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https://www.readbyqxmd.com/read/29849951/frequently-rearranged-and-overexpressed-%C3%AE-catenin-is-responsible-for-low-sensitivity-of-prostate-cancer-cells-to-androgen-receptor-and-%C3%AE-catenin-antagonists
#1
Piyan Zhang, Janet Schaefer-Klein, John C Cheville, George Vasmatzis, Irina V Kovtun
The mechanism of prostate cancer (PCa) progression towards the hormone refractory state remains poorly understood. Treatment options for such patients are limited and present a major clinical challenge. Previously, δ-catenin was reported to promote PCa cell growth in vitro and its increased level is associated with PCa progression in vivo. In this study we show that re-arrangements at Catenin Delta 2 (CTNND2) locus, including gene duplications, are very common in clinically significant PCa and may underlie δ-catenin overexpression...
May 11, 2018: Oncotarget
https://www.readbyqxmd.com/read/29786792/protocols-for-the-study-of-taxanes-chemosensitivity-in-prostate-cancer
#2
M Luz Flores, Carmen Sáez
Prostate cancer is major cause of cancer-related death among men in Western countries. Locally advanced prostate cancers are treated with castration therapy, which is initially effective, but after months the disease progresses to a hormone-refractory state whose treatment is chemotherapy based on taxanes. Although taxanes improve the survival of patients with castration-resistant prostate cancers, these patients often develop chemotherapy resistance, and new therapeutic strategies are necessary. Taxanes exert their action through interaction with β-tubulin which triggers cell cycle arrest in mitosis and the subsequent induction of the intrinsic apoptotic pathway...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29730257/regulation-of-the-antioxidant-response-by-myod-transcriptional-coactivator-in-castration-resistant-prostate-cancer-cells
#3
Shun Zhang, Lin-Hu Li, Hong-Mei Qiao, Xue Yang, Liang Chen, Xiao-Hui Luo
OBJECTIVE: To reveal the potential role of the basic helix-loop-helix myogenic transcription regulator MyoD in the regulation of of castration-resistant prostate cancer (CRPC). METHODS: Expression levels of MyoD was assessed in PCa tissues using quantitative RT-PCR (RT-qPCR) and immunohistochemistry and in experimentally induced castration-resistant LNCaP/R cells using RT-qPCR and immunoblotting. Effect of MyoD knockdown on LNCaP/R cells progression was determined by assessing cell proliferation, apoptosis and colony formation rate...
May 3, 2018: Urology
https://www.readbyqxmd.com/read/29714668/-223-ra-chloride-therapy-in-men-with-hormone-refractory-prostate-cancer-and-skeletal-metastases-real-world-experience
#4
Giuseppe Boni, Sara Mazzarri, Claudia Cianci, Luca Galli, Azzurra Farnesi, Eugenio Borsatti, Roberto Bortolus, Lucia Fratino, Carlo Gobitti, Elda Lamaj, Pietro Ghedini, Elisa Lodi Rizzini, Francesco Massari, Valeria Dionisi, Stefano Fanti, Duccio Volterrani, Fabio Monari
BACKGROUND: Radium-223 (223 Ra) chloride, an alpha emitter, has been shown to improve overall survival (OS) and pain control, and to delay skeletal-related events, in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Our retrospective observational study presents the first Italian experience on the efficacy and safety of 223 Ra therapy in routine clinical practice. METHODS: A total of 83 patients with metastatic CRPC were treated with 223 Ra at 3 Italian centers between August 2013 and August 2016...
