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https://www.readbyqxmd.com/read/28641211/specific-interactions-between-androgen-receptor-and-its-ligand-ab-initio-molecular-orbital-calculations-in-water
#1
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
#2
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/28637005/cxcl13-is-androgen-responsive-and-involved-in-androgen-induced-prostate-cancer-cell-migration-and-invasion
#3
Long Fan, Qingyi Zhu, Li Liu, Cuicui Zhu, Haojie Huang, Shan Lu, Ping Liu
Androgen receptor (AR) is a key transcription factor playing a critical role in prostate cancer (PCa) initiation and progression. However, the molecular mechanisms of AR action in prostate cancer are not very clear. CXCL13, known as B cell attracting chemokine1 (BCA-1), is a member of CXC chemokine family and relevant to cancer metastasis. This study shows that CXCL13 is an androgen-responsive gene and involved in AR-induced PCa cell migration and invasion. In clinical specimens, expression of CXCL13 in PCa tissues is markedly higher than that in adjacent normal tissues...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636139/review-of-hplc-and-lc-ms-ms-assays-for-the-determination-of-various-non-steroidal-anti-androgens-nsaa-used-in-the-treatment-of-prostate-cancer
#4
REVIEW
P S Suresh, Nuggehally R Srinivas, Ramesh Mullangi
Prostate cancer is the most common cancer and one of the leading causes for cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first generation non-steroidal anti-androgens (NSAA) namely flutamide, nilutamide, bicalutamide and topilutamide. Most of the prostate cancer patients who are initially responsive develop a most aggressive form of disease called castration-resistant prostate cancer (CRPC). Second generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat CRPC...
June 21, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28635565/prostate-cancer-stem-cells-from-theory-to-practice
#5
Jan Adamowicz, Katayoon Pakravan, Babak Bakhshinejad, Tomasz Drewa, Sadegh Babashah
None of the generally accepted theories on prostate cancer development can fully explain many distinguishing features of the disease, such as intratumoral heterogeneity, metastatic growth, drug resistance and tumor relapse. Prostate stem cells are a heterogeneous and small subpopulation of self-renewing cells which can actively proliferate in response to changes in the androgen level and give rise to all the cell lineages that build the prostate epithelium. According to the cancer stem cell hypothesis, prostate cancer could be a stem cell disease...
February 7, 2017: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/28634757/a-uhplc-ms-ms-method-for-profiling-multifunctional-steroids-in-human-hair
#6
Zhen Dong, Caihong Wang, Jinlan Zhang, Zhe Wang
It is important to profile steroids in many physiological and pathological processes. Recently, hair has been used for the long-term measurement of endogenous steroid hormones. Analyzing hair has advantages of being noninvasive and time sequential compared with other bio-specimens. Liquid chromatography-mass spectrometry (LC-MS) techniques have been widely used over the past decades; however, it is challenging to profile estrogens in hair by LC-MS, and more comprehensive steroid profiling is required. In this paper, an ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to simultaneously profile 28 multifunctional steroids, including corticosteroids (n = 6), estrogens (n = 13), androgens (n = 5) and progestogens (n = 4), in human scalp hair in a single run...
June 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28634053/using-short-term-bioassays-to-evaluate-the-endocrine-disrupting-capacity-of-the-pesticides-linuron-and-fenoxycarb
#7
Petra Spirhanzlova, Bert De Groef, Freda E Nicholson, Sylvia V H Grommen, Giulia Marras, Anthony Sébillot, Barbara A Demeneix, Sophie Pallud-Mothré, Gregory F Lemkine, Andrew J Tindall, David Du Pasquier
Several short-term whole-organism bioassays based on transgenic aquatic models are now under validation by the OECD (Organization for Economic Co-operation and Development) to become standardized test guidelines for the evaluation of the endocrine activity of substances. Evaluation of the endocrine disrupting capacity of pesticides will be a domain of applicability of these future reference tests. The herbicide linuron and the insecticide fenoxycarb are two chemicals commonly used in agricultural practices...
