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https://www.readbyqxmd.com/read/28645211/akr1c3-mediated-adipose-androgen-generation-drives-lipotoxicity-in-women-with-polycystic-ovary-syndrome
#1
Michael W O'Reilly, Punith Kempegowda, Mark Walsh, Angela E Taylor, Konstantinos N Manolopoulos, J William Allwood, Robert K Semple, Daniel Hebenstreit, Warwick B Dunn, Jeremy W Tomlinson, Wiebke Arlt
Context: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder, occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS...
June 22, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28645209/genome-wide-mapping-of-in-vivo-er%C3%AE-binding-sites-in-male-mouse-efferent-ductules
#2
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
#3
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/28644303/prostate-cancer-immunotherapy-the-path-forward
#4
Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: To provide an overview of current strategies being investigated in the development of immunotherapy in prostate cancer. RECENT FINDINGS: Development of immunotherapy in prostate cancer actually began in 2010 with FDA approval of sipuleucel-T. Given that immune checkpoint inhibitor trials have either been negative at the phase III level or underwhelming in smaller studies, it is likely that combination strategies will be required to further maximize the impact immune-based therapies on the clinical course of the disease...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28644090/transdermal-administration-of-melatonin-coupled-to-cryopass-laser-treatment-as-noninvasive-therapy-for-prostate-cancer
#5
Laura Terraneo, Paola Bianciardi, Eleonora Virgili, Elena Finati, Michele Samaja, Rita Paroni
Melatonin, a pineal gland hormone, exerts oncostatic activity in several types of human cancer, including prostate, the most common neoplasia and the third most frequent cause of male cancer death in the developed world. The growth of androgen-sensitive LNCaP prostate cancer cells in mice is inhibited by 3 mg/kg/week melatonin (0.09 mg/mouse/week) delivered by i.p. injections, which is equivalent to a dose of 210 mg/week in humans. The aim of this study is to test an alternative noninvasive delivery route based on transdermal administration of melatonin onto the tumor area followed by cryopass-laser treatment...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28643815/-greater-saphenous-vein-thrombosis-and-testosterone-replacement-therapy-an-occasional-association
#6
Giorgio Bertola, Roberto Bianchi, Salvatore Giambona, Simona Sada, Sergio Antonio Berra
We describe a case of greater saphenous vein thrombosis in a 50-year-old previously healthy man, occurred only 3 weeks after starting testosterone (T) replacement therapy (20 mg/day, gel) for hypergonadotropic hypogonadism. There were no clinical known risk factors for thrombosis. Laboratory assessment of thrombophilia, performed later, revealed only methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism. On the basis of other recently reported cases, we suppose a relationship between androgenic therapy and venous thrombosis...
May 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28643028/polycystic-ovary-syndrome-adipose-tissue-and-metabolic-syndrome
#7
REVIEW
Alessandro P Delitala, Giampiero Capobianco, Giuseppe Delitala, Pier Luigi Cherchi, Salvatore Dessole
PURPOSE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age and is characterized by ovulatory dysfunction and/or androgen excess or polycystic ovaries. Women with PCOS present a number of systemic symptoms in addition to those related to the reproductive system. It has been associated with functional derangements in adipose tissue, metabolic syndrome, type 2 diabetes, and an increased risk of cardiovascular disease (CVD). METHODS: A detailed literature search on Pubmed was done for articles about PCOS, adipokines, insulin resistance, and metabolic syndrome...
