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Natali Froese, Honghui Wang, Carolin Zwadlo, Yong Wang, Andrea Grund, Anna Gigina, Melanie Hofmann, Katja Kilian, Gesine Scharf, Mortimer Korf-Klingebiel, Anna Melchert, Maria Elena Ricci Signorini, Caroline Halloin, Robert Zweigerdt, Ulrich Martin, Ina Gruh, Kai C Wollert, Robert Geffers, Johann Bauersachs, Joerg Heineke
Maladaptive cardiac remodeling after myocardial infarction (MI) is increasingly contributing to the prevalence of chronic heart failure. Women show less severe remodeling, a reduced mortality and a better systolic function after MI compared to men. Although sex hormones are being made responsible for these differences, it remains currently unknown how this could be translated into therapeutic strategies. Because we had recently demonstrated that inhibition of the conversion of testosterone to its highly active metabolite dihydrotestosterone (DHT) by finasteride effectively reduces cardiac hypertrophy and improves heart function during pressure overload, we asked here whether this strategy could be applied to post-MI remodeling...
August 14, 2018: Journal of Molecular and Cellular Cardiology
Hai-Ping Zhao, Xue-Zhe Cui, Wei Zhang, Guang-Xin Chen, Wan-Yun Yang, Quan-Wei Wang, Chun-Yi Li
To investigate the effects of anti-androgen drugs and melengestrol acetate (MGA) on development of regrowth antlers in 6 year old sika deer, twenty healthysika deerwith similar body weight and antler weightwere randomly divided into five groups by using single factor test design: flutamide ( n =4), bicalutamide ( n =4), progesterone acetate (CPA, n =4), melengestrol acetate (MGA, n =4), control( n =4). All deer were fed with same diets and were housed outside together in an opened fence of 15 m×30 m with free access to water and feed...
July 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Rafael Sebastián Fort, Juan M Trinidad Barnech, Juliette Dourron, Marcos Colazzo, Francisco J Aguirre-Crespo, María Ana Duhagon, Guzmán Álvarez
Prostate cancer is the most common cancer in men around the world. It is a complex and heterogeneous disease in which androgens and their receptors play a crucial role in the progression and development. The current treatment for prostate cancer is a combination of surgery, hormone therapy, radiation and chemotherapy. Therapeutic agents commonly used in the clinic include steroidal and non-steroidal anti-androgens, such as cyproterone acetate, bicalutamide and enzalutamide. These few agents have multiple adverse effects and are not 100% effective...
August 14, 2018: Pharmaceuticals
Thomas MacFarlane, Jeffrey D Zajac, Ada S Cheung
BACKGROUND: Cancers are a leading cause of death worldwide and transgender individuals are no exception. The effects of gender-affirming hormone therapy (GAHT) on sex hormone-dependent tumours are unclear. Therefore, this review seeks to determine if tumour risk in transgender individuals differs from the general population, to guide clinical screening recommendations. METHODS: We performed a systematic review based on the PRISMA guidelines. MEDLINE, Embase and PsycINFO databases were searched for studies examining tumour incidence, prevalence or cancer-related mortality in transgender individuals...
August 14, 2018: Clinical Endocrinology
Iwona J Stanisławska, Jakub P Piwowarski, Sebastian Granica, Anna K Kiss
BACKGROUND: Urolithins are bioavailable products of gut microbiota metabolism of ellagitannins. Their biological activity includes anti-cancer effects. PURPOSE: The aim of this study was to explore the effects of urolithins on prostate cancer cells and activity of clinically used anti-androgen, bicalutamide. METHODS: Prostate cancer cells were treated with urolithin A, urolithin B, urolithin C or their combinations with bicalutamide. Cell proliferation was determined by DNA fluorescence with Hoechst 33258...
