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Emilio Ríos González, Luis Martínez-Piñeiro
Androgen deprivation therapy is part of the initial treatment of patients with metastatic prostate cancer. Nevertheless, after an initial response and despite maintaining an effective testosterone suppression, the tumor is able to continue growing.Enzalutamide is an oral second generation pure antiandrogen that acts at various levels in the signal activation cascade of the androgen receptor and has demonstrated being effective in this phase of the disease. In the clinical trials completed, it has demonstrated benefits in overall patient survival in patients with the diagnosis of metastatic castration resistant prostate cancer...
September 2018: Archivos Españoles de Urología
Monika Beszterda, Rafał Frański
Endocrine disrupting compounds (EDCs) are heterogenous in structure and include synthetic organic compounds such as pharmaceutical agents, plant protection products, plastics, plasticizers, polychlorinated biphenyls, dioxins, flame-retardants, and antifoulant paint additive, as well, as natural plant-derived EDCs termed phytoestrogens and mycoestrogens. Children and adults are exposed daily to EDCs during drinking contaminated water, eating, breathing polluted air or direct contact with chemicals. Prenatal and perinatal period, infancy, childhood, and puberty are critical time of development during which maturing systems are particularly sensitive to hormonal disruptions (small elimination of xenobiotics)...
2018: Pediatric Endocrinology, Diabetes, and Metabolism
Marie-Rose B S Crombag, Merel van Nuland, Andries M Bergman, Hilde Rosing, Jan H M Schellens, Alwin D R Huitema, Jos H Beijnen
BACKGROUND: Oral antiandrogen therapies are predominantly used in older men, but real-life studies evaluating the impact of age on pharmacokinetic exposure are lacking. This study aims to evaluate the impact of age on the pharmacokinetic profiles of abiraterone acetate and enzalutamide in clinical practice. PATIENTS AND METHODS: Retrospective observational study to evaluate the impact of age on the first steady-state sample of patients treated with abiraterone acetate or enzalutamide in routine daily clinical practice...
October 2, 2018: Prostate Cancer and Prostatic Diseases
John Randolph
The provision of hormone therapy, both estrogens and antiandrogens, to adult transgender females is well within the scope of practice of the obstetrician gynecologist. The goal is to induce feminizing changes and suppress previously developed masculinization. Estrogens in sufficient doses will usually achieve both goals with augmentation by antiandrogens. The primary short-term risk of estrogens is thrombosis, but long-term risk in transgender females is unclear. Optimal care requires pretreatment education and assessment, individualized dosing, ongoing routine monitoring, and standard breast and prostate cancer screening...
September 25, 2018: Clinical Obstetrics and Gynecology
L T Pontes, D T Camilo, M R De Bortoli, R S S Santos, W M Luchi
We report an original case of a 27-year-old transgender woman who developed lupus nephritis after male-to-female sex reassignment surgery. The patient had been taking hormones to induce feminization since the age of 18. She was admitted with malar "butterfly" rash, anasarca and hypertension, associated with an increase in serum creatinine (1.7 mg/dl). Renal involvement was characterized by nephritic and nephrotic syndrome. Autoantibody tests were positive for antinuclear antibodies and anti-double-stranded DNA, and complement levels were markedly reduced...
September 19, 2018: Lupus
Yuanjie Niu, Changcheng Guo, Simeng Wen, Jing Tian, Jie Luo, Keliang Wang, Hao Tian, Shuyuan Yeh, Chawnshang Chang
Prostate cancer (PCa) is the most common cancer and the 2nd leading cause of cancer-related deaths among men in the United States. Androgen-deprivation-therapy (ADT) with antiandrogens to target the androgens/androgen receptor (AR) signals remains the standard therapy for advanced PCa. However, most of the PCa patients who received ADT with antiandrogens, including the recently developed Enzalutamide (Enz) that might extend PCa patients survival an extra 4.8 months, will still develop the castration (or antiandrogen) resistance...
September 15, 2018: Cancer Letters
Anna C Ferrari, Joshi J Alumkal, Mark N Stein, Mary-Ellen Taplin, James S Babb, Ethan S Barnett, Alejandro Gomez-Pinillos, Xiaomei Liu, Dirk F Moore, Robert S DiPaola, Tomasz M Beer
PURPOSE: To assess the action of panobinostat, a histone deacetylase inhibitor (HDACI), in restoring sensitivity to bicalutamide in a castration-resistant prostate cancer (CRPC) model; to assess the efficacy and safety of the panobinostat/bicalutamide combination in CRPC patients resistant to second-line antiandrogen therapy (2nd LAARx). EXPERIMENTAL DESIGN: The CWR22PC xenograft and isogenic cell line were tested for drug interactions on tumor cell growth and androgen receptor (AR), AR-splice variant7 and AR targets...
