title: TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.
abstract: Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Greco
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Lena
authors.initials: L
authors.lastname: Tomkötter
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Anne-Kristin
authors.initials: AK
authors.lastname: Vahle
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Rae
authors.initials: R
authors.lastname: Rokosh
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Antonina
authors.initials: A
authors.lastname: Avanzi
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Syed Kashif
authors.initials: SK
authors.lastname: Mahmood
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Deutsch
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Sara
authors.initials: S
authors.lastname: Alothman
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Dalia
authors.initials: D
authors.lastname: Alqunaibit
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ochi
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Zambirinis
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Tasnima
authors.initials: T
authors.lastname: Mohaimin
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rendon
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Elliot
authors.initials: E
authors.lastname: Levie
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Mridul
authors.initials: M
authors.lastname: Pansari
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Torres-Hernandez
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Donnele
authors.initials: D
authors.lastname: Daley
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Rocky
authors.initials: R
authors.lastname: Barilla
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: H Leon
authors.initials: HL
authors.lastname: Pachter
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tippens
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Hassan
authors.initials: H
authors.lastname: Malik
authors.affiliation: Department of Neurology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Allal
authors.initials: A
authors.lastname: Boutajangout
authors.affiliation: Department of Neurology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
authors.affiliation: Department of Surgery, New York University School of Medicine, New York, New York, United States of America; Department of Cell Biology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: George
authors.initials: G
authors.lastname: Miller
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D001823:Body Composition; D002100:Cachexia / Q000150:complications / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009133:Muscular Atrophy / Q000150:complications; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000473:pathology; D016019:Survival Analysis; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D000906:Antibodies; D016212:Transforming Growth Factor beta