Prostate Cell News Volume 8.09 | Mar 10 2017

TOP STORY

By Boosting Innate Immunity, Researchers Eradicate Aggressive Prostate Cancer in Mice

Cabozantinib, a drug already used to treat patients with certain types of thyroid or kidney cancer, was able to eradicate invasive prostate cancers in mice by causing tumor cells to secrete factors that entice neutrophils – the first-responders of the immune system – to infiltrate the tumor, where they triggered an immune response that led to tumor clearance. [Press release from place discussing online prepublication in the journal Cancer Discovery] Press Release | Abstract

(Ranked by impact factor of the journal)

LABORATORY RESEARCH

Lineage Specification from Prostate Progenitor Cells Requires Gata3-Dependent Mitotic Spindle Orientation

Investigators report that GATA3 is expressed in both prostate basal progenitor and luminal cells and that loss of GATA3 leads to a mislocalization of PRKCZ, resulting in mitotic spindle randomization during progenitor cell division. [Stem Cell Reports] Full Article | Graphical Abstract

miR-875-5p Counteracts Epithelial-to-Mesenchymal Transition and Enhances Radiation Response in Prostate Cancer through Repression of the EGFR-ZEB1 Axis

Researchers demonstrated that reconstitution of miR-875-5p, whose expression is down-regulated in prostate cancer (PCa) clinical samples and directly correlates with that of E-cadherin, was able to enhance radiation response in PCa cell lines and xenografts through EGFR direct targeting. Consistent with the established role of EGFR in sustaining epithelial-to-mesenchymal transition (EMT) and promoting DNA repair following radiation-induced nuclear translocation, they found that miR-875-5p reconstitution in PCa cells counteracted EMT and impaired DNA lesion clearance. [Cancer Lett] Abstract

1,4-Substituted Triazoles as Non-Steroidal Antiandrogens for Prostate Cancer Treatment

Investigators report the preparation of a small library of novel 1,4-substituted triazoles with androgen receptor (AR) antagonistic activity. Biological and theoretical evaluation demonstrated that the introduction of the triazole core in the scaffold of non-steroidal antiandrogens allowed the development of small molecules with improved overall AR-antagonist activity. Compound 14d displayed promising in vitro antitumor activity toward three different prostate cancer cell lines and was able to induce 60% tumor growth inhibition of the CW22Rv1 in vivo xenograft model. [J Med Chem] Abstract

Androgen Receptor Is a Potential Novel Prognostic Marker and Oncogenic Target in Osteosarcoma with Dependence on CDK11

Scientists performed cyclin-dependent kinase 11 (CDK11) siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes between CDK11 knock down and wild type osteosarcoma cells. Reconstructed networks of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. [Sci Rep] Full Article

Activation of Mutated TRPA1 Ion Channel by Resveratrol in Human Prostate Cancer Associated Fibroblasts (CAF)

The authors investigated the effects of resveratrol (RES) on the physiology of prostate cancer (PCa) CAF in the context of tumor microenvironment (TME). Using a prostate cancer CAF cell line and primary cultures of CAF from prostate cancers, they showed that RES activates the N-terminal mutated transient receptor potential ankyrin 1 (TRPA1) channel leading to an increase in intracellular calcium concentration and the expression and secretion of growth factors without inducing apoptosis in these cells. [Mol Carcinog] Abstract

Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator

Transwell assays were performed to evaluate the effects of aspirin on cell invasion. INvestigators found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 and upregulation of tissue inhibitors of metalloproteinase-1 activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. [Cell Physiol Biochem] Full Article

Cyproterone Acetate Enhances TRAIL-Induced Androgen-Independent Prostate Cancer Cell Apoptosis via Up-Regulation of Death Receptor 5

Researchers report the effects of cyproterone acetate, an antiandrogen steroid, on the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of androgen receptor (AR)-negative prostate cancer cells. Cyproterone acetate but not AR antagonist bicalutamide dramatically increased the susceptibility of androgen receptor-negative human prostate cancer PC-3 and DU145 cells to TRAIL-induced apoptosis but no effects on immortalized human prostate stromal PS30 cells and human embryonic kidney HEK293 cells. [BMC Cancer] Full Article

