keyword
MENU ▼
Read by QxMD icon Read
search

Selective androgen receptor mediators

keyword
https://www.readbyqxmd.com/read/29666640/investigating-the-interactive-effects-of-sex-steroid-hormones-and-brain-derived-neurotrophic-factor-during-adolescence-on-hippocampal-nmda-receptor-expression
#1
Cushla R McCarthny, Xin Du, YeeWen Candace Wu, Rachel A Hill
Sex steroid hormones have neuroprotective properties which may be mediated by brain-derived neurotrophic factor (BDNF). This study sought to determine the interactive effects of preadolescent hormone manipulation and BDNF heterozygosity (+/- ) on hippocampal NMDA-R expression. Wild-type and BDNF+/- mice were gonadectomised, and females received either 17 β -estradiol or progesterone treatment, while males received either testosterone or dihydrotestosterone (DHT) treatment. Dorsal (DHP) and ventral hippocampus (VHP) were dissected, and protein expression of GluN1, GluN2A, GluN2B, and PSD-95 was assessed by Western blot analysis...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29662238/structural-underpinnings-of-oestrogen-receptor-mutations-in-endocrine-therapy-resistance
#2
REVIEW
John A Katzenellenbogen, Christopher G Mayne, Benita S Katzenellenbogen, Geoffrey L Greene, Sarat Chandarlapaty
Oestrogen receptor-α (ERα), a key driver of breast cancer, normally requires oestrogen for activation. Mutations that constitutively activate ERα without the need for hormone binding are frequently found in endocrine-therapy-resistant breast cancer metastases and are associated with poor patient outcomes. The location of these mutations in the ER ligand-binding domain and their impact on receptor conformation suggest that they subvert distinct mechanisms that normally maintain the low basal state of wild-type ERα in the absence of hormone...
April 16, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29594945/nur77-suppression-facilitates-androgen-deprivation-induced-cell-invasion-of-prostate-cancer-cells-mediated-by-tgf-%C3%AE-signaling
#3
J Wu, H Sun, X Yang, X Sun
BACKGROUND: Androgen deprivation therapy (ADT) remains a standard treatment for advanced prostate cancers. However, recent studies revealed that while inhibiting the growth of certain types of prostate cancer cells, ADT promotes invasion. In the current study, we explored the effects of Nur77, an orphan nuclear receptor, on prostate cancer cell invasion following ADT. METHODS: Androgen receptor (AR) and Nur77 protein expression in patient tissues and cell lines were quantified via ELISA and western blot...
March 28, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29523594/dual-inhibition-of-akt-mtor-and-ar-signaling-by-targeting-hdac3-in-pten-or-spop-mutated-prostate-cancer
#4
Yuqian Yan, Jian An, Yinhui Yang, Di Wu, Yang Bai, William Cao, Linlin Ma, Junhui Chen, Zhendong Yu, Yundong He, Xin Jin, Yunqian Pan, Tao Ma, Shangqian Wang, Xiaonan Hou, Saravut John Weroha, R Jeffrey Karnes, Jun Zhang, Jennifer J Westendorf, Liguo Wang, Yu Chen, Wanhai Xu, Runzhi Zhu, Dejie Wang, Haojie Huang
AKT-mTOR and androgen receptor (AR) signaling pathways are aberrantly activated in prostate cancer due to frequent PTEN deletions or SPOP mutations. A clinical barrier is that targeting one of them often activates the other. Here, we demonstrate that HDAC3 augments AKT phosphorylation in prostate cancer cells and its overexpression correlates with AKT phosphorylation in patient samples. HDAC3 facilitates lysine-63-chain polyubiquitination and phosphorylation of AKT, and this effect is mediated by AKT deacetylation at lysine 14 and 20 residues and HDAC3 interaction with the scaffold protein APPL1...
