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https://www.readbyqxmd.com/read/29156772/stat3-and-stat5a-are-potential-therapeutic-targets-in-castration-resistant-prostate-cancer
#1
Sambit K Mohanty, Kader Yagiz, Dinesh Pradhan, Daniel J Luthringer, Mahul B Amin, Serhan Alkan, Bekir Cinar
Mechanisms of castration-resistant prostate cancer (CRPC) are not well understood, thus hindering rational-based drug design. Activation of STAT3/5A, key components of the JAK/STAT pathway, is implicated in aggressive PC, yet their clinical relevance in CRPC remains elusive. Here, we evaluated the possible role of STAT3/5A in CRPC using immunological, quantitative mRNA expression profiling, and pharmacological methods. We observed a strong nuclear immunoreactivity for STAT3 and STAT5A in 93% (n=14/15) and 80% (n=12/15) of CRPC cases, respectively, compared with benign prostatic hyperplasia (BPH)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155210/transition-from-androgenic-to-neurosteroidal-action-of-5%C3%AE-androstane-3%C3%AE-17%C3%AE-diol-through-the-type-a-%C3%AE-aminobutyric-acid-receptor-in-prostate-cancer-progression
#2
Ding Xia, Doan V Lai, Weijuan Wu, Zachary D Webb, Qing Yang, Lichao Zhao, Zhongxin Yu, Jessica E Thorpe, Bryan C Disch, Michael A Ihnat, Muralidharan Jayaraman, Danny N Dhanasekaran, Kelly L Stratton, Michael S Cookson, Kar-Ming Fung, Hsueh-Kung Lin
Androgen ablation is the standard of care prescribed to patients with advanced or metastatic prostate cancer (PCa) to slow down disease progression. Unfortunately, a majority of PCa patients under androgen ablation progress to castration-resistant prostate cancer (CRPC). Several mechanisms including alternative intra-prostatic androgen production and androgen-independent androgen receptor (AR) activation have been proposed for CRPC progression. Aldo-keto reductase family 1 member C3 (AKR1C3), a multi-functional steroid metabolizing enzyme, is specifically expressed in the cytoplasm of PCa cells; and positive immunoreactivity of the type A γ-aminobutyric acid receptor (GABAAR), an ionotropic receptor and ligand-gated ion channel, is detected on the membrane of PCa cells...
November 15, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29152111/reactive-oxygen-species-induction-by-cabazitaxel-through-inhibiting-sestrin-3-in-castration-resistant-prostate-cancer
#3
Takeo Kosaka, Hiroshi Hongo, Yasumasa Miyazaki, Koshiro Nishimoto, Akira Miyajima, Mototsugu Oya
Reactive oxygen species (ROS) production induced by taxanes in cancer cells may influence the taxane-induced cell death or the drug resistance. We investigated the correlation between the cytotoxic effect of taxanes and ROS production in human castration-resistant prostate cancer (CRPC) cell lines. Three human prostate cancer cell lines were treated with increasing concentrations of docetaxel or cabazitaxel in vitro. Cabazitaxel showed significantly higher cytotoxic efficacy than docetaxel in human CRPC cells, accompanied by elevated ROS production detected by FACS analysis...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149413/tctp-has-a-crucial-role-in-the-different-stages-of-prostate-cancer-malignant-progression
#4
Virginie Baylot, Sara Karaki, Palma Rocchi
Prostate cancer (PC) is the second most common cause of cancer-related mortality in men in the western world after lung cancer. Many patients are not candidates for resection given the advanced stage of their cancer. The primary treatment for advanced PC is the castration therapy which supresses the production of androgens, hormone that promotes PC growth. Despite the efficiency of the castration therapy, most patients develop castration resistant disease which remains uncurable. Clearly, novel approaches are required to effectively treat castration resistant PC (CRPC)...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29147733/-inhibitors-of-the-androgen-receptor-n%C3%A2-terminal-domain-therapies-targeting-the-achilles-heel-of-various-androgen-receptor-molecules-in-advanced-prostate-cancer
#5
REVIEW
M C Hupe, A Offermann, F Perabo, C Chandhasin, S Perner, A S Merseburger, M V Cronauer
Although prostate cancer responds well to primary endocrine therapies, tumor progression with castration resistant tumor cells almost invariably occurs within a few years. Unfortunately, some CRPC patients do not respond to second-line therapies with abiraterone or enzalutamide. Moreover, patients who initially responded well to second-line hormone therapy develop resistance to abiraterone and/or enzalutamide within a short period of time. Besides an increase of intracellular androgen receptor (AR) levels, the predominant resistance mechanisms include AR aberrations (point mutations, AR splice variants) occurring predominantly at the androgen or ligand binding domain of the AR...