July 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ewa Otto-Buczkowska, Karolina Grzyb, Natalia Jainta
Polycystic ovary syndrome (PCOS) usually arises during puberty and is marked by insulin resistance, hyperinsulinemia, and hyperandrogenism. The principle is that the diagnosis of PCOS must be based on the presence of at least two of the following three criteria: chronic anovulation, hyperandrogenism (clinical or biological), and polycystic ovaries. The diagnosis of PCOS in adolescents is particularly difficult due to developmental problems in this group. Many symptoms of PCOS, including acne, menstrual irregularities, and hyperinsulinemia, are common in normal puberty...
2018: Pediatric Endocrinology, Diabetes, and Metabolism
Michael Fernandez, Fuqiang Ban, Godwin Woo, Michael Hsing, Takeshi Yamazaki, Eric LeBlanc, Paul S Rennie, William J Welch, Artem Cherkasov
The majority of computational methods for predicting toxicity of chemicals are typically based on "nonmechanistic" cheminformatics solutions, relying on an arsenal of QSAR descriptors, often vaguely associated with chemical structures, and typically employing "black-box" mathematical algorithms. Nonetheless, such machine learning models, while having lower generalization capacity and interpretability, typically achieve a very high accuracy in predicting various toxicity endpoints, as unambiguously reflected by the results of the recent Tox21 competition...
August 15, 2018: Journal of Chemical Information and Modeling
Zohreh Rezaeifar, Gholam Hossein Rounaghi, Zarrin Es'haghi, Mahmoud Chamsaz
Flutamide (FLT) is a non-steroidal anti-androgen drug that has a specific anti-androgenic activity so that it is used in the treatment of prostate cancer. FLT may also be used to treat excess androgen levels in women. A sensitive electrochemical sensor based on hyperbranchedpolyglycerol functionalized- graphene oxide developed, using ionic liquid mediated hollow fiber-pencil graphite electrode (HF/HBP-GO/PGE) as a working electrode for determination of an anticancer drug, flutamide (FLT. In this design, a two centimeter piece of porous polypropylene hollow fiber membrane was impregnated with ionic liquid (1-Pentyl-3-methylimidazoliumbromide), and a graphite rod modified with hyperbranchedpolyglycerol/graphene oxide (HBP-GO), was located inside the fiber lumen...
October 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
Piyush Kumar, Anupam Das, Niharika Ranjan Lal, Sourabh Jain, Anupama Ghosh
Paternally transmitted damage to offspring is recognized as a complex issue. Each parent contributes 23 chromosomes to a child; hence, it is necessary to know the effects of both maternal and paternal pre-and peri-conceptional exposure to drugs on pregnancy outcome. While there are many studies on the effects of maternal drug exposure on pregnancy outcome, literature on paternal exposure is scarce. Of late however, paternal exposure has been receiving increasing attention. We present a brief review on the safety of commonly used drugs in dermatology, focused on retinoids, immune suppressants, anti androgens and thalidomide...
July 9, 2018: Indian Journal of Dermatology, Venereology and Leprology
Pavel Šauer, Adam Bořík, Oksana Golovko, Roman Grabic, Andrea Vojs Staňová, Olga Valentová, Alžběta Stará, Marie Šandová, Hana Kocour Kroupová
Unknown compounds with (anti-)androgenic activities enter the aquatic environment via municipal wastewater treatment plants (WWTPs). Progestins are well-known environmental contaminants capable of interfering with androgen receptor (AR) signaling pathway. The aim of the present study was to determine if 15 selected progestins have potential to contribute to (anti-)androgenic activities in municipal wastewaters and the respective recipient surface waters. AR-specific Chemically Activated LUciferase gene eXpression bioassay in agonistic (AR-CALUX) and antagonistic (anti-AR-CALUX) modes and liquid chromatography tandem atmospheric pressure chemical ionization/atmospheric photoionization with hybrid quadrupole/orbital trap mass spectrometry operated in high resolution product scan mode (LC-APCI/APPI-HRPS) methods were used to assess (anti-)androgenic activity and to detect the target compounds, respectively...