September 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Krittika Krishnan, Nitish Mittal, Lindsay M Thompson, Mariana Rodriguez-Santiago, Christine L Duvauchelle, David Crews, Andrea C Gore
BACKGROUND: Exposure to endocrine-disrupting chemicals (EDCs) during gestation influences development of the F1 generation offspring and can result in disease and dysfunction in adulthood. Limited evidence suggests consequences on the F2 generation, exposed as germ cells within the F1 fetus. These F2s provide a unique window into the programming effects of EDCs. OBJECTIVE: This study assessed intergenerational effects of EDC exposure on adult physiology and behavior in Sprague-Dawley rats...
September 2018: Environmental Health Perspectives
Lingyan Wang, Tianqing Song, Xin Wang, Jiazhong Li
Androgen receptor (AR), an important target in the current androgen derivation therapy, plays a critical role in the development and progress of prostate cancer (PCa). Nonsteroidal antiandrogens, such as enzalutamide and bicalutamide, are commonly used in clinic to treat PCa. Though they are very effective at the beginning, drug resistance problem appears after about 18 months. One of the reasons is that these antiandrogens share similar structure skeleton. Therefore, it is urgent to discover novel antiandrogens with different skeletons for resistance problem...
2018: Frontiers in Pharmacology
Kazutoshi Fujita, Norio Nonomura
Androgen receptor (AR) is a steroid receptor transcriptional factor for testosterone and dihydrotestosterone consisting of four main domains, the N-terminal domain, DNA-binding domain, hinge region, and ligand-binding domain. AR plays pivotal roles in prostate cancer, especially castration-resistant prostate cancer (CRPC). Androgen deprivation therapy can suppress hormone-naïve prostate cancer, but prostate cancer changes AR and adapts to survive under castration levels of androgen. These mechanisms include AR point mutations, AR overexpression, changes of androgen biosynthesis, constitutively active AR splice variants without ligand binding, and changes of androgen cofactors...
September 10, 2018: World Journal of Men's Health
Maria Ines Conte, Maria Eugenia Cabrillana, Tania Estefania Saez Lancellotti, Layla Simon, Abi Karenina Funes, Niubys Cayado-Gutiérrez, Matias Gustavo Tagle-Delgado, Amanda Edith Vincenti, Maria Elis Lopez, Elisa Olivia Pietrobon, Miguel Walter Fornes, Maria Angeles Monclus
Pigment epithelium derived factor (PEDF) expression has been described in many organs as showing neurotrophic, anti-angiogenic, anti-apoptotic, anti-inflammatory, anti-oxidant and pro-cell survival properties. However, references to its activity in the male reproductive system are scarce. We aimed to characterize the expression of PEDF in the male reproductive tract of Wistar rats by using RT-PCR, western blot and immunostaining and also evaluate the effect of flutamide in PEDF expression. We found that PEDF is expressed in the epididymis, prostate and seminal vesicles in Wistar rats, but notably not in the testes...
September 26, 2018: Biochemical and Biophysical Research Communications
Omer Demir, Inci Sema Tas, Berrin Gunay, Funda Gungor Ugurlucan
BACKGROUND: Rosacea is a common, chronic disorder that can present with a variety of cutaneous or ocular manifestations. Skin involvement primarily affects the central face, with findings such as persistent centrofacial redness, papules, pustules, flushing, telangiectasia, and phymatous skin changes. The pathways that lead to the development of rosacea are not well understood. The relationship of pyoderma faciale (also known as rosacea fulminans) to rosacea also is uncertain. We aimed to write this article with the aim of showing how a pregnant patient who has been aggravated by the degree of lesions on the face during the first trimester of pregnancy is treated and to show what is in the literature in this issue...
August 20, 2018: Open Access Macedonian Journal of Medical Sciences
Marta Díaz, José Miguel Gallego-Escuredo, Abel López-Bermejo, Francis de Zegher, Francesc Villarroya, Lourdes Ibáñez
Background: Fetuin-A is a glycoprotein produced in the liver and related to metabolic syndrome; fetuin-A secretion is divergently regulated in different pathological conditions. In girls with polycystic ovary syndrome (PCOS), insulin sensitization results in a more favorable endocrine-metabolic outcome than oral contraception; we assessed whether those differences are underscored by changes in circulating fetuin-A. Methods: Fetuin-A concentration endocrine-metabolic markers and hepatovisceral fat were measured longitudinally in 35 PCOS girls [age, 16 yr; body mass index (BMI), 23 kg/m2 ] randomized to receive either oral contraception [ethinylestradiol-levonorgestrel ( n = 18)] or a low-dose combination of spironolactone, pioglitazone, and metformin (SPIOMET, n = 17) over 12 months...
