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https://www.readbyqxmd.com/read/28430389/combination-of-carmustine-and-selenite-inhibits-egfr-mediated-growth-signaling-in-androgen-independent-prostate-cancer-cells
#1
Vijayalakshmi Thamilselvan, Mani Menon, Gary S Stein, Fred Valeriote, Sivagnanam Thamilselvan
Although aberrant androgen receptor (AR) signaling is a central mechanism for castration resistant prostate cancer (CRPC) progression, AR-independent survival and growth signaling is also present in CRPC. The current therapeutic options for patients with CRPC are limited and new drugs are desperately needed to eliminate these crucial growth signaling pathways. Overexpression of EGFR in CRPC primarily mediates the proliferation of androgen-independent prostate cancer (AIPC) cells. We have previously shown that combination of carmustine and selenite effectively induces apoptosis and growth inhibition by targeting AR and AR-variants in castration resistant prostate cancer cells...
April 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28427194/alternative-rna-splicing-of-the-meaf6-gene-facilitates-neuroendocrine-prostate-cancer-progression
#2
Ahn R Lee, Yinan Li, Ning Xie, Martin E Gleave, Michael E Cox, Colin C Collins, Xuesen Dong
Although potent androgen receptor pathway inhibitors (ARPI) improve overall survival of metastatic prostate cancer patients, treatment-induced neuroendocrine prostate cancer (t-NEPC) as a consequence of the selection pressures of ARPI is becoming a more common clinical issue. Improved understanding of the molecular biology of t-NEPC is essential for the development of new effective management approaches for t-NEPC. In this study, we identify a splice variant of the MYST/Esa1-associated factor 6 (MEAF6) gene, MEAF6-1, that is highly expressed in both t-NEPC tumor biopsies and neuroendocrine cell lines of prostate and lung cancers...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422721/functional-analysis-implicating-the-snp-rs61552325-in-erbb2-as-an-effector-for-androgen-insensitive-prostate-cancer-cell-invasion
#3
Xianxiang Xin, Yinmin Gu, Yang Chen, Yuanjie Huang, Zengnan Mo, Yanling Hu
BACKGROUND: As one of the most common cancers in men, the pathogenesis of prostate cancer has been widely researched. Aberrant activation of the erb-b2 receptor tyrosine kinase 2 (ERBB2) has been found to play a critical role in metastatic prostate cancer. In our previous study, we demonstrated that rs61552325 (Pro1140Ala) located in ERBB2 is strongly correlated to prostate cancer. Therefore, we initially studied the effect of rs61552325 on androgen-independent prostate cancer cell metastasis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415632/the-combined-effect-of-usp7-inhibitors-and-parp-inhibitors-in-hormone-sensitive-and-castration-resistant-prostate-cancer-cells
#4
Francesco Morra, Francesco Merolla, Virginia Napolitano, Gennaro Ilardi, Caterina Miro, Simona Paladino, Stefania Staibano, Aniello Cerrato, Angela Celetti
PURPOSE OF THE STUDY: Reduced levels of the tumor suppressor protein CCDC6 sensitize cancer cells to the treatment with PARP-inhibitors. The turnover of CCDC6 protein is regulated by the de-ubiquitinase USP7, which also controls the androgen receptor (AR) stability. Here, we correlated the expression levels of CCDC6 and USP7 proteins in primary prostate cancers (PC). Moreover, we tested the efficacy of the USP7 inhibitors, in combination with PARP-inhibitors as a novel therapeutic option in advanced prostate cancer...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414609/association-between-androgen-receptor-splice-variants-and-prostate-cancer-resistance-to-abiraterone-and-enzalutamide
#5
Glenn J Bubley, Steven P Balk
No abstract text is available yet for this article.
April 17, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28397338/glycogen-synthase-kinase-3-inhibitors-suppress-the-ar-v7-mediated-transcription-and-selectively-inhibit-cell-growth-in-ar-v7-positive-prostate-cancer-cells
#6
Daisuke Nakata, Ryokichi Koyama, Kazuhide Nakayama, Satoshi Kitazawa, Tatsuya Watanabe, Takahito Hara
BACKGROUND: Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. METHODS: High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system...
April 10, 2017: Prostate
https://www.readbyqxmd.com/read/28394264/the-androgen-receptor-and-vegf-mechanisms-of-androgen-regulated-angiogenesis-in-prostate-cancer
#7
REVIEW
Kurtis Eisermann, Gail Fraizer
Prostate cancer progression is controlled by the androgen receptor and new blood vessel formation, or angiogenesis, which promotes metastatic prostate cancer growth. Angiogenesis is induced by elevated expression of vascular endothelial growth factor (VEGF). VEGF is regulated by many factors in the tumor microenvironment including lowered oxygen levels and elevated androgens. Here we review evidence delineating hormone mediated mechanisms of VEGF regulation, including novel interactions between the androgen receptor (AR), epigenetic and zinc-finger transcription factors, AR variants and the hypoxia factor, HIF-1...
