Prostate Cell News Volume 7.44 | Dec 2 2016

TOP STORY

Internalization of Secreted Antigen–Targeted Antibodies by the Neonatal Fc Receptor for Precision Imaging of the Androgen Receptor Axis

Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. Scientists report intracellular accumulation of a secreted antigen–targeted antibody that can be used to characterize disease, guide therapy, and monitor response. [Sci Transl Med] Abstract | Press Release

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Truncation and Constitutive Activation of the Androgen Receptor by Diverse Genomic Rearrangements in Prostate Cancer

The authors define diverse androgen receptor genomic structural rearrangements as a class of molecular alterations occurring in one third of castration-resistant prostate cancer-stage tumors. [Nat Commun] Full Article | Press Release

Castration Resistance in Prostate Cancer Is Mediated by the Kinase NEK6

Investigators performed a high-throughput genetic screen to identify kinases that enable tumor formation by androgen-dependent prostate epithelial cells under androgen-deprived conditions. [Cancer Res] Abstract

MicroRNA-383 Located in Frequently Deleted Chromosomal Locus 8p22 Regulates CD44 in Prostate Cancer

Researchers demonstrated for the first time that a microRNA component of this region—miR-383—is frequently downregulated in prostate cancer, has a critical role in determining tumor-initiating potential and is involved in prostate cancer metastasis via direct regulation of CD44, a ubiquitous marker of prostate cancer tumor-initiating cells/stem cells. [Oncogene] Abstract

Distinct Outcomes of CRL–Nedd8 Pathway Inhibition Reveal Cancer Cell Plasticity

Investigators provided new insights into Cullin-RING E3 ligases (CRL) inhibition as a potential anti-cancer approach by elucidating its cancer-specific consequences in prostate cancer cells. They demonstrated that suppression of androgen receptor, Cullin-associated and neddylation-dissociated 1 protein, and unknown PS1145 targets sensitize cancer cells to CRL inhibition. [Cell Death Dis] Full Article

Long Non-Coding RNA Urothelial Carcinoma Associated 1 (UCA1) Mediates Radiation Response in Prostate Cancer

The authors showed that irradiation-resistant prostate cancer cells expressed a significantly higher level of urothelial carcinoma associated 1 (UCA1) in vitro and UCA1-knockdown reverses the aggressive phenotype and improves radiosensitivity. Their data suggests that UCA1 contributes to radiotherapy resistance through regulation of the PI3K/Akt pathway. [Oncotarget] Full Article

Evidence for Feedback Regulation following Cholesterol Lowering Therapy in a Prostate Cancer Xenograft Model

The authors compared the effects of the cholesterol lowering drugs simvastatin and ezetimibe alone or in combination on the growth of LAPC-4 prostate cancer in vivo xenografts. [Prostate] Abstract

Cardamonin Represses Proliferation, Invasion, and Causes Apoptosis through the Modulation of Signal Transducer and Activator of Transcription 3 Pathway in Prostate Cancer

Investigators evaluated the potential of cardamonin, a 2′,4′-dihydroxy-6′-methoxychalcone, to modulate signal transducer and activator of transcription 3 (STAT3) activation in prostate cancer cells and found that this chalcone can indeed exhibit significant anticancer effects through negatively regulating STAT3 activation by diverse molecular mechanism(s). [Apoptosis] Abstract

Activation of GPR30 Stimulates GTP-Binding of Gαi1 Protein to Sustain Activation of Erk1/2 in Inhibition of Prostate Cancer Cell Growth and Modulates Metastatic Properties

Previously, scientists reported that GPR30 activation by the receptor-specific, non-estrogenic ligand G-1 inhibited in vitro and in vivo growth of prostate cancer (PCa) cells via sustained Erk1/2 activation. The mechanism underlying the sustained Erk1/2 activation for PCa cell growth inhibition remains unclear. They report that G-1, through GPR30, activated Gαi1 proteins to sustain Erk1/2 activation but failed to activate adenylyl cyclase for cAMP production in PCa cells. [Exp Cell Res] Abstract

Nimbolide Inhibits Androgen Independent Prostate Cancer Cells Survival and Proliferation by Modulating Multiple Pro-Survival Signaling Pathways

Researchers examined the effect of nimbolide at 1 and 2 μM concentrations on TNF-α/TNFR1 mediated signaling molecules involved in cell survival and proliferation in PC-3 cell line via NF-κB and MAPK pathways by real time PCR and western blot. [Biomed Pharmacother] Abstract

Mapping Complex Traits in a Diversity Outbred F1 Mouse Population Identifies Germline Modifiers of Metastasis in Human Prostate Cancer

To provide one controlled answer to this problem, researchers crossed a dominant, penetrant mouse model of prostate cancer to Diversity Outbred mice, a collection of animals that carries over 40 million SNPs. Integration of disease phenotype and SNP variation data in 493 F1 males identified a metastasis modifier locus on Chromosome 8; further analysis identified the genes Rwdd4, Cenpu, and Casp3 as functional effectors of this locus. [Cell Syst] Abstract | Graphical Abstract

