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https://www.readbyqxmd.com/read/28432720/androgen-receptor-dysfunction-as-a-prevalent-manifestation-in-young-male-carriers-of-a-flna-gene-mutation
#1
Laura Carrera-García, Maximiliano Francisco Rivas-Crespo, María Soledad Fernández García
Androgenic actions require the proper signal transmission by the androgen receptor (AR), a nuclear transcription factor. This is initially located in the cell cytoplasm and should translocates to the nucleus to interact with DNA. AR functional impairment causes diverse blockage degrees of androgenic steroid action, known as androgen insensitivity syndromes. Filamin A, a protein coded by the FLNA gene, is a co-activator of various cytoplasmic factors, including AR. The mutational inactivation of the FLNA gene induces insufficiency of translocation and activation of AR...
April 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28432091/suppressive-effects-of-tnf%C3%AE-il6-and-macrophages-on-thecal-androgen-production
#2
Moafaq S Samir, Claire Glister, Dareen Mattar, Mhairi Laird, Philip G Knight
Pro-inflammatory cytokines secreted by macrophages and other cell-types are implicated as intra-ovarian factors affecting different aspects of ovarian function including follicle and corpus luteum 'turnover', steroidogenesis and angiogenesis. Here, we compared granulosal (GC) and thecal (TC) expression of TNF, IL6 and their receptors (TNFR1, TNFRSF1B, IL6R) during bovine antral follicle development; all five mRNA transcripts were detected in both GC and TC and statistically significant cell-type and follicle stage-related differences were evident...
April 21, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28431277/endocrine-disruption-by-environmental-gestagens-in-amphibians-a-short-review-supported-by-new-in%C3%A2-vitro-data-using-gonads-of-xenopus-laevis
#3
REVIEW
Andrea Ziková, Claudia Lorenz, Frauke Hoffmann, Wibke Kleiner, Ilka Lutz, Matthias Stöck, Werner Kloas
Endocrine disruption caused by various anthropogenic compounds is of persisting concern, especially for aquatic wildlife, because surface waters are the main sink of these so-called endocrine disruptors (ED). In the past, research focused on (anti)estrogenic, (anti)androgenic, and (anti)thyroidal substances, affecting primarily reproduction and development in vertebrates; however, other endocrine systems might be also targeted by ED. Environmental gestagens, including natural progestogens (e.g. progesterone (P4)) and synthetic progestins used for contraception, are supposed to affect vertebrate reproduction via progesterone receptors...
April 5, 2017: Chemosphere
https://www.readbyqxmd.com/read/28430631/loss-of-steroid-hormone-receptors-is-common-in-malignant-pleural-and-peritoneal-effusions-of-breast-cancer-patients-treated-with-endocrine-therapy
#4
Willemijne A M E Schrijver, Karianne Schuurman, Annelot van Rossum, Ton Peeters, Natalie Ter Hoeve, Wilbert Zwart, Paul J van Diest, Cathy B Moelans
Discordance in estrogen receptor alpha (ERα), progesterone receptor (PR), androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancers and solid distant metastases ("conversion") has been reported previously. Even though metastatic spread to the peritoneal and pleural cavities occurs frequently and is associated with high mortality, the rate of receptor conversion and the prognostic implications thereof remain elusive.We therefore determined receptor conversion in 91 effusion metastases (78 pleural, 13 peritoneal effusions) of 69 patients by immunohistochemistry (IHC) and in situ hybridization...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430630/estrogen-and-androgen-converting-enzymes-17%C3%AE-hydroxysteroid-dehydrogenase-and-their-involvement-in-cancer-with-a-special-focus-on-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-2-and-breast-cancer
#5
REVIEW
Erik Hilborn, Olle Stål, Agneta Jansson