April 1, 2018: Tumori
https://www.readbyqxmd.com/read/29666834/androgen-action-in-prostate-function-and-disease
#5
REVIEW
Partha P Banerjee, Subhadra Banerjee, Terry R Brown, Barry R Zirkin
Benign prostatic hyperplasia (BPH) is an enlargement of the prostate gland that is frequently found in aging men. Androgens are essential for the development and differentiated function of the prostate, as well as for proliferation and survival of prostatic cells. In man, dog and rodent, there are age-related decreases in serum testosterone. Despite the lower serum testosterone levels, benign prostatic hyperplasia increases with age in men and dogs, while age-dependent prostatic hyperplasia develops in the dorsal and lateral lobes of the rat prostate...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29658567/hepacam-inhibits-the-malignant-behavior-of-castration-resistant-prostate-cancer-cells-by-downregulating-notch-signaling-and-pf-3084014-a-%C3%AE-secretase-inhibitor-partly-reverses-the-resistance-of-refractory-prostate-cancer-to-docetaxel-and-enzalutamide-in-vitro
#6
Zhongbo Du, Luo Li, Wei Sun, Xiao Wang, Yao Zhang, Zhixiong Chen, Mengjuan Yuan, Zhen Quan, Nanjing Liu, Yanni Hao, Ting Li, Jinhua Wang, Chunli Luo, Xiaohou Wu
Castration-resistant prostate cancer (CRPC) continues to be a major challenge in the treatment of prostate cancer (PCa). The expression of hepatocyte cell adhesion molecule (HepaCAM), a novel tumor suppressor, is frequently downregulated or lost in PCa. Overactivated Notch signaling is involved in the development and progression of PCa, including CRPC. In this study, we found that the activities of Notch signaling were elevated, while HepaCAM expression was decreased in CRPC tissues compared with matched primary prostate cancer (PPC) tissues...
July 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29487219/a-phase-ii-trial-of-selinexor-an-oral-selective-inhibitor-of-nuclear-export-compound-in-abiraterone-and-or-enzalutamide-refractory-metastatic-castration-resistant-prostate-cancer
#7
Xiao X Wei, Adam P Siegel, Rahul Aggarwal, Amy M Lin, Terence W Friedlander, Lawrence Fong, Won Kim, Mirela Louttit, Emily Chang, Li Zhang, Charles J Ryan
LESSONS LEARNED: In abiraterone- and/or enzalutamide-refractory metastatic castration-resistant prostate cancer (mCRPC) patients, selinexor led to prostate-specific antigen and/or radiographic responses in a subset of patients, indicating clinical activity in this indication.Despite twice-a-week dosing and maximal symptomatic management, selinexor was associated with significant anorexia, nausea, and fatigue in mCRPC patients refractory to second-generation anti-androgen therapies, limiting further clinical development in this patient population...
February 27, 2018: Oncologist
https://www.readbyqxmd.com/read/29432837/vitamin-k2-a-menaquinone-present-in-dairy-products-targets-castration-resistant-prostate-cancer-cell-line-by-activating-apoptosis-signaling
#8
Subramanyam Dasari, Angela Lincy Prem Antony Samy, Andre Kajdacsy-Balla, Maarten C Bosland, Gnanasekar Munirathinam
The aim of this study was to evaluate the therapeutic effects of vitamin K2 (VK2) on castration-resistant prostate cancer (CRPC) and its anti-cancer mechanisms in a pre-clinical study using a VCaP cell line (ATCC® CRL-2876™) which was established from a vertebral bone metastasis from a patient with hormone refractory prostate cancer. Our data showed that VK2 significantly inhibited CRPC VCaP cell proliferation in a dose-dependent manner at 48 h treatment in vitro. In addition, VK2 reduced the migration potential of VCaP cells and inhibited anchorage-independent growth of these cells...
February 9, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29327812/hyper-acetylation-contributes-to-the-sensitivity-of-chemo-resistant-prostate-cancer-cells-to-histone-deacetylase-inhibitor-trichostatin-a
#9
Qingqing Xu, Xiaofei Liu, Shiqin Zhu, Xuelei Hu, Huanmin Niu, Xiulei Zhang, Deyu Zhu, Effat Un Nesa, Keli Tian, Huiqing Yuan
Therapeutic agents are urgently needed for treating metastatic castration-refractory prostate cancer (mCRPC) that is unresponsive to androgen deprivation and chemotherapy. Our screening assays demonstrated that chemotherapy-resistant prostate cancer (PCa) cells are more sensitive to HDAC inhibitors than paired sensitive PCa cells, as demonstrated by cell proliferation and apoptosis in vitro and in vivo. Kinetic study revealed that TSA-induced apoptosis was significantly dependent on enhanced transcription and protein synthesis in an early stage, which subsequently caused ER stress and apoptosis...