CLINICAL RESEARCH

Investigational Serine/Threonine Kinase Inhibitors against Prostate Cancer Metastases

The author provides data on serine/threonine protein kinase (STK) expression and activity in the development of castration resistant disease as well as summarizes recent reports of different strategies to block STK activity for the control of prostate cancer progression. [Expert Opin Investig Drugs] Abstract

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MDNA Selects Phi Life Sciences as its First US Distribution Partner for Its New Liquid Biopsy Test for Prostate Cancer

MDNA Life Sciences Inc. announced that it has entered into a license agreement with Phi Life Sciences. Under the agreement, Phi is the first US partner to distribute MDNA’s proprietary liquid biopsy test for prostate cancer, the Prostate Mitomic Test. [MDNA Life Sciences Inc. (PR Newswire Association LLC)] Press Release

VA Partners with Prostate Cancer Foundation to Expand Clinical Research

The Department of Veterans Affairs (VA) announced an a $50-million precision oncology initiative and substantial partnership with the Prostate Cancer Foundation (PCF) to prevent, screen and promote research to speed the development of treatments and cures for prostate cancer among Veterans. [Prostate Cancer Foundation] Press Release

The V Foundation Announces Multi-Million Dollar Challenge to Further the Study of BRCA Mutation Research

The V Foundation for Cancer Research announced a new partnership with the San Francisco-based BRCA Foundation and the Gray Foundation to fund research of cancers that derive from BRCA or BRCA-like mutations. Each organization will provide a $1.5 million challenge to the V Foundation for BRCA Research Collaborative Grants. This research will advance the study of inherited mutations in BRCA1 and BRCA2, genes that produce tumor suppressor proteins. [The V Foundation for Cancer Research] Press Release

American Urological Association Testifies to Congress on U.S. Preventive Services Task Force Reform

Dr. John H. Lynch, prominent urologist and prostate cancer survivor, testified before Congress on behalf of the American Urological Association during a special hearing titled, “Examining the United States Preventive Services Task Force.” The hearing was called by the House Energy & Commerce Subcommittee on Health and specifically referenced the USPSTF Transparency and Accountability Act, introduced by Reps. Marsha Blackburn and Bobby Rush. [American Urological Association (PR Newswire Association LLC)] Press Release

US Health-Reform Legislation Clears Big Hurdle

Legislation that would streamline research and development at the US National Institutes of Health and drug regulation at the Food and Drug Administration is one step closer to becoming law. The US House of Representatives approved the nearly 1,000-page bill — known as the 21st Century Cures Act — on 30 November. The Senate is expected to take up the controversial US$6.3-billion measure as early as next week. [Nature News] Editorial

Battle over US Overtime Pay Rules Leaves Many Postdocs in Limbo

Institutions struggle to respond after court blocks regulations that would have increased wages for junior researchers. Some universities are proceeding with planned salary increases for postdocs, but others have cancelled — or at least, temporarily halted — changes to researchers’ pay. The uncertainty over how the legal battle will play out is already affecting some postdocs’ career and family plans. [Nature News] Editorial

FDA Chief Pushes Back against Criticism of Stem Cell Treatment Regulations

The country’s top drug regulators pushed back on claims they move too slowly in approving new stem cell treatments and sought to temper expectations for the field’s potential to benefit patients, emphasizing the hazards and the unknowns that persist with developing such therapies. [STAT News] Editorial

Big Biology Projects Warm Up to Preprints

The 4D Nucleome, a major research consortium funded by the US National Institutes of Health, is now requiring that all manuscripts related to its US$120-million, five-year program are posted to an online preprint server ahead of peer review. And a privately funded, US$600-million biomedical research initiative in California is considering whether to demand its investigators do the same. [Nature News] Editorial

NEW Translational Opportunities in Stem Cell Research
February 27-March 1, 2017
Basel, Switzerland

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NEW Postdoctoral Researcher – Prostate Carcinogenesis (The University of Alabama)

NEW Postdoctoral Researcher – Prostate Cancer (Cleveland Clinic Lerner Research Institute)

NEW Postdoctoral Fellow – Molecular Oncology (Institute of Oncology Research)

Faculty Position – Cancer Immunology (University of New Mexico School of Medicine)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College / Geisel School of Medicine)

Faculty Position – Cancer Immunology (University of New Mexico)

Postdoctoral Fellowship – Cancer Biology (The University of Maryland)

Assistant, Associate or Full Professor – Cancer Biology (University of Pennsylvania)

Postdoctoral Associate – Cancer Research (University of Minnesota)

Postdoctoral Fellow – Pharmacogenomics Prostate Cancer (Moffitt Cancer Center)

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