Prostate Cell News Volume 4.25 | Jul 5 2013

Synthesis and Vaccine Evaluation of the Tumor Associated Carbohydrate Antigen RM2 from Prostate Cancer
The authors developed a [1+2+3] one-pot strategy to synthesize the RM2 antigen hexasaccharide that was proposed to be a prostate tumor antigen. The induced mouse antibodies mediated effective complement-dependent cytotoxicity against the prostate cancer cell line LNCap. [J Am Chem Soc] Abstract

JAK-STAT Blockade Inhibits Tumor Initiation and Clonogenic Recovery of Prostate Cancer Stem-Like Cells
Researchers showed that stem-like cells from prostate cancer patients secrete higher levels of IL-6 than their counterparts in non-neoplastic prostate. Tumor grade did not influence the levels of expression or secretion. Stem-like and progenitor cells expressed the IL-6 receptor gp80 with concomitant expression of pSTAT3. [Cancer Res] Abstract | Full Article

Cross Modulation between the Androgen Receptor Axis and Protocadherin-PC in Mediating Neuroendocrine Transdifferentiation and Therapeutic Resistance of Prostate Cancer
Researchers explored the potential relationship between the androgen receptor (AR) axis and a novel putative marker of neuroendocrine (NE) differentiation, the human male protocadherin-prostate cancer (PCDH-PC), in vitro and in human situations. They found evidence for an NE transdifferentiation process and PCDH-PC expression as an early-onset adaptive mechanism following androgen deprivation therapy and elucidated AR as a key regulator of PCDH-PC expression. [Neoplasia] Full Article

Chronic Exposure to Arsenic, Estrogen, and Their Combination Causes Increased Growth and Transformation in Human Prostate Epithelial Cells Potentially by Hypermethylation-Mediated Silencing of MLH1
Scientists evaluated the effects of chronic exposure to arsenic, estrogen, and their combination, on cell growth and transformation, and identified the mechanism behind these effects. Exposure to arsenic, estrogen, and their combinations increases cell growth and transformation in RWPE-1 cells. [Prostate] Abstract

Prostate Cancer Cells Differ in Testosterone Accumulation, Dihydrotestosterone Conversion, and Androgen Receptor Signaling Response to Steroid 5a-Reductase Inhibitors
The expression of three 5a-reductase isozymes, as determined by immunohistochemistry and qRT-PCR, was studied in five human prostate cancer cell lines. Prostate cancer cells were capable of accumulating testosterone to a level 15-50 times higher than that in the medium. The profile and expression of 5a-reductase isozymes did not predict the capacity to convert testosterone to dihydrotestosterone. [Prostate] Abstract

Targeted Delivery of Epirubicin to Cancer Cells by PEGylated A10 Aptamer
A10 (Apt), an aptamer for prostate-specific membrane anytigen (PSMA), was applied for targeted delivery of Epirubicin (Epi) to LNCaP cells. Flow cytometry analysis showed that PEG-Apt-Epi complex was internalized effectively to LNCaP cells, but not to PC3 cells. [J Drug Target] Abstract

In Vitro Antimetastatic Effect of Phosphatidylinositol 3-Kinase Inhibitor ZSTK474 on Prostate Cancer PC3 Cells
Antimetastatic activities of ZSTK474 were investigated in vitro by determining the effects on the main metastatic processes. ZSTK474 exhibited inhibitory effects on migration, invasion and adhesive ability of prostate cancer PC3 cells. Furthermore, ZSTK474 inhibited phosphorylation of Akt substrate-Girdin, and the secretion of matrix metalloproteinase, both of which were reported to be closely involved in migration and invasion. [Int J Mol Sci] Abstract | Full Article

Effects of Calorie Restriction and IGF-1 Receptor Blockade on the Progression of 22Rv1 Prostate Cancer Xenografts
Scientists hypothesized that combining calorie restriction with IGF-1 receptor blockade would have an additive effect on prostate cancer growth. Results showed that calorie restriction (CR) alone decreased final tumor weight, plasma insulin and IGF-1 levels, and increased apoptosis. The combination therapy (CR/(antibody) Ab) further decreased final tumor weight and proliferation, increased apoptosis in comparison to the Ad libitum feeding/intraperitoneal saline (Ad-lib) group, and lowered plasma insulin levels relative to the Ad-lib and Ad-lib/Ab groups. [Int J Mol Sci] Abstract | Full Article

CLINICAL RESEARCH

A Phase II Study of Intravenous Panobinostat in Patients with Castration-Resistant Prostate Cancer
This phase II study evaluated the efficacy of intravenous panobinostat in patients with castration-resistant prostate cancer who had previously received chemotherapy. The primary end point was 24-week progression-free survival. Of 35 enrolled patients, four were alive without progression of disease at 24 weeks. [Cancer Chemother Pharmacol] Abstract

The Effectiveness of the TAX 327 Nomogram in Predicting Overall Survival in Chinese Patients with Metastatic Castration-Resistant Prostate Cancer
Based on the results of TAX 327, a nomogram was developed to predict the overall survival of metastatic castration-resistant prostate cancer after first-line chemotherapy. The nomogram, however, has not been validated in an independent dataset, especially in a series out of clinical trials. Thus, the objective of the current study was to validate the TAX 327 nomogram in a community setting in China. [Asian J Androl] Abstract

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Sidra to Open First Reprogrammable Cell Therapy Facility in the Region
Sidra Medical and Research Center will open the MENA region’s first reprogrammable cell therapy facility as part of its state-of-the-art hospital and research center. The facility will investigate a novel treatment approach, called reprogrammable cell therapy, where cells are altered to treat or cure disease. [Sidra Medical and Research Center] Press Release

Immunocore and Genentech Enter Strategic Alliance to Develop ImmTACs for Multiple Cancer Targets
Immunocore Limited, the Oxford-based biotechnology company developing novel biological drugs known as ImmTACs to treat cancer and viral disease, announced that it has entered into a research collaboration and licensing agreement with Genentech, a member of the Roche Group for the discovery and development of multiple novel cancer targets using Immunocore’s ImmTAC technology. [Immunocore Limited] Press Release

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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Project Scientist – Prostate Cancer Research (University of California at Los Angeles)

Postdoctoral Position – Cancer Biology and Chemotherapy Resistance (Dalhousie University)

Postdoctoral Fellow – Drug Discovery/GU Oncology (Moffitt Cancer Center & Research Institute)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Postdoctoral Position – Castrate Resistant Prostate Cancer (Mount Sinai School)

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

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