November 16, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29141691/involvement-of-aberrantly-activated-hotair-ezh2-mir-193a-feedback-loop-in-progression-of-prostate-cancer
#6
Zhixin Ling, Xiaoyan Wang, Tao Tao, Lei Zhang, Han Guan, Zonghao You, Kai Lu, Guangyuan Zhang, Shuqiu Chen, Jianping Wu, Jinke Qian, Hui Liu, Bin Xu, Ming Chen
BACKGROUND: Though androgen deprivation therapy is the standard treatment for prostate cancer (PCa), most patients would inevitably progress to castration-resistant prostate cancer (CRPC) which is the main cause of PCa death. Therefore, the identification of novel molecular mechanism regulating cancer progression and achievement of new insight into target therapy would be necessary for improving the benefits of PCa patients. This study aims to study the function and regulatory mechanism of HOTAIR/EZH2/miR-193a feedback loop in PCa progression...
November 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29138344/targeting-the-mycn-parp-dna-damage-response-pathway-inneuroendocrine-prostate-cancer
#7
Wei Zhang, Bo Liu, Wenhui Wu, Likun Li, Bradley M Broom, Spyridon M Basourakos, Dimitrios Korentzelos, Yang Luan, Jianxiang Wang, Guang Yang, Sanghee Park, Abul K Azad, Xuhong Cao, Jeri Kim, Paul Corn, Christopher Logothetis, Ana M Aparicio, Arul M Chinnayan, Nora M Navone, Patricia Troncoso, Timothy C Thompson
PURPOSE: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphological criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for NEPC. RESULTS: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public datasets and a panel of 28 PDX models we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29137489/androgen-deprivation-therapy-for-the-treatment-of-prostate-cancer-a-focus-on-pharmacokinetics
#8
Charles F Polotti, Christopher J Kim, Nadiya Chuchvara, Alyssa B Polotti, Eric A Singer, Sammy Elsamra
Medical therapy has undergone many changes as our understanding of prostate cancer cell biology has improved. Androgen deprivation therapy (ADT) remains the mainstay of therapy for metastatic disease. Metastatic castrate-resistant prostate cancer (CRPC) is an important concern since we are unable to stop progression with currently available agents. Areas covered: Pharmacologic ADT is the most commonly used treatment for metastatic prostate cancer. Multiple agents are available for both first-line and second-line use: antiandrogens, estrogens, luteinizing hormone-releasing hormone agonists/antagonists, and CYP17 inhibitors...
November 15, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29136407/phospholipase-d-inhibitors-reduce-human-prostate-cancer-cell-proliferation-and-colony-formation
#9
Amanda R Noble, Norman J Maitland, Daniel M Berney, Martin G Rumsby
BACKGROUND: Phospholipases D1 and D2 (PLD1/2) hydrolyse cell membrane glycerophospholipids to generate phosphatidic acid, a signalling lipid, which regulates cell growth and cancer progression through effects on mTOR and PKB/Akt. PLD expression and/or activity is raised in breast, colorectal, gastric, kidney and thyroid carcinomas but its role in prostate cancer (PCa), the major cancer of men in the western world, is unclear. METHODS: PLD1 protein expression in cultured PNT2C2, PNT1A, P4E6, LNCaP, PC3, PC3M, VCaP, 22RV1 cell lines and patient-derived PCa cells was analysed by western blotting...
November 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29134562/seom-clinical-guidelines-for-the-treatment-of-metastatic-prostate-cancer-2017
#10
J Cassinello, J Á Arranz, J M Piulats, A Sánchez, B Pérez-Valderrama, B Mellado, M Á Climent, D Olmos, J Carles, M Lázaro
Androgen deprivation treatment was the only treatment available for metastatic prostate cancer until recently, with docetaxel as the only treatment with a proven survival benefit in castration-resistant prostate cancer (CRPC). Several drugs have been approved in the castration-resistant disease (sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, radium-223). More recently, docetaxel and abiraterone have been moved to the hormone-sensitive disease setting, achieving better patient survival. The purpose of this article is to define the state of the art in the treatment of prostate carcinoma...
