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https://www.readbyqxmd.com/read/28803809/improved-androgen-specificity-of-ar-ecoscreen-by-crispr-based-glucocorticoid-receptor-knockout
#1
Nick Zwart, Dave Andringa, Willem-Jan de Leeuw, Hiroyuki Kojima, Mitsuru Iida, Corine Houtman, Jacob de Boer, Jeroen Kool, Marja 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...
August 10, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28802954/creation-of-a-neovagina-by-laparoscopic-modified-davydov-vaginoplasty-in-patients-with-partial-androgen-insensitivity-syndrome
#2
Stefano Bianchi, Nicola Berlanda, Federica Brunetti, Alessandro Bulfoni, Cecilia Ferrero Caroggio, Luigi Fedele
OBJECTIVE: To evaluate the feasibility, safety and outcome of the laparoscopic modified Davydov vaginoplasty in subjects with partial androgen insensitivity syndrome (PAIS). DESIGN: Retrospective cohort study. CANADIAN TASK FORCE CLASSIFICATION OF STUDY DESIGN: III. SETTING: Tertiary referral Center. PATIENTS: Ten continuous patients operated between October 2008 and May 2014. INTERVENTIONS: Laparoscopic modified Davydov vaginoplasty...
August 9, 2017: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/28791271/female-with-46-xy-karyotype
#3
Eun Jung Jung, Do Hwa Im, Yong Hee Park, Jung Mi Byun, Young Nam Kim, Dae Hoon Jeong, Moon Su Sung, Ki Tae Kim, Hyo Jung An, Soo Jin Jung, Kyung Bok Lee
Disorders of sex development (DSD) are congenital conditions characterized by atypical development of chromosomal, gonadal, and phenotypic sex. 46, XY DSD can result from disorders of testicular development or disorders of androgen synthesis/action. Prophylactic gonadectomy should be considered in patients with 46, XY DSD because of the increased risk of gonadal malignancy. We report two rare cases of 46, XY DSD, including XY pure gonadal dysgenesis and complete androgen insensitivity syndrome, who underwent a prophylactic gonadectomy...
July 2017: Obstetrics & Gynecology Science
https://www.readbyqxmd.com/read/28783760/total-glucosides-of-paeony-inhibits-lipopolysaccharide-induced-proliferation-migration-and-invasion-in-androgen-insensitive-prostate-cancer-cells
#4
Zhi-Hui Zhang, Dong-Dong Xie, Shen Xu, Mi-Zhen Xia, Zhi-Qiang Zhang, Hao Geng, Lei Chen, Da-Ming Wang, Wei Wei, De-Xin Yu, De-Xiang Xu
Previous studies demonstrated that inflammatory microenvironment promoted prostate cancer progression. This study investigated whether total glucosides of paeony (TGP), the active constituents extracted from the root of Paeonia Lactiflora Pall, suppressed lipopolysaccharide (LPS)-stimulated proliferation, migration and invasion in androgen insensitive prostate cancer cells. PC-3 cells were incubated with LPS (2.0 μg/mL) in the absence or presence of TGP (312.5 μg /mL). As expected, cells at S phase and nuclear CyclinD1, the markers of cell proliferation, were increased in LPS-stimulated PC-3 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28756013/5-or-and-20-o-alkyl-2-3-dehydrosilybins-synthesis-and-biological-profiles-on-prostate-cancer-cell-models
#5
Bao Vue, Xiaojie Zhang, Timmy Lee, Nandini Nair, Sheng Zhang, Guanglin Chen, Qiang Zhang, Shilong Zheng, Guangdi Wang, Qiao-Hong Chen
To investigate the effects of alkylation at 5-OH and 20-OH of 2,3-dehydrosilybin on prostate cancer cell proliferation, the synthetic approaches to 5- or/and 20-O-alkyl-2,3-dehydrosilybins, through a multi-step sequence from commercially available silybin, have been successfully developed. The first three reactions in the syntheses were completed through a one-pot procedure by managing anaerobic and aerobic conditions. With these synthetic methods in hand, twenty-one 2,3-dehydrosilybins, including seven 20-O-alkyl, seven 5,20-O-dialkyl, and seven 5-O-alkyl-2,3-dehydrosilybins, have been achieved for the evaluation of their biological profiles...
July 20, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28754872/tunicamycin-induced-endoplasmic-reticulum-stress-promotes-apoptosis-of-prostate-cancer-cells-by-activating-mtorc1
#6
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...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28743543/a-recurrent-synonymous-mutation-in-the-human-androgen-receptor-gene-causing-complete-androgen-insensitivity-syndrome
#7
Rafael Loch Batista, Andresa di Santi Rodrigues, Mirian Yumie Nishi, Nathalia Lisboa Rosa Almeida Gomes, José Antonio Diniz Faria, Daniela Rodrigues de Moraes, Luciani Renata Carvalho, Elaine Maria Costa Frade, Sorahia Domenice, Berenice Bilharinho de Mendonca
Androgen insensitivity syndrome (AIS) is the most common cause of 46,XY disorders of sex development (46,XY DSD). This syndrome is an X-linked inheritance disease and it is caused by mutations in the human androgen receptor (AR) gene. Non-synonymous point AR mutations are frequently described in this disease, including in the complete phenotype. We present a novel synonymous mutation in the human AR gene (c.1530C > T) in four 46,XY patients from two unrelated families associated with complete androgen insensitivity syndrome (CAIS)...
