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Characterization of an Abiraterone Ultraresponsive Phenotype in Castration-Resistant
Author Manuscript Published OnlineFirst on December 19, 2016; DOI: 10.1158/1078-0432.CCR-16-2054 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. 1 Characterization of an Abiraterone Ultraresponsive Phenotype in Castration-Resistant 2 Prostate Cancer Patient-Derived Xenografts 3 4 Hung-Ming Lam1,2*, Ryan McMullin3*†, Holly M. Nguyen1, Ilsa Coleman4, Michael Gormley5, 5 Roman Gulati4, Lisha G. Brown1, Sarah K. Holt1, Weimin Li5, Deborah S. Ricci6, Karin 6 Verstraeten7, Shibu Thomas5, Elahe A. Mostaghel4, 8, Peter S. Nelson4, 8, Robert L. Vessella1, 7 9, and Eva Corey1 8 9 Affiliation of authors: 1Department of Urology, University of Washington School of 10 Medicine, Seattle, Washington; 2State Key Laboratory of Quality Research in Chinese 11 Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of 12 Science and Technology, Macau (SAR), China; 3LabConnect, Seattle, Washington; 4Fred 13 Hutchinson Cancer Research Center, Seattle, Washington; 5Janssen Research & 14 Development, Spring House, Pennsylvania; 6Janssen Research & Development, Raritan, 15 New Jersey; 7Janssen Research & Development, Beerse, Belgium; 8Department of 16 Medicine, University of Washington, Seattle, Washington; 9Department of Veterans Affairs 17 Medical Center, Seattle, Washington 18 19 *Co-primary lead authors 20 †Current affiliation: Janssen Research & Development, Spring House, Pennsylvania 21 22 23 Running title (60 characters max): Abiraterone Response and Resistance 24 25 Keywords: abiraterone acetate, prostate cancer, xenografts, biomarkers, androgen 26 receptor, glucocorticoid receptor, castration resistance 27 28 Grant/funding support: The work was supported by The Richard M. Lucas Foundation, the 29 Prostate Cancer Foundation, SU2C, a NIH PO1 CA085859, and the PNW Prostate Cancer 1 Downloaded from clincancerres.aacrjournals.org on September 23, 2021. -
Effect of Vitamin C on Bisphenol a Induced Hepato& Nephrotoxicity in Albino Rats
Haroun et al. 57 EFFECT OF VITAMIN C ON BISPHENOL A INDUCED HEPATO& NEPHROTOXICITY IN ALBINO RATS Marcelle R. Haroun,M.D.*, Ibrahim S. Zamzam, M.D.*,Eslam S. Metwally, M.D.*, and Rabab Sh. EL-Shafey, M.S.C. * *Forensic Medicine & Clinical Toxicology Department, Faculty of Medicine, Benha University, Egypt [email protected] [email protected] [email protected] [email protected] ABSTRACT Bisphenol-A (BPA) is a worldwide used endocrine disruptor that is incorporated in many plastic industries. The exposure of humans to that substance starts early during the fetal life. Many agencies raised warnings against the excessive use of such substances. The present study aimed to evaluate the oxidative stress effect of BPA on liver and kidney of albino rats, and whether co-administration of vitamin C can ameliorate this oxidative damage. Albino rats were divided into six groups: -ve control group,+ve control group,vitamin C (60mglkg) treated group, BPA treated group, BPA+ high dose of vitamin C (60mglkg) treated group, and BPA+ low dose of vitamin C (5.5mglkg) treated group The oxidative stress arising from BPA was evaluated in liver and kidney tissues. In addition, serum creatinine, uric acid levels, (AST) and (ALT) activities as markers of kidney and liver function were measured. Biochemical analysis revealed significant reduction in activities of enzymatic antioxidants in BPA treated group and BPA + vitamin C treated groups in high & low doses as compared to control group. In addition, there were significant increase in AST, ALT, uric acid, and creatinine levels in BPA treated group and reduction in their concentrations BPA + vitamin C treated groups in high & low doses as compared to control group. -
Pesticides Reduce Symbiotic Efficiency of Nitrogen-Fixing Rhizobia and Host Plants