April 10, 2017: Cancers
https://www.readbyqxmd.com/read/28384066/clinical-significance-of-androgen-receptor-splice-variant-7-mrna-detection-in-circulating-tumor-cells-of-men-with-metastatic-castration-resistant-prostate-cancer-treated-with-first-and-second-line-abiraterone-and-enzalutamide
#8
Emmanuel S Antonarakis, Changxue Lu, Brandon Luber, Hao Wang, Yan Chen, Yezi Zhu, John L Silberstein, Maritza N Taylor, Benjamin L Maughan, Samuel R Denmeade, Kenneth J Pienta, Channing J Paller, Michael A Carducci, Mario A Eisenberger, Jun Luo
Purpose We reported previously that the detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumor cells (CTCs) correlated with poor outcomes from the use of abiraterone and enzalutamide in patients with castration-resistant prostate cancer (CRPC). Here, we expanded our cohort size to better characterize the prognostic significance of AR-V7 in this setting. Methods We prospectively enrolled 202 patients with CRPC starting abiraterone or enzalutamide and investigated the prognostic value of CTC detection (+ v -) and AR-V7 detection (+ v -) using a CTC-based AR-V7 mRNA assay...
April 6, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28380417/prospects-of-estrogen-receptor-%C3%AE-activation-in-the-treatment-of-castration-resistant-prostate-cancer
#9
Julia Gehrig, Silke Kaulfuß, Hubertus Jarry, Felix Bremmer, Mark Stettner, Peter Burfeind, Paul Thelen
Advanced prostate cancer can develop into castration-resistant prostate cancer (CRPC). This process is mediated either by intratumoral ligand synthesis or by mutations or aberrations of the androgen receptor (AR) or its cofactors. To date, no curative therapy for CRPC is available, as AR-targeted therapies eventually result in the development of resistance. The human prostate cancer cell line VCaP (vertebral cancer of the prostate) overexpresses AR and its splice variants (ARVs) as a mechanism of resistance to androgen-deprivation therapy (ADT) of external and intratumoral origin...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28373004/natural-killer-cells-suppress-enzalutamide-resistance-and-cell-invasion-in-the-castration-resistant-prostate-cancer-via-targeting-the-androgen-receptor-splicing-variant-7-arv7
#10
Shin-Jen Lin, Fu-Ju Chou, Lei Li, Chang-Yi Lin, Shuyuan Yeh, Chawnshang Chang
Despite the success of androgen-deprivation therapy (ADT) with the newly developed anti-androgen enzalutamide (Enz, also known as MDV3100) to suppress castration resistant prostate cancer (CRPC) in extending patient survival by an extra 4.8 months, eventually patients die with the development of Enz resistance that may involve the induction of the androgen receptor (AR) splicing variant ARv7. Here we identify an unrecognized role of Natural Killer (NK) cells in the prostate tumor microenvironment that can be better recruited to the CRPC cells to suppress ARv7 expression resulting in suppressing the Enz resistant CRPC cell growth and invasion...
March 31, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28368512/androgen-receptor-rearrangement-and-splicing-variants-in-resistance-to-endocrine-therapies-in-prostate-cancer
#11
Yeung Ho, Scott M Dehm
The past few years have witnessed a significant improvement in the survival of patients with castration-resistant prostate cancer (CRPC) due to the development of second generation androgen deprivation therapies (ADT) such as abiraterone and second generation antagonists such as enzalutamide. However, CRPC patients rapidly develop resistance to these drugs, in many cases due to re-activation of the therapeutic target, the androgen receptor (AR) transcription factor. Several mechanisms responsible for AR transcriptional re-activation have been demonstrated, including mutation, amplification, or rearrangement of the AR gene, transcriptional compensation by alternative steroid receptors, and mutation or copy number alteration of genes encoding AR co-regulators...
March 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28361223/emerging-variants-of-castration-resistant-prostate-cancer
#12
REVIEW
Panagiotis J Vlachostergios, Loredana Puca, Himisha Beltran
Metastatic castration-resistant prostate cancer (CRPC) is associated with substantial clinical, pathologic, and molecular heterogeneity. Most tumors remain driven by androgen receptor (AR) signaling, which has clinical implications for patient selection for AR-directed approaches. However, histologic and clinical resistance phenotypes can emerge after AR inhibition, in which the tumors become less dependent on the AR. In this review, we discuss prostate cancer variants including neuroendocrine (NEPC) and aggressive variant (AVPC) prostate cancers and their clinical implications...
