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https://www.readbyqxmd.com/read/28645209/genome-wide-mapping-of-in-vivo-er%C3%AE-binding-sites-in-male-mouse-efferent-ductules
#1
Guangxin Yao, Shuanggang Hu, Lu Yu, Yanfei Ru, Charlie Degui Chen, Qiang Liu, Yonglian Zhang
As an important nuclear hormone receptor, estrogen receptor alpha (ERα), which is encoded by Esr1 gene, regulates the expression of hundreds of genes in a stimulus-specific, temporal and tissue-specific fashion, mainly by binding to specific DNA sequences-estrogen response elements (EREs). As an important estrogen target tissue in males, the function of the efferent ductules relies on the presence of the ERα protein, but the underlying regulatory mechanisms are poorly illustrated. In this study, genome-wide ERα-binding sites in mouse efferent ductules were mapped by ChIP-seq...
June 22, 2017: Endocrinology
https://www.readbyqxmd.com/read/28644440/lncrna-sarcc-suppresses-renal-cell-carcinoma-rcc-progression-via-altering-the-androgen-receptor-ar-mirna-143-3p-signals
#2
Wei Zhai, Yin Sun, Changcheng Guo, Guanghui Hu, Mingchao Wang, Jiayi Zheng, WanYing Lin, Qingbo Huang, Gonghui Li, Junhua Zheng, Chawnshang Chang
While the androgen receptor (AR) might promote renal cell carcinoma (RCC) initiation and progression, the molecular mechanisms involved remain largely unclear. Here, we discovered the novel LncRNA-SARCC, which was suppressed and associated with better prognosis in RCC. Preclinical studies using multiple RCC cells and in vivo mouse model indicated that LncRNA-SARCC could attenuate RCC cell invasion, migration and proliferation in vitro and in vivo. Mechanistically, LncRNA-SARCC bound and destabilized AR protein with an inhibition of AR function, which led to transcriptionally de-repress miR-143-3p expression, thus inhibition of its downstream signals including AKT, MMP-13, K-RAS and P-ERK...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28643022/androgen-receptor-expression-and-breast-cancer-mortality-in-a-population-based-prospective-cohort
#3
Karin Elebro, Pär-Ola Bendahl, Helena Jernström, Signe Borgquist
PURPOSE: The increase in clinical trials with androgen receptor (AR)-targeting drugs emphasizes the need of clarifying the role of AR expression in different breast cancer subtypes. AR confers good prognosis in estrogen receptor positive (ER+) breast cancer, but its role in ER-negative (ER-) breast cancer is unclear. The aim of this study was to elaborate on previous findings of a differential prognostic role for AR depending on ER status, using breast cancer mortality (BCM) as endpoint, in a population-based cohort from the Malmö Diet and Cancer Study...
June 22, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28642838/adaptive-pathways-and-emerging-strategies-overcoming-treatment-resistance-in-castration-resistant-prostate-cancer
#4
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/28642789/androgen-receptor-localizes-to-plasma-membrane-by-binding-to-caveolin-1-in-mouse-sertoli-cells
#5
Qiong Deng, Yong Wu, Zeng Zhang, Yue Wang, Minghua Li, Hui Liang, Yaoting Gui
The nonclassical androgen signaling pathway translates signals into alterations in cellular function within minutes, and this action is proposed to be mediated by an androgen receptor (AR) localized to the plasma membrane. This study was designed to determine the mechanism underlying the membrane association of androgen receptor in TM4 cells, a mouse Sertoli cell line. Western blot analysis indicated testosterone-induced AR translocation to the cell membrane. Data from coimmunoprecipitation indicated that AR is associated with caveolin-1, and testosterone enhanced this association...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28642037/testosterone-regulates-3t3-l1pre-adipocyte-differentiation-and-epididymal-fat-accumulation-in-mice-through-modulating-macrophage-polarization
#6
Xiaojiao Ren, Xiaojian Fu, Xinhua Zhang, Shiqiang Chen, Shuguang Huang, Lun Yao, Guoquan Liu
Low testosterone levels are strongly related to obesity in males. The balance between the classically M1 and alternatively M2 polarized macrophages also plays a critical role in obesity. It is not clear whether testosterone regulates macrophage polarization and then affects adipocyte differentiation. In this report, we demonstrate that testosterone strengthens interleukin (IL) -4-induced M2 polarization and inhibits lipopolysaccharide (LPS) -induced M1 polarization, but has no direct effect on adipocyte differentiation...
June 19, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28641706/delayed-onset-of-puberty-in-male-offspring-from-bisphenol-a-treated-dams-is-followed-by-the-modulation-of-gene-expression-in-the-hypothalamic-pituitary-testis-axis-in-adulthood
#7
Isabela M Oliveira, Renata M Romano, Patricia de Campos, Monica D Cavallin, Claudio A Oliveira, Marco A Romano
Bisphenol A (BPA) is a synthetic endocrine-disrupting chemical of high prevalence in the environment, which may affect the function of the hypothalamic-pituitary-testis (HPT) axis in adult rats. The aim of the present study was to evaluate whether exposure to BPA during hypothalamic sexual differentiation at doses below the reproductive no observable adverse effect level of the World Health Organization causes changes in the regulation of the HPT axis. For this, 0.5 or 5mgkg-1 BPA was injected subcutaneously to the mothers from gestational day 18 to postnatal day (PND) 5...
