Prostate Cell News 9.22 June 15, 2018 | |
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TOP STORYScientists identified and characterized a somatically acquired androgen receptor (AR) enhancer located 650 kb centromeric to the AR. Systematic perturbation of this enhancer using genome editing decreased proliferation by suppressing AR levels. Insertion of an additional copy of this region sufficed to increase proliferation under low androgen conditions and to decrease sensitivity to enzalutamide. [Cell] Abstract | Press Release | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Inactivation of CDK12 Delineates a Distinct Immunogenic Class of Advanced Prostate Cancer Researchers identified a novel subtype of prostate cancer typified by biallelic loss of CDK12 that is mutually exclusive with tumors driven by DNA repair deficiency, ETS fusions, and SPOP mutations. CDK12 loss was enriched in metastatic castration-resistant prostate cancer relative to clinically localized disease and characterized by focal tandem duplications that lead to increased gene fusions and marked differential gene expression. [Cell] Abstract | Press Release | Graphical Abstract Investigators reported that fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase reprogramed the energy metabolism of prostate cancer cells by regulating expression of lactate dehydrogenase (LDH) isozymes. FGFR1 increased LDHA stability through tyrosine phosphorylation and reduced LDHB expression by promoting its promoter methylation, thereby shifting cell metabolism from oxidative phosphorylation to aerobic glycolysis. [Cancer Res] Abstract | Full Article In vitro, the analogues SK33 and SK51 showed very potent antiandrogenic activity, monitored using LNCaP/androgen receptor (AR)-Luciferase cells where growth, PSA and luciferase activity were used as AR activity measurements. These compounds were 10-fold more potent than bicalutamide and 100-fold more potent than enobosarm within the LNCaP model. [Mol Cancer Ther] Abstract | Full Article Researchers demonstrated the antineoplastic activity of a potent, isoform selective and hydrolytically stable aldo-keto reductase 1C3 (AKR1C3) inhibitor (E)-3-(4-(3-methylbut-2-en-1-yl)-3-(3-phenylpropanamido)phenyl)acrylic acid (KV-37) which reduced prostate cancer cell growth in vitro and in vivo, and sensitized castration-resistant prostate cancer cell lines towards the anti-tumor effects of enzalutamide. [Mol Cancer Ther] Abstract The authors showed that silencing or inhibition of endogenous ANO1 inhibited cell growth, induced apoptosis and upregulated TNF-α expression in prostate cancer PC-3 cells. Enhancement of TNF-α signaling by ANO1 knockdown lead to upregulation of phosphorylated Fas-associated protein with death domain and caspase activation. [Cell Death Dis] Full Article Investigators found that at a physiological concentration, 25(OH)D3 (25D3), the precursor of 1,25D3 and an inactive form of vitamin D because of its much weaker binding activity to the vitamin D receptor compared with 1,25D3, had a gene expression profile similar to that of 1,25D3 in prostate cancer LNCaP cells. [Sci Rep] Full Article Researchers aimed to determine whether extracellular vessicles (EVs) from prostate cells with altered CD9 and CD151 expression could influence cellular behavior and increase the metastatic capabilities of non-tumorigenic prostate cells. Addition of EVs from RWPE1 cells with reduced CD9 or increased CD151 abundance resulted in increased invasion of RWPE1 cells, and increased migration in the case of high CD151 abundance. [Sci Rep] Full Article The putative tumor suppressor, INTS6, was activated by introducing a promoter-targeted small RNA into castration-resistant prostate cancer cells. Following gene activation, cell proliferation and motility were suppressed in vitro. Downregulation of Wnt/β-catenin signaling was observed during the activation period, and the impairment of β-catenin degradation reversed the tumor suppressor effects of INTS6. [Cell Cycle] Abstract Scientists modeled combination drug therapy in PC-3 human prostate cancer cells using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize compositions to achieve the most desirable result. MDRSM combinations were compared with combination index data from the Chou-Talalay method and were found to coincide. [Mol Pharmacol] Abstract | Full Article ASP6432 (potassium 1-(2-{[3,5-dimethoxy-4-methyl-N-(3-phenylpropyl)benzamido]methyl}-1,3-thiazole-4-carbonyl)-3-ethyl-2,2-dioxo-2λ6-diazathian-1-ide), exhibited potent and selective antagonistic activity against type 1 lysophosphatidic acid receptor (LPA1) in cells expressing LPA receptor subtypes. In human prostate stromal cells, ASP6432 significantly and concentration-dependently suppressed LPA-induced bromodeoxyuridine incorporation. [J Pharmacol Exp Ther] Abstract | Full Article | |
