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Bing Song, Su-Hong Park, Jonathan C Zhao, Ka-Wing Fong, Shangze Li, Yongik Lee, Yeqing A Yang, Subhasree Sridhar, Xiaodong Lu, Sarki A Abdulkadir, Robert L Vessella, Colm Morrissey, Timothy M Kuzel, William J Catalona, Ximing J Yang, Jindan Yu
Prostate cancer (PCa) progressed to castration resistance (CRPC) is a fatal disease. CRPC tumors develop resistance to new-generation anti-androgen enzalutamide through lineage plasticity, characterized by epithelial-mesenchymal transition (EMT) and basal-like phenotype. FOXA1 is a transcription factor essential for epithelial lineage differentiation. Here, we demonstrate that FOXA1 loss leads to remarkable up-regulation of transforming growth factor beta 3 (TGFB3), which encodes a ligand of TGF-β pathway...
December 4, 2018: Journal of Clinical Investigation
Hyun-Kyung Woo, Juhee Park, Ja Yoon Ku, Chan Ho Lee, Vijaya Sunkara, Hong Koo Ha, Yoon-Kyoung Cho
Androgen-receptor splice variant 7 (AR-V7) is associated with castration-resistant prostate cancer (CRPC) and resistance to anti-androgen therapy. Despite its clinical importance, the lack of efficient methods for AR-V7 analysis remains a challenge for broader use of this biomarker in routine clinical practice. Herein, we suggest a practical and non-invasive liquid biopsy method for analysis of AR-V7 in the RNA of urine-derived extracellular vesicles (EVs) without the need for blood withdrawal. Urine-derived EVs were isolated by a lab-on-a-disc integrated with six independent nanofiltration units (Exo-Hexa) allowing simultaneous processing of six individual samples...
November 30, 2018: Lab on a Chip
Steven Lehrer, Peter H Rheinstein, Kenneth E Rosenzweig
Background: Two large studies suggest that risk is not increased. But other studies have found increased risk of Alzheimer's disease and impaired cognition. Objective: To determine whether androgen deprivation therapy increases the risk of impaired cognition or Alzheimer's disease in men with prostate cancer. Methods: We used data from MedWatch, the Food and Drug Administration (FDA) Safety Information and Adverse Event Reporting Program. Machine-readable data from MedWatch, including adverse drug reaction reports from manufacturers, are part of a public database...
June 30, 2018: JAD Reports
Bert Dhondt, Sarah Buelens, Jeroen Van Besien, Matthias Beysens, Elise De Bleser, Piet Ost, Nicolaas Lumen
OBJECTIVES:  Disease progression in metastatic castration-resistant prostate cancer (mCRPC) is dependent on androgen signaling. This case describes the complex adaptive androgen signaling mechanisms in mCRPC and illustrates that caution should be exercised when treating these patients with drugs influencing the androgen axis. METHODS:  Single case report and review of the literature. RESULTS:  We report the case of an 86-year-old man with mCRPC, treated with the secondary antihormonal agent abiraterone acetate...
November 26, 2018: Acta Clinica Belgica
Rebecca J Wineland, Michael S Bloom, Lori Cruze, Celeste D Butts, Abby G Wenzel, E Ramsey Unal, Satomi Kohno, Keith B Willan, Roger B Newman
BACKGROUND: Phthalates are used extensively in commercial and personal care products and maternal exposure is ubiquitous. Phthalates are anti-androgenic but the potential effects of phthalates on male penile development have not been assessed in utero. OBJECTIVE: To investigate the association between early pregnancy phthalate exposure and fetal penile development, overall and by race. METHODS: Prospective cohort study of women with singleton pregnancies presenting for prenatal ultrasound between 18-22 weeks' gestation...
November 26, 2018: Prenatal Diagnosis
Daksh Thaper, Sepideh Vahid, Ramandeep Kaur, Sahil Kumar, Shaghayegh Nouruzi, Jennifer L Bishop, Martin Johansson, Amina Zoubeidi
Most prostate cancer patients will progress to a castration-resistant state (CRPC) after androgen ablation therapy and despite the development of new potent anti-androgens, like enzalutamide (ENZ), which prolong survival in CRPC, ENZ-resistance (ENZR ) rapidly occurs. Re-activation of the androgen receptor (AR) is a major mechanism of resistance. Interrogating our in vivo derived ENZR model, we discovered that transcription factor STAT3 not only displayed increased nuclear localization but also bound to and facilitated AR activity...