Pesticides reduce symbiotic efficiency of nitrogen-fixing rhizobia and host plants Jennifer E. Fox*†, Jay Gulledge‡, Erika Engelhaupt§, Matthew E. Burow†¶, and John A. McLachlan†ʈ *Center for Ecology and Evolutionary Biology, University of Oregon, 335 Pacific Hall, Eugene, OR 97403; †Center for Bioenvironmental Research, Environmental Endocrinology Laboratory, Tulane University, 1430 Tulane Avenue, New Orleans, LA 70112-2699; ‡Department of Biology, University of Louisville, Louisville, KY 40292 ; §University of Colorado, Boulder, CO 80309; and ¶Department of Medicine and Surgery, Hematology and Medical Oncology Section, Tulane University Medical School, 1430 Tulane Avenue, New Orleans, LA 70112-2699 Edited by Christopher B. Field, Carnegie Institution of Washington, Stanford, CA, and approved May 8, 2007 (received for review January 8, 2007) Unprecedented agricultural intensification and increased crop by plants, in rotation with non-N-fixing crops (8, 15). The yield will be necessary to feed the burgeoning world population, effectiveness of this strategy relies on maximizing symbiotic N whose global food demand is projected to double in the next 50 fixation (SNF) and plant yield to resupply organic and inorganic years. Although grain production has doubled in the past four N and nutrients to the soil. The vast majority of biologically fixed decades, largely because of the widespread use of synthetic N is attributable to symbioses between leguminous plants (soy- nitrogenous fertilizers, pesticides, and irrigation promoted by the bean, alfalfa, etc.) and species of Rhizobium bacteria; replacing ‘‘Green Revolution,’’ this rate of increased agricultural output is this natural fertilizer source with synthetic N fertilizer would cost unsustainable because of declining crop yields and environmental Ϸ$10 billion annually (16, 17). -
In Vivo Exposure to Bisphenol-A Altered the Reproductive Functionality in Male Coturnix Coturnix Japonica
In Vivo Exposure to Bisphenol-A Altered the Reproductive Functionality in Male Coturnix Coturnix Japonica SUTHAN PERMUAL Central Avian Research Institute GAUTHAM KOLLURI ( [email protected] ) Central Avian Research Institute JAG MOHAN Central Avian Research Institute RAM SINGH Salim Ali Center for Ornithology and Natural History JAGBIR TYAGI Central Avian Research Institute Research Article Keywords: Bisphenol-A, quails, sperm quality, fertility Posted Date: December 21st, 2020 DOI: https://doi.org/10.21203/rs.3.rs-124102/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/21 Abstract Bisphenol-A, is one of the most characterized endocrine disruptors on the reproductive functions in humans and animals. We have previously reported in vitro and in vivo effects of bisphenol-A on functional role of sperm in chicken. Here, the effects of 1 and 5 mg/kg bisphenol-A daily administered by gavage for 3 wk to adult male Japanese quails on reproductive functionality was investigated. Cloacal index and foam frequency were greatly reduced at high dose. Sperm quality attributes were affected at both doses. Sperm quality attributes were affected at both doses. Alkaline phosphatase showed most signicant reduction among seminal enzymes. Dose dependent response (P < 0.01) of bisphenol-A was noticed with modulating testosterone concentrations at low and high doses. Disturbances regarding fertility and hatchability traits were prominent in high and low dose groups. The current study conrms the compromising actions of bisphenol-A on reproductive success in male Japanese quails at lower doses that are considered to be safe (50 mg/kg BW/d) under in vivo exposure module. -
Fighting Bisphenol A-Induced Male Infertility: the Power of Antioxidants
antioxidants Review Fighting Bisphenol A-Induced Male Infertility: The Power of Antioxidants Joana Santiago 1 , Joana V. Silva 1,2,3 , Manuel A. S. Santos 1 and Margarida Fardilha 1,* 1 Department of Medical Sciences, Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal; [email protected] (J.S.); [email protected] (J.V.S.); [email protected] (M.A.S.S.) 2 Institute for Innovation and Health Research (I3S), University of Porto, 4200-135 Porto, Portugal 3 Unit for Multidisciplinary Research in Biomedicine, Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal * Correspondence: [email protected]; Tel.: +351-234-247-240 Abstract: Bisphenol A (BPA), a well-known endocrine disruptor present in epoxy resins and poly- carbonate plastics, negatively disturbs the male reproductive