November 13, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29129028/improved-cancer-specific-free-survival-and-overall-free-survival-in-contemporary-metastatic-prostate-cancer-patients-a-population-based-study
#11
Marco Bandini, Raisa S Pompe, Michele Marchioni, Emanuele Zaffuto, Giorgio Gandaglia, Nicola Fossati, Luca Cindolo, Francesco Montorsi, Alberto Briganti, Fred Saad, Pierre I Karakiewicz
OBJECTIVES: Over the past decade, several systemic agents as docetaxel, cabazitaxel, sipuleucel-T, abiraterone and enzalutamide have improved overall survival (OS) in metastatic prostate cancer (mPCa) patients. However, to date the OS benefit was not demonstrated in population-based analysis. METHODS: Between 2004 and 2014, 19,047 men with de novo mPCa were identified within the Surveillance Epidemiology and End Results database. Median year of diagnosis resulted in two groups: historical (2004-2008) and contemporary (2009-2014)...
November 11, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/29126837/antiandrogens-reduce-intratumoral-androgen-concentrations-and-induce-androgen-receptor-expression-in-castration-resistant-prostate-cancer-xenografts
#12
Matias Knuuttila, Arfa Mehmood, Riikka Huhtaniemi, Emrah Yatkin, Merja R Häkkinen, Riikka Oksala, Teemu D Laajala, Henrik Ryberg, David J Handelsman, Tero Aittokallio, Seppo Auriola, Claes Ohlsson, Asta Laiho, Laura L Elo, Petra Sipilä, Sari I Mäkelä, Matti Poutanen
The development of castration-resistant prostate cancer (CRPC) is associated with the activation of intratumoral androgen biosynthesis and an increase in androgen receptor (AR) expression. We recently demonstrated that similarly to the clinical CRPC, orthotopically grown castration-resistant VCaP (CR-VCaP) xenografts express high levels of AR and retain intratumoral androgen concentrations similar to tumors grown in intact mice. Here, we show that antiandrogen treatment (enzalutamide or ARN-509) significantly reduced (10-fold, P < 0...
November 7, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29118587/consequences-of-different-corticosteroids-on-serum-potassium-and-prostate-specific-antigen-in-patients-receiving-abiraterone-for-castration-resistant-prostate-cancer-a-retrospective-observational-study
#13
Masaomi Tatsuzawa, Ryuichi Ogawa, Naoki Kinjo, Soan Kim, Fumitaka Shimizu, Yoshiro Sakamoto, Kazuyo Shimojima, Hirotoshi Echizen, Akihisa Miyazaki
Background: Abiraterone acetate is an androgen synthesis inhibitor approved for the treatment of castration-resistant prostate cancer (CRPC). Although co-administration of either prednisone or prednisolone at 10 mg/d has been recommended to reduce the risk of abiraterone-induced hyperaldosteronism (notably hypokalemia) and to give adjunctive pain relief effects, whether these glucocorticoids can be substituted by dexamethasone remains unknown. Methods: We performed a retrospective review of medical records of patients who were given abiraterone for the treatment of CRPC with either prednisolone (ABI/PSL) 10 mg/d or dexamethasone (ABI/DEX) 0...
2017: Clinical Medicine Insights. Oncology
https://www.readbyqxmd.com/read/29111539/external-validation-and-newly-development-of-a-nomogram-to-predict-overall-survival-of-abiraterone-treated-castration-resistant-patients-with-metastatic-prostate-cancer
#14
Yun-Jie Yang, Guo-Wen Lin, Gao-Xiang Li, Bo Dai, Ding-Wei Ye, Jun-Long Wu, Hu-Yang Xie, Yao Zhu
Abiraterone acetate is approved for the treatment of castration-resistant prostate cancer (CRPC); however, its effects vary. An accurate prediction model to identify patient groups that will benefit from abiraterone treatment is therefore urgently required. The Chi model exhibits a good profile for risk classification, although its utility for the chemotherapy-naive group is unclear. This study aimed to externally validate the Chi model and develop a new nomogram to predict overall survival (OS). We retrospectively analyzed a cohort of 110 patients...
November 7, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29110173/combination-treatment-with-docetaxel-and-histone-deacetylase-inhibitors-downregulates-androgen-receptor-signaling-in-castration-resistant-prostate-cancer
#15
Sang Eun Park, Ha-Gyeong Kim, Dong Eun Kim, Yoo Jung Jung, Yunlim Kim, Seong-Yun Jeong, Eun Kyung Choi, Jung Jin Hwang, Choung-Soo Kim
Backgrounds Since most patients with castration-resistant prostate cancer (CRPC) develop resistance to its standard therapy docetaxel, many studies have attempted to identify novel combination treatment to meet the large clinical unmet need. In this study, we examined whether histone deacetylase inhibitors (HDACIs) enhanced the effect of docetaxel on AR signaling in CRPC cells harboring AR and its splice variants. Methods HDACIs (vorinostat and CG200745) were tested for their ability to enhance the effects of docetaxel on cell viability and inhibition of AR signaling in CRPC 22Rv1 and VCaP cells by using CellTiter-Glo™ Luminescent cell viability assay, synergy index analysis and Western blotting...