June 23, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28641211/specific-interactions-between-androgen-receptor-and-its-ligand-ab-initio-molecular-orbital-calculations-in-water
#8
Ittetsu Kobayashi, Ryosuke Takeda, Rie Suzuki, Kanako Shimamura, Hiromi Ishimura, Ryushi Kadoya, Kentaro Kawai, Midori Takimoto-Kamimura, Noriyuki Kurita
The Androgen Receptor (AR) is a family of nuclear receptor proteins and a ligand-activated transcription factor. Since its abnormal activation can cause the progression of prostate cancer, numerous types of antagonists against AR have been developed as promising agents for treating prostate cancers. We here investigated the specific interactions between AR and several types of non-steroid agents at an electronic level, using ab initio molecular simulations based on molecular mechanics and ab initio fragment molecular orbital (FMO) methods From the results obtained by FMO, we proposed novel agents as potent ligands against AR and investigated the binding properties between AR and these agents to confirm that some of them can bind more strongly with AR than the existing non-steroid agents and can be strongly effective ligands against AR...
June 13, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28641189/qualitative-and-quantitative-simulation-of-androgen-receptor-antagonists-a-case-study-of-polybrominated-diphenyl-ethers
#9
Yang Wu, Wei Shi, Pu Xia, Xiaowei Zhang, Hongxia Yu
Recently, great attention has been paid to the identification and prediction of the androgen disrupting potencies of polybrominated diphenyl ethers (PBDEs). However, few existing models can discriminate active and inactive compounds, which make the quantitative prediction process including the quantitative structure-activity relationship (QSAR) technique unreliable. In this study, different grouping methods were investigated and compared for qualitative identification, including molecular docking and molecular dynamics simulations (MD)...
June 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28640128/association-between-polymorphic-cag-repeat-lengths-in-the-androgen-receptor-gene-and-susceptibility-to-prostate-cancer-a-systematic-review-and-meta-analysis
#10
Zhiqiang Qin, Xiao Li, Peng Han, Yuxiao Zheng, Hanyu Liu, Jingyuan Tang, Chengdi Yang, Jianzhong Zhang, Kunpeng Wang, Xiaokang Qi, Min Tang, Wei Wang, Wei Zhang
BACKGROUND: Previous studies have been conducted to reveal the relationship between androgen receptor CAG polymorphism and risk of prostate cancer, yet the results were elusive and controversial. Thus, this meta-analysis was performed to clarify this association. METHODS: To obtain the relevant available studies, online databases PubMed, Embase, and Web of science were searched until September 1st, 2016. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28639228/role-of-20-hydroxyeicosatetraenoic-acid-20-hete-in-androgen-mediated-cell-viability-in-prostate-cancer-cells
#11
Cecilia Colombero, Daniela Papademetrio, Paula Sacca, Eduardo Mormandi, Elida Alvarez, Susana Nowicki
20-Hydroxyeicosatetraenoic acid (20-HETE) is generated intracellularly through the ω-hydroxylation of arachidonic acid by the cytochrome P450 (in humans, CYP4A11 and CYP4F2). 20-HETE induces mitogenic responses in different cancer cells. The aim of this study was to analyze how 20-HETE impacts cell survival, proliferation, and apoptosis in prostate cancer cells. Incubation of the human androgen-sensitive cells (LNCaP) with 1-10 μM HET0016 (a selective inhibitor of 20-HETE synthesis) reduced cell viability by 49*-64%* (*p < 0...
June 21, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28638477/triptolide-inhibits-the-ar-signaling-pathway-to-suppress-the-proliferation-of-enzalutamide-resistant-prostate-cancer-cells
#12
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/28637005/cxcl13-is-androgen-responsive-and-involved-in-androgen-induced-prostate-cancer-cell-migration-and-invasion
#13
Long Fan, Qingyi Zhu, Li Liu, Cuicui Zhu, Haojie Huang, Shan Lu, Ping Liu
Androgen receptor (AR) is a key transcription factor playing a critical role in prostate cancer (PCa) initiation and progression. However, the molecular mechanisms of AR action in prostate cancer are not very clear. CXCL13, known as B cell attracting chemokine1 (BCA-1), is a member of CXC chemokine family and relevant to cancer metastasis. This study shows that CXCL13 is an androgen-responsive gene and involved in AR-induced PCa cell migration and invasion. In clinical specimens, expression of CXCL13 in PCa tissues is markedly higher than that in adjacent normal tissues...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636139/review-of-hplc-and-lc-ms-ms-assays-for-the-determination-of-various-non-steroidal-anti-androgens-nsaa-used-in-the-treatment-of-prostate-cancer
#14
REVIEW
P S Suresh, Nuggehally R Srinivas, Ramesh Mullangi
Prostate cancer is the most common cancer and one of the leading causes for cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first generation non-steroidal anti-androgens (NSAA) namely flutamide, nilutamide, bicalutamide and topilutamide. Most of the prostate cancer patients who are initially responsive develop a most aggressive form of disease called castration-resistant prostate cancer (CRPC). Second generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat CRPC...
