Volume 7.19 | May 27

Prostate Cell News 7.19 May 27, 2016
Prostate Cell News
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Researcher Discovers Altering Metabolite of Prostate Cancer Drug More Effective at Treating Aggressive Tumors
Researchers have fine-tuned an FDA-approved antisteroidal prostate cancer drug to alter its drug metabolism and achieve better anti-tumor activity. Nima Sharifi, M.D., discovered a new strategy for fine-tuning how the body processes abiraterone to optimize therapy for men with metastatic, treatment-resistant prostate cancer. [Press release from Cleveland Clinic discussing online prepublication in Nature.] Press Release | Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer
The authors showed that recurrent prostate cancer (PC)-driver mutations in speckle-type POZ protein stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments androgen receptor (AR) signaling, and AR and TRIM24 co-activated genes are significantly upregulated in castration-resistant PC. [Cancer Cell] Abstract | Graphical Abstract

The Metabolic Co-Regulator PGC1α Suppresses Prostate Cancer Metastasis
Scientists showed that the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC1α) suppresses prostate cancer progression and metastasis. [Nat Cell Biol]
Abstract | Press Release

Inhibition of the Hexosamine Biosynthetic Pathway Promotes Castration-Resistant Prostate Cancer
Scientists showed distinct alterations in the hexosamine biosynthetic pathway (HBP) to be critical for castration-resistant prostate cancer (CRPC). Expression of HBP enzyme glucosamine-phosphate N-acetyltransferase 1 is found to be significantly decreased in CRPC compared with localized prostate cancer. [Nat Commun] Full Article | Press Release

The Autophagy Machinery Controls Cell Death Switching between Apoptosis and Necroptosis
Researchers report that Map3k7 deletion in mouse prostate cells sensitizes to cell death by TNF-related apoptosis-inducing ligand. Surprisingly, this death occurred primarily through necroptosis, not apoptosis, due to assembly of the necrosome in association with the autophagy machinery, mediated by p62/SQSTM1 recruitment of RIPK1. [Dev Cell] Abstract | Graphical Abstract

Histone Deacetylase Inhibition in Prostate Cancer Triggers miR-320-Mediated Suppression of the Androgen Receptor
Histone deacetylase (HDAC) alters the epigenetic status of tumor-associated genes, including those for microRNAs (miRNAs), and affects the behavior of cancers. Researchers examined the molecular effects of a HDAC inhibitor, OBP-801, on androgen receptor expression and tumor cell growth in prostate cancers. [Cancer Res] Abstract

BAP18 Coactivates Androgen Receptor Action and Promotes Prostate Cancer Progression
Investigators demonstrated that BPTF associated protein of 18 kDa (BAP18) is identified as a coactivator of androgen receptor (AR) in the Drosophila experimental system and mammalian cells. BAP18 facilitated the recruitment of MLL1 subcomplex and AR to androgen-response element of AR target genes, subsequently increasing histone H3K4 trimethylation and H4K16 acetylation. [Nucleic Acids Res] Full Article

Zoledronic Acid Impairs Stromal Reactivity by Inhibiting M2-Macrophages Polarization and Prostate Cancer-Associated Fibroblasts
The authors unraveled a novel anti-tumor activity of zoledronic acid (ZA) in prostate cancer (PCa), by targeting the pro-tumorigenic properties of both stromal and immune cells. They demonstrated that ZA impairs PCa-induced M2-macrophages polarization, reducing their pro-invasive effect on tumor cells and their pro-angiogenic features. [Oncotarget] Full Article

Regulation of miR-200c and miR-141 by Methylation in Prostate Cancer
Increasing evidence shows that aberrant epigenetic regulation of miRNAs is a contributing factor to their altered expression in cancer. The authors investigated whether expression of miR-200c and miR-141 in prostate cancer is related to the DNA methylation status of their promoter. [Prostate] Abstract


PMH 9907: Long-Term Outcomes of a Randomized Phase III Study of Short-Term Bicalutamide Hormone Therapy and Dose-Escalated External-Beam Radiation Therapy for Localized Prostate Cancer
The authors report the long-term outcome of a Phase III study of dose-escalated external-beam radiotherapy with or without hormone therapy for patients with localized prostate cancer. [Cancer] Abstract