The Effects of 1,4-Dimethylpyridine in Metastatic Prostate Cancer in Mice

The authors investigated whether the previously observed activity of pyridine compounds pertains also to the prevention and the treatment of metastatic prostate tumors, in a combined chemotherapy with docetaxel. The development of prostate tumors in TRAMP mice remained unaffected after administration of 1,4-dimethylpyridine. [BMC Cancer] Full Article

CLINICAL RESEARCH

Phase II Study of Circulating MicroRNA Biomarkers in Castration-Resistant Prostate Cancer

Previously in a Phase I discovery study, scientists identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. They performed a Phase II validation study to verify these findings. They found that the microRNAs were not associated with docetaxel response in the Phase II cohort. [Br J Cancer] Abstract

Long Non-Coding RNA as Potential Biomarker for Prostate Cancer: Is It Making a Difference?

The authors focus on long non-coding (lnc)RNA biomarkers that are already available for clinical use and provides an overview of lncRNA biomarkers that are under investigation for clinical development in prostate cancer. [Int J Environ Res Public Health] Full Article

Visit our reviews page to see a complete list of reviews in the prostate cell research field.

Nonsurgical Treatment for Enlarged Prostate Remains Effective for Years

According to research presented, a minimally invasive treatment that reduces urinary tract symptoms for men with enlarged prostates maintains its effectiveness for at least three years after patients undergo the therapy. [Press release from the Society of Interventional Radiology (SIR) discussing research presented at the SIR’s 2017 Annual Scientific Meeting, Washington, D.C.] Press Release

Defense Department Award Funds Prostate Cancer Study

Weill Cornell Medicine researchers will receive a grant from the Department of Defense to conduct an in-depth study of the molecular machinery driving the most aggressive form of prostate cancer. The grant, an Impact Award, will provide a Weill Cornell Medicine research team with three years of funding to identify patients who are at risk of developing neuroendocrine prostate cancer and to advance early treatment strategies to prevent that progression. [Cornell University] Press Release

BioPact’s MGMR^® Drug Delivery Technology Succeeds in Transporting Cell Impermeable Peptides across Cell Membrane Triggering 100% Cancer Cell Death

BioPact’s nanodelivery technology, MGMR^®, demonstrated highly efficacious intracellular delivery of KLAKLAK, a pro-apoptotic peptide known to be cell membrane impermeable. When loaded on MGMR, KLAKLAK crossed the cell membrane of LNCaP human prostate cancer cells, triggering apoptosis in 100% of the cells in repeated studies. [BioPact Ventures, LLC] Press Release

Patchy Progress on Fixing Global Gender Disparities in Science

Although women are publishing more studies, being cited more often, and securing more coveted first-author positions than they were in the mid 1990s, overall progress towards gender parity in science varies widely by country and field. This is according to a massive report released on 8^th March that is the first to examine such a broad swath of disciplines and regions of the world over time. [Nature News] Editorial

Open-Data Contest Unearths Scientific Gems — and Controversy

When a prestigious medical journal challenged scientists to analyze data from a pivotal blood-pressure study in search of new findings, hundreds of researchers around the world rushed to sign up. The contest, sponsored by the New England Journal of Medicine, offered scientists a rare opportunity to access detailed trial data that otherwise might have remained proprietary for another year — if not indefinitely. But the competition, whose winners were announced on 7^th March, also illustrates the tension between speeding access to data and protecting the interests of those who labored to collect them. [Nature News] Editorial

NEW AACR International Conference on Translational Cancer Medicine
May 4-6, 2017
Sao Paulo, Brazil

NEW Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging
May 21-26, 2017
West Palm Beach, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Fellow – Urological Cancers (Institute of Cancer Research)

NEW PhD Student – Prostate Cancer Research (Vancouver Prostate Center)

Research Assistant – Prostate Cancer Immunotherapeutics (King’s College London)

Postdoctoral Fellow – Prostate Histology (Delft University of Technology)

Assistant/Associate Professor – Urology (Northwestern University)

Postdoctoral Position – Genomics and Molecular Biology (The George Washington University)

PhD Studentships – Translational Research Network for Prostate Cancer (University of Glasgow)

Postdoctoral Researcher – Confocal Raman Spectroscopy and Digital Holographic Microscopy (Maynooth University)

Postdoctoral Researcher – Prostate Cancer Immunotherapy (University of Chicago)

Postdoctoral Fellow – Prostate Cancer Biology (Weill Cornell Medicine)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College / Geisel School of Medicine)

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