June 22, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28643022/androgen-receptor-expression-and-breast-cancer-mortality-in-a-population-based-prospective-cohort
#8
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
#9
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
#10
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/28642484/mir-100-5p-inhibition-induces-apoptosis-in-dormant-prostate-cancer-cells-and-prevents-the-emergence-of-castration-resistant-prostate-cancer
#11
Noushin Nabavi, Nur Ridzwan Nur Saidy, Erik Venalainen, Anne Haegert, Abhijit Parolia, Hui Xue, Yuwei Wang, Rebecca Wu, Xin Dong, Colin Collins, Francesco Crea, Yuzhuo Wang
Carcinoma of the prostate is the most common cancer in men. Treatment of aggressive prostate cancer involves a regiment of radical prostectomy, radiation therapy, chemotherapy and hormonal therapy. Despite significant improvements in the last decade, the treatment of prostate cancer remains unsatisfactory, because a significant fraction of prostate cancers develop resistance to multiple treatments and become incurable. This prompts an urgent need to investigate the molecular mechanisms underlying the evolution of therapy-induced resistance of prostate cancer either in the form of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate cancer (NEPC)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642037/testosterone-regulates-3t3-l1pre-adipocyte-differentiation-and-epididymal-fat-accumulation-in-mice-through-modulating-macrophage-polarization
#12
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/28641939/low-molecular-weight-protein-tyrosine-phosphatase-expression-as-a-prognostic-factor-for-men-with-metastatic-hormone-na%C3%A3-ve-prostate-cancer
#13
Mari Ohtaka, Yasuhide Miyoshi, Takashi Kawahara, Shinji Ohtake, Masato Yasui, Koichi Uemura, Shuko Yoneyama, Yusuke Hattori, Jun-Ichi Teranishi, Yumiko Yokomizo, Hiroji Uemura, Hiroshi Miyamoto, Masahiro Yao
OBJECTIVES: Recent studies have demonstrated that up-front docetaxel combined with androgen deprivation therapy (ADT) prolongs survival in some patients with metastatic hormone-naïve prostate cancer (mHNPC). However, new biomarkers for selecting personalized treatment strategies for mHNPC are warranted. We evaluated the value of low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression as a prognosticator in men with mHNPC. METHODS AND MATERIALS: A total of 48 men with mHNPC diagnosed from 2003 to 2009 were enrolled in this study...
June 19, 2017: Urologic Oncology
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
#14
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
#15
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
#16
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/28640191/phenotypic-plasticity-and-cell-fate-decisions-in-cancer-insights-from-dynamical-systems-theory
#17
REVIEW
Dongya Jia, Mohit Kumar Jolly, Prakash Kulkarni, Herbert Levine
Waddington's epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of "landscape" in the context of dynamical systems theory represents a high-dimensional space, in which each cell phenotype is considered as an "attractor" that is determined by interactions between multiple molecular players, and is buffered against environmental fluctuations. In addition, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes...
June 22, 2017: Cancers
https://www.readbyqxmd.com/read/28640164/associations-between-postmenopausal-endogenous-sex-hormones-and-c-reactive-protein-a-clearer-picture-with-regional-adiposity-adjustment
#18
Shannon M Conroy, Heather K Neilson, Rachel O'Reilly, Christy G Woolcott, Frank Z Stanczyk, Kerry S Courneya, Christine M Friedenreich
OBJECTIVE: To better understand the pathogenesis of inflammatory-related diseases after menopause, we studied the adiposity-independent association between endogenous sex hormones and C-reactive protein (CRP), a biomarker of inflammation. METHODS: We conducted a secondary, cross-sectional analysis of baseline data from the Alberta Physical Activity and Breast Cancer Prevention Trial (2003-2007), including 319 healthy, postmenopausal women not using hormone therapy...
June 19, 2017: Menopause: the Journal of the North American Menopause Society
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
#19
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/28639950/reactive-oxygen-species-generation-and-increase-in-mitochondrial-copy-number-new-insight-into-the-potential-mechanism-of-cytotoxicity-induced-by-aurora-kinase-inhibitor-azd1152-hqpa
#20
Ali Zekri, Yashar Mesbahi, Samad Ghanizadeh-Vesali, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Aurora-B kinase overexpression plays important roles in the malignant progression of prostate cancer (PCa). AZD1152-HQPA, as an inhibitor of Aurora-B, has recently emerged as a promising agent for cancer treatment. In this study, we aimed to investigate the effects of AZD1152-HQPA on reactive oxygen species (ROS) generation and mitochondrial function in PCa. We used AZD1152-HQPA (Barasertib), a highly potent and selective inhibitor of Aurora-B kinase. The effects of AZD1152-HQPA on cell viability, DNA content, cell morphology, and ROS production were studied in the androgen-independent PC-3 PCa cell line...
June 21, 2017: Anti-cancer Drugs
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