A Circulating miRNA Assay as a First-Line Test for Prostate Cancer Screening
Scientists analyzed the levels of circulating microRNAs (miRNAs) in patients with elevated prostate-specific antigen who were diagnosed with either localized prostate cancer or benign prostatic hyperplasia upon biopsy. Real-time RT–PCR with Taqman probes was used to measure plasma levels of miRNAs. [Br J Cancer] Abstract

Independent Validation of the Prognostic Capacity of the ISUP Prostate Cancer Grade Grouping System for Radiation Treated Patients with Long-Term Follow-Up
In a large independent radiotherapy cohort with long-term follow-up, investigators have validated the biochemical recurrence-free survival (bRFS) benefit of the proposed five-tier grade grouping system. [Prostate Cancer Prostatic Dis] Abstract

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Oncolytic Virotherapy for Urological Cancers
Urological cancers have a range of distinctive features, such as specific genetic mutations and cell surface markers, which enable improving both effectiveness and safety of oncolytic virus treatments. The strategies employed in creating advanced oncolytic agents include alteration of the virus tropism, regulating transcription and translation of viral genes, combination with chemotherapy, radiotherapy or gene therapy, arming viruses with factors that stimulate the immune response against tumor cells and delivery technologies to ensure that the viral agent reaches its target tissue. [Nat Rev Urol] Abstract

Diagnostic, Prognostic and Predictive Value of Cell-Free miRNAs in Prostate Cancer: A Systematic Review
The reviewers systematically summarize studies investigating cell-free miRNAs in biofluids of prostate cancer patients and discuss the utility of the identified biomarkers in various clinical scenarios. Furthermore, they discuss the possible mechanisms of miRNA release into biofluids and outline the biological questions and technical challenges that have arisen from these studies. [Mol Cancer] Full Article

Visit our reviews page to see a complete list of reviews in the prostate cell research field.
Genomic Health Announces Presentation of Seven Oncotype DX® Studies at the 2016 American Society of Clinical Oncology Annual Meeting, Including Additional Prospective Outcomes Analysis
Genomic Health, Inc. announced that the company will present results from seven Oncotype DX® studies, which will take place June 3-7 at McCormick Place. [Press release from Genomic Health, Inc. discussing research to be presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

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WntResearch Submits Patent Application for Novel Methods of Measuring Biological Effects of the Company’s Drug Candidate Foxy-5
WntResearch has applied for a patent on two novel methods to measure biological effects in humans of the company’s Wnt-5a-agonist drug candidate Foxy-5. These methods also have the potential to detect the effects of the company’s second drug candidate Box-5, a Wnt-5a-antagonist. [WntResearch] Press Release

First Prostate Cancer Patients Treated with Revolutionary HIFU Technology in Houston
Cordell Nwokeji, MD and Don Berardinucci, MD performed the first two Sonablate HIFU treatments in Houston, Texas at Houston Metro Urology in partnership with HIFU Prostate Services. [HIFU Prostate Services, LLC (PR Newswire Association LLC.)] Press Release
Overtime Pay for Postdoctoral Scientists Is Welcome — But Could Mean Fewer Positions
“In a long-overdue revision of American overtime regulations, the Department of Labor explicitly included postdocs among those who are eligible for overtime pay if they earn less than $47,476 per year.” [Nature News] Editorial

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW European Society for Medical Oncology (ESMO) 2016
October 7-11, 2016
Copenhagen, Denmark

Visit our events page to see a complete list of events in the prostate cell community.
NEW PhD Studentship – Bioinformatics to Classify Prostate Cancer (University of East Anglia)

Scientific Communications and Publishing Coordinator (STEMCELL Technologies Inc.)

Research Technologist – Mammary and Prostate Stem Cell Biology (STEMCELL Technologies Inc.)

Research Associate – Prostate Cancer (University of Cambridge)

Postdoctoral Fellow – Cell Cycle Regulation in Prostate and Pancreatic Cancer (Purdue University)

Senior Scientist – Protein Analytics of Prostate and Other Cancer (Exosome Diagnostics)

Postdoctoral Fellow – Cancer Genomics (Henry Jackson Foundation)

Postdoctoral Fellow – Mechanisms of Castrate Resistance (University of Chicago)

Postdoctoral Research Fellow – Molecular Epidemiology of Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Genetic Determinants of Cancer (Memorial Sloan-Kettering Cancer Center)

Postdoctoral Fellow – Prostate Cancer (Cleveland Clinic)

Postdoctoral Fellow – Prostate Epithelial Homeostasis and Carcinogenesis (Baylor College of Medicine)

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