July 4, 2018: Environmental Pollution
Pedro C Barata, Prateek Mendiratta, Brandie Heald, Stefan Klek, Petros Grivas, Davendra P S Sohal, Jorge A Garcia
INTRODUCTION: Tumor profiling by targeted next-generation sequencing (tNGS) and personalized treatment based on these results is becoming increasingly common in patients with metastatic solid tumors, but it remains unclear whether this strategy results in benefit to patients with metastatic prostate cancer (mPCa). OBJECTIVE: To assess the clinical utility of tNGS in treatment decision-making for patients with mPCa. PATIENTS AND METHODS: Patients with available genomic profiling using tumor tissue (FoundationOne, F1) or cell-free DNA (FoundationACT, Guardant360) were included...
July 4, 2018: Targeted Oncology
Tomohiko Murakami, Hirofumi Obata, Naoko Akitake, Masaki Shiota, Ario Takeuchi, Eiji Kashiwagi, Junichi Inokuchi, Katsunori Tatsugami, Masatoshi Eto
BACKGROUND/AIM: We aimed to identify prognostic and predictive factors for anti-androgen withdrawal syndrome (AWS) to help guide decisions on anti-androgen withdrawal in castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: This study included 95 patients with prostate cancer which progressed to CRPC despite primary androgen-deprivation therapy (ADT). AWS was defined as >50% prostate-specific antigen decline after anti-androgen withdrawal. Associations between AWS, and clinicopathological factors and prognosis were investigated...
July 2018: Anticancer Research
Chao Lu, Yunkai Qie, Shenglai Liu, Changli Wu, Zhihong Zhang, Ranlu Liu, Kuo Yang, Hailong Hu, Yong Xu
Current clinical anti-androgen therapies in advanced prostate cancer (PCa) are driving an increased incidence of neuroendocrine prostate cancer (NEPC), a histological variant exhibiting reduced androgen receptor levels and expression of neuroendocrine markers. The mechanisms underlying the development of NEPC are poorly understood. A set of available data from a well-validated xenograft model of NEPC was used to analyze the exact role of protein kinase (PK) played in the development of NEPC. Fifty-four actionable and druggable PKs, mainly enriched in PI3K-Akt, mTOR, and MAPK signaling pathways, were screened out from the drastically changed PKs during NEPC transdifferentiation...
July 3, 2018: DNA and Cell Biology
Anna Hejmej, Barbara Bilinska
In this review, we summarize recent findings on the effect of the anti-androgen flutamide on cell-cell junctions in the male reproductive system. We outline developmental aspects of flutamide action on the testis, epididymis, and prostate, and describe changes in junction protein expression and organization of junctional complexes in the adult boar following prenatal and postnatal exposure. We also discuss findings on the mechanisms by which flutamide induces alterations in cell-cell junctions in reproductive tissues of adult males, with special emphasis on cytoplasmic effects...
June 26, 2018: Reproductive Toxicology
Jennifer L Beebe-Dimmer, Julie J Ruterbusch, Lauren C Bylsma, Christina Gillezeau, Jon Fryzek, Neil M Schultz, Scott C Flanders, Arie Barlev, Elisabeth Heath, Ruben G W Quek
INTRODUCTION: Bicalutamide (BIC), a non-steroidal anti-androgen, is FDA-indicated for use in combination with a luteinizing hormone-releasing hormone (LHRH) analog for treatment of Stage D2 metastatic carcinoma of the prostate. Lack of consensus exists regarding the clinical benefit of BIC use, either alone or combined use of BIC with an LHRH analog or antagonist (combined androgen blockade or CAB), versus treatment with androgen deprivation therapy (ADT) alone. METHODS: The SEER-Medicare database was used to identify prostate cancer patients aged ≥ 66 years diagnosed between 2007 and 2011 and who filled at least one prescription for BIC...
