oncotarget
Benedetto Farsaci, Renee N Donahue, Italia Grenga, Lauren M Lepone, Peter S Kim, Brendan Dempsey, Janet C Siebert, Nuhad K Ibrahim, Ravi A Madan, Christopher R Heery, James L Gulley, Jeffrey Schlom
Tumor immunoscore analyses, especially for primary colorectal cancer and melanoma lesions, provide valuable prognostic information. Metastatic lesions of many carcinoma types, however, are often not easily accessible. We hypothesized that immune cells in peripheral blood may differ among individual patients with metastatic disease, which, in turn, may influence their response to immunotherapy. We thus analyzed immune cell subsets within peripheral blood mononuclear cells to determine if a "peripheral immunoscore" could have any prognostic significance for patients before receiving immunotherapy...
September 2, 2016: Cancer Immunology Research
Ravi A Madan, James L Gulley, William L Dahut
No abstract text is available yet for this article.
September 2016: Lancet Oncology
Max M Wattenberg, Lawrence Fong, Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: Active investigation suggests immune checkpoint inhibitor therapy and therapeutic cancer vaccines provide clinical benefit for genitourinary malignancies including prostate cancer, renal cell carcinoma, and bladder cancer. Recent developments in the utility of immune checkpoint inhibitor and vaccine therapy for the management of genitourinary malignancies are highlighted in this review. RECENT FINDINGS: Dramatic responses to checkpoint inhibitor therapy have been demonstrated in renal cell carcinoma and bladder cancer with recent Food and Drug Administration approvals in both indications...
November 2016: Current Opinion in Urology
Andrea B Apolo, Fatima H Karzai, Jane B Trepel, Sylvia Alarcon, Sunmin Lee, Min-Jung Lee, Yusuke Tomita, Liang Cao, Yunkai Yu, Maria J Merino, Ravi A Madan, Howard L Parnes, Seth M Steinberg, Beatriz Walter Rodriguez, Ben K Seon, James L Gulley, Philip M Arlen, Nancy A Dawson, William D Figg, William L Dahut
BACKGROUND: In this trial we assessed the efficacy and tolerability of TRC105, a chimeric monoclonal antibody that targets CD105 (endoglin) in patients with advanced, previously treated urothelial carcinoma (UC). PATIENTS AND METHODS: Patients received TRC105 15 mg/kg every 2 weeks on days 1 and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) at 6 months. Secondary end points included safety, toxicity, and overall survival (OS)...
May 27, 2016: Clinical Genitourinary Cancer
Caroline Jochems, Massimo Fantini, Romaine I Fernando, Anna R Kwilas, Renee N Donahue, Lauren M Lepone, Italia Grenga, Young-Seung Kim, Martin W Brechbiel, James L Gulley, Ravi A Madan, Christopher R Heery, James W Hodge, Robert Newton, Jeffrey Schlom, Kwong Y Tsang
Epacadostat is a novel inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1) that suppresses systemic tryptophan catabolism and is currently being evaluated in ongoing clinical trials. We investigated the effects of epacadostat on (a) human dendritic cells (DCs) with respect to maturation and ability to activate human tumor antigen-specific cytotoxic T-cell (CTL) lines, and subsequent T-cell lysis of tumor cells, (b) human regulatory T cells (Tregs), and (c) human peripheral blood mononuclear cells (PBMCs) in vitro...
May 12, 2016: Oncotarget
James L Gulley, Peter Mulders, Peter Albers, Jacques Banchereau, Michel Bolla, Klaus Pantel, Thomas Powles
Sipuleucel-T is an autologous cellular immunotherapy approved in the US for patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). This significant advance for mCRPC treatment provides healthcare professionals with another effective therapy to extend survival. As an immunotherapy, sipuleucel-T possesses specific characteristics differentiating it from traditional therapies. At a roundtable meeting of experts, sipuleucel-T data were discussed, focusing on interpretation and clinical implications...
April 2016: Oncoimmunology
Arun Rajan, Chul Kim, Christopher R Heery, Udayan Guha, James L Gulley
The development of immune checkpoint inhibitors has altered the landscape of treatment of advanced cancers. These drugs are well tolerated and have shown clinical activity against a wide variety of solid tumors and hematological malignancies. The durability of response is particularly impressive when compared to other forms of systemic therapy. Nivolumab (Opdivo) is an IgG4 antibody that causes immune checkpoint blockade by diminishing inhibitory signaling through the programmed death receptor-1 pathway. It is approved for treatment of recurrent non-small cell lung cancer, melanoma, and renal cell carcinoma...
