Showing papers by "Jonathan W. Simons published in 2014"
TL;DR: Advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials are presented.
Abstract: Metastatic prostate cancer is the second leading cause of death from cancer in the United States It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell–based immunotherapy More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine–based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years Exceptional responses to anti–CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP + prostate cancer cells by prostate-specific autoimmunity This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials Cancer Immunol Res; 2(11); 1034–43 ©2014 AACR
22 citations
TL;DR: The Prouts Neck Meetings on Prostate Cancer began in 1985 through the efforts of the Organ Systems Branch of the National Cancer Institute to stimulate new research and focused around specific questions in prostate tumorigenesis and therapy.
Abstract: INTRODUCTION
The Prouts Neck Meetings on Prostate Cancer began in 1985 through the efforts of the Organ Systems Branch of the National Cancer Institute to stimulate new research and focused around specific questions in prostate tumorigenesis and therapy.
METHODS
These meetings were think tanks, composed of around 75 individuals, and divided equally between young investigators and senior investigators. Over the years, many new concepts related to prostate cancer resulted from these meetings and the prostate cancer community has sorely missed them since the last one in 2007.
RESULTS
We report here the first of a new series of meetings. The 2013 meeting focused on defining how the field of treatment for metastatic prostate cancer needs to evolve to impact survival and was entitled: “Beyond AR: New Approaches to Treating Metastatic Prostate Cancer.” As castrate resistant prostate cancers escape second generation anti-androgen agents, three phenotypes/genotypes of CRPC appear to be increasing in prevalence and remain resistant to treatment: NeuroEndocrine Prostate Cancer, Persistent AR—Dependent Prostate Cancer, and Androgen Receptor Pathway Independent Prostate Cancer.
DISCUSSION
It is clear that new treatment paradigms need to be developed for this diverse group of diseases. The Prouts Neck 2013 Meeting on Prostate Cancer helped to frame the current state of the field and jumpstart ideas for new avenues of treatment. Prostate 74:314–320, 2014. © 2013 Wiley Periodicals, Inc.
16 citations
TL;DR: The 20th Annual Prostate Cancer Foundation Scientific Retreat was held from October 24 to 26, 2013, in National Harbor, Maryland, with a focus on results that will lend to treatments for the most life‐threatening stages of this disease.
Abstract: The 20th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 24 to 26, 2013, in National Harbor, Maryland. This event is held annually for the purpose of convening a diverse group of leading experimental and clinical researchers from academia, industry, and government to present and discuss critical and emerging topics relevant to prostate cancer (PCa) biology, and the diagnosis, prognosis, and treatment of PCa patients, with a focus on results that will lend to treatments for the most life‐threatening stages of this disease. The themes that were highlighted at this year's event included: (i) mechanisms of PCa initiation and progression: cellular origins, neurons and neuroendocrine PCa, long non‐coding RNAs, epigenetics, tumor cell metabolism, tumor–immune interactions, and novel molecular mechanisms; (ii) advancements in precision medicine strategies and predictive biomarkers of progression, survival, and drug sensitivities, including the analysis of circulating tumor cells and cell‐free tumor DNA—new methods for liquid biopsies; (iii) new treatments including epigenomic therapy and immunotherapy, discovery of new treatment targets, and defining and targeting mechanisms of resistance to androgen‐axis therapeutics; and (iv) new experimental and clinical epidemiology methods and techniques, including PCa population studies using patho‐epidemiology. Prostate 74:811–819, 2014. © 2014 Wiley Periodicals, Inc.
4 citations
TL;DR: It is reported that 15‐lipoxygenase 1 (15‐LO1), a key member of the lipoxygenases family, promotes HIF‐1α ubiquitination and degradation, and provides a novel mechanism for HIF1α regulation, in which oxygen‐dependent HIF•1 activity is modulated by an oxygen‐insensitive lipid metabolic enzyme.
Abstract: Hypoxia-inducible factor 1α (HIF-1α) is the regulatory subunit of the heterodimeric HIF-1 that plays a critical role in transcriptional regulation of genes in angiogenesis and hypoxic adaptation, while fatty acid metabolism mediated by lipoxygenases has been implicated in a variety of pathogeneses, including cancers. In this study, we report that 15-lipoxygenase 1 (15-LO1), a key member of the lipoxygenase family, promotes HIF-1α ubiquitination and degradation. Altering the level of 15-LO1 yields inverse changes in HIF-1α and HIF-1 transcriptional activity, under both normoxia and hypoxia, and even in CoCl2-treated cells where HIF-1α has been artificially elevated. The antagonistic effect of 15-LO1 is mediated by the Pro564/hydroxylation/26S proteasome system, while both the enzymatic activity and the intracellular membrane-binding function of 15-LO1 appear to contribute to HIF-1α suppression. Our findings provide a novel mechanism for HIF-1α regulation, in which oxygen-dependent HIF-1 activity is modulated by an oxygen-insensitive lipid metabolic enzyme.
4 citations