system affecting male fertility. In vivo studies showed that BPA exposure has deleterious effects on spermatogenesis by disturbing the hypothalamic–pituitary–gonadal axis and inducing oxidative stress in testis. This compound seems to disrupt hormone signalling even at low concentrations, modifying the levels of inhibin B, oestra- diol, and testosterone. The adverse effects on seminal parameters are mainly supported by studies based on urinary BPA concentration, showing a negative association between BPA levels and sperm concentration, motility, and sperm DNA damage. Recent studies explored potential approaches to treat or prevent BPA-induced testicular toxicity and male infertility. Since the effect of BPA on testicular cells and spermatozoa is associated with an increased production of reactive oxygen species, most of the pharmacological approaches are based on the use of natural or synthetic antioxidants. -
Toxicological Profile for Bisphenol A
TT TOXICOLOGICAL PROFILE FOR BISPHENOL A September 2009 Integrated Risk Assessment Branch Office of Environmental Health Hazard Assessment California Environmental Protection Agency Toxicological Profile for Bisphenol A September 2009 Prepared by Office of Environmental Health Hazard Assessment Prepared for Ocean Protection Council Under an Interagency Agreement, Number 07-055, with the State Coastal Conservancy LIST OF CONTRIBUTORS Authors Jim Carlisle, D.V.M., Ph.D., Senior Toxicologist, Integrated Risk Assessment Branch Dave Chan, D. Env., Staff Toxicologist, Integrated Risk Assessment Branch Mari Golub, Ph.D., Staff Toxicologist, Reproductive and Cancer Hazard Assessment Branch Sarah Henkel, Ph.D., California Sea Grant Fellow, California Ocean Science Trust Page Painter, M.D., Ph.D., Senior Toxicologist, Integrated Risk Assessment Branch K. Lily Wu, Ph.D., Associate Toxicologist, Reproductive and Cancer Hazard Assessment Branch Reviewers David Siegel, Ph.D., Chief, Integrated Risk Assessment Branch i Table of Contents Executive Summary ................................................................................................................................ iv Use and Exposure ............................................................................................................................... iv Environmental Occurrence ................................................................................................................. iv Effects on Aquatic Life ...................................................................................................................... -
Polystyrene Microplastics Do Not Affect Juvenile Brown Trout (Salmo Trutta F
Schmieg et al. Environ Sci Eur (2020) 32:49 https://doi.org/10.1186/s12302-020-00327-4 RESEARCH Open Access Polystyrene microplastics do not afect juvenile brown trout (Salmo trutta f. fario) or modulate efects of the pesticide methiocarb Hannah Schmieg1*, Sven Huppertsberg2, Thomas P. Knepper2, Stefanie Krais1, Katharina Reitter1, Felizitas Rezbach1, Aki S. Ruhl3,4, Heinz‑R. Köhler1 and Rita Triebskorn1,5 Abstract Background: There has been a rising interest within the scientifc community and the public about the environmen‑ tal risk related to the abundance of microplastics in aquatic environments. Up to now, however, scientifc knowledge in this context has been scarce and insufcient for a reliable risk assessment. To remedy this scarcity of data, we inves‑ tigated possible adverse efects of polystyrene particles (10 4 particles/L) and the pesticide methiocarb (1 mg/L) in juvenile brown trout (Salmo trutta f. fario) both by themselves as well as in combination after a 96 h laboratory expo‑ sure. PS beads (density 1.05 g/mL) were cryogenically milled and fractionated resulting in irregular‑shaped particles (< 50 µm). Besides body weight of the animals, biomarkers for proteotoxicity (stress protein family Hsp70), oxidative stress (superoxide dismutase, lipid peroxidation), and neurotoxicity (acetylcholinesterase, carboxylesterases) were analyzed. As an indicator of overall health, histopathological efects were studied in liver and gills of exposed fsh. Results: Polystyrene particles by themselves did not infuence any of the investigated biomarkers. In contrast, the exposure to methiocarb led to a signifcant reduction of the activity of acetylcholinesterase and the two carboxy‑ lesterases. Moreover, the tissue integrity of liver and gills was impaired by the pesticide. -
