Prostate Cell News Volume 8.18 | May 19 2017

TOP STORY

In Vivo Hemin Conditioning Targets the Vascular and Immunological Compartments and Restrains Prostate Tumor Development

The authors assessed how hemin, a pharmacological inducer of Heme Oxygenase-1, impacts upon prostate cancer development in an in vivo conditioning model. The stroma of C57BL/6 mice was conditioned by subcutaneous administration of hemin prior to TRAMP-C1 tumor challenge. Complementary in vitro and in vivo assays were performed to evaluate hemin effect on both angiogenesis and the immune response. [Clin Cancer Res] Abstract

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LABORATORY RESEARCH

Increased T Cell Infiltration Elicited by Erk5 Deletion in a Pten-Deficient Mouse Model of Prostate Carcinogenesis

Researchers report evidence that ablating the growth regulatory kinase Erk5 can increase T cell infiltration in an established Pten-deficient mouse model of human prostate cancer. Mice that were doubly mutant in prostate tissue for Pten and Erk5 exhibited a markedly increased median survival with reduced tumor size and proliferation compared to control Pten-mutant mice, the latter of which exhibited increased Erk5 mRNA expression. [Cancer Res] Abstract

ING3 Promotes Prostate Cancer Growth by Activating the Androgen Receptor

Biopsies of 265 patients with prostate cancer were stained for inhibitor of growth (ING) 3, pan-cytokeratin, and DNA. LNCaP and C4-2 androgen-responsive cells were used for in vitro assays including immunoprecipitation, western blotting, Luciferase reporter assay and quantitative polymerase chain reaction. Cell viability and migration assays were performed in prostate cancer cell lines using scrambled siRNA or siRNA targeting ING3. [BMC Med] Full Article

RET-Mediated Glial Cell Line Derived Neurotrophic Factor Signaling Inhibits Mouse Prostate Development

Investigators established novel roles of glial cell line-derived neurotrophic factor (GDNF) signaling in mouse prostate development. Utilizing an organ culture system for prostate development and Ret mutant mice, they demonstrated that RET-mediated GDNF signaling in urogenital sinus increased proliferation of mesenchyme cells and suppressed androgen-induced proliferation and differentiation of prostate epithelial cells, inhibiting prostate development. [Development] Abstract

Kallikrein-Related Peptidase 4 Induces Cancer-Associated Fibroblast Features in Prostate-Derived Stromal Cells.

Scientists report that kallikrein-related peptidase-4 (KLK4) promotes cancer-associated fibroblasts (CAF) differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant and malignant lesions compared to normal prostate epithelia, especially at the peri-stromal interface. KLK4 induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line, including increased expression of alpha-SMA, ESR1 and SFRP1. [Mol Oncol] Abstract | Full Article

Up Regulation and Nuclear Translocation of Y-Box Binding Protein 1 (YB-1) Is Linked to Poor Prognosis in ERG-Negative Prostate Cancer

YB-1 is an RNA and DNA binding factor with potential prognostic cancer. To evaluate the clinical impact of YB-1, a tissue microarray with 11,152 prostate cancers was analyzed by immunohistochemistry. Cytoplasmic and nuclear staining was separately analyzed. Cytoplasmic YB-1 was absent or weak in normal epithelium but seen in 86.3% of carcinomas. [Sci Rep] Full Article

The Prohibitin-Repressive Interaction with E2F1 Is Rapidly Inhibited by Androgen Signaling in Prostate Cancer Cells

Scientists investigated the mechanisms of cell cycle inhibition by prohibitin (PHB) and how this is modulated by androgen receptor in prostate cancer. Using a prostate cancer cell line overexpressing PHB, they analyzed the gene expression changes associated with PHB-mediated cell cycle arrest. [Oncogenesis] Full Article

Glutamine Transporters are Targets of Multiple Oncogenic Signaling Pathways in Prostate Cancer