July 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28742384/antiproliferative-effects-of-red-and-white-wine-extracts-in-pc-3-prostate-cancer-cells
#8
Roxane Tenta, Elizabeth Fragopoulou, Magafoula Tsoukala, Marianna Xanthopoulou, Maria Skyrianou, Harris Pratsinis, Dimitris Kletsas
Experimental and epidemiological studies have shown that antioxidant polyphenols can act as chemopreventive agents against prostate cancer. Cabernet Sauvignon and Rombola wine were extracted in order to obtain fractions containing different classes of compounds. All extracts inhibited the androgen-insensitive human prostate cancer cells (PC-3) proliferation in a dose-dependent manner. The most potent compounds were selected to be further tested.Treatment of PC-3 cells with the selected wine extracts marginally increased the cell distribution in S phase, while producing a remarkable induction of autophagy...
July 25, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28719918/-the-wish-for-a-child-in-the-case-of-permanent-infertility-development-of-the-german-questionnaire-on-attitudes-toward-motherhood
#9
Maike Fliegner, Hertha Richter-Appelt, Kerstin Krupp, Franziska Brunner
Study 1 Development of the questionnaire Most questionnaires on attitudes toward motherhood presume that the subject is fertile and positive and negative attitudes are represented on a one-dimensional scale. Moreover, the questionnaires often do not provide German versions and German norms. The aim of this study is to examine whether the German Questionnaire on Attitudes toward Motherhood ("FEMu") can be used to describe attitudes toward motherhood multi-dimensionally and whether it is applicable independent of a person's fertility status...
July 18, 2017: Psychotherapie, Psychosomatik, Medizinische Psychologie
https://www.readbyqxmd.com/read/28719904/gonadectomy-in-complete-androgen-insensitivity-syndrome-why-and-when
#10
Ulla Döhnert, Lutz Wünsch, Olaf Hiort
Prophylactic gonadectomy has been recommended in complete androgen insensitivity syndrome (CAIS) because of an increased risk for the development of malignant germ cell tumors in the intra-abdominal gonads. No reliable screening parameters are available to detect early (pre-)malignant changes. Because the tumor risk before puberty is very low, the timing of gonadectomy has been postponed to allow spontaneous puberty and involvement of the patients in important decisions affecting their body and health. Gonadectomy after puberty is still discussed controversially...
July 19, 2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28719895/update-on-the-pathophysiology-and-risk-factors-for-the-development-of-malignant-testicular-germ-cell-tumors-in-complete-androgen-insensitivity-syndrome
#11
Martine Cools, Leendert Looijenga
Prophylactic gonadectomy in young adult women with complete androgen insensitivity syndrome (CAIS) to avoid development of an invasive testicular germ cell tumor (TGCT) is currently advised in most centers. However, women with CAIS increasingly question the need of this procedure. In order to provide optimal counseling and follow-up of these women, insight in the mechanisms underlying TGCT development in androgen insensitivity syndrome (AIS), data regarding the incidence of TGCT in AIS adults specifically, and an overview of existing and novel screening tools for in situ and invasive neoplastic lesions are crucial...
July 19, 2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28715798/bone-mineral-density-in-women-living-with-complete-androgen-insensitivity-syndrome-and-intact-testes-or-removed-gonads
#12
Silvano Bertelloni, Maria C Meriggiola, Elenora Dati, Antonio Balsamo, Giampiero I Baroncelli
Complete androgen insensitivity syndrome (CAIS) is due to complete androgen resistance in androgen-dependent tissues. Since androgens are involved in growth, development, and mass maintenance of the skeleton, bone health may be a relevant clinical issue for improving quality of life of women living with CAIS. Bone mineral density (BMD) in women with CAIS and intact gonads has been reported in a normal range, although exceptions are known showing a low BMD mainly at the lumbar level. In women with CAIS and removed gonads, BMD is usually reduced at both the lumbar spine and femoral neck...
July 18, 2017: Sexual Development: Genetics, Molecular Biology, Evolution, Endocrinology, Embryology, and Pathology of Sex Determination and Differentiation
https://www.readbyqxmd.com/read/28688959/from-gene-to-therapy-in-spinal-and-bulbar-muscular-atrophy-are-we-there-yet
#13
REVIEW
Maria Pennuto, Carlo Rinaldi
Abnormal polyglutamine expansions in the androgen receptor (AR) cause a muscular condition, known as Kennedy's disease or spinal and bulbar muscular atrophy (SBMA). The disease is transmitted in an X-linked fashion and is clinically characterized by weakness, atrophy and fasciculations of the limb and bulbar muscles as a result of a toxic gain-of-function of the mutant protein. Notably, affected males also show signs of androgen insensitivity, such as gynaecomastia and reduced fertility. The characterization of the natural history of the disease, the increasing understanding of the mechanism of pathogenesis and the elucidation of the functions of normal and mutant AR have offered a momentum for developing a rational therapeutic strategy for this disease...
