Your browser doesn't support javascript.
loading
Increased glucose availability sensitizes pancreatic cancer to chemotherapy.
Vaziri-Gohar, Ali; Hue, Jonathan J; Abbas, Ata; Graor, Hallie J; Hajihassani, Omid; Zarei, Mehrdad; Titomihelakis, George; Feczko, John; Rathore, Moeez; Chelstowska, Sylwia; Loftus, Alexander W; Wang, Rui; Zarei, Mahsa; Goudarzi, Maryam; Zhang, Renliang; Willard, Belinda; Zhang, Li; Kresak, Adam; Willis, Joseph E; Wang, Gi-Ming; Tatsuoka, Curtis; Salvino, Joseph M; Bederman, Ilya; Brunengraber, Henri; Lyssiotis, Costas A; Brody, Jonathan R; Winter, Jordan M.
Afiliação
  • Vaziri-Gohar A; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA. avaziri1@luc.edu.
  • Hue JJ; Department of Cancer Biology, Cardinal Bernardin Cancer Center, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA. avaziri1@luc.edu.
  • Abbas A; Department of Surgery, Division of Surgical Oncology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA.
  • Graor HJ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
  • Hajihassani O; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
  • Zarei M; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
  • Titomihelakis G; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
  • Feczko J; Department of Surgery, Division of Surgical Oncology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA.
  • Rathore M; Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
  • Chelstowska S; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Loftus AW; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
  • Wang R; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
  • Zarei M; Department of Surgery, Division of Surgical Oncology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA.
  • Goudarzi M; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
  • Zhang R; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
  • Willard B; Proteomics and Metabolomics Core, Cleveland Clinic, Cleveland, OH, USA.
  • Zhang L; Proteomics and Metabolomics Core, Cleveland Clinic, Cleveland, OH, USA.
  • Kresak A; Proteomics and Metabolomics Core, Cleveland Clinic, Cleveland, OH, USA.
  • Willis JE; Department of Molecular and Integrative Physiology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
  • Wang GM; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
  • Tatsuoka C; Department of Pathology, Case Western Reserve University and Department of Pathology Cleveland Medical Center, Cleveland, OH, USA.
  • Salvino JM; Department of Pathology, Case Western Reserve University and Department of Pathology Cleveland Medical Center, Cleveland, OH, USA.
  • Bederman I; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Brunengraber H; Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA.
  • Lyssiotis CA; Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA.
  • Brody JR; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Winter JM; Department of Nutrition and Biochemistry, Case Western Reserve University, Cleveland, OH, USA.
Nat Commun ; 14(1): 3823, 2023 06 28.
Article em En | MEDLINE | ID: mdl-37380658
ABSTRACT
Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies the suppressive effect of forced hyperglycemia in mouse models of PDAC, while rescuing this pathway mitigates anti-tumor effects observed with chemotherapy and high glucose.
Assuntos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Idioma: En Revista: Nat Commun Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Idioma: En Revista: Nat Commun Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos