Prostate Cell News Volume 8.16 | May 5 2017

TOP STORY

Analysis of Circulating Cell-Free DNA Identifies Multi-Clonal Heterogeneity of BRCA2 Reversion Mutations Associated with Resistance to PARP Inhibitors

Scientists identified BRCA2 reversion mutations associated with olaparib and talazoparib resistance in prostate cancer patients. Analysis of circulating cell-free DNA revealed reversion mutation heterogeneity not discernable from a single solid tumor biopsy and potentially allows monitoring for the emergence of PARP inhibitors resistance. [Cancer Discov] Abstract

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Lipid-Oligonucleotide Conjugates Improve Cellular Uptake and Efficiency of TCTP-Antisense in Castration-Resistant Prostate Cancer

Researchers showed that lipid-modified antisense oligonucleotides (LASO) have improved penetration and efficiency in inhibiting translationally controlled tumor protein (TCTP) expression in the absence of additional transfection agents, both in vitro and in vivo. Transfection with TCTP-LASO led to rapid and prolonged internalization via macropinocytosis, TCTP downregulation and significant decreased cell viability. [J Control Release] Full Article

HIC1 Loss Promotes Prostate Cancer Metastasis by Triggering Epithelial-Mesenchymal Transition

The authors showed that hypermethylation of the hypermethylated in cancer 1 (HIC1) promoter markedly reduces its suppressive function in metastatic prostate cancer tissues compared to primary and adjacent normal prostate tissues, and is associated with poor patient survival. Prostate cancers in cancer-prone mice homozygous for a prostate-targeted Hic1 conditional knockout displayed stronger metastatic behavior than heterozygous animals, as a result of epithelial–mesenchymal transition. [J Pathol] Abstract

The ErbB Family and Androgen Receptor Signaling Are Targets of Celecoxib in Prostate Cancer

Researchers determined the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent prostate cancer cells and provided a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells. [Cancer Lett] Abstract

Double Targeting Ligands with Modulated Pharmacokinetics for Endoradiotherapy of Prostate Cancer

Six novel urea-based ligands with varying affinities for PSMA and human serum albumin were synthesized, labeled with ¹³¹I and evaluated by in vitro binding and uptake assays in LNCaP cells. Four compounds were advanced for further evaluation in a preclinical model of prostate cancer. The compounds were compared to MIP-1095, a PSMA ligand currently in clinical evaluation. [J Nucl Med] Abstract

Metformin Inhibits SUV39H1-Mediated Migration of Prostate Cancer Cells

Scientists found that metformin was able to inhibit prostate cancer cell migration, which correlated with tumor metastatic capability. The pathogenesis and progression of tumors were closely related to dysregulated gene expression in tumor cells through epigenetic alterations such as DNA methylation and histone modifications. [Oncogenesis] Full Article

Glyoxalase 2 Drives Tumorigenesis in Human Prostate Cells in a Mechanism Involving Androgen Receptor and p53-p21 Axis

The authors examined the immunohistochemical profile of glyoxalase 2 (Glo2) in human prostate cancer (PCa) and benign adjacent tissues and investigated Glo2 involvement in PCa development in human prostate cell lines. PCa and matched adjacent normal tissues were obtained from paraffin sections of primary PCa from 20 patients who had undergone radical prostatectomy. [Mol Carcinog] Abstract

DHRS7 (SDR34C1) – A New Player in the Regulation of Androgen Receptor Function by Inactivation of 5α-Dihydrotestosterone?

Recombinant human DHRS7 was expressed in intact HEK-293 cells in order to investigate whether glucocorticoids and androgens serve as substrates at sub-micromolar concentrations and at physiological cofactor concentrations. The membrane topology of DHRS7 was revisited using redox-sensitive green-fluorescent protein fusions in living cells. [J Steroid Biochem Mol Biol] Abstract

Development of Prostate Specific Membrane Antigen Targeted Ultrasound Microbubbles Using Bioorthogonal Chemistry

Prostate specific membrane antigen (PSMA) targeted microbubbles (MBs) were developed using bioorthogonal chemistry. Streptavidin-labeled MBs were treated with a biotinylated tetrazine and targeted to PSMA expressing cells using trans-cyclooctene-functionalized anti-PSMA antibodies. The extent of MB binding to PSMA positive cells for two different targeting strategies was determined using an in vitro flow chamber. [PLoS One] Full Article

Aggressive Rat Prostate Tumors Reprogram the Benign Parts of the Prostate and Regional Lymph Nodes Prior to Metastasis

Poorly metastatic or highly metastatic rat prostate tumor cells were injected into the ventral prostate lobe of immunocompetent rats. After ten days—when the tumors occupied about 30% of the prostate lobe and lymph node metastases were undetectable—the global gene expression in tumors, benign parts of the prostate, and regional iliac lymph nodes were examined to define tumor-induced changes related to preparation for future metastasis. [PLoS One] Full Article

CLINICAL RESEARCH

Androgen Receptor Gene Status in Plasma DNA Associates with Worse Outcome on Enzalutamide or Abiraterone for Castration-Resistant Prostate Cancer: A Multi-Institution Correlative Biomarker Study

Investigators aimed to clinically qualify androgen receptor gene status measurement in plasma DNA using multiplex droplet digital PCR in pre- and post-chemotherapy castration-resistant prostate cancer. [Ann Oncol] Full Article

Immunotherapy in Genitourinary Malignancies

The authors review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. They also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination. [J Hematol Oncol] Full Article

Visit our reviews page to see a complete list of reviews in the prostate cell research field.

New $21 Million Gift Puts Basser Center for BRCA at the Forefront of Advancements for Patients at Risk of Inherited Cancers

A new $21 million gift to the Basser Center for BRCA at the Abramson Cancer Center of the University of Pennsylvania from alumni Mindy and Jon Gray will cement and propel Penn’s preeminence as a leader in research to improve treatment and prevention strategies for hereditary cancers. [Penn Medicine] Press Release

Historic Victory for Prostate Cancer: Congress Adds $10 Million for Research Program

The Prostate Cancer Research Program (PCRP) has received its first increase in funding in over a decade. Prostate cancer advocates saw a major advancement as the Senate passed the 2017 Defense Appropriations Bill, which includes $90 million for the Department of Defense’s PCRP. The President is expected to sign the bill this week. [ZERO – The End of Prostate Cancer] Press Release

Augmenix Announces First Prostate Cancer Patient Treated with SpaceOAR^® Hydrogel in Canada

Augmenix, Inc. announced that the first patient in Canada has been treated with SpaceOAR hydrogel at the Princess Margaret Cancer Centre, University Health Network, Toronto. SpaceOAR hydrogel is the first absorbable spacer designed to separate the rectum and prostate to reduce the risk of rectal toxicity during radiotherapy. [Augmenix, Inc. (Business Wire, Inc.)] Press Release

Sperling Prostate Center Joins MR-Guided Focused Ultrasound Clinical Study

The Sperling Prostate Center announced its participation as a new study site for a clinical study of MR-guided focused ultrasound for the focal treatment of localized low and intermediate risk prostate lesions. They are now recruiting patients. [Sperling Prostate Center (PR Newswire Association LLC.)] Press Release

NxThera to Receive Eureka! Innovation Award for Minimally Invasive Rezūm^® System BPH Treatment

NxThera, Inc. was named a recipient of the 2017 Eureka! Innovation Awards, honoring the most innovative companies, products and ideas in Minnesota. [NxThera, Inc. (PR Newswire Association LLC.)] Press Release

NIH to Limit the Amount of Grant Money a Scientist Can Receive

For the first time, the US National Institutes of Health (NIH) will restrict the amount of funding that an individual scientist can hold at any one time, based on a new point system. The move is part of an ongoing effort to make obtaining grants easier for early and mid-career scientists, who face much tougher odds than their more-experienced colleagues. [Nature News] Editorial

Angering Animal Welfare Activists, Mauritius Invites Primate Research Labs to Set Up Shop

Mauritius has decided to get into the business of nonhuman primate experimentation itself even as such work is becoming increasingly constrained in North America and Europe. Last month the move touched off a heated debate in Mauritius’s National Assembly about whether the government could adequately protect the macaques used in research and whether the new industry might endanger a far bigger lifeline for the island—tourism. [ScienceInsider] Editorial

NEW 3^rd CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
September 6-9, 2017
Mainz/Frankfurt, Germany

NEW Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond
September 24-27, 2017
Orlando, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Senior Fellow – Microbiology, Genetics, and Translational Prostate Cancer Research (University of Washington)

NEW Postdoctoral Fellow – Mammalian Stem Cell Biology (NYU School of Medicine)

Postdoctoral Fellow – Translational Prostate Cancer Research (Weill Cornell Medicine)

Postdoctoral Fellow Positions – Gene Regulation in Cancer Progression (University of Texas Health Science Center at San Antonio)

Postdoctoral Scientist – Structural Studies (Medical Research Council)

Postdoctoral Fellow – Prostate Cancer (University of South Carolina-School of Medicine)

Faculty Position – Genitourinary Oncology (Northwestern University)

Scientist – Prostate Cancer Research (Dana-Farber Cancer Institute)

Postdoctoral Fellow – Cancer Biology (Northwestern University)

Postdoctoral Fellow – Prostate Cancer (Johns Hopkins University)

Postdoctoral Fellow – Prostate/Pancreatic Cancer (Medical College of Wisconsin)

Postdoctoral Fellow – Prostate Cancer Research (Vancouver Prostate Center)

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