Estrogen-Like Effect of Mitotane Explained by Its Agonist Activity on Estrogen Receptor-Α
biomedicines Article Estrogen-Like Effect of Mitotane Explained by Its Agonist Activity on Estrogen Receptor-α Elisa Rossini 1,†, Edoardo Giacopuzzi 2,3,† , Fabrizio Gangemi 4,† , Mariangela Tamburello 1, Deborah Cosentini 5, Andrea Abate 1, Marta Laganà 5, Alfredo Berruti 5 , Salvatore Grisanti 5,‡ and Sandra Sigala 1,*,‡ 1 Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy; [email protected] (E.R.); [email protected] (M.T.); [email protected] (A.A.) 2 Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK; [email protected] 3 National Institute for Health Research Oxford Biomedical Research Centre, Oxford OX4 2PG, UK 4 Unit of Physics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy; [email protected] 5 Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia at A.S.S.T. Spedali Civili di Brescia, 25123 Brescia, Italy; [email protected] (D.C.); [email protected] (M.L.); [email protected] (A.B.); [email protected] (S.G.) * Correspondence: [email protected] † These Authors equally contributed to this paper. ‡ These authors are co-senior authors of this paper. Citation: Rossini, E.; Giacopuzzi, E.; Abstract: Mitotane is the cornerstone of medical treatment of adrenocortical carcinoma. Estrogenic- Gangemi, F.; Tamburello, M.; like side effects frequently occur in patients, and previous studies explored the chemical nature Cosentini, D.; Abate, A.; Laganà, M.; of the interaction between estrogen receptor-α (ER-α) and toxic compounds, including the DDD Berruti, A.; Grisanti, S.; Sigala, S. -
Toxicological Evaluation of Bisphenol a and Its Analogues Bisfenol a Ve Analoglarının Toksikolojik Değerlendirilmesi
Turk J Pharm Sci 2020;17(4):457-462 DOI: 10.4274/tjps.galenos.2019.58219 REVIEW Toxicological Evaluation of Bisphenol A and Its Analogues Bisfenol A ve Analoglarının Toksikolojik Değerlendirilmesi İrem İYİGÜNDOĞDU1, Aylin ÜSTÜNDAĞ2*, Yalçın DUYDU2 1Gazi University Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey 2Ankara University Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey ABSTRACT Bisphenol A (BPA) is known as one of the oldest synthetic compounds with endocrine disrupting activity. It is commonly used in the production of epoxy resins, polycarbonates, dental fillings, food storage containers, baby bottles, and water containers. BPA is associated with various health problems such as obesity, diabetes, chronic respiratory diseases, cardiovascular diseases, renal diseases, behavior disorders, breast cancer, tooth development disorders, and reproductive disorders. Increasing health concerns have led the industry to seek alternatives to BPA. As BPA is now being excluded from several consumer products, the use of alternative compounds is increasing. However, the chemicals used to replace BPA are also BP analogues and may have similar or higher toxicological effects on organisms. The aim of this review is to focus on the toxicological profiles of different BP analogues (i.e. BPS and BPF) which are increasingly used today as alternative to BPA. Key words: Bisphenols, bisphenol A, endocrine disruptor, bisphenol S, bisphenol F ÖZ Bisfenol A (BPA) endokrin aktiviteye sahip bilinen en eski bileşiklerden biridir. BPA epoksi reçineler, polikarbonatlar, diş dolguları, yemek saklama kapları, bebek biberonları ve su bidonlarının üretiminde yaygın olarak kullanılmaktadır. BPA obezite, diyabet, kronik solunum hastalıkları, kardiyovasküler hastalıklar, renal hastalıklar, davranış bozuklukları, meme kanseri, diş gelişimi bozuklukları ve üreme bozuklukları gibi çeşitli sağlık sorunlarıyla ilişkilendirilmiştir. -
Abiraterone and MDV3100 Inhibits the Proliferation and Promotes The
