Prostate Cell News Volume 6.12 | Apr 10 2015

A Functional Screen Identifies miRNAs that Inhibit DNA Repair and Sensitize Prostate Cancer Cells to Ionizing Radiation
A prostate cancer Metridia luciferase cell model was applied to examine the effects of individual microRNAs (miRNAs) on ionizing radiation (IR) sensitivity. A large percentage of miRNA mimetics were found to increase cellular sensitivity to IR, while a smaller percentage were protective. [Nucleic Acids Res] Abstract

Prostate Tumorigenesis Induced by PTEN Deletion Involves Estrogen Receptor β Repression
Scientists found that ERβ is targeted for repression in prostate cancer caused by PTEN deletion and that loss of ERβ is important for tumor formation. ERβ transcription is repressed by BMI-1, which is induced by PTEN deletion and important for prostate tumorigenesis. [Cell Rep] Full Article | Graphical Abstract

TR4 Nuclear Receptor Alters the Prostate Cancer CD133⁺ Stem/Progenitor Cell Invasion via Modulating the EZH2-Related Metastasis Gene Expression
Researchers demonstrated that testicular nuclear receptor 4 (TR4) may play a positive role in prostate cancer (PCa) CD133⁺ stem/progenitor (S/P) cell invasion. Targeting TR4 with lentiviral silencing RNA significantly suppressed PCa CD133⁺ S/P cell invasion both in vitro and in vivo. [Mol Cancer Ther] Abstract

Cytokine Profiling of Docetaxel-Resistant Castration-Resistant Prostate Cancer
The authors examined whether changes in cytokine levels predict for docetaxel resistance in vitro and in a clinical cohort. PC3 cells or their docetaxel-resistant subline were co-cultured with U937 monocytes, with and without docetaxel treatment, and cytokine levels were measured. [Br J Cancer] Abstract

Cyclin-Dependent Kinase 5 Acts as a Critical Determinant of AKT-Dependent Proliferation and Regulates Differential Gene Expression by the Androgen Receptor in Prostate Cancer Cells
Investigators studied the cancer-promoting mechanisms of CDK5 in prostate cancer. They observed that CDK5 is necessary for proliferation of several prostate cancer cell lines. [Mol Biol Cell] Abstract

Dual Targeting of the Androgen Receptor and Hypoxia-Inducible Factor 1α Pathways Synergistically Inhibits Castration-Resistant Prostate Cancer Cells
Crosstalk of the androgen receptor (AR) and hypoxia inducible factor 1-α signaling pathways were examined in prostate cancer cell lines with assays measuring the effect of androgen and hypoxia on AR-dependent and hypoxia-inducible gene transcription, protein expression, cell proliferation, and apoptosis. [Mol Pharmacol] Abstract

FGF19 Promotes Progression of Prostate Cancer
Under androgen-deprived conditions achieved by incubation in medium with FGF19, the expression of N‑cadherin in LNCaP cells was enhanced, that of E-cadherin and caspase 3 was suppressed, and the viability of LNCaP and PC3 cells was significantly enhanced. [Prostate] Abstract

The In Vitro and In Vivo Anti-Cancer Activities of a Standardized Quassinoids Composition from Eurycoma longifolia on LNCaP Human Prostate Cancer Cells
Scientists investigated the effects of a standardized total quassinoids composition (SQ40) containing 40% of the total quassinoids found in E. longifolia on LNCaP human prostate cancer cell line. SQ40 inhibited LNCaP cell growth at IC₅₀ value of 5.97 μg/mL while the IC₅₀ on RWPE-1 human prostate normal cells was 59.26 μg/mL. [PLoS One] Full Article

