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Androgen receptor

Alexis Hugentobler, Laurent Gilbeau, Jean-Noel Talbot, Mathieu Gauthé
Breast cancer is approximately 100 times less common among men. Estrogen-related receptor α was detected in human prostate cancer tissue, and androgen receptors are expressed in both normal and malignant breast tissue. Thus, prostate cancer hormonal therapy may increase breast cancer risk. A 67-year-old man with prostate cancer history presented with rising prostate-specific antigen level. F-Fluorocholine PET/CT showed intense uptake in his right breast and moderate uptake in right axillary lymph node. Complementary F-FDG PET/CT demonstrated more intense tracer uptakes in both the right breast and axillary lymph node...
October 21, 2016: Clinical Nuclear Medicine
Takashi Dejima, Kenjiro Imada, Ario Takeuchi, Masaki Shiota, Jeffrey Leong, Tabitha Tombe, Kevin Tam, Ladan Fazli, Seiji Naito, Martin E Gleave, Christopher J Ong
BACKGROUND: LIM and SH3 domain protein 1 (LASP1) has been implicated in several human malignancies and has been shown to predict PSA recurrence in prostate cancer. However, the anti-tumor effect of LASP1 knockdown and the association between LASP1 and the androgen receptor (AR) remains unclear. The aim of this study is to clarify the significance of LASP1 as a target for prostate cancer, and to test the effect of silencing LASP1 in vivo using antisense oligonucleotides (ASO). METHODS: A tissue microarray (TMA) was performed to characterize the differences in LASP1 expression in prostate cancer treated after hormone deprivation therapy...
October 24, 2016: Prostate
Amita Shukla-Dave, Mireia Castillo-Martin, Ming Chen, Jose Lobo, Nataliya Gladoun, Ana C Lorduy, Faisal M Khan, Vladimir Ponomarev, Zhengzi Yi, Weijia Zhang, Pier P Pandolfi, Hedvig Hricak, Carlos Cordon-Cardo
Increased polyamine synthesis is known to play an important role in prostate cancer. We aimed to explore its functional significance in prostate tumor initiation and its link to androgen receptor (AR) signaling. For this purpose, we generated a new cell line derived from normal epithelial prostate cells (RWPE-1) with overexpression of ornithine decarboxylase (ODC) and used it for in vitro and in vivo experiments. We then comprehensively analyzed the expression of the main metabolic enzymes of the polyamine pathway and spermine abundance in 120 well-characterized cases of human prostate cancer and high-grade prostate intraepithelial neoplasia (HGPIN)...
October 19, 2016: American Journal of Pathology
Jay S Mishra, Gary D Hankins, Sathish Kumar
INTRODUCTION: Blood pressure is lower in females than males. Angiotensin II type-2 receptor (AT2R) induces vasodilation. This study determined whether sex differences in vascular AT2R expression occur and if androgens exert control on AT2R expression in the vasculature. METHODS: AT2Rs in the aorta of male and female Sprague-Dawley rats were examined following alteration in androgen levels by gonadectomy or hormone supplementation. RESULTS: AT2R mRNA and protein expression levels were lower in the aortas of males than females...
October 2016: Journal of the Renin-angiotensin-aldosterone System: JRAAS
Nada Lallous, Eric Leblanc, Ravi Sn Munuganti, Mohamed D H Hassona, Nader Al Nakouzi, Shannon Awrey, Helene Morin, Mani Roshan-Moniri, Kriti Singh, Sam Lawn, Takeshi Yamazaki, Hans H Adomat, Christophe Andre, Mads Daugaard, Robert N Young, Emma S Tomlinson Guns, Paul S Rennie, Artem Cherkasov
The development of new anti-androgens such as enzalutamide or androgen synthesis inhibitors like abiraterone have improved patient outcomes in the treatment of advanced prostate cancer (PCa). However, due to the development of drug resistance and tumor cell survival, the majority of these patients progress to the refractory state of castration-resistant prostate cancer (CRPC). Thus, newer therapeutic agents and a better understanding of their mode of action are needed for treating these CRPC patients. We demonstrated previously that targeting the Binding Function 3 (BF3) pocket of the androgen receptor (AR) has great potential for treating patients with CRPC...
October 7, 2016: Molecular Cancer Therapeutics
Ion Cristobal, Blanca Torrejón, Manuel Pedregal, Federico G Rojo, Jesús García-Foncillas
Dear Editor, We have read with great interest the recent published manuscript by Caiazza et al. (2016), which provides novel exciting findings about the potential therapeutic value of enzalutamide in patients with androgen receptor (AR)-positive triple negative breast cancer (TNBC). Some previous studies have shown promising antitumor effects of this drug in breast tumors. Thus, enzalutamide-mediated AR inhibition has been reported to reduce proliferation, anchorage-independent growth, migration, and invasion and increases apoptosis of TNBC cells in vitro and decrease viability of TNBC xenografts in vivo (Cochrane et al...
