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https://www.readbyqxmd.com/read/28642838/adaptive-pathways-and-emerging-strategies-overcoming-treatment-resistance-in-castration-resistant-prostate-cancer
#1
Cameron M Armstrong, Allen C Gao
The therapies available for prostate cancer patients whom progress from hormone-sensitive to castration resistant prostate cancer include both systemic drugs, including docetaxel and cabazitaxel, and drugs that inhibit androgen signaling such as enzalutamide and abiraterone. Unfortunately, it is estimated that up to 30% of patients have primary resistance to these treatments and over time even those who initially respond to therapy will eventually develop resistance and their disease will continue to progress regardless of the presence of the drug...
October 2016: Asian Journal of Urology
https://www.readbyqxmd.com/read/28638477/triptolide-inhibits-the-ar-signaling-pathway-to-suppress-the-proliferation-of-enzalutamide-resistant-prostate-cancer-cells
#2
Yangyang Han, Weiwei Huang, Jiakuan Liu, Dandan Liu, Yangyan Cui, Ruimin Huang, Jun Yan, Ming Lei
Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown...
2017: Theranostics
https://www.readbyqxmd.com/read/28628013/modulation-of-antitumor-immune-response-in-mouse-prostate-cancer-model
#3
N Mitskevich, T Tsertsvadze, K Mchedlishvili, K Matchavariani, G Guruli
Aim of study - prostate cancer is second most common cancer in men worldwide, and fifth leading cause of death from cancer in men (6.6% of the total men deaths). Unfortunately, once cancer spreads outside of prostate, it becomes incurable. Androgen deprivation can provide some relief, but resistance will develop eventually, and at that time no effective treatment options are left to the patient. Therefore, the search of alternative treatment modalities is paramount. In this article we evaluated the role of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator - Lenalidomide and their possible impact on the immune response in the murine prostate cancer model...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28614057/dual-effects-of-constitutively-active-androgen-receptor-and-full-length-androgen-receptor-for-n-cadherin-regulation-in-prostate-cancer
#4
Félicie Cottard, Pauline Ould Madi-Berthélémy, Eva Erdmann, Frédérique Schaff-Wendling, Céline Keime, Tao Ye, Jean-Emmanuel Kurtz, Jocelyn Céraline
Constitutively active androgen receptor (AR) variants have been involved in the expression of mesenchymal markers such as N-cadherin in prostate cancer (PCa). However, the underlying molecular mechanisms remain elusive. It remains unclear, whether N-cadherin gene (CDH2) is a direct transcriptional target of AR variants or whether the observed upregulation is due to indirect effects through additional regulatory factors. Moreover, the specific contribution of full-length AR and AR variants in N-cadherin regulation in PCa has never been explored deeply...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28609657/ack1-tnk2-regulates-histone-h4-tyr88-phosphorylation-and-ar-gene-expression-in-castration-resistant-prostate-cancer
#5
Kiran Mahajan, Pavani Malla, Harshani R Lawrence, Zhihua Chen, Chandan Kumar-Sinha, Rohit Malik, Sudhanshu Shukla, Jongphil Kim, Domenico Coppola, Nicholas J Lawrence, Nupam P Mahajan
The androgen receptor (AR) is critical for the progression of prostate cancer to a castration-resistant (CRPC) state. AR antagonists are ineffective due to their inability to repress the expression of AR or its splice variant, AR-V7. Here, we report that the tyrosine kinase ACK1 (TNK2) phosphorylates histone H4 at tyrosine 88 upstream of the AR transcription start site. The WDR5/MLL2 complex reads the H4-Y88-phosphorylation marks and deposits the transcriptionally activating H3K4-trimethyl marks promoting AR transcription...
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28604629/androgen-receptor-dependent-and-independent-mechanisms-involved-in-prostate-cancer-therapy-resistance
#6
REVIEW
Daniel J Crona, Young E Whang
Despite the initial efficacy of androgen deprivation in prostate cancer, virtually all patients progress to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling is critically required for CRPC. A new generation of medications targeting AR, such as abiraterone and enzalutamide, has improved survival of metastatic CRPC (mCRPC) patients. However, a significant proportion of patients presents with primary resistance to these agents, and in the remainder, secondary resistance will invariably develop, which makes mCRPC the lethal form of the disease...
June 12, 2017: Cancers
https://www.readbyqxmd.com/read/28600675/a-novel-capillary-nano-immunoassay-for-assessing-androgen-receptor-splice-variant-7-in-plasma-correlation-with-cd133-antigen-expression-in-circulating-tumor-cells-a-pilot-study-in-prostate-cancer-patients
#7
J L García, R Lozano, I Misiewicz-Krzeminska, J Fernández-Mateos, P Krzeminski, S Alfonso, R A Marcos, R García, F Gómez-Veiga, Á Virseda, M Herrero, D Olmos, J J Cruz-Hernández
PURPOSE: Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients. METHODS: Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform...