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REVIEWSIntratumor Heterogeneity in Prostate Cancer The authors present a comprehensive review of the various studies addressing intra-tumor heterogeneity in prostate cancer and in the context of that seen in other solid tumors. They discuss the impact of heterogeneity on clinical decision-making in treating both primary and metastatic lesions and how our understanding of this heterogeneity might help in developing better diagnostic tools and biomarkers and in guiding the selection of better therapeutic strategies. [Urol Oncol] Abstract Visit our reviews page to see a complete list of reviews in the prostate cell research field. | |
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INDUSTRY NEWSU.K. Creates £2.5B Investment Program to Help Startups Grow The U.K. has set up a £2.5 billion ($3.6 billion) patient capital program. The fund is part of an initiative to help British biotechs grow into standalone midsized businesses, rather than sell up at the first sign of a takeover bid from overseas. [Fierce Biotech] Press Release ITUS Corporation Announces First Commercial Focus for Cchek™ Will Be Prostate Cancer ITUS Corporation announced that it has chosen prostate cancer as the first commercial focus for its Cchek™, non-invasive liquid biopsy cancer detection platform. [ITUS Corporation] Press Release Astellas Pharma Inc. announced that it launched 40 mg XTANDI® tablets and 80 mg XTANDI® tablets in Japan for the treatment of castration-resistant prostate cancer, which add additional dosage forms to the previously available 40 mg XTANDI® Capsules. XTANDI® is an oral androgen receptor signaling inhibitor. [Astellas Pharma Inc.] Press Release Trials Begin of a Saliva Test for Prostate Cancer Doctors have begun a trial of a simple saliva test that aims to spot the top 10% of men who are most at risk of developing prostate cancer. The test draws on more than 150 DNA markers to identify the 10% of men who have nearly a threefold greater risk of the disease than the general population, and the 1% of men with a sixfold greater risk. [The Guardian] Press Release | |
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POLICY NEWSNew Zealand Appoints First Female Chief Scientific Adviser The New Zealand government has appointed biochemist Juliet Gerrard as its next chief scientific adviser — the first woman to hold the position. [Nature News] Editorial Bill to Encourage Generic-Drug Development Passes a Key Hurdle A key Senate committee voted to advance legislation that aims to spur the development of new generic drugs and in turn, lower drug prices. [Stat News] Editorial Sexual Harassment Is Rife in the Sciences, Finds Landmark US Study The analysis concludes that policies to fight the problem are ineffective because they are set up to protect institutions, not victims — and that universities, funding agencies, scientific societies and other organizations must take stronger action. [Nature News] Editorial House Bill Gives NIH a 3% Boost in 2019, to $38.3 Billion A draft bill released by a House of Representatives spending panel would give the National Institutes of Health (NIH) in Bethesda, Maryland, a $1.25 billion raise in 2019, to $38.3 billion. That is 3% more than this year’s level and $4.1 billion more than President Donald Trump’s administration had requested. [ScienceInsider] Editorial
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EVENTSNEW The American Society for Cell Biology (ASCB) Annual Meeting 2018 Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Cancer Research (Princess Margaret Cancer Centre) Postdoctoral Positions – Ribosome Modifications (University of Copenhagen) Research Fellow – Prostate Cancer (Sechenov University) Research Associate – Computational Biology (University College London) Academic Position – Cancer Research (Cedars-Sinai Medical Center) Postdoctoral Fellow – Prostate Cancer (Moffitt Cancer Center) Postdoctoral Associate – Prostate Research (Baylor College of Medicine) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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