March 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29290796/prlz-increases-prostate-cancer-docetaxel-resistance-by-inhibiting-lkb1-ampk-mediated-autophagy
#10
Jin Zeng, Wei Liu, Yi-Zeng Fan, Da-Lin He, Lei Li
Rationale : Docetaxel-mediated chemotherapy is the first-line standard approach and has been determined to show a survival advantage for metastatic castration-resistant prostate cancer (mCRPC) patients. However, a substantial proportion of patients eventually becomes refractory due to drug resistance. The detailed mechanisms remain unclear. We have previously reported that Prostate Leucine Zipper (PrLZ), a specific oncogene of prostate cancer (PCa), promotes PCa cell growth at the castration-resistant stage, thus suggesting a vital role of PrLZ in the progression of CRPC...
2018: Theranostics
https://www.readbyqxmd.com/read/29212226/transcribed-ultraconserved-region-uc-63-promotes-resistance-to-docetaxel-through-regulation-of-androgen-receptor-signaling-in-prostate-cancer
#11
Yohei Sekino, Naoya Sakamoto, Keisuke Goto, Ririno Honma, Yoshinori Shigematsu, Kazuhiro Sentani, Naohide Oue, Jun Teishima, Akio Matsubara, Wataru Yasui
Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance. The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29173976/phase-2-study-of-weekly-paclitaxel-plus-estramustine-in-metastatic-hormone-refractory-prostate-carcinoma-ecog-acrin-cancer-research-group-e1898-trial
#12
Yu-Ning Wong, Judith Manola, Gary R Hudes, Bruce J Roth, Judd W Moul, Andrea M Barsevick, Richard M Scher, Michael J Volk, David J Vaughn, Stephen D Williams, Michael J Fisch, David Cella, Michael A Carducci, George Wilding
INTRODUCTION: This multicenter phase 2 study assessed the combination of estramustine and weekly paclitaxel with metastatic castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: We enrolled 77 patients who had received no prior chemotherapy for CRPC between 1998 and 2000; a total of 74 subjects were eligible for the study. Each 8-week cycle included paclitaxel 90 mg/m2 provided intravenously weekly for 6 weeks, followed by 2 weeks off therapy and oral estramustine 280 mg twice daily for 3 days beginning 24 hours before the first dose of paclitaxel...
April 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29153623/abiraterone-acetate-prednisolone-treatment-beyond-prostate-specific-antigen-and-radiographic-progression-in-metastatic-castration-resistant-prostate-cancer-patients
#13
Krisztina Biró, Barna Budai, Márta Szőnyi, Zsófia Küronya, Fruzsina Gyergyay, Krisztián Nagyiványi, Lajos Géczi
OBJECTIVES: To investigate the overall survival (OS) of chemotherapy refractory patients with metastatic castration-resistant prostate cancer who were treated with abiraterone acetate + prednisolone (AA + P) beyond prostate specific antigen (PSA) and radiographic progression (PRP) until clinical progression in comparison to patients treated until PRP. METHODS: At our institute the AA + P treatment started in 2011 in an early-access protocol trial. In October 2012 AA became generally available...
