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Polyphenols Regulate Lipid Inflamm Processes in Pancreatic Cancer/Harris, Diane

多酚调节胰腺癌的脂质炎症过程/Harris, Diane

基本信息

批准号：
7394046
负责人：
Vay Liang W Go
金额：
$ 8.44万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-12-01 至 2012-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7394046
关键词：
Acids Adenocarcinoma Cell Affect Andro-Diane Animal Model Anti-Inflammatory Agents Anti-inflammatory Apoptosis Arachidonic Acids Biology Botanicals Breast Cancer Etiology Cell Cycle Progression Cell Cycle Regulation Cell Proliferation Cessation of life Chemopreventive Agent Clinical Trials Design Combined Modality Therapy Condition Data Development Diagnosis Dinoprostone Disease Ductal Epithelium Eicosanoid Production Eicosanoids Electrocardiogram Epigallocatechin Gallate Epithelium Food Future Glucose Green tea Growth Human In Vitro Incidence Indomethacin Inflammatory Knowledge LOX gene Label Lesion Leukotriene B4 Lipids Lipoxygenase Literature Malignant Neoplasms Malignant neoplasm of pancreas Mediating Metabolic Metabolic Pathway Modeling Molecular Nordihydroguaiaretic Acid Pancreas Pancreatic Diseases Pancreatic Ductal Adenocarcinoma Pancreatic Intraepithelial Neoplasia Pancreatitis Pathogenesis Pathway interactions Patients Personal Satisfaction Pharmacologic Substance Phenotype Physiological Polyphenon E Prevention Preventive Process Proliferation Marker Property Prostaglandin-Endoperoxide Synthase Prostate Protein-Lysine 6-Oxidase Range Recommendation Recovery Relative (related person)Research Personnel Risk Role Scutellaria baicalensis Source Staging Standards of Weights and Measures Technology Testing Therapeutic Therapeutic Effect Time Today Toxic effect Tracer Transgenic Animals Transgenic Mice Transgenic Model Tumor Tissue United States Xenograft Model Xenograft procedure baicalin base cancer cell carcinogenesis cell growth cyclooxygenase 1 cyclooxygenase 2 design dietary supplements in vivo metabolomics mouse model neoplastic polyphenol programs research study stable isotope tumor growth tumor progression wogonin

项目摘要

Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States. At the time of diagnosis most patients have metastatic disease and despite attempts to employ unique combination therapies the 5-year survival remains 4%. Although important progress has been made in understanding its biology, this knowledge has not yet resulted in a substantial change in patient survival and there is clearly a need to develop new and better strategies for the treatment of PDA. Inflammatory processes are instrumental to carcinogenesis and cancer progression. Eicosanoids, formed by cyclooxygenase and lipoxygenase activity, are important bioactive lipids produced in inflammatory and neoplastic conditions. Inhibition of eicosanoid production reduces the incidence and diminishes the progression of human cancers. Polyphenolic compounds from food sources and dietary supplements have been shown to possess anti-inflammatory properties via inhibition of cyclooxygenase and/or lipoxygenase activity. Based on data from our preliminary and the available literature, we hypothesize that polyphenolic compounds from green tea and Scutellaria baicalensis (SB): 1) inhibit proliferation and eicosanoid production in PDA cells; 2) lower the risk of developing PDA (preventive effect); and, 3) reduce the growth and spread of established PDA (therapeutic effect). We will study mechanisms of green tea (polyphenon E) and SB polyphenol action on proliferation, apoptosis, and cell cycle regulation in vitro as well as using stable isotopebased dynamic metabolic profiling (SIDMAP) technology to evaluate the overall phenotypic effect of polyphenols on PDA cells. In addition we will use mouse models to determine if polyphenon E and SB on can inhibit pancreatic carcinogenesis in a transgenic model of PDA (prevention model) and reduce PDA cell growth in the orthotopic xenograft model (treatment model). A unique aspect of our proposal is to use stable isotope-based metabolomics approach to relate changes in metabolic flux occuring at different stages in the carcinogenisis process in the transgenic mice. Our findings will form the rationale for future dietary recommendations involving phytonutrients and provide the scientific background for developing clinical trials designed to evaluate the potentially therapeutic and preventive benefit of polyphenolic compounds from green tea, SB, and other botanicals in PDA.

胰腺导管腺癌（PDA）是美国癌症相关死亡的第四大原因