October 20, 2016: Endocrine-related Cancer
Ahmed Bulldan, Mazen Shihan, Sandra Goericke-Pesch, Georgios Scheiner-Bobis
A gonadotropin-releasing hormone agonist (GnRH-A) implant induces hormonal castration in dogs that is associated with reduced prostate and testes size. We address the molecular events associated with hormonal castration by examining GnRH-A effects on expression and phosphorylation of a number of key signaling proteins. Male beagles were treated for 5 months with a GnRH-A implant, and then surgically castrated at 0, 3, 6, 12, and 24 weeks after implant removal; untreated animals served as controls. GnRH-A treatment led to activation of c-Raf, Erk1/2, and p53 in the testes...
October 20, 2016: Molecular Reproduction and Development
Meng Wu, Lishann Ingram, Ezequiel J Tolosa, Renzo E Vera, Qianjin Li, Sungjin Kim, Yongjie Ma, Demetri D Spyropoulos, Zanna Beharry, Jiaoti Huang, Martin E Fernandez-Zapico, Houjian Cai
Although the differentiation of oncogenically transformed basal progenitor cells is one of the key steps in prostate tumorigenesis, the mechanisms mediating this cellular process are still largely unknown. Here we demonstrated that an expanded p63+ and CK5+ basal/progenitor cell population, induced by the concomitant activation of oncogenic Kras(G12D) and androgen receptor (AR) signaling, underwent cell differentiation in vivo. The differentiation process led to suppression of the p63 expressing cells with a decreased number of CK5+ basal cells, but an increase of CK8+ luminal tumorigenic cells, and revealed a hierarchal lineage pattern consisting of p63+/CK5+ progenitor, CK5+/CK8+ transitional progenitor, and CK8+ differentiated luminal cells...
October 19, 2016: Journal of Biological Chemistry
Shuai Gao, Yanfei Gao, Housheng Hansen He, Dong Han, Wanting Han, Amy Avery, Jill A Macoska, Xiaming Liu, Sen Chen, Fen Ma, Shaoyong Chen, Steven P Balk, Changmeng Cai
Although well characterized as a transcriptional activator that drives prostate cancer (PCa) growth, androgen receptor (AR) can function as a transcriptional repressor, and high-level androgens can suppress PCa proliferation. The molecular basis for this repression activity remains to be determined. Genes required for DNA replication are highly enriched among androgen-repressed genes, and AR is recruited to the majority of these genes, where it rapidly represses their transcription. This activity is enhanced in PCa cells expressing high AR levels and is mediated by recruitment of hypophosphorylated retinoblastoma protein (Rb)...
October 18, 2016: Cell Reports
C Yding Andersen
The aim of the present paper is to expand the concept on how follicular selection takes place in the follicular phase of the natural menstrual cycle. It is suggested that inhibin-B exerts a more intimate role in this process than previously understood. Inhibin-B shows a peak in the circulation around cycle day 7, simultaneous with selection of the dominant follicle, whereas levels of estradiol and inhibin-A only start to increase a few days later suggesting that inhibin-B is mainly responsible for down-regulating pituitary FSH release...
October 18, 2016: Molecular Human Reproduction
Rashid Sayyid, Andrew Evans, Karen Hersey, Ranjena Maloni, Antonio Hurtado-Coll, Girish Kulkarni, Antonio Finelli, Alexandre R Zlotta, Robert Hamilton, Martin Gleave, Neil Fleshner
PURPOSE: Degarelix, a new GnRH receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer, possesses some theoretical advantages over LHRH analogues in terms of avoiding "testosterone flare" and lower FSH levels. We set out to determine if pre-operative degarelix influenced surrogates of disease control in a randomized phase II study. EXPERIMENTAL DESIGN: 39 patients were randomly assigned to one of 3 different neo-adjuvant arms: degarelix only, degarelix/bicalutmaide, or LHRH agonist/bicalutamide...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Zheng Zhang, Bo Jin, Yaqiong Jin, Shengquan Huang, Xiaohua Niu, Zebin Mao, Dianqi Xin
Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex...
October 15, 2016: Experimental Cell Research
Yoko Yamada, Nobuaki Matsubara, Ken-Ichi Tabata, Takefumi Satoh, Naoto Kamiya, Hiroyoshi Suzuki, Takashi Kawahara, Hiroji Uemura, Akihiro Yano, Satoru Kawakami
BACKGROUND: Both abiraterone acetate (AA) and enzalutamide are promising agents for patients with pre- and post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC). Several retrospective analysis suggested clinical cross-resistance between these agents in patients previously treated with docetaxel. However, data on the antitumor activity of AA as a second androgen receptor-targeting new agent after the failure of enzalutamide in chemotherapy-naive mCRPC patients is unavailable...