July 5, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28687949/controversies-of-sex-re-assignment-in-genetic-males-with-congenital-inadequacy-of-the-penis
#14
Venkatachalam Raveenthiran
Sex assignment in 46XY genetic male children with congenital inadequacy of the penis (CIP) is controversial. Traditionally, children with penile length less than 2 cm at birth are considered unsuitable to be raised as males. They are typically re-assigned to female-sex and feminizing genitoplasty is usually done in infancy. However, the concept of cerebral androgen imprinting has caused paradigm shift in the philosophy of sex re-assignment. Masculinization of the brain, rather than length of the penis, is the modern criterion of sex re-assignment in CIP...
July 8, 2017: Indian Journal of Pediatrics
https://www.readbyqxmd.com/read/28670533/mutational-analysis-of-androgen-receptor-gene-in-two-families-with-androgen-insensitivity
#15
Radha Ramadevi Akella
BACKGROUND: Androgen insensitivity syndrome (AIS) is a rare X-linked disorder due to mutations in the androgen receptor (AR) gene causing end-organ resistance to the androgenic hormone. SUBJECTS AND METHODS: Genetic studies were carried out in two families by karyotype and targeted exome sequencing of the AR gene. RESULTS: Two novel missense mutations were identified, p.L822P and p.P392S, in two families with complete androgen insensitivity (CAIS) and partial androgen insensitivity (PAIS), respectively...
July 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28667915/knockdown-of-tnf-receptor-associated-factor-2-traf2-modulates-in-vitro-growth-of-trail-treated-prostate-cancer-cells
#16
Bingbing Wei, Jun Ruan, Yuanyuan Mi, Jimeng Hu, Jian Zhang, Zhirong Wang, Qiang Hu, Haowen Jiang, Qiang Ding
TNF receptor-associated factor 2 (TRAF2) is documented to regulate tumor development and progression. Currently, the effect of TRAF2 on growth of androgen-refractory prostate cancer in response to TRAIL and the molecular mechanisms are not well understood. Here, we aim to investigate the effect of TRAF2 on in vitro growth of human androgen-insensitive prostate cancer DU-145 cells in the presence of TRAIL. Bioinformatics analysis of the Cancer Genome Atlas (TCGA) data was performed to examine TRAF2 expression and the prognostic value in prostate cancer...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28659371/mild-androgen-insensitivity-syndrome-mais-the-identification-of-c-1783c-t-mutation-in-two-unrelated-infertile-men
#17
Ghalia Abou Alchamat, Ammar Madania, Marwan Alhalabi
Two unrelated men complaining of primary male infertility presented to Orient Hospital in Damascus city. Physical examination showed moderate hypoandrogenic features. Both men were azoospermic. Hormone profiles revealed an elevation of follicle-stimulating hormone in one patient, but all the other hormones tested were within normal limits for both patients. Further genetic analyses, including karyotype and microdeletions in the AZF region of the Y chromosome, were normal in both patients. Mild androgen insensitivity syndrome was expected in the two patients...
June 28, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28645352/r%C3%A3-sistances-aux-hormones-st%C3%A3-ro%C3%A3-des-physiologie-et-pathologie-pathophysiology-of-steroid-resistance-syndrome
#18
N Ramos, M Lombès
Steroid resistance syndrome (mineralocorticoids, glucocorticoids, estrogens, androgens) is a rare clinical disorder, androgen insensitivity syndrome being the most commonly described. Resistance syndromes are characterized by elevated steroid hormone levels, secondary to an impaired signal transduction and a lack of negative feedback, without any specific clinical signs of steroid excess. In most cases, steroid hormone resistance is generally caused by steroid receptor mutations. Several nonsense and missense mutations or deletions have already been described for all steroid receptors, except for the progesterone receptor...
October 2016: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28639228/role-of-20-hydroxyeicosatetraenoic-acid-20-hete-in-androgen-mediated-cell-viability-in-prostate-cancer-cells
#19
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...
August 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28624954/ar-mutations-in-28-patients-with-androgen-insensitivity-syndrome-prader-grade-0-3
#20
Yi Wang, Chunxiu Gong, Xiou Wang, Miao Qin
We investigated the androgen receptor (AR) gene mutation profiles of Chinese patients exhibiting severe androgen insensitivity syndrome (AIS) phenotypes. The present study enrolled 28 patients with genetically diagnosed AIS, who presented with severe phenotypes (Prader grade 0-3). Patients and some family members were screened via amplification and sequencing of their AR exons 1-8, including the corresponding intronic flanking regions. Luteinizing (LH), follicle-stimulating (FSH), and testosterone (T) hormone levels were found to be slightly, but not significantly, higher in patients with complete androgen insensitivity syndrome (CAIS) than in patients with partial androgen insensitivity syndrome (PAIS) (P>0...
June 14, 2017: Science China. Life Sciences
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