Omega-3 Fatty Acid Effects on Pancreatitis and Adenocarcinoma Development


Principal Investigator: Christopher A Jolly
Abstract: DESCRIPTION (provided by applicant): Pancreatic cancer is the fourth leading cause of cancer death in the United States. The five- year survival rate is only 5% because no diagnostic markers are available for early detection. Inflammation has emerged as an important risk factor for the development of many types of cancers including pancreatic cancer. We hypothesize that suppressing inflammation with the anti-inflammatory omega-3 polyunsaturated fatty acids (PUFAs) found in fish oil will suppress inflammation and subsequent pancreatic adenocarcinoma development. To test this hypothesis, we will use the cyclooxygenase 2 (COX-2) transgenic mouse model fed diets enriched in either the omega-3 fatty acid eicosapentaenoic acid (EPA) or the omega-6 fatty acid linoleic acid prior to the onset of pancreatitis. The COX-2 Tg mouse overexpresses the COX-2 gene which causes spontaneous pancreatitis and subsequent development of pancreatic adenocarcinomas. This model is highly relevant because high COX-2 expression is found in human pancreatitis and pancreatic cancer. Histopathological examination of the pancreata will be performed to determine if dietary EPA suppresses immune cell recruitment and subsequent pancreatitis leading to adenocarcinoma development. Cytokine gene expression in the pancreata and T cell subset analysis in draining lymph nodes will also be performed to establish whether the beneficial effects of EPA are linked to modulation of innate or adaptive immunity or both. Lipodomic analysis will also be carried out for prostanoid production and fatty acid composition of the pancreata to evaluate how these lipid changes correlate with alterations in pancreatitis. Identifying novel immune targets of suppressing inflammation by omega-3 PUFAs will provide the necessary data to propose additional focused experiments aimed at elucidating the immune mechanism(s) by which omega-3 PUFAs and inflammation regulate pancreatic cancer development. This data may show an important role for the omega-3 PUFAs, especially EPA, in cancer prevention because they are well known anti-inflammatory agents and are widely consumed by people in the United States.
Funding Period: 2012-09-01 - 2014-08-31
more information: NIH RePORT

Detail Information

Research Grants31

    John C Crabbe; Fiscal Year: 2013
    ..An Education and Outreach component trains pre- and post-doctoral students in alcohol research, disseminates research findings to the public, and engages in a range of activities with elementary-to-high school students. ..
  2. Omega-3 Fatty Acids and Hepatic Carcinogenesis
    Tong Wu; Fiscal Year: 2013
    ..Results from the proposed studies will provide important mechanistic insight and therapeutic implications for utilizing omega-3 PUFAs for the chemoprevention and treatment of human hepatocellular carcinoma. ..
  3. Structural bases of the functions of RNA-protein machines
    THOMAS ARTHUR STEITZ; Fiscal Year: 2013
    ..Also of interest will be the ways in which the structures and properties of RNA molecules can be utilized to carry out various biological functions often analogous to those performed by proteins. ..
    Joseph L Goldstein; Fiscal Year: 2013
    ..Such an integrated interdisciplinary approach is possible only through continued support of this PPG. ..
  5. Functional Annotation of the Pancreatic Cancer Genome
    Steven D Leach; Fiscal Year: 2013
    ..Together, these studies will dramatically accelerate the functional annotation of the pancreatic cancer genome, setting the stage for future therapeutic applications. ..
  6. Chemopreventive effect of fish oil derived EPA in lung cancer
    Peiying Yang; Fiscal Year: 2013
    ..This proposal intends to define a novel targeted natural chemopreventive agent against lung cancer. ..
  7. Discovery and Development of Therapeutic Genes for CHF
    H Kirk Hammond; Fiscal Year: 2013
    ..Four Cores will support the Program: Digital Imaging (Dr. Farquhar);Vector Production (Dr. Miyanohara);Translational Systems (Dr. Hammond) and Clinical &Administrative (Dr. Hammond). ..
  8. Host-pathogen competition in IFN mediated antiviral defense
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  9. Effect of Omega-3 Fatty Acids on Cancer Stem Cells
    KUMBLE SANDEEP PRABHU; Fiscal Year: 2013
    ..Our long-term goal is to understand the health benefits of bioactive metabolites of ?-3 fatty acids and translate these findings in CML patients. ..
    Graham A Colditz; Fiscal Year: 2013
    ..To address these aims, we propose four research projects and five cores that form a cohesive, transdisciplinary center focused on research, training/career development, and dissemination. ..
  11. Mentoring Research Excellence in Aging and Regenerative Medicine
    S Michal Jazwinski; Fiscal Year: 2013
    ..This COBRE will represent the centerpiece of the Tulane Center for Aging, and it will contribute strongly to our building of an exceptional biomedical aging research enterprise in Louisiana. ..