2018: International Journal of Endocrinology
Pedro Isaacsson Velho, Michael A Carducci
Despite the heterogeneity of prostate cancer (PCa), androgen stimulation is fundamental to its development, growth, and lethality. Therefore, the blockade of androgen receptor (AR) signaling is critical to controlling the disease, even after progression with castrate levels of androgens. Areas covered: We review the current understanding of new ways to block the AR, using novel antiandrogen inhibitors, which act on different parts of the AR signaling pathway in PCa. We also review new approaches, such as the use of poly(ADP-ribose) polymerase (PARP) inhibitors, targeting both the AR and the DNA repair pathway, potentially adding synergy and improving efficacy and the combination of AR inhibitors and immunotherapy...
August 31, 2018: Expert Opinion on Investigational Drugs
Md Faruque Ahmad
Ganoderma lucidum comprises probably 400 different biologically active constituents principally polysaccharides, triterpenoids, proteins, enzymes, steroids, sterols, nucleotides, fatty acids, vitamins and minerals which have been proved to have several therapeutical properties to control various diseases. Broad spectrum of its pharmacological actions have been established which include immunomodulation, anticancer, antidiabetic, antioxidant, antiatherosclerotic, antifibrotic, chemopreventive, antitumor, anticancer drug toxicity prevention, analgesic, anti inflammatory, antinociceptive, antimicrobial, hypolipidemic, hepatoprotective, antiandrogenic, antiangiogenic, antiherpetic, antiarthritic, antiosteoporotic, antiaging, antiulcer properties and estrogenic activity...
November 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jin-Ge Zhao, Jian-Dong Liu, Peng-Fei Shen, Xin Tang, Guang-Xi Sun, Xing-Ming Zhang, Jun-Ru Chen, Kun-Peng Shu, Ming Shi, Hao Zeng
Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly...
August 14, 2018: Asian Journal of Andrology
Dana E Rathkopf, Howard I Scher
Five new agents have been shown to prolong survival in patients with metastatic castration-resistant prostate cancer, including two targeting androgen receptor signaling (abiraterone acetate plus prednisone; enzalutamide). Recognition that these tumors remain driven by androgen receptor signaling has prompted clinical evaluation of these agents at earlier states in the prostate cancer disease continuum, along with the continued development of new agents targeting this pathway. Areas covered: This article focuses on apalutamide, a next-generation nonsteroidal antiandrogen, with current literature queried in PubMed/Medline...
September 2018: Expert Review of Anticancer Therapy
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
Ecem Özdemir, Nurhayat Barlas, Mehmet Alper Çetinkaya
Propyl paraben is a widely used preservative in pharmaceuticals, cosmetics, and foods preventing microbial and fungal contamination. This study was designed to investigate antiandrogenic profiles of propyl paraben following oral doses at 10, 250, and 750 mg kg-1 day to immature male rats using the Hershberger Bioassay. Rats were divided into six groups including solvent control, negative control (0.4 mg kg-1 day testosterone propionate = TP), positive control (3 mg kg-1 day flutamide = FLU) and treatment groups (10, 250, and 750 mg kg-1 day testosterone propionate + Propyl paraben)...
March 1, 2018: Toxicology Research
Yifan Kong, Lijun Cheng, Fengyi Mao, Zhuangzhuang Zhang, Yanquan Zhang, Elia Farah, Jacob Bosler, Yunfeng Bai, Nihal Ahmad, Shihuan Kuang, Lang Li, Xiaoqi Liu
Enzalutamide, a nonsteroidal second-generation antiandrogen, has been recently approved for the management of castration-resistant prostate cancer (CRPC). Although patients can benefit from enzalutamide at the beginning of this therapy, acquired enzalutamide resistance usually occurs within a short period. This motivated us to investigate the mechanism involved and possible approaches for overcoming enzalutamide resistance in CRPC. In the present study, we found that 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), a crucial enzyme in the mevalonate pathway for sterol biosynthesis, is elevated in enzalutamide-resistant prostate cancer cell lines...
September 14, 2018: Journal of Biological Chemistry
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