November 23, 2018: Scientific Reports
Yunlu Jia, Qiqing Chen, Sarah E Crawford, Lirong Song, Wei Chen, Monika Hammers-Wirtz, Tido Strauss, Thomas-Benjamin Seiler, Andreas Schäffer, Henner Hollert
Cyanobacterial blooms are of global concern due to the multiple harmful risks they pose towards aquatic ecosystem and human health. However, information on the fate of organic pollutants mediated by cyanobacterial blooms in eutrophic water remains elusive. In the present study, endocrine disruptive potentials of phytoplankton samples were evaluated throughout a year-long surveillance in a large and eutrophic freshwater lake. Severe cyanobacterial blooms persisted during our sampling campaigns. Estrogenic agonistic, anti-estrogenic, anti-androgenic, and anti-glucocorticogenic effects were observed in the phytoplankton samples using in vitro reporter gene bioassays...
November 12, 2018: Environmental Pollution
Bhuvanenthiran Mutharani, Palraj Ranganathan, Shen-Ming Chen
Chitosan-gold collapse gel (CS-Au CG) was prepared by reducing chloroauric acid (HAuCl4 ) with a polysaccharide, chitosan (CS), in the absence of chemical and physical agents. CS-Au CG was used for the first time as a suitable nano-biocomposite sensing film for efficient one-step electrochemical deposition of poly (bromophenol blue) (PBPB) redox mediator through amino-hydroxyl reaction to prepare a novel anti-androgen drug flutamide (FLU) sensor using glassy carbon electrode (GCE). The effect of electropolymerization cycle, scan rate, pH, and concentration of CS-Au CG/PBPB film on electrochemical behavior of FLU molecules was investigated...
November 16, 2018: International Journal of Biological Macromolecules
Ami R Zota, Ruth J Geller, Antonia M Calafat, Cherie Q Marfori, Andrea A Baccarelli, Gaby N Moawad
OBJECTIVES: To examine the association between phthalate exposure and two measures of uterine fibroid burden: diameter of largest fibroid and uterine volume. DESIGN: Pilot, cross-sectional study. SETTING: Academic medical center. PATIENT(S): Fifty-seven premenopausal women undergoing either hysterectomy or myomectomy for fibroids. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The diameter of the largest fibroid and uterine dimensions were abstracted from medical records...
November 12, 2018: Fertility and Sterility
Chengfei Liu, Wei Lou, Joy C Yang, Liangren Liu, Cameron M Armstrong, Alan P Lombard, Ruining Zhao, Onika D V Noel, Clifford G Tepper, Hong-Wu Chen, Marc Dall'Era, Christopher P Evans, Allen C Gao
Protein homeostasis (proteostasis) is a potential mechanism that contributes to cancer cell survival and drug resistance. Constitutively active androgen receptor (AR) variants confer anti-androgen resistance in advanced prostate cancer. However, the role of proteostasis involved in next generation anti-androgen resistance and the mechanisms of AR variant regulation are poorly defined. Here we show that the ubiquitin-proteasome-system (UPS) is suppressed in enzalutamide/abiraterone resistant prostate cancer...
November 16, 2018: Nature Communications
Ross Gillette, Min Ji Son, Lexi Ton, Andrea C Gore, David Crews
All animals have body burdens of polychlorinated biphenyls (PCBs) despite their ban decades ago. These and modern endocrine-disrupting chemicals (EDCs) such as the fungicide vinclozolin (VIN) perturb hormone signaling and lead to dysfunctions following prenatal exposures. Beyond direct exposures, transgenerational disease phenotypes can persist for multiple generations without subsequent exposure. The mechanisms of action of these EDCs differ: VIN is anti-androgenic while the PCB mixture Aroclor 1221 (A1221) is weakly estrogenic...
November 16, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Camilla Lindgren Schwartz, Sofie Christiansen, Anne Marie Vinggaard, Marta Axelstad, Ulla Hass, Terje Svingen
Male reproductive development is intricately dependent on fetal androgen action. Consequently, disrupted androgen action during fetal life can interfere with the development of the reproductive system resulting in adverse effects on reproductive function later in life. One biomarker used to evaluate fetal androgen action is the anogenital distance (AGD), the distance between the anus and the external genitalia. A short male AGD is strongly associated with genital malformations at birth and reproductive disorders in adulthood...
November 14, 2018: Archives of Toxicology
Wen Zhong Zhang, Na Na Sun, Shang Quan Ma, Zhen Chao Zhao, Yu Cao, Chao Zhang
To evaluate hormesis induced by Yttrium (Y) nitrate in male rats, Y was offered to F0 mother rats and F1 offspring at concentrations of 0, 20, 80, and 320 ppm daily from gestational day (GD) 0 through postnatal day 70 (PND 70). The F1 offspring were evaluated with respect to motor function, learning and memory, and histopathology. Administration of Y improved motor function in a dose dependent manner. In the 20 ppm group, body weight and spatial learning and memory were increased, while the latter was decreased in the 320 ppm group...