Sex steroid hormones such as estrogens and androgens are involved in the development and differentiation of the breast tissue. The activity and concentration of sex steroids is determined by the availability from the circulation, and on local conversion. This conversion is primarily mediated by aromatase, steroid sulfatase, and 17β-hydroxysteroid dehydrogenases. In postmenopausal women, this is the primary source of estrogens in the breast. Up to 70-80% of all breast cancers express the estrogen receptor-α, responsible for promoting the growth of the tissue...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430389/combination-of-carmustine-and-selenite-inhibits-egfr-mediated-growth-signaling-in-androgen-independent-prostate-cancer-cells
#6
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/28429718/a-computational-systems-approach-identifies-synergistic-specification-genes-that-facilitate-lineage-conversion-to-prostate-tissue
#7
Flaminia Talos, Antonina Mitrofanova, Sarah K Bergren, Andrea Califano, Michael M Shen
To date, reprogramming strategies for generating cell types of interest have been facilitated by detailed understanding of relevant developmental regulatory factors. However, identification of such regulatory drivers often represents a major challenge, as specific gene combinations may be required for reprogramming. Here we show that a computational systems approach can identify cell type specification genes (master regulators) that act synergistically, and demonstrate its application for reprogramming of fibroblasts to prostate tissue...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28428880/long-term-complete-remission-with-ipilimumab-in-metastatic-castrate-resistant-prostate-cancer-case-report-of-two-patients
#8
Luc Cabel, Elika Loir, Gwenaelle Gravis, Pernelle Lavaud, Christophe Massard, Laurence Albiges, Giulia Baciarello, Yohann Loriot, Karim Fizazi
BACKGROUND: Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428445/pectinase-treated-panax-ginseng-protects-heat-stress-induced-testicular-damage-in-rats
#9
Min Kyoung Kim, Kyu-Min Cha, Seock-Yeon Hwang, Un-Kyu Park, Seok Kyo Seo, Sang-Ho Lee, Min-Sik Jeong, SiHyun Cho, Spandana Rajendra Kopalli, Si-Kwan Kim
Testicular hyperthermia is well studied to cause impaired spermatogenesis. In the present study, the protective effect of enzymatically modified (pectinase-treated) Panax ginseng (GINST) against intermittent sub-chronic heat stress-induced testicular damage in rats was investigated. Male Sprague-Dawley rats were divided into four groups: normal control (NC), heat-stressed control (HC), heat-stressed plus GINST-100 mg/kg/day (HG100) and heat-stressed plus GINST-200 mg/kg/day (HG200) treatment groups. GINST (100 and 200 mg/kg/day) was mixed separately with a regular pellet diet and was administered orally for 8 weeks starting from 1 week before heat exposure...
June 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28428441/selective-glucocorticoid-receptor-modulators-sgrms-delay-castrate-resistant-prostate-cancer-growth
#10
Jacob Kach, Tiha M Long, Phillip Selman, Eva Y Tonsing-Carter, Maria A Bacalao, Ricardo R Lastra, Larischa de Wet, Shane Comiskey, Marc Gillard, Calvin VanOpstall, Diana C West, Wen-Ching Chan, Donald Vander Griend, Suzanne D Conzen, Russell Z Szmulewitz
Increased glucocorticoid receptor (GR) expression and activity following androgen blockade can contribute to castration-resistant prostate cancer (CRPC) progression. Therefore, we hypothesized that GR antagonism will have therapeutic benefit in CRPC. However, the FDA-approved nonselective, steroidal GR antagonist, mifepristone, lacks GR specificity, reducing its therapeutic potential. Here we report that two novel non-steroidal and highly selective GR modulators (SGRMs), CORT118335 and CORT108297, have the ability to block GR activity in prostate cancer (PC) and slow CRPC progression...