June 9, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28590268/ar-v7-liquid-biopsy-for-treatment-stratification-in-prostate-cancer-how-close-are-we
#8
Claire Fletcher
PURPOSE OF REVIEW: Recent clinical introduction of the novel antiandrogen, Enzalutamide (Enza), CYP17 inhibitor, Abiraterone (Abi), and the second-generation chemotherapeutic, Cabazitaxel, has increased survival of patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). However, de novo and acquired resistance rates are high. A liquid biopsy that can rapidly, sensitively and robustly identify which patients will respond to treatment in a minimally invasive manner is urgently required to permit switch to a potentially more efficacious drug regimen, thus increasing survival whilst avoiding debilitating side effects associated with unnecessary treatment...
June 5, 2017: Current Opinion in Urology
https://www.readbyqxmd.com/read/28589901/resveratrol-enhances-polyubiquitination-mediated-arv7-degradation-in-prostate-cancer-cells
#9
Sarah Wilson, Lucia Cavero, Dali Tong, Qiuli Liu, Kyla Geary, Nicholas Talamonti, Jing Xu, Junjiang Fu, Jun Jiang, Dianzheng Zhang
Although androgen deprivation therapy (ADT) serves as the primary treatment option for localized or metastatic prostate cancer, most cases eventually develop into castration-resistant prostate cancer (CRPC). However, androgen receptor (AR) continues to be functional in CRPC through various mechanisms, including the development of AR splicing variants, especially ARV7. Since it lacks the ligand binding domain but retains the intact DNA binding domain, ARV7 is constitutively active, which makes ARV7-positive prostate cancer responsive to neither abiraterone nor enzalutamide...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28561752/melatonin-inhibits-androgen-receptor-splice-variant-7-ar-v7-induced-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-activation-and-nf-%C3%AE%C2%BAb-activator-induced-ar-v7-expression-in-prostate-cancer-cells-potential-implications-for-the-use-of-melatonin-in-castration-resistant-prostate
#10
Vincent Wing Sun Liu, Wing Lung Yau, Chun Wai Tam, Kwok-Ming Yao, Stephen Yuen Wing Shiu
A major current challenge in the treatment of advanced prostate cancer, which can be initially controlled by medical or surgical castration, is the development of effective, safe, and affordable therapies against progression of the disease to the stage of castration resistance. Here, we showed that in LNCaP and 22Rv1 prostate cancer cells transiently overexpressing androgen receptor splice variant-7 (AR-V7), nuclear factor-kappa B (NF-κB) was activated and could result in up-regulated interleukin (IL)-6 gene expression, indicating a positive interaction between AR-V7 expression and activated NF-κB/IL-6 signaling in castration-resistant prostate cancer (CRPC) pathogenesis...
May 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28556958/downregulation-of-androgen-receptors-by-naaso2-via-inhibition-of-akt-nf-%C3%AE%C2%BAb-and-hsp90-in-castration-resistant-prostate-cancer
#11
Yunlim Kim, Sang Eun Park, Jeong-Weon Moon, Bong-Min Kim, Ha-Gyeong Kim, In Gab Jeong, Sangjun Yoo, Jae Beom Ahn, Dalsan You, Jhang Ho Pak, Sujong Kim, Jung Jin Hwang, Choung-Soo Kim
BACKGROUND: Androgen and androgen receptor (AR) play essential roles in the development and maintenance of prostate cancer. The recently identified AR splice variants (AR-Vs) have been considered as a plausible mechanism for the primary resistance against androgen deprivation therapy (ADT) in castration-resistant prostate cancer (CRPC). Sodium meta-arsenite (NaAsO2 ; KML001; Kominox), a trivalent arsenical, is an orally bioavailable and water soluble, which is currently in phase I/II clinical trials for the treatment of prostate cancer...
May 30, 2017: Prostate
https://www.readbyqxmd.com/read/28551687/recent-highlights-of-research-on-androgen-receptors-in-women
#12
Kamil Zaręba, Iwona Sidorkiewicz
In this brief review we present an outline of the current state of research on examples of hyperandrogenism that can be strongly associated with diverse modifications in the androgen signaling pathway. We discuss the most prominent clinical features of androgen excess and correlate them with studies on androgen receptor (AR) alterations. For the first time we summarize the confirmed localizations of all known AR receptors in women. The knowledge of ARs may be the basis for AR-targeted therapies of androgenic disorders in women, including malignancy, as it has recently been demonstrated for triple-negative breast cancer...
2017: Developmental Period Medicine
https://www.readbyqxmd.com/read/28528814/preclinical-study-using-malat1-small-interfering-rna-or-androgen-receptor-splicing-variant-7-degradation-enhancer-asc-j9-%C3%A2-to-suppress-enzalutamide-resistant-prostate-cancer-progression
#13
Ronghao Wang, Yin Sun, Lei Li, Yuanjie Niu, Wanying Lin, Changyi Lin, Emmanuel S Antonarakis, Jun Luo, Shuyuan Yeh, Chawnshang Chang
BACKGROUND: While androgen-deprivation-therapy with the recently developed antiandrogen enzalutamide (Enz) shows promising therapeutic benefits in men with metastatic castration-resistant prostate cancer (PCa), many patients develop resistance to Enz, which may involve the induction of the androgen receptor (AR) splicing variant 7 (AR-v7). OBJECTIVE: Our aim is to identify the mechanisms responsible for AR-v7 production and to develop novel preclinical approaches to suppress the Enz-resistant (EnzR) PCa...