Investigators demonstrated that androgens increase the metabolism of glutamine in prostate cancer (PCa) cells. This metabolism was required for maximal cell growth under conditions of serum starvation. Mechanistically, androgen receptor signaling promoted glutamine metabolism by increasing the expression of the glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in PCa. [Mol Cancer Res] Abstract

CLINICAL RESEARCH

Phase II Trial of the PI3 Kinase Inhibitor Buparlisib (BKM-120) with or without Enzalutamide in Men with Metastatic Castration Resistant Prostate Cancer

Researchers performed multisite single arm Phase II trial of buparlisib 100 mg ± enzalutamide daily in men with metastatic castration resistant prostate cancer whose disease progressed on or who were not candidates for docetaxel. The primary end-point was the rate of radiographic/clinical progression-free survival at six months. [Eur J Cancer] Abstract

Advances in Medical Imaging for the Diagnosis and Management of Common Genitourinary Cancers

Medical imaging of the 3 most common genitourinary (GU) cancers—prostate adenocarcinoma, renal cell carcinoma, and urothelial carcinoma of the bladder—has evolved significantly during the last decades. The most commonly used imaging modalities for the diagnosis, staging, and follow-up of GU cancers are computed tomography, magnetic resonance imaging, and positron emission tomography. [Urol Oncol] Full Article

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Aytu BioScience Presents New Research Findings for Its Natesto^® Testosterone Nasal Gel

Aytu BioScience, Inc. announced that it presented one poster presentation illustrating safety benefits of Natesto^® therapy and its preservation of pituitary gonadotropin hormones, which are integral in male fertility. [Press release from Aytu BioScience, Inc. discussing research presented at the 112^th American Urological Association Annual Meeting, Boston] Press Release

Dendreon Announces Results of New PROCEED Registry Analysis Showing Overall Survival Benefit with PROVENGE^® in Men with Metastatic Prostate Cancer

Dendreon announced findings from a new analysis of its PROCEED registry, which followed men with metastatic castrate-resistant prostate cancer treated with PROVENGE^® in a real-world treatment setting. The analysis found that African-American patients demonstrated an additional median OS benefit of 9.3 months compared with Caucasian patients. [Press release from Dendreon discussing research presented at the 112^th American Urological Association Annual Meeting, Boston] Press Release

Tolmar Pharmaceuticals Announces That FDA Approval Has Been Received for Eligard (Leuprolide Acetate for Injectable Suspension) Storage at Room Temperature for up to Eight Weeks

TOLMAR Pharmaceuticals, Inc. announced that approval has been received from FDA for a label update for ELIGARD^®, indicated for the palliative treatment of advanced prostate cancer. Stability studies demonstrated that, prior to mixing, ELIGARD may be stored at room temperature for up to eight weeks following removal from refrigeration. [TOLMAR Pharmaceuticals, Inc.] Press Release

CSHL to Lead International Team Developing Next-Generation Organoid Cancer Research Models

Cold Spring Harbor Laboratory (CSHL) has been awarded a research subcontract by Leidos Biomedical Research to lead a Cancer Model Development Center for pancreatic, breast, colorectal, lung, liver and other upper-gastrointestinal cancers. The new center will generate three-dimensional organoid culture systems of cancers – next-generation models that improve upon current two-dimensional model systems used to study cancers and develop therapeutics [Cold Spring Harbor Laboratory] Press Release

NEW Tumor Immunology and Immunotherapy
October 1-4, 2017
Boston, United States

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NEW Assistant Professor – Prostate Cancer, Carcinogenesis and Chemoprevention, Advanced Tissue Imaging (University of Illinois at Chicago)

Pathology Clinical Research Fellow – Treatment of Men with Advanced Prostate Cancer (Institute of Cancer Research)

Postdoctoral Fellow – Androgen Action in Prostate Cancer (Lerner Research Institute, Cleveland Clinic)

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

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 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)

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