June 26, 2018: Advances in Therapy
Océane Albert, Thomas C Nardelli, Claudia Lalancette, Barbara F Hales, Bernard Robaire
Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, is a ubiquitous environmental contaminant and may act as an endocrine disruptor. Early life exposures to DEHP may result in anti-androgenic effects, impairing the development of the male reproductive tract. However, data on the long-lasting consequences of such DEHP exposures on adult male reproductive function are still rare and discrepant. Previously, we identified 2 novel plasticizers, 1,4-butanediol dibenzoate (BDB) and dioctyl succinate (DOS), as potential substitutes for DEHP that did not reproduce classically described endocrine disrupting phenotypes in prepubertal male offspring after maternal exposure...
July 1, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
L Gerratana, D Basile, G Buono, S De Placido, M Giuliano, S Minichillo, A Coinu, F Martorana, I De Santo, L Del Mastro, M De Laurentiis, F Puglisi, G Arpino
Triple negative breast cancer (TNBC) represents the 15-20% of all breast cancers (BC) and is characterized by a very aggressive behavior. Recent data suggest that TNBC is not a single disease, but it is rather an umbrella for different ontology-profiles such as basal like 1 and 2, mesenchymal, and the luminal androgen receptor (LAR). The LAR subtype is characterized by the expression of the Androgen Receptor (AR) and its downstream effects. Notwithstanding the role of the AR in several signaling pathways, its impact on a biological and clinical standpoint is still controversial...
July 2018: Cancer Treatment Reviews
Jr-Di Yang, Shing-Hwa Liu, Mei-Hsiu Liao, Ruei-Ming Chen, Pei-Yu Liu, Tzuu-Huei Ueng
The major objective of the present study was to determine the ability of a triazole fungicide tebuconazole to induce cytochrome P450-dependent monooxygenases, oxidative stress, and endocrine-disrupting activity using male rats treated with tebuconazole at 10, 25, and 50 mg/kg p.o. once daily for 28 days. In liver, tebuconazole dose-dependently increased microsomal contents of cytochrome P450 and cytochrome b5 and the activities of NADPH-cytochrome P450 reductase, 7-ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, pentoxyresorufin O-dealkylase, 7-ethoxycoumarin O-deethylase, aniline hydroxylase, and erythromycin N-demethylase...
June 19, 2018: Environmental Toxicology
Jessica Abramowitz, Vin Tangpricha
Transfeminine individuals are treated with estradiol and anti-androgen agents to transition to a more feminine appearance. The physical changes that occur with estradiol therapy include breast development, body fat redistribution, and decreased muscle mass. Transfeminine treatment regimens require monitoring and dose adjustments to achieve appropriate physiologic targets to enhance feminization and decrease risk of adverse outcomes. Adverse effects associated with estradiol use include thromboembolic disease, macroprolactinoma, breast cancer, coronary artery disease, cerebrovascular disease, cholelithiasis, and hypertriglyceridemia...
July 2018: Clinics in Plastic Surgery
F Orton, M Säfholm, E Jansson, Y Carlsson, A Eriksson, J Fick, T Uren Webster, T McMillan, M Leishman, B Verbruggen, T Economou, C R Tyler, C Berg
Amphibians are threatened on a global scale and pollutants may be contributing to population declines, but how chemicals impact on their reproduction is poorly understood. We conducted a life cycle analysis to investigate the impacts of early life exposure to two anti-androgens (exposure until completion of metamorphosis;stage 66): flutamide, (50 µg/L)/linuron (9 and 45 µg/L)) on sexual development and breeding competence in Xenopus tropicalis. Our analyses included: mRNA levels of dmrt1, cyp17, amh, cyp19, foxl2 and ar (tadpoles/metamorphs), gonadal histomorphology (metamorphs/adults), mRNA levels of ar/gr (adult male brain/gonad/forelimb), testosterone/corticosterone levels (adult males), secondary sexual characteristics (forelimb width/nuptial pad: adult males) and breeding competence (amplexus/fertility: adult males)...
June 14, 2018: Scientific Reports
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