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Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes.
Gordon, Ryan R; Wu, Mengchu; Huang, Chung-Ying; Harris, William P; Sim, Hong Gee; Lucas, Jared M; Coleman, Ilsa; Higano, Celestia S; Gulati, Roman; True, Lawrence D; Vessella, Robert; Lange, Paul H; Garzotto, Mark; Beer, Tomasz M; Nelson, Peter S.
Afiliação
  • Gordon RR; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Wu M; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Huang CY; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Harris WP; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Sim HG; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Lucas JM; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Coleman I; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Higano CS; Department of Medicine, University of Washington, Seattle, Washington, United States of America; Department of Urology, University of Washington, Seattle, Washington, United States of America.
  • Gulati R; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • True LD; Department of Pathology, University of Washington, Seattle, Washington, United States of America; Department of Urology, University of Washington, Seattle, Washington, United States of America.
  • Vessella R; Department of Urology, University of Washington, Seattle, Washington, United States of America.
  • Lange PH; Department of Urology, University of Washington, Seattle, Washington, United States of America.
  • Garzotto M; Department of Urology and Cancer Institute, Oregon Health and Sciences University, Portland, Oregon, United States of America; Section of Urology, Portland VA Medical Center, Portland, Oregon, United States of America.
  • Beer TM; Department of Medicine, Oregon Health and Sciences University, Portland, Oregon, United States of America.
  • Nelson PS; Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Medicine, University of Washington, Seattle, Washington, United States of America; Department of Pathology, University of Washington, Seattle, Washin
PLoS One ; 9(9): e104271, 2014.
Article em En | MEDLINE | ID: mdl-25198178
To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA). In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1α. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1α, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Resistência a Medicamentos / Protocolos de Quimioterapia Combinada Antineoplásica / Regulação Enzimológica da Expressão Gênica / Regulação Neoplásica da Expressão Gênica / Monoaminoxidase / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adult / Animals / Humans / Male / Middle aged Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Resistência a Medicamentos / Protocolos de Quimioterapia Combinada Antineoplásica / Regulação Enzimológica da Expressão Gênica / Regulação Neoplásica da Expressão Gênica / Monoaminoxidase / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adult / Animals / Humans / Male / Middle aged Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos