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

• 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
• 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; 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

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）是联合癌症相关死亡的第四个主要原因 国家。在诊断时，大多数患者患有转移性疾病，尽管试图采用 独特的组合疗法5年生存率仍然为4％。尽管已经取得了重要进展 在理解其生物学时，这些知识尚未导致患者生存的实质性变化 显然，有必要制定新的，更好的策略来治疗PDA。炎症 过程对癌变和癌症的进展有用。 eicosanoids，由 环加氧酶和脂氧合酶活性是在炎症和 肿瘤条件。抑制类类生产可降低发生率并减少 人类癌症的进展。食物来源和饮食补充剂的多酚化合物具有 被证明通过抑制环氧合酶和/或脂氧酶具有抗炎特性 活动。根据我们的初步和可用文献的数据，我们假设多酚 绿茶和黄霉菌（SB）的化合物（SB）：1）抑制增殖和类黄花酱的产生 在PDA细胞中； 2）降低发展PDA的风险（预防效果）； 3）减少增长和扩散 已建立的PDA（治疗效应）。我们将研究绿茶（Polyphenon E）和SB的机制 多酚对增殖，凋亡和细胞周期调节的作用以及使用稳定同位素的作用 动态代谢分析（SIDMAP）技术，以评估 PDA细胞上的多酚。此外，我们将使用鼠标模型来确定Polyphenon E和SB是否在 可以抑制PDA的转基因模型（预防模型）中的胰腺癌发生并减少PDA细胞 原位异种移植模型的增长（治疗模型）。我们提案的一个独特方面是使用稳定 基于同位素的代谢组学方法，用于关联在不同阶段发生的代谢通量变化的方法 转基因小鼠的致癌过程。我们的发现将构成未来饮食的基本原理 涉及植物营养素的建议，并为开发临床试验提供科学背景 旨在评估多酚化合物的潜在治疗和预防益处 PDA中的绿茶，SB和其他植物药。