October 2018: Biomedical and Environmental Sciences: BES
Rachel Bleach, Marie McIlroy
Androgen receptor (AR) is the most widely expressed steroid receptor protein in normal breast tissue and is detectable in approximately 90% of primary breast cancers and 75% of metastatic lesions. However, the role of AR in breast cancer development and progression is mired in controversy with evidence suggesting it can either inhibit or promote breast tumorigenesis. Studies have shown it to antagonize estrogen receptor alpha (ERα) DNA binding, thereby preventing pro-proliferative gene transcription; whilst others have demonstrated AR to take on the mantle of a pseudo ERα particularly in the setting of triple negative breast cancer...
2018: Frontiers in Endocrinology
Trude B Wedde, Milada C Småstuen, Sigmund Brabrand, Sophie D Fosså, Stein Kaasa, Gunnar Tafjord, Kjell M Russnes, Taran P Hellebust, Wolfgang Lilleby
BACKGROUND: The survival benefit of dose-escalation with High-Dose-Rate brachytherapy (HDR-BT) boost combined with External Beam Radiotherapy (EBRT) for the treatment of high-risk prostate cancer (PCa) remains debatable. We investigated 10-year PCa-specific mortality (PCSM) and overall mortality (OM) in high-risk patients treated with HDR-BT/EBRT (calculated EQD2 = 102 Gy) compared to EBRT alone (70 Gy). METHODS: HDR-BT boosts (10 Gy × 2) were given 2 weeks apart followed by 50 Gy conformal EBRT (2 Gy × 25) to the prostate and seminal vesicles...
October 30, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Yingchun Zhang, Jingjing Xu, Jing Jing, Xianjie Wu, Zhongfa Lv
BACKGROUND Androgenic alopecia (AGA) is the most common type of hair loss in men. However, the pathogenesis is not yet fully understood and therapeutic approaches are limited. This retrospective study investigated the association between levels of androgen-associated hormones and curative effect in androgenic alopecia in young male AGA patients. MATERIAL AND METHODS By using chemiluminescence immunoassay, serum levels of androgens and upstream regulated hormones were measured in 178 young male patients with AGA and in 61 normal controls before therapy, 1 and 2 weeks after administration of finasteride...
October 30, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Frederik Birkebæk Thomsen, Cecilia Bosco, Hans Garmo, Jan Adolfsson, Niklas Hammar, Pär Stattin, Mieke Van Hemelrijck
BACKGROUND: In randomised controlled trials, men with advanced, non-metastatic prostate cancer (PCa) treated with anti-androgen monotherapy (AA) had similar all-cause mortality as men treated with gonadotropin-releasing hormone (GnRH) agonists. Using real-world evidence (i.e., observational data), we aimed to further assess the difference in mortality between these two drug categories. MATERIAL AND METHODS: We emulated a trial using data from Prostate Cancer data Base Sweden 3...
October 30, 2018: Acta Oncologica
Hisashi Matsushima
Androgen deprivation therapy(ADT)is a standard systemic therapy for prostate cancer. ADT induces bone loss(ADTIBL)and muscle loss(sarcopenia)leading to falls and farctures. There are 2 aims in bone management of prostate cancer:one is to prevent fragility fractures in patients without bone metastasis and the other is to prevent symptomatic skeletal events(SSE)which are pathologic fractures, spinal compression, radiation to bones and surgery to bones. Bone fractures and SSE are both correlated with worse overall survival(OS)...
2018: Clinical Calcium
Hanne Tøndel, Jo-Åsmund Lund, Stian Lydersen, Anne D Wanderås, Bjørg Y Aksnessæther, Christer Andre Jensen, Stein Kaasa, Arne Solberg
Background: Erectile dysfunction is a common side effect of prostate cancer (PC) therapy. In this randomized study (The RIC-study) we used patient reported outcomes to evaluate sexual function 18 months after combined endocrine therapy and radical radiotherapy (RT) given with either wide or tight planning target volume (PTV) margins. We also analyzed the impact of radiation dose to penile bulb on sexual function. Methods: The RIC-study included 257 men with intermediate and high-risk PC...
November 2018: Clinical and Translational Radiation Oncology
Hirokazu Tarui, Yoshitaka Tomigahara, Hirohisa Nagahori, Kenji Sugimoto, Masayuki Mogi, Satoshi Kawamura, Naohiko Isobe, Hideo Kaneko
To clarify species differences in the developmental toxicity of procymidone (Sumilex®, a fungicide for agricultural use), placental transfer studies were conducted using 14 C-labeled procymidone in pregnant rats, rabbits, and monkeys. These studies demonstrated that maternal-to-fetal transfer of the parent compound and its hydroxylated metabolite, which are both weak anti-androgenic agents, occurred more easily than that of other metabolites, with much higher absolute concentrations achieved in the fetal circulation of rats than of rabbits or monkeys...
May 20, 2018: Journal of Pesticide Science
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