June 17, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28634006/testosterone-differentially-affects-t-cells-and-neurons-in-murine-and-human-models-of-neuroinflammation-and-neurodegeneration
#8
Megan G Massa, Christina David, Stefanie Jörg, Johannes Berg, Barbara Gisevius, Sarah Hirschberg, Ralf A Linker, Ralf Gold, Aiden Haghikia
The high female-to-male sex ratio of multiple sclerosis (MS) prevalence has continuously confounded researchers, especially in light of male patients' accelerated disease course at later stages of MS. Although multiple studies have concentrated on estrogenic mechanisms of disease modulation, fairly little attention has been paid to androgenic effects in a female system, and even fewer studies have attempted to dissociate hormonal effects on the neurodegenerative and neuroinflammatory processes of MS. Herein, we demonstrate the differential effects of hormone treatment on the acute inflammatory and chronic neurodegenerative phases of murine experimental autoimmune encephalomyelitis...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28633436/membrane-androgen-receptor-zip9-induces-croaker-ovarian-cell-apoptosis-via-stimulatory-g-protein-alpha-subunit-and-mapkinase-signaling
#9
Aubrey Converse, Chenan Zhang, Peter Thomas
Recent studies show that androgen-induced apoptosis in Atlantic croaker primary granulosa/theca (G/T) cells and in human breast and prostate cancer cell lines is mediated by the novel membrane androgen receptor ZIP9 which belongs to the SLC39A zinc transporter family. However, the apoptotic signaling pathways remain unclear because ZIP9 activates an inhibitory G protein in human cancer cells, whereas recombinant croaker ZIP9 activates a stimulatory G protein (Gs) in transfected cancer cells. Here we investigated androgen-dependent apoptotic pathways in order to identify the signaling pathways regulated through wild-type croaker ZIP9 in ovarian follicle cells...
June 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28633425/androgen-receptor-mutations-in-patients-with-castration-resistant-prostate-cancer-treated-with-apalutamide
#10
D E Rathkopf, M R Smith, C J Ryan, W R Berry, N D Shore, G Liu, C S Higano, J J Alumkal, R Hauke, R F Tutrone, M Saleh, E Chow Maneval, S Thomas, D S Ricci, M K Yu, C J de Boer, A Trinh, T Kheoh, R Bandekar, H I Scher, E S Antonarakis
Background: : Mutations in the androgen receptor (AR) ligand-binding domain (LBD), such as F877L and T878A, have been associated with resistance to next-generation AR-directed therapies. ARN-509-001 was a phase I/II study that evaluated apalutamide activity in castration-resistant prostate cancer (CRPC). Here we evaluated the type and frequency of 11 relevant AR-LBD mutations in apalutamide-treated CRPC patients. Patients and methods: : Blood samples from men with non-metastatic CRPC (nmCRPC) and metastatic CRPC (mCRPC) pre- or post abiraterone acetate and prednisone (AAP) treatment (≥6 months' exposure) were evaluated at baseline and disease progression in trial ARN-509-001...
June 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28632494/long-term-dutasteride-therapy-in-men-with-benign-prostatic-hyperplasia-alters-glucose-and-lipid-profiles-and-increases-severity-of-erectile-dysfunction
#11
Abdulmaged Traish, Karim Sultan Haider, Gheorghe Doros, Ahmad Haider
Background Dutasteride has been successfully used in treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, dutasteride inhibits 5α-reductase type 1 and type 2 enzymes and may compromises glucocorticoids and androgen metabolism and alters metabolic function resulting in undesirable metabolic and sexual adverse side effects. Aim The aim of this study was to investigate the long-term adverse effects of dutasteride therapy in men with BPH on: i) blood glucose, ii) glycated hemoglobin (HbA1c), iii) low density lipoprotein-cholesterol (LDL-C); high density lipoprotein-cholesterol (HDL-C) and total cholesterol (TC), iv) testosterone (T), v) liver alanine and aspartate aminotransferases (ALT and AST) and vi) erectile dysfunction (ED)...