September 2016: Human Vaccines & Immunotherapeutics
Brian A Altman, Kelly H Gulley, Carlo Rossi, Kandra Strauss-Riggs, Kenneth Schor
The National Center for Disaster Medicine and Public Health (NCDMPH), in collaboration with over 20 subject matter experts, created a competency-based curriculum titled Caring for Older Adults in Disasters: A Curriculum for Health Professionals. Educators and trainers of health professionals are the target audience for this curriculum. The curriculum was designed to provide breadth of content yet flexibility for trainers to tailor lessons, or select particular lessons, for the needs of their learners and organizations...
August 2016: Disaster Medicine and Public Health Preparedness
Kush Paul, Shuo Kang, Charles L Cox, Joshua M Gulley
Behavioral sensitization following repeated amphetamine (AMPH) exposure is associated with changes in GABA function in the medial prefrontal cortex (mPFC). In rats exposed to AMPH during adolescence compared to adulthood, there are unique patterns of sensitization that may reflect age-dependent differences in drug effects on prefrontal GABAergic function. In the current study, we used a sensitizing regimen of repeated AMPH exposure in adolescent and adult rats to determine if a post-withdrawal AMPH challenge would alter inhibitory transmission in the mPFC in a manner that depends on age of exposure...
August 1, 2016: Behavioural Brain Research
Stephanie R Land, Graham W Warren, Jennifer L Crafts, Dorothy K Hatsukami, Jamie S Ostroff, Gordon B Willis, Veronica Y Chollette, Sandra A Mitchell, Jasmine N M Folz, James L Gulley, Eva Szabo, Thomas H Brandon, Sonia A Duffy, Benjamin A Toll
BACKGROUND: To the authors' knowledge, there are currently no standardized measures of tobacco use and secondhand smoke exposure in patients diagnosed with cancer, and this gap hinders the conduct of studies examining the impact of tobacco on cancer treatment outcomes. The objective of the current study was to evaluate and refine questionnaire items proposed by an expert task force to assess tobacco use. METHODS: Trained interviewers conducted cognitive testing with cancer patients aged ≥21 years with a history of tobacco use and a cancer diagnosis of any stage and organ site who were recruited at the National Institutes of Health Clinical Center in Bethesda, Maryland...
June 1, 2016: Cancer
Julius Strauss, Ravi A Madan, James L Gulley
INTRODUCTION: Over the past few years, trials evaluating immunotherapies, particularly immune checkpoint inhibitors, have revolutionized the standard model of cancer treatment, demonstrating significant antitumor responses and improved clinical outcomes across a wide array of tumors types. Yet, despite these compelling data, a major limitation has been that only a fraction of patients mount a response to single-agent immune checkpoint inhibition. However, a growing amount of preclinical and clinical data suggests that combining immune checkpoint inhibition, either with other immune checkpoint inhibitors or with therapeutic cancer vaccines, has the potential to improve the proportion of patients seeing long-term durable responses with these therapies...
July 2016: Expert Opinion on Biological Therapy
Lisa M Cordes, James L Gulley, Ravi A Madan
PURPOSE OF REVIEW: In recent clinical trials, immunotherapeutic agents have demonstrated promising results for the treatment of prostate cancer. This review discusses emerging immunotherapies for prostate cancer and their evolving role in sequencing and combination therapy. RECENT FINDINGS: Therapeutic vaccines including PROSTVAC and DCVAC/PCa have completed promising phase 2 trials for the treatment of prostate cancer and phase 3 trials are underway. Recent evidence supports a synergistic relationship between immunotherapy agents themselves, antiandrogens and with cytotoxic chemotherapy...
May 2016: Current Opinion in Oncology
Daniel G Kougias, Suzanne O Nolan, Wendy A Koss, Taehyeon Kim, Emily R Hankosky, Joshua M Gulley, Janice M Juraska
Beta-hydroxy-beta-methylbutyrate (HMB), a supplement commonly used to maintain muscle in elderly and clinical populations, has been unexplored in the aging brain. In both healthy aging humans and rat models, there are cognitive deficits associated with age-related dendritic shrinkage within the prefrontal cortex. The present study explores the effects of relatively short- and long-term (7 and 31 weeks) oral HMB supplementation starting at 12 months of age in male and female rats on the dendritic tree of layer 5 pyramidal neurons in the medial prefrontal cortex...
April 2016: Neurobiology of Aging
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