Han et al. Cancer Cell Int (2019) 19:332 https://doi.org/10.1186/s12935-019-1021-9 Cancer Cell International PRIMARY RESEARCH Open Access Abiraterone and MDV3100 inhibits the proliferation and promotes the apoptosis of prostate cancer cells through mitophagy Jingli Han1† , Junhua Zhang1†, Wei Zhang2, Dalei Zhang3, Ying Li1, Jinsong Zhang2, Yaqun Zhang3, Tongxiang Diao3, Luwei Cui3, Wenqing Li1, Fei Xiao1,2,4, Ming Liu3* and Lihui Zou1* Abstract Background: Abiraterone and MDV3100 are two efective anticancer agents for prostate cancer, however, the mechanism of their downstream action remains undefned. Methods: A dual fuorescent biosensor plasmid was transfected in LNCaP cells to measure mitophagy. The DNA of LNCaP cells was extracted and performed with quantitative real-time PCR to detect mitochondrial DNA copy number. JC-1 staining was utilized to detect the mitochondrial membrane potential and electron microscope was performed to analyze mitochondrial morphology. Moreover, the protein levels of mitochondrial markers and apoptotic markers were detected by western blot. At last, the proliferation and apoptosis of LNCaP cells were analyzed with CCK-8 assay and fow cytometry after abiraterone or MDV3100 treatment. Results: Mitophagy was induced by abiraterone and MDV3100 in LNCaP cells. The low expression level of mito- chondrial DNA copy number and mitochondrial depolarization were further identifed in the abiraterone or MDV3100 treatment groups compared with the control group. Besides, severe mitochondria swelling and substantial autophagy-lysosomes were observed in abiraterone- and MDV3100-treated LNCaP cells. The expression of mito- chondria-related proteins, frataxin, ACO2 and Tom20 were signifcantly downregulated in abiraterone and MDV3100 treated LNCaP cells, whereas the expression level of inner membrane protein of mitochondria (Tim23) was signif- cantly upregulated in the same condition. -
The Fates of Endocrine Disruptors in Consumer Products: Bisphenol A
The Fates of Endocrine Disruptors in Consumer Products: Bisphenol A Prepared by Dr. Matthew A. DeNardo for the One Health One Planet Conference on March 8, 2018 at Phipps Conservatory The Fates of Endocrine Disruptors in Consumer Products: Bisphenol A Prepared by Dr. Matthew A. DeNardo for the One Health One Planet Conference on March 8, 2017 at Phipps Conservatory The Fates of Endocrine Disruptors in Consumer Products: Bisphenol A Prepared by Dr. Matthew A. DeNardo for the One Health One Planet Conference on March 8, 2017 at Phipps Conservatory A multidisciplinary investigation of the technical and environmental performances of TAML/peroxide elimination of Bisphenol A compounds from water. Green Chemistry doi:10.1039/C7GC01415E The Fates of Endocrine Disruptors in Consumer Products: Bisphenol A Prepared by Dr. Matthew A. DeNardo for the One Health One Planet Conference on March 8, 2017 at Phipps Conservatory HO OH Bisphenol A HO OH Phenol Bisphenol A HO OH Phenol Phenol Bisphenol A A HO OH Phenol Phenol Bisphenol A A HO OH Phenol Phenol Bisphenol A + O H 1 + 2 + H2O HO Δ HO OH Acetone Phenol Bisphenol A Water A HO OH Phenol Phenol Bisphenol A + O H 1 + 2 + H2O HO Δ HO OH Acetone Phenol Bisphenol A Water + A HO OH Phenol Phenol Bisphenol A + O H 1 + 2 + H2O HO Δ HO OH Acetone Phenol Bisphenol A Water + Bhandari 2015 HO OH Bisphenol A HO OH Bisphenol A HO OH Bisphenol A HO OH Bisphenol A O NaOH Cl Cl (Sodium (Phosgene) HO Hydroxide) o H2O, 25 C Bisphenol A OH O Cl O O Cl NaOH (Phosgene) O O O O (Sodium o C Hydroxide)O, 25 Bisphenol A Polycarbonate -
Toxicological and Health Aspects of Bisphenol A
Toxicological and Health Aspects of Bisphenol A Report of Joint FAO/WHO Expert Meeting 2–5 November 2010 and Report of Stakeholder Meeting on Bisphenol A 1 November 2010 Ottawa, Canada Food and Agriculture Organization of the United Nations WHO Library Cataloguing-in-Publication Data Joint FAO/WHO expert meeting to review toxicological and health aspects of bisphenol A: final report, including report of stakeholder meeting on bisphenol A, 1-5 November 2010, Ottawa, Canada. 1.Phenols - toxicity. 2.Food contamination. 3.Food packing. I.World Health Organization. II.Food and Agriculture Organization of the United Nations. ISBN 978 92 14 156427 4 (NLM classification: QV 223) © World Health Organization 2011 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.