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Androgen insensitivity

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https://www.readbyqxmd.com/read/29134684/enhanced-radiosensitization-of-enzalutamide-via-schedule-dependent-administration-to-androgen-sensitive-prostate-cancer-cells
#1
Maryam Ghashghaei, Miltiadis Paliouras, Mitra Heravi, Hamed Bekerat, Mark Trifiro, Tamim M Niazi, Thierry Muanza
BACKGROUND: Prostate cancer (PCa) is a progressive disease and the most diagnosed cancer in men. The current standard of care for high-risk localized PCa is a combination of androgen deprivation therapy (ADT) and radiation (XRT). The majority of these patients however become resistant due to incomplete responses to ADT as a result of selective cells maintaining androgen receptor (AR) activity. Improvement can be made if increasing radiosensitivity is realized. Therefore, the aim of this study is to investigate the efficacy of the next-generation PCa drug Enzalutamide (ENZA), as a radiosensitizer in XRT therapy...
November 14, 2017: Prostate
https://www.readbyqxmd.com/read/29121256/malignant-testicular-germ-cell-tumors-in-postpubertal-individuals-with-androgen-insensitivity-prevalence-pathology-and-relevance-of-single-nucleotide-polymorphism-based-susceptibility-profiling
#2
M Cools, K P Wolffenbuttel, R Hersmus, B B Mendonca, J Kaprová, S L S Drop, H Stoop, A J M Gillis, J W Oosterhuis, E M F Costa, S Domenice, M Y Nishi, L Wunsch, C A Quigley, G T'Sjoen, L H J Looijenga
STUDY QUESTION: What is the prevalence of malignant testicular germ cell tumors (TGCT) and its precursors, (pre-) germ cell neoplasia in situ (GCNIS), in late teenagers and adults who have androgen insensitivity syndrome (AIS) and the impact of an individual's genetic susceptibility to development of TGCT? SUMMARY ANSWER: No GCNIS or TGCT was diagnosed, but pre-GCNIS was identified in 14 and 10% of complete and partial AIS patients, respectively, and was associated with a higher genetic susceptibility score (GSS), with special attention for KITLG (rs995030) and ATFZIP (rs2900333)...
November 7, 2017: Human Reproduction
https://www.readbyqxmd.com/read/29118296/mismatch-between-fetal-sexing-and-birth-phenotype-a%C3%A2-case-of-complete-androgen-insensitivity-syndrome
#3
Keisuke Yoshii, Yasuhiro Naiki, Yumiko Terada, Maki Fukami, Reiko Horikawa
With advancing maternal age, the number of prenatal genetic tests is increasing in many countries. Prenatal genetic tests, such as amniocentesis, chorionic villus sampling and non-invasive prenatal testing, can disclose fetal chromosomal sex, although these tests were originally designed to prenatally diagnose chromosomal aneuploidies, such as trisomy 21, 18 and 13. Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive disorder caused by an androgen receptor dysfunction leading to hormone resistance...
November 9, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/29102238/endocrinal-description-of-two-chinese-kennedy-s-disease-pedigrees
#4
Fang Li, Gulibositan Aji, Fei Leng, Jia-Chao Chen, Yu Luo, Jing Zhang, Ke Hu, Zi-Yun Cheng, Xi Xu, Zhi-Qiang Lu
Kennedy's disease (KD), also known as X-linked spinal and bulbar muscular atrophy (SBMA), is caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the first exon of the androgen receptor (AR) gene. KD is a late-onset neural-endocrinal disease that is characterized by the degeneration of motor neurons in the brainstem and spinal cord. In addition, partial androgen insensitivity is an important manifestation of KD. Here, we report two Chinese KD pedigrees that reveal the clinical and genetic manifestations and fully elaborate the endocrinal characteristics of KD patients...