October 18, 2016: BMC Research Notes
Yuen Ting Lam, Laura Lecce, Joanne T M Tan, Christina A Bursill, David J Handelsman, Martin K C Ng
Increasing evidence indicates that androgens regulate ischemia-induced neovascularization. However, the role of genomic androgen action mediated by androgen receptor (AR), a ligand-activated nuclear transcription factor, remains poorly understood. Using an AR knockout mouse strain that contains a transcriptionally inactive AR (AR(Δex3)KO), we examined the role of AR genomic function in modulating androgen-mediated augmentation of ischemia-induced neovascularization. Castrated wildtype (AR(WT)) and AR(Δex3)KO mice were implanted with dihydrotestosterone (DHT) or placebo pellets following hindlimb ischemia (HLI)...
October 18, 2016: Endocrinology
Ari L Mendell, Carolyn E Creighton, Bettina E Kalisch, Neil J MacLusky
Low free testosterone levels in men are associated with age-related cognitive decline and increased risk for neurotoxicity, resulting in disease. The mechanisms underlying these observations remain poorly defined. While rapid, androgen receptor-dependent activation of extracellular signal-regulated kinase (ERK) has been postulated as a neurotrophic and neuroprotective mechanism, actions of testosterone metabolites such as 5α-androstane-3α,17β-diol (3α-diol) may also be involved. We investigated the influence of 3α-diol on the induction of ERK phosphorylation in SH-SY5Y human female neuroblastoma cells and primary cortical neurons from male and female mice...
October 18, 2016: Endocrinology
John Chan, Chao-Sheng Lo, Yixuan Shi, Isabelle Chenier, Shao-Ling Zhang
OBJECTIVE: We aimed to investigate whether overexpression of heterogeneous nuclear ribonucleoprotein F (HnRNP F, a transcription factor) in renal proximal tubular cells (RPTCs) prevents systemic hypertension and kidney injury in type 2 diabetic db/db transgenic (Tg) mice and study its underlying mechanism (s) of action. DESIGN AND METHOD: Db/db hnRNP F-Tg mice (BKS strain) were generated by cross-breeding of db/m + mice with Tg mice specifically overexpressing HnRNP F in their RPTCs using kidney-specific androgen-regulated protein promoter (KAP2)...
September 2016: Journal of Hypertension
Daniel Nava Rodrigues, Gunther Boysen, Semini Sumanasuriya, George Seed, Angelo M De Marzo, Johann de Bono
Prostate cancer (PCa) is a clinically heterogeneous disease and current treatment strategies are based largely on anatomical and pathological parameters. In the recent past, several DNA sequencing studies of primary and advanced PCa have revealed recurrent patterns of genomic aberrations that expose mechanisms of resistance to available therapies and potential new drug targets. Suppression of androgen receptor (AR) signalling is the cornerstone of advanced prostate cancer treatment. Genomic aberrations of the androgen receptor or alternative splicing of its mRNA are increasingly recognized as biomarkers of resistance to AR-targeted therapy such as abiraterone or enzalutamide...
October 18, 2016: Journal of Pathology
Siavash Rahimi, Iolia Akaev, Costa Repanos, Peter A Brennan, Jean Daniel Dubois
Primary lingual intestinal-type adenocarcinomas are extremely rare with only a few cases described. A case with immunohistochemical expression of Androgen Receptor (AR) which was treated solely by chemo-radiotherapy is reported herein. A 54-year-old male was referred with symptoms of fullness in his tongue. Clinical examination showed an asymmetry of the tongue with a hard mass palpable within the middle of the tongue. Biopsy showed intestinal-type adenocarcinoma. The tumour showed positive staining with cytokeratin 7, cytokeratin 20, CDX2, AR, β-catenin and was mismatch repair proteins (MMR) proficient...
October 17, 2016: Head and Neck Pathology
Giuseppe Loverro, Leonardo Resta, Miriam Dellino, Di Naro Edoardo, Maria Arcangela Cascarano, Matteo Loverro, Salvatore Andrea Mastrolia
OBJECTIVE: Female-to-male transition remains a specific clinical indication for long-term testosterone administration. There is a limited number of studies dealing with the effect of androgen treatment on their female receptive targets (mainly breast and uterus) and the knowledge in this field is scarce and, sometimes, contradictory. MATERIALS AND METHODS: We performed a prospective study including 12 patients aged between 20 years and 32 years, with a diagnosis of gender dysphoria, treated with parenteral testosterone administration before sexual reassignment surgery...
October 2016: Taiwanese Journal of Obstetrics & Gynecology
Alessio Soggiu, Cristian Piras, Viviana Greco, Paola Devoto, Andrea Urbani, Luigino Calzetta, Marco Bortolato, Paola Roncada
The enzyme 5α-reductase (5αR) catalyzes the conversion of progesterone and testosterone into neuroactive steroids implicated in a wide array of behavioral functions. The prototypical 5αR inhibitor, finasteride (FIN), is clinically approved for the treatment of androgenic alopecia and benign prostatic hyperplasia. Recent evidence has shown that FIN, albeit generally well tolerated, can induce untoward psychological effects in a subset of patients; furthermore, this drug may have therapeutic efficacy for a number of different neuropsychiatric conditions, ranging from Tourette syndrome to schizophrenia...
October 6, 2016: Psychoneuroendocrinology
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