May 18, 2017: European Urology
https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#14
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
June 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28500234/niclosamide-and-bicalutamide-combination-treatment-overcomes-enzalutamide-and-bicalutamide-resistant-prostate-cancer
#15
Chengfei Liu, Cameron M Armstrong, Wei Lou, Alan P Lombard, Vito Cucchiara, Xinwei Gu, Joy C Yang, Nagalakshmi Nadiminty, Chong-Xian Pan, Christopher P Evans, Allen C Gao
Activation of the androgen receptor (AR) and its splice variants is linked to advanced prostate cancer and drives resistance to antiandrogens. The roles of AR and AR variants in the development of resistance to androgen deprivation therapy (ADT) and bicalutamide treatment, however, are still incompletely understood. To determine whether AR variants play a role in bicalutamide resistance, we developed bicalutamide resistant LNCaP cells (LNCaP-BicR) and found that these resistant cells express significantly increased levels of AR variants, particularly AR-V7, both at the mRNA and protein levels...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28498452/calpain-and-ar-v7-two-potential-therapeutic-targets-to-overcome-acquired-docetaxel-resistance-in-castration-resistant-prostate-cancer-cells
#16
Lei Liu, Ning Lou, Xiang Li, Guanghua Xu, Hailong Ruan, Wen Xiao, Bin Qiu, Lin Bao, Changfei Yuan, Xinmian Huang, Keshan Wang, Qi Cao, Ke Chen, Hongmei Yang, Xiaoping Zhang
Docetaxel-based chemotherapy has been widely used as the first-line treatment for castration-resistant prostate cancer (CRPC) patients. However, the mechanisms of docetaxel-resistance remain unclear. In the present study with the establishment of 2 in vitro models of docetaxel-resistant CRPC cell sublines, we firstly reported that activation of calpain may play a promotional role in the resistance of docetaxel in prostate cancer, meanwhile using the calpain inhibitor combined with docetaxel improved the efficiency of docetaxel in docetaxel-resistant cell sublines...
May 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28498319/ctc-mrna-ar-v7-analysis-from-blood-samples-impact-of-blood-collection-tube-and-storage-time
#17
Alison W S Luk, Yafeng Ma, Pei N Ding, Francis P Young, Wei Chua, Bavanthi Balakrishnar, Daniel T Dransfield, Paul de Souza, Therese M Becker
Circulating tumour cells (CTCs) are an emerging resource for monitoring cancer biomarkers. New technologies for CTC isolation and biomarker detection are increasingly sensitive, however, the ideal blood storage conditions to preserve CTC-specific mRNA biomarkers remains undetermined. Here we tested the preservation of tumour cells and CTC-mRNA over time in common anticoagulant ethylene-diamine-tetra-acetic acid (EDTA) and acid citrate dextrose solution B (Citrate) blood tubes compared to preservative-containing blood tubes...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28489755/kennedy-disease-with-difficulty-in-differential-diagnosis-a-case-report
#18
Yating Chen, Peng Luo, Zhongli Li, Hengping Hu, Duobin Wu, Tingting Xu, Xingzuo Wang, Haiting Xie
RATIONALE: Kennedy disease (KD) is also known as spinal bulbar muscular dystrophy. As KD has similar symptoms with most neuromuscular diseases, so it is difficult to make a rapid diagnosis clinically. PATIENT CONCERNS: We report a case of a 43-year-old male with progressive limb proximal weakness without family history. Physical examination showed gynecomastia, erectile dysfunction, bilateral tendon reflex and quadriceps weakness, and tongue muscle atrophy. DIAGNOSES: Laboratory examination found increased creatine kinase, impaired glucose tolerance, and abnormal lactic acid values...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28475016/dissecting-the-roles-of-the-androgen-receptor-in-prostate-cancer-from-molecular-perspectives
#19
REVIEW
Jieping Hu, Gongxian Wang, Ting Sun
Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28473535/androgen-receptor-variant-ar-v9-is-co-expressed-with-ar-v7-in-prostate-cancer-metastases-and-predicts-abiraterone-resistance
#20
Manish Kohli, Yeung Ho, David W Hillman, Jamie L Van Etten, Christine Henzler, Rendong Yang, Jame M Sperger, Yingming Li, Elizabeth Tseng, Ting Hon, Tyson Clark, Winston Tan, Rachel E Carlson, Liguo Wang, Hugues Sicotte, Ho Thai, Rafael Jimenez, Haojie Huang, Peter T Vedell, Bruce W Eckloff, J Fernando Quevedo, Henry C Pitot, Brian Costello, Jin Jen, Eric D Wieben, Kevin A T Silverstein, Joshua M Lang, Liewei Wang, Scott M Dehm
Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies.  Accordingly, efforts are underway to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC).  The purpose of this study was to understand whether other AR variants may be co-expressed with AR-V7 and promote resistance to AR-targeted therapies.<br /><br /> Experimental Design:  We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models...
May 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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