October 25, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29066975/a-standardized-wedelia-chinensis-extract-overcomes-the-feedback-activation-of-her2-3-signaling-upon-androgen-ablation-in-prostate-cancer
#5
Chin-Hsien Tsai, Sheue-Fen Tzeng, Shih-Chuan Hsieh, Chia-Jui Tsai, Yu-Chih Yang, Mong-Hsun Tsai, Pei-Wen Hsiao
Crosstalk between the androgen receptor (AR) and other signaling pathways in prostate cancer (PCa) severely affects the therapeutic outcome of hormonal therapy. Although anti-androgen therapy prolongs overall survival in PCa patients, resistance rapidly develops and is often associated with increased AR expression and upregulation of the HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually fails due to the reciprocal feedback loop. Previously, we reported that wedelolactone, apigenin, and luteolin are the active compounds in Wedelia chinensis herbal extract, and act synergistically to inhibit the AR activity in PCa...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29051026/mutational-analysis-of-the-androgen-receptor-nr3c4-gene-in-patients-with-46-xy-dsd
#6
L Ramos, B Chávez, L Mares, E Valdés, F Vilchis
Androgen insensitivity syndrome (AIS) is an X-linked disorder caused by mutations in the NR3C4 gene, which encodes the androgen receptor (AR). In this study, we performed mutational analyses to identify AR molecular defects, in individuals with 46,XY disorders of sex development (46,XY DSD) and a presumptive diagnosis of AIS. Eighteen different gene mutations, including seven previously unreported new variants, were detected in 26 unrelated cases. These included two deletion mutations (P49fs*185 and E308f*320) in exon 1 and five substitution mutations (p...
October 16, 2017: Gene
https://www.readbyqxmd.com/read/29046359/androgens-trigger-different-growth-responses-in-genetically-identical-human-hair-follicles-in-organ-culture-that-reflect-their-epigenetic-diversity-in-life
#7
Benjamin H Miranda, Matthew R Charlesworth, Desmond J Tobin, David T Sharpe, Valerie A Randall
Male sex hormones-androgens-regulate male physique development. Without androgen signaling, genetic males appear female. During puberty, increasing androgens harness the hair follicle's unique regenerative ability to replace many tiny vellus hairs with larger, darker terminal hairs (e.g., beard). Follicle response is epigenetically varied: some remain unaffected (e.g., eyelashes) or are inhibited, causing balding. How sex steroid hormones alter such developmental processes is unclear, despite high incidences of hormone-driven cancer, hirsutism, and alopecia...
October 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28978108/tunicamycin-induced-endoplasmic-reticulum-stress-promotes-apoptosis-of-prostate-cancer-cells-by-activating-mtorc1
#8
Prasun Guha, Engin Kaptan, Padmaja Gade, Dhananjaya V Kalvakolanu, Hafiz Ahmed
Studies suggest that tunicamycin may work as a therapeutic drug to cancer cells by inducing stress in the endoplasmic reticulum (ER) through unfolded protein response (UPR) and thereby promoting apoptosis. However, mechanisms of the prolonged activation of the UPR under sustained ER stress in the regulation of cell apoptosis are largely unknown. To delineate the role of candidate genes in the apoptotic process under ER stress and to search for new therapeutic strategies to treat metastatic castration resistant prostate cancer, we performed whole genome expression microarray analysis in tunicamycin treated metastatic androgen-insensitive prostate cancer cells, PC-3...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28949385/effects-of-testosterone-and-17%C3%AE-%C3%A2-estradiol-on-angiotensin%C3%A2-induced-changes-in-tyrosine-kinase-activity-in-the-androgen%C3%A2-independent-human-prostate-cancer-cell-line-du145
#9
Kamila Domińska, Antoni Kowalski, Tomasz Ochędalski, Elżbieta Rębas
Angiotensin II (AngII), the main peptide of the renin‑angiotensin system (RAS), is involved in the proliferation of different types of cells, normal and pathological as well. The protein tyrosine kinases (PTKs) play an important role in the growth, differentiation and apoptosis of cells. AngII action depends on the hormonal milieu of the cell, and on sex steroid influence. Angiotensin 1‑7 (Ang1‑7), metabolite of AngII, shows opposite action to AngII in cells. The present study aimed to examine the influence of 17β‑estradiol and testosterone on AngII and Ang1‑7 action on PTK activity in androgen‑independent humane prostate cancer cell line DU145...