April 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28427194/alternative-rna-splicing-of-the-meaf6-gene-facilitates-neuroendocrine-prostate-cancer-progression
#11
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/28426320/transient-exposure-to-androgens-induces-a-remarkable-self-sustained-quiescent-state-in-dispersed-prostate-cancer-cells
#12
Anh Thu Bui, Meng-Er Huang, Maryline Havard, Fanny Laurent-Tchenio, François Dautry, Thierry Tchenio
Cellular quiescence is a reversible cell growth arrest that is often assumed to require a persistence of non-permissive external growth conditions for its maintenance. In this work, we showed that androgen could induce a quiescent state that is self-sustained in a cell-autonomous manner through a "hit and run" mechanism in androgen receptor-expressing prostate cancer cells. This phenomenon required the set-up of a sustained redox imbalance and TGFβ/BMP signaling that were dependent on culturing cells at low density...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28424556/nonalcoholic-steatohepatitis-related-hepatocellular-carcinoma-is-there-a-role-for-the-androgen-receptor-pathway
#13
REVIEW
Mahmoud A Ali, Sahin Lacin, Reham Abdel-Wahab, Mark Uemura, Manal Hassan, Asif Rashid, Dan G Duda, Ahmed O Kaseb
The epidemic of insulin resistance, obesity, and metabolic syndrome has led to the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of liver disease in the US. Patients with NASH are at an increased risk for hepatic disease-related morbidity and death, and chronic inflammation in NASH patients can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in males than in females, and genetic studies have identified androgen and androgen receptors (ARs) as partially responsible for the gender disparity in the development of liver disease and HCC...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28423563/regulation-of-p53wt-glioma-cell-proliferation-by-androgen-receptor-mediated-inhibition-of-small-vcp-p97-interacting-protein-expression
#14
Dejun Bao, Chuandong Cheng, Xiaoqiang Lan, Rong Xing, Zhuo Chen, Hua Zhao, Junyan Sun, Yang Wang, Chaoshi Niu, Bo Zhang, Shengyun Fang
The incidence of glioma in men is higher than that in women; however, little is known about the expression and basic function of the androgen receptor (AR) in gliomas. AR inhibited the small VCP/p97-interacting protein (SVIP) on the transcriptional level was previously reported. The present study shows that the protein level of AR is highly expressed in cell lines of the nervous system. Moreover, the AR expression is increased while SVIP expression is decreased in tumor tissue of glioma patients, which is in agreement with the progressing WHO grades...
April 4, 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
#15
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/28422308/androgen-receptor-regulated-mirna-193a-3p-targets-ajuba-to-promote-prostate-cancer-cell-migration
#16
Li Jia, Bin Gui, Dali Zheng, Keith F Decker, Ilker Tinay, Mingyue Tan, Xiaowei Wang, Adam S Kibel
Background Dysregulation of microRNA (miRNA) expression is implicated in cancer development and progression by modulating oncogenes or tumor suppressors at the post-transcriptional level. Methods To investigate the role of miRNAs in prostate cancer (PCa) progression, we performed small RNA-sequencing (RNA-seq) analysis in androgen-dependent LNCaP cells and LNCaP-derived castration-resistant prostate cancer (CRPC) C4-2B cells. For functional validation, we specifically investigated miR-193a-3p, which is highly upregulated in C4-2B cells and modulated by the androgen receptor (AR)...
April 19, 2017: Prostate
https://www.readbyqxmd.com/read/28420128/ar-signaling-and-the-pi3k-pathway-in-prostate-cancer
#17
REVIEW
Megan Crumbaker, Leila Khoja, Anthony M Joshua
Prostate cancer is a leading cause of cancer-related death in men worldwide. Aberrant signaling in the androgen pathway is critical in the development and progression of prostate cancer. Despite ongoing reliance on androgen receptor (AR) signaling in castrate resistant disease, in addition to the development of potent androgen targeting drugs, patients invariably develop treatment resistance. Interactions between the AR and PI3K pathways may be a mechanism of treatment resistance and inhibitors of this pathway have been developed with variable success...
April 15, 2017: Cancers
https://www.readbyqxmd.com/read/28416763/hormone-receptor-expression-profiles-differ-between-primary-and-recurrent-high-grade-serous-ovarian-cancers
#18
Zheng Feng, Hao Wen, Xingzhu Ju, Rui Bi, Xiaojun Chen, Wentao Yang, Xiaohua Wu
Hormone receptor status assessment is necessary for selecting cancer patients who might potentially benefit from endocrine therapy. To determine whether hormone receptor status changes during tumor progression, we retrospectively examined 107 high-grade serous ovarian cancer (HGSC) patients with paired primary and recurrent tumor specimens. Hormone receptor expression discordance rates between primary and recurrent tumors were as follows: estrogen receptor (ER) 34.9%, progesterone receptor (PR) 12.4%, androgen receptor (AR) 41...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416760/the-histone-demethylase-kdm3a-regulates-the-transcriptional-program-of-the-androgen-receptor-in-prostate-cancer-cells
#19
Stephen Wilson, Lingling Fan, Natasha Sahgal, Jianfei Qi, Fabian V Filipp
The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity, and tumor progression. We matched transcriptomic and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415742/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#20
Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J Small, Julie N Graff, Joshi J Alumkal, Tomasz M Beer, George V Thomas
Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH)...
March 13, 2017: Oncotarget
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