Flavonoids in Pancreatic Carcinogenesis & Angiogenesis/Hines, Oscar

黄酮类化合物在胰腺癌发生中的作用

• 批准号: 7914047
• 负责人: Oscar Joe Hines
• 金额: $ 20.05万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7914047
• 关键词: Accounting; Angiogenic Switch; Animal Model; Animals; Antioxidants; Apigenin; Apoptosis; Attenuated; Biological Factors; Biology; Cancer Biology; Cancer Etiology; Cancer cell line; Cells; Cessation of life; Chemoprevention; Chemopreventive Agent; Chemoprotective Agent; Clinical; Clinical Trials; Combined Modality Therapy; Development; Diagnosis; Diet; Dietary Factors; Dietary Intervention; Dietary intake; Disease; Disease Management; Disease Progression; Environment; Europe; Excision; Flavones; Flavonoids; Foundations; Genistein; Growth Factor; Hormonal; Human; Induction of Apoptosis; Knowledge; Laboratories; Lesion; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of pancreas; Mediating; Metabolic; Modeling; Mus; Neoplasm Metastasis; Nutrient; Oncogenic; Operative Surgical Procedures; Pancreas; Pancreatic Adenocarcinoma; Pancreatic Diseases; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraepithelial Neoplasia; Patients; Phenotype; Phytochemical; Plants; Play; Premalignant; Prevention; Primary Neoplasm; Process; Protocols documentation; Quercetin; Reading; Recruitment Activity; Research Personnel; Role; Signal Transduction; Soybeans; Structure; Supplementation; Target Populations; Testing; Time; Tracer; Transgenic Model; Transgenic Organisms; Tumor-Derived; United States; Vascular blood supply; Vertebral column; angiogenesis; base; cancer cell; cancer prevention; carcinogenesis; cell growth; chemotherapeutic agent; chemotherapy; epidemiologic data; flavone; fruits and vegetables; gemcitabine; high risk; improved; in vivo; metabolomics; novel; novel strategies; novel therapeutics; polyphenol; prevent; programs; protective effect; research study; response; soy; treatment strategy; tumor

Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Most of the estimated 32,000 annual new cases in the U.S. and 60,000 annual new cases in Europe will die within a year of diagnosis. There is an urgent a need to develop new and better strategies for the treatment of pancreatic cancer. This will require novel approaches to both chemoprevention and chemotherapy, and phytochemicals offer to possibilty of this. For a cancer cell to develop an alteration in the cellular metabolic profile must occur. Once the normal pancreatic cell has converted to an cancer cell, then a group of cancer cells must recruit additional blood supply to grow and metastasize - a process is termed the angiogenic switch. We and others have found that genistein, a flavonoid, may be a useful approach in impacting the metabolic profile of the pancreatic cancer cell and may inhibit the factors stimulated by the angiogenic switch. Preliminary evidence in our laboratory suggests that genistein can alter the pancreatic cancer cell metabolic profile, inhibit cell growth, induce apoptosis, diminish metastatic spread in vivo, and decrease angiogenesis. We hypothesize that flavonoids prevent the progression to pancreatic cancer, and that flavonoids may act as a chemotherapeutic in established pancreatic cancer. We will pursue the following specific aims: Specific Aim I). Determine the ability of flavonoids to prevent the progression of pancreatic intraepithelial neoplasia (PanIN) to invasive pancreatic ductal adenocarcinoma using a novel transgenic pancreatic cancer animal model. Specific Aim II). Assess the effect of flavonoids on immortalized human pancreatic cancer cell lines in an orthotopic xenograph model. Specific Aim III). Determine the impact of flavonoids in patients with pancreatic cancer. To complete these aims we will perform experiments investigating genistein, quercetin, and apigenin in a transgenic model (LSL-KRAS G12D;PDX-1-Cre) that recaputulates premalignant and malignant pancreatic lesions. Also we will test these flavonoids in an orthotopic murine model and compare these to standard gemcitabine treatment. Finally, we will take advantage our large clinical volume of patients with pancreatic cancer and study the impact of soy supplementation in patients with this disease.

在美国，胰腺腺癌是癌症相关死亡的第四大原因。大多数