The Program Project Grant Targeting diet-induced promotion of Kras-initiated pancreatic adenocarcinoma constitutes a highly collaborative, multidisciplinary research program designed to make a significant impact on the investigation of diet in the development of pancreatic cancer. A detailed understanding of the biological mechanisms of action of a typical Western-style diet, rich in fats and calories, on pancreatic cancer development can form the rationale for biologically-based practices and scientifically-founded dietary recommendations in the prevention of this disease. Our Program Project includes expertise from the UCLA campus and VA Greater Los Angeles Healthcare System - West Los Angeles (VAGLAHS-WLA). The Program is led by experienced pancreatic cancer researchers, who have organized investigative teams to develop highly interactive and synergistic research programs. Our goal is to study the mechanisms, by which a Western-style diet, rich in fats and calories, promotes pancreatic cancer development and to explore interventional, cancer-preventing strategies. Innovative animal and cell culture models and novel concepts strongly supported by a wealth of preliminary data are proposed. The Projects will focus on: Inflammatory processes in diet-induced pancreatic cancer promotion (Project 1); Chemoprevention of pancreatic cancer with antidiabetic agents (Project 2); Inefficient autophagy, mitochondrial dysfunction, and pancreatic tumorigenesis (Project 3); Alcohol abuse and metabolic syndrome promote desmoplasia of pancreatic cancer (Project 4). The projects will utilize our Shared Core Resources including the Administrative Core (with Biostatistics Sub-Core) and the Animal Core (with Pathology Sub-Core). An External Advisory Board comprised of nationally and internationally recognized translational pancreatic cancer investigators and advocates has been assembled. The Program Project is designed for maximum integration and synergy of research and key investigators, who have been collaborating over the years so that the proposed Program can be focused on the most promising investigations with the greatest translational potential and impact.

Public Health Relevance

Insights gained from the proposed Program Project will be extremely valuable for understanding the tumor promoting effects of a Western-style diet, which will lead to efficacious preventive strategies and general health-promoting dietary recommendations. Successful confirmation of our hypothesis that dietary factors are sufficient to fully promote and accelerate tumor formation has the potential to shift current research and clinical practice.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
4P01CA163200-05
Application #
9105358
Study Section
Special Emphasis Panel (ZCA1-RPRB-B (M1))
Program Officer
Ross, Sharon A
Project Start
2012-08-01
Project End
2017-07-31
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
5
Fiscal Year
2016
Total Cost
$1,304,539
Indirect Cost
$457,436
Name
University of California Los Angeles
Department
Surgery
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Eibl, Guido; Cruz-Monserrate, Zobeida; Korc, Murray et al. (2018) Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer. J Acad Nutr Diet 118:555-567
Xu, Mu; Jung, Xiaoman; Hines, O Joe et al. (2018) Obesity and Pancreatic Cancer: Overview of Epidemiology and Potential Prevention by Weight Loss. Pancreas 47:158-162
Zheng, Han; You, Yang; Hua, Meiyun et al. (2018) Chlorophyllin Modulates Gut Microbiota and Inhibits Intestinal Inflammation to Ameliorate Hepatic Fibrosis in Mice. Front Physiol 9:1671
Waldron, Richard T; Su, Hsin-Yuan; Piplani, Honit et al. (2018) Ethanol Induced Disordering of Pancreatic Acinar Cell Endoplasmic Reticulum: An ER Stress/Defective Unfolded Protein Response Model. Cell Mol Gastroenterol Hepatol 5:479-497
Kaur, Kawaljit; Chang, Hui-Hua; Topchyan, Paytsar et al. (2018) Deficiencies in Natural Killer Cell Numbers, Expansion, and Function at the Pre-Neoplastic Stage of Pancreatic Cancer by KRAS Mutation in the Pancreas of Obese Mice. Front Immunol 9:1229
Jin, Yi-Ping; Valenzuela, Nicole M; Zhang, Xiaohai et al. (2018) HLA Class II-Triggered Signaling Cascades Cause Endothelial Cell Proliferation and Migration: Relevance to Antibody-Mediated Transplant Rejection. J Immunol 200:2372-2390
Edderkaoui, Mouad; Chheda, Chintan; Soufi, Badr et al. (2018) An Inhibitor of GSK3B and HDACs Kills Pancreatic Cancer Cells and Slows Pancreatic Tumor Growth and Metastasis in Mice. Gastroenterology 155:1985-1998.e5
Tomasi, Maria Lauda; Cossu, Carla; Spissu, Ylenia et al. (2017) S-adenosylmethionine and methylthioadenosine inhibit cancer metastasis by targeting microRNA 34a/b-methionine adenosyltransferase 2A/2B axis. Oncotarget 8:78851-78869
Liou, Geou-Yarh; Bastea, Ligia; Fleming, Alicia et al. (2017) The Presence of Interleukin-13 at Pancreatic ADM/PanIN Lesions Alters Macrophage Populations and Mediates Pancreatic Tumorigenesis. Cell Rep 19:1322-1333
Setiawan, Veronica Wendy; Pandol, Stephen J; Porcel, Jacqueline et al. (2017) Dietary Factors Reduce Risk of Acute Pancreatitis in a Large Multiethnic Cohort. Clin Gastroenterol Hepatol 15:257-265.e3

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