May 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28359301/bromodomain-protein-4-discriminates-tissue-specific-super-enhancers-containing-disease-specific-susceptibility-loci-in-prostate-and-breast-cancer
#13
Verena Zuber, Francesco Bettella, Aree Witoelar, Ole A Andreassen, Ian G Mills, Alfonso Urbanucci
BACKGROUND: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs...
March 31, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28359237/influence-of-aldo-keto-reductase-1c3-in-prostate-cancer-a-mini-review
#14
Nishi Karunasingh, Jonathan Masters, Jack U Flanagan, Lynnette R Ferguson
Aldo-keto reductase 1C3 (AKR1C3) is an important oxidoreductase with multiple substrates, that is involved in producing extra-testicular androgens. Its activity is influenced by environmental exposures, as well as by genetic variants. These genetic variants could therefore produce variable testosterone levels and subsequent androgen receptor (AR) activation. This could lead to differential downstream production of the prostate-specific antigen (PSA). As PSA level is used for clinical evaluation of the prostate, these variations could impact prostate cancer (PC) diagnosis, as well as PC management outcomes...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28353036/resistance-to-hormonal-therapy-in-prostate-cancer
#15
Alfredo Berruti, Alberto Dalla Volta
Several therapeutic strategies are actually available in the management of prostate cancer: Targeting the androgen receptor (AR) is the goal both for initial androgen deprivation therapy (ADT) and second-generation androgen ablative agents (abiraterone and enzalutamide). Chemotherapy with taxanes, administered upon progression or as first line approach in association with ADT, is another therapeutic option. Unfortunately, none of these therapies is curative and patients are destined to develop a resistant phenotype...
March 29, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28342996/induction-of-neuroendocrine-differentiation-in-prostate-cancer-cells-by-dovitinib-tki-258-and-its-therapeutic-implications
#16
Shalini S Yadav, Jinyi Li, Jennifer A Stockert, Bryan Herzog, James O'Connor, Luis Garzon-Manco, Ramon Parsons, Ashutosh K Tewari, Kamlesh K Yadav
Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC...
March 24, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28342317/high-androgen-receptor-mrna-expression-is-independently-associated-with-prolonged-cancer-specific-and-recurrence-free-survival-in-stage-t1-bladder-cancer
#17
Danijel Sikic, Johannes Breyer, Arndt Hartmann, Maximilian Burger, Philipp Erben, Stefan Denzinger, Markus Eckstein, Robert Stöhr, Sven Wach, Bernd Wullich, Bastian Keck, Ralph M Wirtz, Wolfgang Otto
INTRODUCTION: High-risk non-muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder...
March 22, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28334513/the-number-of-cag-and-ggn-triplet-repeats-in-the-androgen-receptor-gene-exert-combinatorial-effect-on-hormonal-and-sperm-parameters-in-young-men
#18
M Grigorova, M Punab, T Kahre, M Ivandi, N Tõnisson, O Poolamets, V Vihljajev, B Žilaitienė, J Erenpreiss, V Matulevičius, M Laan
Androgen receptor (AR) is a transcription factor that is activated upon binding to testosterone (T) and is implicated in regulating the expression of reproduction-related genes. The human AR gene (Xq11-12) spans 186,588 bp and eight exons. N-terminal transactivation domain of the encoded AR protein harbours two polymorphic stretches of identical amino acids, a polyglutamine tract (encoded by 8-37 CAG-repeats) and a polyglycine tract (encoded by 10-30 GGN-repeats). We set forward to analyse independent and combinatory effects of the length of these repetitive tracts on male reproductive hormones, testicular and sperm parameters in a population-based cohort of Baltic young men (n = 974; aged 20...
March 23, 2017: Andrology
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#19
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
April 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28246761/-antihormonal-therapy-in-prostate-cancer-side-effects
#20
C H Ohlmann, P Thelen
Androgen deprivation is still standard therapy for prostate cancer, either as primary androgen deprivation therapy or with the use of secondary hormonal drugs including abiraterone and enzalutamide. However, especially the clinically occult side effects like metabolic changes or cardiovascular complications and effects on the psyche of the patient are often not recognized in daily practice. Active monitoring of such side effects is essential for prevention and early intervention. In addition, the efficacy of androgen deprivation therapies is limited by primary and secondary resistance...
February 28, 2017: Der Urologe. Ausg. A
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