September 25, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28948813/peripheral-sensitivity-to-steroids-revisited
#10
R Hampl, K Vondra
Resistance to steroid hormones presents a serious problem with respect to their mass use in therapy. It may be caused genetically by mutation of genes involved in hormonal signaling, not only steroid receptors, but also other players in the signaling cascade as co-regulators and other nuclear factors, mediating the hormone-born signal. Another possibility is acquired resistance which may develop under long-term steroid treatment, of which a particular case is down regulation of the receptors. In the review recent knowledge is summarized on the mechanism of main steroid hormone action, pointing to already proven or potential sites causing steroid resistance...
September 26, 2017: Physiological Research
https://www.readbyqxmd.com/read/28947719/clinical-and-genetic-characterization-of-six-cases-with-complete-androgen-insensitivity-syndrome-in-china
#11
Jing He, Shuwu Qi, Huijun Zhang, Jingjing Guo, Shu Chen, Qi Zhang, Baosheng Zhu
Themutations of androgen receptor (AR) gene are the most common cause for complete androgen insensitivity syndrome (CAIS). We aimed to characterize the six cases enrolled in our hospital (the First People's Hospital of Yunnan, China) and explore the molecular mechanism of CAIS. Between 2010 and 2013, six female cases were enrolled in our hospital for the agenesis of secondary sexual characteristics. The clinical examinations such as sex hormone test and B ultrasound were performed and the genetic characterization of patients were evaluated by karyotype analysis, polymerase chain reaction and DNA sequencing...
September 2017: Journal of Genetics
https://www.readbyqxmd.com/read/28933733/melatonin-decreases-glucose-metabolism-in-prostate-cancer-cells-a-13-c-stable-isotope-resolved-metabolomic-study
#12
David Hevia, Pedro Gonzalez-Menendez, Mario Fernandez-Fernandez, Sergio Cueto, Pablo Rodriguez-Gonzalez, Jose I Garcia-Alonso, Juan C Mayo, Rosa M Sainz
The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the "Warburg effect" only occurs in advanced tumors and in the metastatic stage...
July 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28905769/re-topical-dihydrotestosterone-to-treat-micropenis-secondary-to-partial-androgen-insensitivity-syndrome-pais-before-during-and-after-puberty-a-case-series
#13
https://www.readbyqxmd.com/read/28879700/whole-exome-sequencing-identifies-a-c-c2566t-mutation-in-the-androgen-receptor-in-a-chinese-family
#14
Zengge Wang, Yulin Zhou, Ruijuan Yang, Zhongmin Xia, Huan Zeng, Liya Du, Jun Ren, Qiwei Guo
BACKGROUND: Whole exome sequencing (WES) is one of the most valuable tools for the detection of Mendelian diseases in clinical laboratory. We performed WES for a family of 46,XY disorders of gender development and compared the applicability of public databases for the subsequent phenotype studies of WES-identified mutations. METHODS: DNA samples from the two patients were analyzed by WES. The mutated protein was studied using the HomoloGene database, Polyphen2, and SIFT...
September 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28867417/increased-psychiatric-morbidity-in-women-with-complete-androgen-insensitivity-syndrome-or-complete-gonadal-dysgenesis
#15
Hedvig Engberg, Anna Strandqvist, Anna Nordenström, Agnieszka Butwicka, Agneta Nordenskjöld, Angelica Lindén Hirschberg, Louise Frisén
OBJECTIVE: Knowledge concerning mental health outcomes is important to optimize the health of individuals with disorders or differences of sex development (DSD). Thus, the aim of this study was to estimate if the prevalence of psychiatric morbidity in adult women diagnosed with complete androgen insensitivity syndrome (CAIS) or complete gonadal dysgenesis (46,XY GD and 46,XX GD) differs from that in women with premature ovarian insufficiency (POI) or age-matched population controls. METHODS: This cross-sectional study was conducted at the Karolinska University Hospital, Stockholm, Sweden, and included 33 women with different DSDs: 20 CAIS, 6 46,XY GD, 7 46,XX GD, 21 women with POI and 61 population-derived controls...