Sesamin Inhibits Lipopolysaccharide-Induced Proliferation and Invasion through the p38-MAPK and NF‑κB Signaling Pathways in Prostate Cancer Cells
The authors explored the mechanism underlying the protective effect of sesamin on prostate cancer cell proliferation and invasion induced by lipopolysaccharide (LPS). They found that the proliferation of PC3 cells, as determined using the MTT assay, and the expression of cyclin D1, COX-2, Bcl-2 and survivin proteins elevated by LPS were distinctly inhibited by sesamin in a dose-dependent manner. [Oncol Rep] Abstract

CLINICAL RESEARCH

SWOG S0925: A Randomized Phase II Study of Androgen Deprivation Combined with Cixutumumab Versus Androgen Deprivation Alone in Patients with New Metastatic Hormone-Sensitive Prostate Cancer
Patients with new metastatic prostate cancer were randomly assigned within 30 days of initiating androgen deprivation (AD) to cixutumumab added to a luteinizing hormone-releasing hormone agonist with bicalutamide versus AD alone. [J Clin Oncol] Abstract

Targeting the Interleukin-11 Receptor α in Metastatic Prostate Cancer: A First-in-Man Study
Limited numbers of patients who had castrate-resistant prostate cancer with osteoblastic bone metastases were enrolled into a Phase 0 trial with biology-driven endpoints. The authors demonstrated biopsy-verified localization of bone metastasis-targeting peptidomimetic-11 to tumors in the bone marrow and drug-induced apoptosis in all patients. [Cancer] Abstract

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ESSA Pharma Inc. Announces Filing of Investigational New Drug Application for EPI-506
ESSA Pharma Inc. announced that it has filed with the Food and Drug Administration in the US an investigational new drug application related to the company’s proposed clinical trial of EPI-506 in prostate cancer patients. [ESSA Pharma Inc.] Press Release

FDA Approves Label Update for ZYTIGA^® to Include Statistically Significant Overall Survival Results in Chemotherapy-Naive Men with Metastatic Castration-Resistant Prostate Cancer
The U.S. Food and Drug Administration (FDA) has approved a label update for ZYTIGA^® plus prednisone based on the final analysis of the Phase III, randomized, double-blind, placebo-controlled COU-AA-302 study, which showed that ZYTIGA plus prednisone significantly prolonged median overall survival, compared to placebo plus prednisone, in chemotherapy-naive men with metastatic castration-resistant prostate cancer. [Janssen Research & Development, LLC (PR Newswire Association LLC)] Press Release

Enzalutamide Demonstrates Statistically Significant Improvement in Progression Free Survival Compared with Bicalutamide in Strive Trial
Medivation, Inc. and Astellas Pharma Inc. announced topline results from the Phase II STRIVE trial comparing enzalutamide with bicalutamide in a study population of men with non-metastatic or metastatic castration-resistant prostate cancer. [Astellas Pharma Inc.] Press Release

Advaxis and Merck Announce Initiation of Enrollment in the Phase I/II Study of ADXS-PSA in Combination with Anti-PD-1 Therapy, KEYTRUDA^® (Pembrolizumab), for the Treatment of Advanced Prostate Cancer
Advaxis, Inc. and Merck announced that enrollment has initiated in the Phase I/II clinical trial evaluating the combination of ADXS-PSA, an investigational Lm-LLO immunotherapy, and KEYTRUDA^® in patients with previously treated, metastatic castration-resistant prostate cancer. [Advaxis, Inc.] Press Release

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NEW PhD Student – Thermal Treatment Modalities in Prostate Cancer Care (Philips Research)

NEW Cancer Biologist (Wake Forest Baptist Medical Center)

NEW Postdoctoral Positions – Stem Cells and Cancer (Brigham & Women’s Hospital)

Postdoctoral Position – Systems Genetics of Aggressive Prostate Cancer (National Institutes of Health)

Postdoctoral Research Fellow – Prostate Cancer and Breast Cancer (Baylor College of Medicine)

Postdoctoral Research Scientist – Prostate Cancer (Columbia University Medical Center)

Postdoctoral Fellow – Development, Progression and Chemotherapy Resistance of Cancers (University of Maryland Baltimore – School of Medicine)

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