March 9, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29518658/in-vitro-profiling-of-toxic-effects-of-prominent-environmental-lower-chlorinated-pcb-congeners-linked-with-endocrine-disruption-and-tumor-promotion
#5
Kateřina Pěnčíková, Lucie Svržková, Simona Strapáčová, Jiří Neča, Iveta Bartoňková, Zdeněk Dvořák, Martina Hýžďalová, Jakub Pivnička, Lenka Pálková, Hans-Joachim Lehmler, Xueshu Li, Jan Vondráček, Miroslav Machala
The mechanisms contributing to toxic effects of airborne lower-chlorinated PCB congeners (LC-PCBs) remain poorly characterized. We evaluated in vitro toxicities of environmental LC-PCBs found in both indoor and outdoor air (PCB 4, 8, 11, 18, 28 and 31), and selected hydroxylated metabolites of PCB 8, 11 and 18, using reporter gene assays, as well as other functional cellular bioassays. We focused on processes linked with endocrine disruption, tumor promotion and/or regulation of transcription factors controlling metabolism of both endogenous compounds and xenobiotics...
March 5, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29491216/selective-androgen-receptor-modulator-yk11-up-regulates-osteoblastic-proliferation-and-differentiation-in-mc3t3-e1-cells
#6
Tomofumi Yatsu, Taichi Kusakabe, Keisuke Kato, Yoshio Inouye, Kiyomitsu Nemoto, Yuichiro Kanno
Androgens are key regulators that play a critical role in the male reproductive system and have anabolic effects on bone mineral density and skeletal muscle mass. We have previously reported that YK11 is a novel selective androgen receptor modulator (SARM) and induces myogenic differentiation and selective gene regulation. In this study, we show that treatment of YK11 and dihydrotestosterone (DHT) accelerated cell proliferation and mineralization in MC3T3-E1 mouse osteoblast cells. Further, YK11-treated cells increased osteoblast specific differentiation markers, such as osteoprotegerin and osteocalcin, compared to untreated cells...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29285272/baicalein-suppresses-the-androgen-receptor-ar-mediated-prostate-cancer-progression-via-inhibiting-the-ar-n-c-dimerization-and-ar-coactivators-interaction
#7
Defeng Xu, Qiulu Chen, Yalin Liu, Xingqiao Wen
Background: Androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Androgen deprivation therapy with antiandrogens to reduce androgen biosynthesis or prevent androgens from binding to AR are widely used to suppress AR-mediated PCa growth. However, most of ADT may eventually fail with development of the castration resistance after 12-24 months. Here we found that a natural product baicalein can effectively suppress the PCa progression via targeting the androgen-induced AR transactivation with little effect to AR protein expression...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29261702/combination-of-palbociclib-with-enzalutamide-shows-in-vitro-activity-in-rb-proficient-and-androgen-receptor-positive-triple-negative-breast-cancer-cells
#8
Chun-Yu Liu, Ka-Yi Lau, Chia-Chi Hsu, Ji-Lin Chen, Chia-Han Lee, Tzu-Ting Huang, Yi-Ting Chen, Chun-Teng Huang, Po-Han Lin, Ling-Ming Tseng
OBJECTIVES: Triple negative breast cancer (TNBC) lacks specific drug targets and remains challenging. Palbociclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor is approved for metastatic estrogen receptor (ER)-positive and human epithermal growth factor 2 (HER2)-negative breast cancer. The nature of cell cycle inhibition by palbociclib suggests its potential in TNBC cells. Retinoblastoma (RB, a known substrate of CDK4/6) pathway deregulation is a frequent occurrence in TNBC and studies have revealed that pharmacological CDK4/6 inhibition induces a cooperative cytostatic effect with doxorubicin in RB-proficient TNBC models...
2017: PloS One
https://www.readbyqxmd.com/read/29243324/validation-of-histone-deacetylase-3-as-a-therapeutic-target-in-castration-resistant-prostate-cancer
#9
Abigail B McLeod, James P Stice, Suzanne E Wardell, Holly M Alley, Ching-Yi Chang, Donald P McDonnell
BACKGROUND: Whereas the androgen receptor (AR) signaling axis remains a therapeutic target in castration-resistant prostate cancer (CRPC), the emergence of AR mutations and splice variants as mechanisms underlying resistance to contemporary inhibitors of this pathway highlights the need for new therapeutic approaches to target this disease. Of significance in this regard is the considerable preclinical data, indicating that histone deacetylase (HDAC) inhibitors may have utility in the treatment of CRPC...
March 2018: Prostate
https://www.readbyqxmd.com/read/29216311/amelioration-of-sexual-behavior-and-motor-activity-deficits-in-a-castrated-rodent-model-with-a-selective-androgen-receptor-modulator-sarm-2f
#10
Megumi Morimoto, Yuichiro Amano, Masahiro Oka, Ayako Harada, Hisashi Fujita, Yukiko Hikichi, Ryuichi Tozawa, Masuo Yamaoka, Takahito Hara
Sarcopenia and cachexia present characteristic features of a decrease in skeletal muscle mass and strength, anorexia, and lack of motivation. Treatments for these diseases have not yet been established, although selective androgen receptor modulators (SARMs) are considered as therapeutic targets. We previously reported that a novel SARM compound, SARM-2f, exhibits anabolic effect on muscles, with less stimulatory effect on prostate weight compared with testosterone, in rat Hershberger assays and cancer cachexia models...
2017: PloS One
https://www.readbyqxmd.com/read/29199581/molecular-dynamics-and-virtual-screening-analysis-of-lanosterol-derivatives-from-ganoderma-medicinal-mushrooms-agaricomycetes-as-selective-ligands-of-human-androgen-receptor
#11
Abraham M Vidal-Limon, Oscar Daniel Luna-Martinez, Fausto Rojas-Durán, Thuluz Meza-Menchaca, Maria Elena Hernández-Aguilar, Angel Trigos, Jorge Suárez-Medellín
Male sex hormones such as testosterone and dihydrotestosterone play important roles in several physiological and pathological processes. The biological activities of the aforementioned metabolites are mediated by the multidomain androgen receptor (AR), which is therefore a well-studied drug target. Ganoderma mushroom lanostanoid extracts have previously been shown to exert antiandrogenic activity; therefore, this work aims to identify which lanostane derivatives might act as selective ligands for AR. Because protein flexibility is of paramount importance for ligand binding, different conformations of AR were sampled to account for binding modes within a ligand binding site, then subjected to virtual screening against a metabolite library...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/29157894/selective-inhibition-reveals-cyclin-dependent-kinase-2-as-another-kinase-that-phosphorylates-the-androgen-receptor-at-serine-81
#12
Radek Jorda, Zuzana Bučková, Eva Řezníčková, Jan Bouchal, Vladimír Kryštof
Several studies have revealed that cyclin-dependent kinases (CDK) can mediate phosphorylation of steroid receptors at multiple sites, including serine 81 of the androgen receptor (AR). Phosphorylation of S81 is required for AR nuclear translocation, an association with chromatin and also regulates endogenous AR-regulated transcription in response to hormones. Up to date, S81-phosphorylation has been studied using different CDK inhibitors. Nevertheless, most inhibitors are non-selective or have unknown selectivity...
February 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#13
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29117944/small-molecule-sigma1-modulator-induces-autophagic-degradation-of-pd-l1
#14
Christina M Maher, Jeffrey D Thomas, Derick A Haas, Charles G Longen, Halley M Oyer, Jane Y Tong, Felix J Kim
Emerging evidence suggests that Sigma1 ( SIGMAR1 , also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)-associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway...
February 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29063285/songbird-chemical-signals-reflect-uropygial-gland-androgen-sensitivity-and-predict-aggression-implications-for-the-role-of-the-periphery-in-chemosignaling
#15
Danielle J Whittaker, Kimberly A Rosvall, Samuel P Slowinski, Helena A Soini, Milos V Novotny, Ellen D Ketterson
Chemical signals can provide useful information to potential mates and rivals. The production mechanisms of these signals are poorly understood in birds, despite emerging evidence that volatile compounds from preen oil may serve as chemosignals. Steroid hormones, including testosterone (T), may influence the production of these signals, yet variation in circulating T only partly accounts for this variation. We hypothesized that odor is a T-mediated signal of an individual's phenotype, regulated in part by androgen sensitivity in the uropygial gland...
January 2018: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/29032351/testosterone-induced-modulation-of-peroxisomal-morphology-and-peroxisome-related-gene-expression-in-brown-trout-salmo-trutta-f-fario-primary-hepatocytes
#16
Célia Lopes, Fernanda Malhão, Cláudia Guimarães, Ivone Pinheiro, José F Gonçalves, L Filipe C Castro, Eduardo Rocha, Tânia V Madureira
Disruption of androgenic signaling has been linked to possible cross-modulation with other hormone-mediated pathways. Therefore, our objective was to explore effects caused by testosterone - T (1, 10 and 50μM) in peroxisomal signaling of brown trout hepatocytes. To study the underlying paths involved, several co-exposure conditions were tested, with flutamide - F (anti-androgen) and ICI 182,780 - ICI (anti-estrogen). Molecular and morphological approaches were both evaluated. Peroxisome proliferator-activated receptor alpha (PPARα), catalase and urate oxidase were the selected targets for gene expression analysis...
December 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28978635/novel-selective-agents-for-the-degradation-of-androgen-receptor-variants-to-treat-castration-resistant-prostate-cancer
#17
Suriyan Ponnusamy, Christopher C Coss, Thirumagal Thiyagarajan, Kate Watts, Dong-Jin Hwang, Yali He, Luke A Selth, Iain J McEwan, Charles B Duke, Jayaprakash Pagadala, Geetika Singh, Robert W Wake, Christopher Ledbetter, Wayne D Tilley, Tudor Moldoveanu, James T Dalton, Duane D Miller, Ramesh Narayanan
Androgen receptor (AR) mediates the growth of prostate cancer throughout its course of development, including in abnormal splice variants (AR-SV)-driven advanced stage castration-resistant disease. AR stabilization by androgens makes it distinct from other steroid receptors, which are typically ubiquitinated and degraded by proteasomes after ligand binding. Thus, targeting AR in advanced prostate cancer requires the development of agents that can sustainably degrade variant isoforms for effective therapy. Here we report the discovery and characterization of potent selective AR degraders (SARD) that markedly reduce the activity of wild-type and splice variant isoforms of AR at submicromolar doses...
November 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28974548/selective-androgen-receptor-modulator-rad140-inhibits-the-growth-of-androgen-estrogen-receptor-positive-breast-cancer-models-with-a-distinct-mechanism-of-action
#18
Ziyang Yu, Suqin He, Dannie Wang, Hitisha K Patel, Chris P Miller, Jeffrey L Brown, Gary Hattersley, Jamal C Saeh
Purpose: Steroidal androgens suppress androgen receptor and estrogen receptor positive (AR/ER+ ) breast cancer cells and were used to treat breast cancer, eliciting favorable response. The current study evaluates the activity and efficacy of the oral selective AR modulator RAD140 in in vivo and in vitro models of AR/ER+ breast cancer. Experimental Design: A series of in vitro assays were used to determine the affinity of RAD140 to 4 nuclear receptors and evaluate its tissue-selective AR activity. The efficacy and pharmacodynamics of RAD140 as monotherapy or in combination with palbociclib were evaluated in AR/ER+ breast cancer xenograft models...
December 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28900498/correlation-between-erg-fusion-protein-and-androgen-receptor-expression-by-immunohistochemistry-in-prostate-possible-role-in-diagnosis-and-therapy
#19
Amir Hassan Navaei, Beatriz A Walter, Vanessa Moreno, Svetlana D Pack, Peter Pinto, Maria J Merino
Background: Recent discovery of gene rearrangements have brought a new look to the molecular pathogenesis of cancer. Gene fusions occur in nearly 60% of prostate adenocarcinoma, being the TMPRSS2-ERG one of the most common. Evidence supports the role of ERG fusion in tumorigenesis, progression and invasion via effecting pathways such as WNT, MYC, uPA, PI3K/AKT/PTEN, RAS/RAF/MAPF, NKX3.1, GST-pi and androgen receptor (AR) mediated signaling. Most of the ERG fusions involve 5'-partners androgen responsive. Therefore, we aimed to evaluate AR and ERG fusion protein expression on prostate tissue to find clinicopathological applications and possible role in therapy...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28891793/regulation-of-the-glucocorticoid-receptor-via-a-bet-dependent-enhancer-drives-antiandrogen-resistance-in-prostate-cancer
#20
Neel Shah, Ping Wang, John Wongvipat, Wouter R Karthaus, Wassim Abida, Joshua Armenia, Shira Rockowitz, Yotam Drier, Bradley E Bernstein, Henry W Long, Matthew L Freedman, Vivek K Arora, Deyou Zheng, Charles L Sawyers
In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals...
September 11, 2017: ELife
keyword
keyword
95951
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"