February 2018: Urologic Oncology
https://www.readbyqxmd.com/read/29142311/a-standardized-herbal-extract-mitigates-tumor-inflammation-and-augments-chemotherapy-effect-of-docetaxel-in-prostate-cancer
#14
Chin-Hsien Tsai, Sheue-Fen Tzeng, Shih-Chuan Hsieh, Yu-Chih Yang, Yi-Wen Hsiao, Mong-Hsun Tsai, Pei-Wen Hsiao
Activation of the NFκB pathway is often associated with advanced cancer and has thus been regarded as a rational therapeutic target. Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Interestingly, our evaluation of a standardized Wedelia chinensis herbal extract (WCE) concluded its efficacy on hormone-refractory prostate cancer through systemic mechanisms. Oral administration of WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 and DU145 xenografts...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100389/targeting-hsp27-eif4e-interaction-with-phenazine-compound-a-promising-alternative-for-castration-resistant-prostate-cancer-treatment
#15
Hajer Ziouziou, Claudia Andrieu, Erik Laurini, Sara Karaki, Maurizio Fermeglia, Ridha Oueslati, David Taieb, Michel Camplo, Olivier Siri, Sabrina Pricl, Maria Katsogiannou, Palma Rocchi
The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype. However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be accompanied with cytotoxic effects. To avoid this problem, an alternative therapeutic strategy relies on the identification and use of compounds that disrupt specific protein-protein interactions involved in androgen withdrawal...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29094395/estrogen-receptor-signaling-in-prostate-cancer-implications-for-carcinogenesis-and-tumor-progression
#16
REVIEW
Helmut Bonkhoff
BACKGROUND: The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression. METHODS: Recent experimental and clinical data were reviewed to elucidate pathogenetic mechanisms how estrogens and their receptors may affect prostate carcinogenesis and tumor progression. RESULTS: The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells...
January 2018: Prostate
https://www.readbyqxmd.com/read/29061069/effects-of-ferroportin-mediated-iron-depletion-in-cells-representative-of-different-histological-subtypes-of-prostate-cancer
#17
Zhiyong Deng, David H Manz, Suzy V Torti, Frank M Torti
AIMS: Ferroportin (FPN) is an iron exporter that plays an important role in cellular and systemic iron metabolism. Our previous work has demonstrated that FPN is decreased in prostate tumors. We sought to identify the molecular pathways regulated by FPN in prostate cancer cells. RESULTS: We show that overexpression of FPN induces profound effects in cells representative of multiple histological subtypes of prostate cancer by activating different but converging pathways...
December 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29022046/-radium-223-dichloride-in-patients-with-castration-refractory-prostate-cancer
#18
REVIEW
B M Winter, F-C von Rundstedt, M-O Grimm
Since November 2013, the alpha emitter radium-223 dichloride (Alpharadin/Xofigo®) has been approved for the treatment of men with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. In the ASYMPCA clinical trial, radium-223 was shown to improve overall survival and to reduce the time to the first symptomatic skeletal event. The use of radium-223 was associated with a reduction of pain and an improvement of health-related quality of life compared to the placebo arm...
November 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28928839/analysis-of-resistance-associated-gene-expression-in-docetaxel-resistant-prostate-cancer-cells
#19
Sangchul Lee, Kwangtaek Kim, Jin-Nyoung Ho, Hyunjin Jin, Seok-Soo Byun, Eunsik Lee
Docetaxel-based chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (CRPC). However, a number of patients with metastatic CRPC are refractory to docetaxel or develop docetaxel resistance. The underlying molecular mechanisms of docetaxel resistance remain unclear, which is a significant burden to the management of metastatic prostate cancer. In the present study, the differential gene expression between docetaxel-sensitive (PC3) and docetaxel-resistant (PC3DR2) prostate cancer cells was identified using DNA microarrays, western blot analysis and reverse transcription-quantitative polymerase chain reaction...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28874892/treatment-patterns-and-trends-in-patients-dying-of-prostate-cancer-in-quebec-a-population-based-study
#20
A Dragomir, J Rocha, M Vanhuyse, F L Cury, W Kassouf, J Hu, A G Aprikian
INTRODUCTION: Since just after the year 2000 in Quebec, the management of metastatic castration-resistant prostate cancer (mcrpc) has evolved considerably, with the inclusion of docetaxel-based chemotherapy, bone-targeted therapies (zoledronic acid and denosumab), and more recently, abiraterone, enzalutamide, and cabazitaxel for docetaxel-refractory patients. In the present study, we aimed to analyze contemporary mcrpc management patterns and therapy utilization trends in Quebec. METHODS: The study cohort consisted of patients dying of prostate cancer (pca) between January 2001 and December 2013, selected from Quebec public health care insurance databases...
August 2017: Current Oncology
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