August 8, 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28846663/chemopreventive-potential-of-ethanolic-extracts-of-luobuma-leaves-apocynum-venetum-l-in-androgen-insensitive-prostate-cancer
#16
Szu-Ping Huang, Tzu-Ming Ho, Chih-Wen Yang, Ya-Ju Chang, Jie-Fu Chen, Ning-Sing Shaw, Jia-Cherng Horng, Shih-Lan Hsu, Ming-Yuan Liao, Li-Chen Wu, Ja-An Annie Ho
Luobuma (Apocynum venetum L. (AVL)) is a popular beverage in Asia and has been reportedly to be associated with the bioactivities such as cardiotonic, diuretic, antioxidative, and antihypertensive. However, its biofunction as chemoprevention activity is seldom addressed. Herein, we aimed to characterize the anti-androgen-insensitive-prostate-cancer (anti-AIPC) bioactive compounds of Luobuma, and to investigate the associated molecular mechanisms. Activity-guided-fractionation (antioxidative activity and cell survivability) of Luobuma ethanolic extracts was performed to isolate and characterize the major bioactive compounds using Ultra Performance Liquid Chromatography (UPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR)...
August 28, 2017: Nutrients
https://www.readbyqxmd.com/read/28835168/structure-activity-relationship-analysis-of-carbobicyclo-and-oxabicyclo-succinimide-analogues-as-potential-androgen-receptor-antagonists
#17
Lingyan Wang, Jiazhong Li
Prostate cancer (PCa) is a frequently diagnosed male cancer and the second leading cause of cancer-related death in many countries. Due to various amino acid mutations occurred in the ligand binding domain of androgen receptor (AR), the patients were observed insensitive, even resistant to the marketed antiandrogens such as bicalutamide and enzalutamide, which emphasizes the urgent need for novel antiandrogens to solve drug resistance problem. Recently a series of carbobicyclo and oxabicyclo succinimide analogues were reported to effectively antagonize AR...
August 23, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28821302/participation-of-adults-with-disorders-differences-of-sex-development-dsd-in-the-clinical-study-dsd-life-design-methodology-recruitment-data-quality-and-study-population
#18
Robert Röhle, Katharina Gehrmann, Maria Szarras-Czapnik, Hedi Claahsen-van der Grinten, Catherine Pienkowski, Claire Bouvattier, Peggy Cohen-Kettenis, Anna Nordenström, Ute Thyen, Birgit Köhler
BACKGROUND: dsd-LIFE is a comprehensive cross-sectional clinical outcome study of individuals with disorders/differences of sex development (DSD). This study focuses on various rare genetic conditions characterized by impaired gonadal or adrenal functionality. METHODS/DESIGN: The study aims to assess quality of life (QoL) as a measure of psychosocial adaptation, psychosexual and mental health aspects as major outcomes. Health status and functioning, medical and surgical therapies, participants' views on health care, psychological and social support, sociodemographic factors and their interrelations will be investigated as factors associated with the outcomes...
August 18, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28816296/-complete-androgen-insensitivity-syndrome-associated-with-vesical-fistula-a-case-report-and-literature-review
#19
K H Hua, L Yang, X W Zhang, W J Bai, Q Li, T Xu
Androgen insensitivity syndrome (AIS) is a very uncommon genetic disorder that results from the resistance of androgen receptor (AR) to androgen, which influences the formation of the male genitalia and in turn presents with female phenotype. Surgical resection of undesceaded testicle and different kinds of genitoplasty are crucial methods to correct the deformity of reproductive system, as well as hormone replacement therapy, which is an essential therapy for postoperational rehabilitation in AIS patients...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28803809/improved-androgen-specificity-of-ar-ecoscreen-by-crispr-based-glucocorticoid-receptor-knockout
#20
Nick Zwart, Dave Andringa, Willem-Jan de Leeuw, Hiroyuki Kojima, Mitsuru Iida, Corine J Houtman, Jacob de Boer, Jeroen Kool, Marja H Lamoree, Timo Hamers
The AR-EcoScreen is a widely used reporter assay for the detection of androgens and anti-androgens. Endogenous expression of glucocorticoid receptors and their affinity for the androgen responsive element that drives reporter expression, however, makes the reporter cells sensitive to interference by glucocorticoids and less specific for (anti-)androgens. To create a glucocorticoid insensitive derivative of the AR-EcoScreen, CRISPR/Cas9 genome editing was used to develop glucocorticoid receptor knockout mutants by targeting various sites in the glucocorticoid gene...
December 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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