June 21, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28632486/randomized-noncomparative-phase-ii-trial-of-early-switch-from-docetaxel-to-cabazitaxel-or-vice-versa-with-integrated-biomarker-analysis-in-men-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#12
Emmanuel S Antonarakis, Scott T Tagawa, Giuseppe Galletti, Daniel Worroll, Karla Ballman, Marie Vanhuyse, Guru Sonpavde, Scott North, Costantine Albany, Che-Kai Tsao, John Stewart, Atef Zaher, Ted Szatrowski, Wei Zhou, Ada Gjyrezi, Shinsuke Tasaki, Luigi Portella, Yang Bai, Timothy B Lannin, Shalu Suri, Conor N Gruber, Erica D Pratt, Brian J Kirby, Mario A Eisenberger, David M Nanus, Fred Saad, Paraskevi Giannakakou
Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327)...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28631914/-impact-of-cpap-therapy-on-erectile-function-during-sleep-and-testosterone-level-in-men-with-sleep-apnea-syndrome
#13
I M Madaeva, O N Berdina, N V Semenova, V V Madaev, I N Gutnik, L I Kolesnikova
The article presents the results of a polysomnographic study with simultaneous monitoring spontaneous nocturnal erections - Nocturnal Penile Tumescences (NPT) in 69 men with age-related androgen deficiency (AAD). Of these, 45 patients were diagnosed with obstructive sleep apnea syndrome (OSAS). In 34 of the 45 patients with OSAS, regimens of non-invasive ventilation with positive-positive airway pressure (CPAP) were selected. Titration was carried out using automatic CPAP-devices for 2 months. The control group (n=24) comprised men with AAD, matched by the "copy-pair" type without clinical manifestations of respiratory disturbances during sleep...
June 2017: Urologii︠a︡
https://www.readbyqxmd.com/read/28631746/prevalence-of-androgen-deficiency-in-chronic-spinal-cord-injury-patients-suffering-from-erectile-dysfunction
#14
M Behnaz, Z Majd, M Radfar, H Ajami, M Qorbani, A Kokab
STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVES: To estimate the prevalence of biochemical androgen deficiency in Iranian spinal cord injured men suffering from erectile dysfunction (ED) and to determine factors related to this problem. SETTING: An andrology clinic of a teaching hospital in Tehran. METHODS: Men, 18 years of age and older, with chronic (>2 years) spinal cord injury (SCI) suffering from ED were recruited...
June 20, 2017: Spinal Cord
https://www.readbyqxmd.com/read/28629183/an-amyloidogenic-sequence-at-the-n-terminus-of-the-androgen-receptor-impacts-polyglutamine-aggregation
#15
Emmanuel Oppong, Gunter Stier, Miriam Gaal, Rebecca Seeger, Melanie Stoeck, Marc-André Delsuc, Andrew C B Cato, Bruno Kieffer
The human androgen receptor (AR) is a ligand inducible transcription factor that harbors an amino terminal domain (AR-NTD) with a ligand-independent activation function. AR-NTD is intrinsically disordered and displays aggregation properties conferred by the presence of a poly-glutamine (polyQ) sequence. The length of the polyQ sequence as well as its adjacent sequence motifs modulate this aggregation property. AR-NTD also contains a conserved KELCKAVSVSM sequence motif that displays an intrinsic property to form amyloid fibrils under mild oxidative conditions...
June 19, 2017: Biomolecules
https://www.readbyqxmd.com/read/28629181/knockout-of-murine-mamld1-impairs-testicular-growth-and-daily-sperm-production-but-permits-normal-postnatal-androgen-production-and-fertility
#16
Mami Miyado, Kaoru Yoshida, Kenji Miyado, Momori Katsumi, Kazuki Saito, Shigeru Nakamura, Tsutomu Ogata, Maki Fukami
MAMLD1 has been implicated in testicular function in both human and mouse fetuses. Although three patients with MAMLD1 mutations were reported to have hypergonadotropic hypogonadism in their teens, the functional significance of MAMLD1 in the postnatal testis remains unclear. Here, we analyzed the phenotype of Mamld1 knockout (KO) male mice at reproductive ages. The reproductive organs of KO male mice were morphologically unremarkable, except for relatively small testes. Seminiferous tubule size and number of proliferating spermatogonia/spermatocytes were reduced in the KO testis...
