Volume 4.45 | Nov 22

Prostate Cell News 4.45 November 22, 2013
Prostate Cell News
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Metastatic Castration-Resistant Prostate Cancer Reveals Intrapatient Similarity and Interpatient Heterogeneity of Therapeutic Kinase Targets
Scientists evaluated active kinases using phosphotyrosine peptide enrichment and quantitative mass spectrometry to identify druggable targets in metastatic castration-resistant prostate cancer obtained at rapid autopsy. They identified distinct phosphopeptide patterns in metastatic tissues compared with treatment-naive primary prostate tissue and prostate cancer cell line-derived xenografts. [Proc Natl Acad Sci USA] Abstract | Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)

PRH/HHex Inhibits the Migration of Breast and Prostate Epithelial Cells through Direct Transcriptional Regulation of Endoglin
Researchers showed that proline-rich homeodomain protein (PRH) is involved in the regulation of cell migration and cancer cell invasion. They showed for the first time that PRH is expressed in prostate cells and that a decrease in PRH protein levels increases the migration of normal prostate epithelial cells. [Oncogene] Abstract

miRNA-296-3p-ICAM-1 Axis Promotes Metastasis of Prostate Cancer by Possible Enhancing Survival of Natural Killer Cell-Resistant Circulating Tumor Cells
Scientists found that the expression level of microRNA-296-3p is much lower in the non-metastatic human prostate cancer cell line P69 than that in the highly metastatic cell line M12, which is derived from P69. [Cell Death Dis] Full Article

A Naturally-Derived Small Molecule Disrupts Ligand-Dependent and Ligand-Independent Androgen Receptor Signaling in Human Prostate Cancer Cells
Scientists showed that mahanine possesses the ability to inhibit ligand-dependent and ligand-independent androgen receptor (AR) transactivation, leading to a prominent decline in AR target gene expression. Mahanine treatment causes a time- and dose- dependent decline in AR protein levels, including truncated AR splice variants, in a panel of androgen-responsive and androgen-independent prostate cancer cells. [Mol Cancer Ther] Abstract

TBLR1 as an AR Coactivator Selectively Activates AR Target Genes to Inhibit Prostate Cancer Growth
Scientists characterized TBLR1 as a coactivator of androgen receptor (AR) in prostate cancer cells and the activation is both phosphorylation and 19S proteosome dependent. They showed that TBLR1 physically interacts with AR and directly occupies the androgen response elements of affected AR target genes in an androgen-dependent manner. [Endocr Relat Cancer] Abstract

MicroRNA-663 Induces Castration-Resistant Prostate Cancer Transformation and Predicts Clinical Recurrence
Researchers report that microRNA (miR)-663 is upregulated in castration-resistant prostate cancer tissues. Overexpression of miR-663 in prostate LNCaP cells promotes cell proliferation and invasion, neuroendocrine differentiation, and reduction in dihydrotestosterone-induced upregulation of prostate-specific antigen expression. [J Cell Physiol] Abstract

Pifithrin-μ, an Inhibitor of Heat-Shock Protein 70, Can Increase the Antitumor Effects of Hyperthermia Against Human Prostate Cancer Cells
Researchers investigated the sensitizing effect of pifithrin-μ, a small molecule inhibitor of heat-shock protein 70 (HSP70), when three human prostate cancer cell lines were treated with hyperthermia (HT). All cell lines constitutively expressed HSP70, and HT further increased its expression in LNCaP and DU-145. [PLoS One] Full Article

Prostate Cancer Derived Prostatic Acid Phosphatase Promotes an Osteoblastic Response in the Bone Microenvironment
To demonstrate that prostatic acid phosphatase (PAP) promotes mineralization, scientists stimulated MC3T3-E1 cells with PAP and observed increased mineralization, which could be blocked with the specific PAP inhibitor, phosphonic acid. [Clin Exp Metastasis] Abstract

