Volume 4.17 | May 10

Prostate Cell News 4.17 May 10, 2013
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs
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The Steroid Receptor Coactivator-3 Is Required for the Development of Castration-Resistant Prostate Cancer
Scientists documented elevated SRC-3 in human castration resistant prostate cancer (CaP) and in PTEN-negative human CaP. Patients with high SRC-3 and undetectable PTEN exhibited decreased recurrence-free survival. To explore the causal relationship in these observations, scientists generated mice in which both Pten and SRC-3 were inactivated in prostate epithelial cells, comparing them to mice in which only Pten was inactivated in these cells. SRC-3 deletion impaired cellular proliferation and reduced tumor size. [Cancer Res] Abstract

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Carbonic Anhydrase IX from Cancer-Associated Fibroblasts Drives Epithelial-Mesenchymal Transition in Prostate Carcinoma Cells
Investigators report that for aggressive prostate carcinoma, acknowledged to be reprogrammed toward an anabolic phenotype and to upload lactate to drive proliferation, extracellular acidification is mainly mediated by stromal cells engaged in a molecular cross-talk circuitry with cancer cells. [Cell Cycle] Abstract

Impact of Tumor Vascularity on Responsiveness to Antiangiogenesis in a Prostate Cancer Stem Cell-Derived Tumor Model
Researchers report that three angiogenesis inhibitors (axitinib, sorafenib, and DC101) all induced significantly greater decreases in tumor blood flow and microvessel density in PC3/2G7 tumors compared with PC3 tumors, as well as significantly greater decreases in tumor cell proliferation and cell viability and a greater increase in apoptosis. [Mol Cancer Ther] Abstract

Epigenetic Modifications of Nrf2 by 3,3′-Diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors
Researchers investigated the in vitro and in vivo epigenetics modulation of 3,3′-diindolylmethane (DIM) in TRAMP-C1 cells and in TRAMP mouse model. In vitro study utilizing TRAMP-C1 cells showed that DIM suppressed DNMT expression and reversed CpG methylation status of Nrf2 resulting in enhanced expression of Nrf2 and Nrf2-target gene NQO1. [AAPS J] Abstract

OXER1, A G Protein-Coupled Oxoeicosatetraenoid Receptor, Mediates the Survival-Promoting Effects of Arachidonate 5-Lipoxygenase in Prostate Cancer Cells
Researchers found that prostate cancer cells express high levels of 5-oxoeicosatetraenoic acid (5-oxoETE) receptor (OXER1), a G protein-coupled 5-oxoETE receptor, which delivers signals by generating diacyl-glycerol through phospholipase C-beta. [Cancer Lett] Abstract

Evidence for a Pro-Proliferative Feedback Loop in Prostate Cancer: The Role of Epac1 and COX-2-Dependent Pathways
Scientists examined the role of inflammatory mediators in Epac1-induced cellular proliferation by determining the expression of the pro-inflammatory markers p-cPLA2, COX-2, and PGE2 in prostate cancer cells treated with 8-CPT-2Me-cAMP. 8-CPT-2Me-cAMP treatment caused a 2-2.5-fold increase of p-cPLA2S505, COX-2, and PGE2 levels in human prostate cancer cell lines. [PLoS One] Full Article

SATB1 Is Overexpressed in Metastatic Prostate Cancer and Promotes Prostate Cancer Cell Growth and Invasion
120 cases of prostatic carcinoma and 60 cases of benign prostate hyperplasia were analyzed for special AT-rich sequence binding protein 1 (SATB1) expression by immunohistochemistry. Researchers report that SATB1 staining was stronger in prostatic carcinomas with metastasis than in those without metastasis, but was absent in benign prostate hyperplasia. [J Transl Med]
Abstract | Full Article

Dishevelled-2 Silencing Reduces Androgen-Dependent Prostate Tumor Cell Proliferation and Migration and Expression of Wnt-3a and Matrix Metalloproteinases
This study aimed to identify if dishevelled-2 (Dvl2) is a prostate cancer-associated gene and aimed to analyze the effects on the growth and invasive capacity of human prostate cancer cells. Silencing of Dvl2 mRNA expression significantly reduced LNCaP cell proliferation, motility, invasiveness and Wnt-3a, AR, matrix metalloproteinase (MMP)-2, and MMP-9 expression. [Mol Biol Rep] Abstract

Prognostication of OCT4 Isoform Expression in Prostate Cancer
The prognostic function of OCT4 isoforms in prostate cancer samples was examined by immunohistochemistry (IHC) and sensitivity and specificity of the antibodies used were evaluated by molecular biology techniques. IHC expression of OCT4 isoforms correlated with biochemical and pathological parameters, particularly biochemical recurrence-free survival. [Tumor Biol] Abstract