November 7, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29105980/extracellular-vesicles-in-the-adaptive-process-of-prostate-cancer-during-inhibition-of-androgen-receptor-signalling-by-enzalutamide
#16
Carolina Soekmadji, Anja Rockstroh, Grant A Ramm, Colleen C Nelson, Pamela J Russell
Current treatments for advanced prostate cancer focus on inhibition of the androgen receptor (AR) by androgen deprivation therapy (ADT). However, complex interactions mediated by tumour suppressors, oncogenes, aberrations of AR expression, or de novo androgen production have been shown to induce the adaptive response of prostate cancer, leading to the development of castration resistant prostate cancer (CRPC). In this study, we report the effects of AR antagonist, enzalutamide on the protein contents of extracellular vesicles (EVs)...
November 6, 2017: Proteomics
https://www.readbyqxmd.com/read/29100379/gambogic-acid-inhibits-thioredoxin-activity-and-induces-ros-mediated-cell-death-in-castration-resistant-prostate-cancer
#17
Hong Pan, Keith H Jansson, Michael L Beshiri, JuanJuan Yin, Lei Fang, Supreet Agarwal, Holly Nguyen, Eva Corey, Ying Zhang, Jie Liu, HuiTing Fan, HongSheng Lin, Kathleen Kelly
Advanced prostate cancer (PrCa) is treated with androgen deprivation therapy, and although there is usually a significant initial response, recurrence arises as castrate resistant prostate cancer (CRPC). New approaches are needed to treat this genetically heterogeneous, phenotypically plastic disease. CRPC with combined homozygous alterations to PTEN and TP53 comprise about 30% of clinical samples. We screened eleven traditional Chinese medicines against a panel of androgen-independent Pten/Tp53 null PrCa-derived cell lines and identified gambogic acid (GA) as a highly potent growth inhibitor...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099380/-consensus-on-castration-resistant-prostate-cancer-management-in-spain
#18
Antonio Alcaraz, Luís Martínez-Piñeiro, Alfredo Rodríguez, José Rubio, Ángel Borque, Javier Burgos, Joaquín Carballido, José Manuel Cózar, Itziar Crespo, Salvador Esquena, Francisco Gómez-Veiga, Dionisio López, Bernardino Miñana, Juan Morote, María José Ribal, Eduardo Solsona, José Francisco Suárez, Miguel Unda
OBJECTIVES: To move towards a more standardized approach in clinical practice to manage patients with castration-resistant prostate cancer (CRPC) in Spain. METHODS: A panel of 18 Spanish experts in Urology with expertise managing CRPC followed a modified Delphi process with two rounds and a final face-to-face consensus meeting. The panel considered a total of 106 clinical questions divided into the following 6 sections: definition of CRPC, diagnosis of metastases by imaging techniques, symptoms of CRPC, progression of CRPC, M0 and M1 management and therapeutic sequencing...
November 2017: Archivos Españoles de Urología
https://www.readbyqxmd.com/read/29098395/additive-naftopidil-treatment-synergizes-docetaxel-induced-apoptosis-in-human-prostate-cancer-cells
#19
Kenichiro Ishii, Izumi Matsuoka, Shinya Kajiwara, Takeshi Sasaki, Manabu Miki, Manabu Kato, Hideki Kanda, Kiminobu Arima, Taizo Shiraishi, Yoshiki Sugimura
PURPOSE: Docetaxel (DTX) is a standard chemotherapeutic drug for castration-resistant prostate cancer (CRPC), although adverse events are common. To overcome this problem, researchers have evaluated the efficacy of DTX treatment in combination with other drugs. Naftopidil is a tubulin-binding drug with fewer adverse events, implying the usefulness of this drug in clinical applications when combined with DTX. Here, we investigated the efficacy of additive naftopidil treatment in combination with DTX on prostate cancer (PCa) cells...
November 2, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29094381/platelets-harbor-prostate-cancer-biomarkers-and-the-ability-to-predict-therapeutic-response-to-abiraterone-in-castration-resistant-patients
#20
Lee-Ann Tjon-Kon-Fat, Marie Lundholm, Mona Schröder, Thomas Wurdinger, Camilla Thellenberg-Karlsson, Anders Widmark, Pernilla Wikström, Rolf Jonas Andreas Nilsson
BACKGROUND: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance. METHOD: The isolated platelet population of blood samples and digital-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis inhibiting therapy...
November 2, 2017: Prostate
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