June 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28629112/european-demonstration-program-on-the-effect-based-and-chemical-identification-and-monitoring-of-organic-pollutants-in-european-surface-waters
#17
Zuzana Tousova, Peter Oswald, Jaroslav Slobodnik, Ludek Blaha, Melis Muz, Meng Hu, Werner Brack, Martin Krauss, Carolina Di Paolo, Zsolt Tarcai, Thomas-Benjamin Seiler, Henner Hollert, Sanja Koprivica, Marijan Ahel, Jennifer E Schollée, Juliane Hollender, Marc J-F Suter, Anita O Hidasi, Kristin Schirmer, Manoj Sonavane, Selim Ait-Aissa, Nicolas Creusot, Francois Brion, Jean Froment, Ana Catarina Almeida, Kevin Thomas, Knut Erik Tollefsen, Sara Tufi, Xiyu Ouyang, Pim Leonards, Marja Lamoree, Victoria Osorio Torrens, Annemieke Kolkman, Merijn Schriks, Petra Spirhanzlova, Andrew Tindall, Tobias Schulze
Growing concern about the adverse environmental and human health effects of a wide range of micropollutants requires the development of novel tools and approaches to enable holistic monitoring of their occurrence, fate and effects in the aquatic environment. A European-wide demonstration program (EDP) for effect-based monitoring of micropollutants in surface waters was carried out within the Marie Curie Initial Training Network EDA-EMERGE. The main objectives of the EDP were to apply a simplified protocol for effect-directed analysis, to link biological effects to target compounds and to estimate their risk to aquatic biota...
June 14, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28628013/modulation-of-antitumor-immune-response-in-mouse-prostate-cancer-model
#18
N Mitskevich, T Tsertsvadze, K Mchedlishvili, K Matchavariani, G Guruli
Aim of study - prostate cancer is second most common cancer in men worldwide, and fifth leading cause of death from cancer in men (6.6% of the total men deaths). Unfortunately, once cancer spreads outside of prostate, it becomes incurable. Androgen deprivation can provide some relief, but resistance will develop eventually, and at that time no effective treatment options are left to the patient. Therefore, the search of alternative treatment modalities is paramount. In this article we evaluated the role of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator - Lenalidomide and their possible impact on the immune response in the murine prostate cancer model...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28626448/the-common-follicle-stimulating-hormone-receptor-fshr-promoter-polymorphism-fshr-29g%C3%A2-%C3%A2-a-affects-androgen-production-in-normal-human-small-antral-follicles
#19
Tanni Borgbo, Hana Klučková, Milan Macek, Jana Chrudimska, Stine Gry Kristensen, Lise Lotte Hansen, Claus Yding Andersen
Follicle-stimulating hormone receptors (FSHRs) are almost exclusively expressed on granulosa cells, and FSH action is probably most clearly reflected in intrafollicular hormone milieu of antral follicles. Little is known about the possible effects of the common single nucleotide polymorphism (SNP) FSHR -29G > A (rs1394205) on hormonal conditions in humsan small antral follicles (hSAFs) obtained from women in the natural menstrual cycle. This study investigated the follicle fluid (FF) concentrations of anti-Müllerian hormone, estradiol, progesterone, androstenedione, and testosterone in hSAF in relation to the different genotypes of FSHR -29G > A...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28626107/-molecular-basis-for-prostate-carcinogenesis
#20
Fangzhi Chen, Xiaokun Zhao
Prostate cancer is the most prevalent male urogenital malignancy. Androgen deprivation therapy is the principal method for initial treatment for the patients, but the majority of them will eventually develop progressive disease, a status called castration-resistant prostate carcinoma. Lots of susceptibility genes, tumor suppressor genes and oncogenes, and their variations relevant to the occurrence and development of prostate cancer have been revealed by the studies of molecular oncology. These findings on the molecular basis of prostate carcinogenesis will further improve the strategies on prevention, diagnosis and clinical management for prostate carcinoma...
May 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
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