ERG Overexpression and PTEN Status Predict Capsular Penetration in Prostate Carcinoma
The authors examined the combined effect of two common genetic alterations, ERG and PTEN, in prostate carcinoma progression. This study presents the first evidence that ERG over expression and PTEN deletion is associated with greater risk of capsular penetration. [Prostate] Abstract

A Phase II Trial of Dasatinib in Patients with Metastatic Castration-Resistant Prostate Cancer Treated Previously with Chemotherapy
Investigators report that dasatinib induced a decrease in phytohemagglutinin-stimulated CSF2, CD40L, GZMB, and IL-2 mRNAs in blood cells, indicating target engagement. Decreases in plasma IL-6 and bone alkaline phosphatase, and in urinary N-telopeptide, were associated with disease control. [Anti-Cancer Drug] Abstract

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Molecular Aspects of Androgenic Signaling and Possible Targets for Therapeutic Intervention in Prostate Cancer
Recent studies revealed that tumor cells have the ability to synthesize androgenic hormones in an intracrine manner. This recognition opened the way for the development of a novel drug, abiraterone acetate, which shows benefits in clinical trials. [Steroids] Abstract

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Study Shows GenomeDx’s Decipher™ Test Effectively Predicts Rapid Metastatic Prostate Cancer
GenomeDx Biosciences announced that data presented by researchers demonstrated that Decipher™, a transformative genomic test that provides a readout of the risk of metastatic disease for individual men with prostate cancer, predicted the onset of rapid metastatic disease in patients following radical prostatectomy. [Press release from GenomeDx Biosciences discussing research presented at the 2013 Annual Meeting for the American Urological Association, San Diego] Press Release

Genomic Health Announces Availability of Oncotype DX® Prostate Cancer Test with Potential to Triple the Number of Patients Who Can Confidently Choose Active Surveillance and Avoid Side Effects of Invasive Treatments
Genomic Health, Inc. is making its Oncotype DX® prostate cancer test available to physicians and their patients. Results showed that the test, developed in collaboration with University of California, San Francisco and Cleveland Clinic, strongly predicted disease aggressiveness offering information beyond currently available clinical factors, such as PSA and biopsy Gleason Score, to help physicians and their prostate cancer patients confidently choose the most appropriate treatment based on an individualized risk assessment. [Press release from Genomic Health, Inc. discussing research presented at the 2013 American Urological Association Annual Meeting, San Diego] Press Release

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Surveyed Physicians Indicate that Xtandi Is Prescribed to Nearly One Quarter of Metastatic Castrate-Resistant Prostate Cancer Patients Who Have Failed to Respond to Prior Docetaxel Treatment
BioTrends Research Group, found that at six months following launch of Xtandi, surveyed urologists and medical oncologists prescribed Xtandi to a respective 19 percent and 24 percent of their metastatic castrate-resistant prostate cancer patients who have failed to respond or had very rapid progression from docetaxel treatment. [BioTrends Research Group] Press Release

PSA Test Remains a Valued Tool to Detect Prostate Cancer Early
The American Association of Clinical Urologists, an organization representing specialists who manage prostate cancer and urologic health, issued a policy statement concerning early detection of prostate cancer. [PR Newswire Association LLC] Press Release

Emergent BioSolutions Presents Preclinical Efficacy Data on ES414 Its Lead ADAPTIR Bispecific Therapeutic for Prostate Cancer
Emergent BioSolutions Inc. announced that it presented preclinical data on its lead bispecific ADAPTIRTM (Modular Protein Technology) molecule, ES414. ES414 is being developed as a potential therapeutic for metastatic castration-resistant prostate cancer. [Press release from Emergent BioSolutions Inc. discussing research presented at the 9th Annual Protein and Antibody Engineering Summit, Boston] Press Release

PROVENGE® (Sipuleucel-T) Data Presented at An Annual Scientific Urology Meeting

Dendreon Corporation announced the presentation of three PROVENGE® (sipuleucel-T) abstracts from new and ongoing clinical trials. [Press release from Dendreon Corporation discussing research presented at the 2013 American Urological Association Annual Meeting, San Diego] Press Release


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Therapeutic Goods Administration (Australia)


NEW International Society for Stem Cell Research (ISSCR): Stem Cells in Translation
September 15-18, 2013
Florence, Italy

NEW International Society for Stem Cell Research (ISSCR): Stem Cells in Science & Medicine
October 14-17, 2013
Suzhou, China

January 28-29, 2014
San Diego, United States

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NEW Postdoctoral Position – Molecular Biology and Cancer Research (University of California San Francisco)

NEW PhD Position – Identification and Validation of New Biomarkers (University of Bergen)

NEW Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

PhD Studentship – Investigation into Chemokine Receptor Induced Cell Migration (University of East Anglia)

Researcher – Prostate Cancer (Prostate Cancer UK)

Postdoctoral Position – Metabolic and Molecular Mechanisms of Advanced Prostate Cancer (Cleveland Clinic)

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