Inhibition of PARP1 by Small Interfering RNA Enhances Docetaxel Activity against Human Prostate Cancer PC3 Cells
Scientists revealed that inhibition of poly(ADP-ribose) polymerase 1 (PARP1) by small interfering RNA could enhance docetaxel’s activity against PC3 cells, which is associated with an accelerate repression of EGF/Akt/FOXO1 signaling pathway. [Biochem Biophys Res Commun] Abstract


Long-Term Survival and Biomarker Correlates of Tasquinimod Efficacy in a Multicenter Randomized Study of Men with Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer
Tasquinimod is an oral immunomodulatory, anti-angiogenic, and anti-metastatic agent that delayed metastatic disease progression in a randomized placebo-controlled Phase II trial in men with metastatic castration-resistant prostate cancer. Here, researchers report long-term survival with biomarker correlates from this trial. [Clin Cancer Res] Abstract | Press Release

Immunohistochemical Expression of PDGFR, VEGF-C, and Proteins of the mToR Pathway before and after Androgen Deprivation Therapy in Prostate Carcinoma: Significant Decrease after Treatment
Platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor C (VEGF-C), mammalian target of rapamycin (mToR), and p70 ribosomal protein S6 kinase 1 expression was significantly reduced after androgen deprivation therapy (ADT), whereas expression of epidermal growth factor receptor, human epidermal growth factor receptor 2, and carbonic anhydrase IX was not influenced by ADT. [Target Oncol] Abstract

Diethylstilbestrol for the Treatment of Patients with Castration-Resistant Prostate Cancer: Retrospective Analysis of a Single Institution Experience
Investigators evaluated the efficacy and safety of diethylstilbestrol (DES) as treatment for patients with castration-resistant prostate cancer and to identify predicting factors of response to DES. [Oncol Rep] Abstract

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Diethylstilboestrol for the Treatment of Prostate Cancer: Past, Present and Future
The authors discuss the most recent data from current trials of diethylstilboestrol to identify its present role in advanced prostate cancer treatment as new hormonal therapies emerge. [Scand J Urol] Abstract

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OncoGenex Announces Update on Phase III SYNERGY Trial Evaluating Custirsen in Men with Metastatic Castrate-Resistant Prostate Cancer
OncoGenex Pharmaceuticals, Inc. announced that the SYNERGY trial is continuing as planned per the recommendation of the Independent Data Monitoring Committee. The primary registration Phase III SYNERGY trial is designed to evaluate a survival benefit for custirsen in combination with first-line docetaxel chemotherapy in men with metastatic castrate-resistant prostate cancer. [OncoGenex Pharmaceuticals, Inc.] Press Release

Transparency Life Sciences Partners with Oncology Researchers at Icahn School Of Medicine at Mount Sinai to Assess Metformin in Prostate Cancer
Transparency Life Sciences, LLC, the world’s first drug development company based on open innovation, announced that it is collaborating with Dr. Matthew Galsky, Associate Professor of Medicine, Division of Hematology/Oncology at the Icahn School of Medicine at Mount Sinai, to design and conduct a pilot trial assessing metformin as a potential treatment for prostate cancer. [PR Newswire Association LLC]
Press Release

ZYTIGA® Now Available for Men with Metastatic Prostate Cancer in British Columbia Prior to Chemotherapy
Effective November 15, 2013, British Columbia is the first province to include ZYTIGA® on its public formulary for men living with metastatic prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy. [Janssen Inc.] Press Release

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NEW Lorne Cancer Conference
February 13-15, 2014
Mantra Lorne, Australia

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NEW Postdoctoral Researcher – Prostate Cancer (NUI Galway)

NEW Postdoctoral Fellow – Mechanisms Promoting Castrate Resistant Prostate Cancer (Mount Sinai School of Medicine)

PhD Studentship – Prostate Cancer Research (Cardiff University)

Postdoctoral Fellow – Development and Progression of Prostate Cancer (University of Maryland Baltimore, School of Medicine)

Postdoctoral Fellow / Instructor Position – Endocrine Therapies for Cancer (Baylor College of Medicine)

Experienced Researcher Position – Molecular Biology (ServiceXS B.V.)

Postdoctoral Position – Prostate Cancer Biology (University Of Rochester School Of Medicine)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

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