June 21, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28634053/using-short-term-bioassays-to-evaluate-the-endocrine-disrupting-capacity-of-the-pesticides-linuron-and-fenoxycarb
#15
Petra Spirhanzlova, Bert De Groef, Freda E Nicholson, Sylvia V H Grommen, Giulia Marras, Anthony Sébillot, Barbara A Demeneix, Sophie Pallud-Mothré, Gregory F Lemkine, Andrew J Tindall, David Du Pasquier
Several short-term whole-organism bioassays based on transgenic aquatic models are now under validation by the OECD (Organization for Economic Co-operation and Development) to become standardized test guidelines for the evaluation of the endocrine activity of substances. Evaluation of the endocrine disrupting capacity of pesticides will be a domain of applicability of these future reference tests. The herbicide linuron and the insecticide fenoxycarb are two chemicals commonly used in agricultural practices...
June 17, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28633436/membrane-androgen-receptor-zip9-induces-croaker-ovarian-cell-apoptosis-via-stimulatory-g-protein-alpha-subunit-and-mapkinase-signaling
#16
Aubrey Converse, Chenan Zhang, Peter Thomas
Recent studies show that androgen-induced apoptosis in Atlantic croaker primary granulosa/theca (G/T) cells and in human breast and prostate cancer cell lines is mediated by the novel membrane androgen receptor ZIP9 which belongs to the SLC39A zinc transporter family. However, the apoptotic signaling pathways remain unclear because ZIP9 activates an inhibitory G protein in human cancer cells, whereas recombinant croaker ZIP9 activates a stimulatory G protein (Gs) in transfected cancer cells. Here we investigated androgen-dependent apoptotic pathways in order to identify the signaling pathways regulated through wild-type croaker ZIP9 in ovarian follicle cells...
June 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28633425/androgen-receptor-mutations-in-patients-with-castration-resistant-prostate-cancer-treated-with-apalutamide
#17
D E Rathkopf, M R Smith, C J Ryan, W R Berry, N D Shore, G Liu, C S Higano, J J Alumkal, R Hauke, R F Tutrone, M Saleh, E Chow Maneval, S Thomas, D S Ricci, M K Yu, C J de Boer, A Trinh, T Kheoh, R Bandekar, H I Scher, E S Antonarakis
Background: : Mutations in the androgen receptor (AR) ligand-binding domain (LBD), such as F877L and T878A, have been associated with resistance to next-generation AR-directed therapies. ARN-509-001 was a phase I/II study that evaluated apalutamide activity in castration-resistant prostate cancer (CRPC). Here we evaluated the type and frequency of 11 relevant AR-LBD mutations in apalutamide-treated CRPC patients. Patients and methods: : Blood samples from men with non-metastatic CRPC (nmCRPC) and metastatic CRPC (mCRPC) pre- or post abiraterone acetate and prednisone (AAP) treatment (≥6 months' exposure) were evaluated at baseline and disease progression in trial ARN-509-001...
June 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28632486/randomized-noncomparative-phase-ii-trial-of-early-switch-from-docetaxel-to-cabazitaxel-or-vice-versa-with-integrated-biomarker-analysis-in-men-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#18
Emmanuel S Antonarakis, Scott T Tagawa, Giuseppe Galletti, Daniel Worroll, Karla Ballman, Marie Vanhuyse, Guru Sonpavde, Scott North, Costantine Albany, Che-Kai Tsao, John Stewart, Atef Zaher, Ted Szatrowski, Wei Zhou, Ada Gjyrezi, Shinsuke Tasaki, Luigi Portella, Yang Bai, Timothy B Lannin, Shalu Suri, Conor N Gruber, Erica D Pratt, Brian J Kirby, Mario A Eisenberger, David M Nanus, Fred Saad, Paraskevi Giannakakou
Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327)...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28629183/an-amyloidogenic-sequence-at-the-n-terminus-of-the-androgen-receptor-impacts-polyglutamine-aggregation
#19
Emmanuel Oppong, Gunter Stier, Miriam Gaal, Rebecca Seeger, Melanie Stoeck, Marc-André Delsuc, Andrew C B Cato, Bruno Kieffer
The human androgen receptor (AR) is a ligand inducible transcription factor that harbors an amino terminal domain (AR-NTD) with a ligand-independent activation function. AR-NTD is intrinsically disordered and displays aggregation properties conferred by the presence of a poly-glutamine (polyQ) sequence. The length of the polyQ sequence as well as its adjacent sequence motifs modulate this aggregation property. AR-NTD also contains a conserved KELCKAVSVSM sequence motif that displays an intrinsic property to form amyloid fibrils under mild oxidative conditions...
June 19, 2017: Biomolecules
https://www.readbyqxmd.com/read/28628013/modulation-of-antitumor-immune-response-in-mouse-prostate-cancer-model
#20
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
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