LIPID DIET EFFECTS ON COLON TUMOR GROWTH AND METASTASES

脂质饮食对结肠肿瘤生长和转移的影响

• 批准号: 3176236
• 负责人: SELWYN A BROITMAN
• 金额: $ 18.65万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3176236
• 关键词: arachidonate; carcinogenesis; carcinogenesis inhibitor; colon neoplasms; dexamethasone; dietary lipid; fatty acid biosynthesis; laboratory mouse; metastasis; neoplasm /cancer transplantation; neoplastic growth; nutrition aspect of cancer; nutrition related neoplasm /cancer; nutrition related tag; prostaglandin endoperoxide synthase; prostaglandins; unsaturated fatty acids

The long term objectives of this laboratory are to identify nutritional factors which contribute to, or could reduce, the high incidence of colon cancer in western cultures. Hypothesis: in BALB/c mice the growth of colon tumor CT-26 when implanted into the colon, a nutrition responsive site (NR), is enhanced by increasing dietary essential fatty acids (EFA). These effects are mediated via the cyclooxygenase pathway in the synthesis of prostaglandin (PG's) of the 1 and 2 series. Inhibition of tumor growth in the colon and of pulmonary colonization is related to inhibition of arachidonic acid metabolism in the cyclooxygenase pathway by the constituents of dietary marine oils, eicosopentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are utilized for PG's of the 3 series. These events, if indeed nutrition related, are less likely to occur when CT-26 is implanted in the mid scapula area, a nutrition non responsive site (NNR). Using CT-26 tumors implanted in colon (NR), and in mild scapula (NNR), various isocaloric nutritional lipid intervention are planned, including varying EFA with and without varying marine oils. Corollary studies are conducted in tissue culture with CT-26 cells. Nutritional interventions will be evaluated on tumor latency time, tumor growth, pulmonary colonization, metastatic potential, and the demise of the host. Effects of EFA, EPA, and indomethacin on prostaglandin synthesis and lipid profiles of tumors and tissues is assessed. These studies should provide: 1) an understanding of the relationship of EFA's to tumor growth and metastasis, 2) insights on the relationship of EPA and DHA inhibition of colon tumors, 3) data on the feasibility of mixtures of marine oil with other dietary lipids as colon tumor inhibitors, 4) guidelines for nutritional interventions aimed at colon tumor prevention, and the management of patients with colon cancer following resection in conjunction with radiation or chemotherapy.

该实验室的长期目标是确定 营养因素，有助于，或可以减少，高 在西方文化中结肠癌的发病率。 假设：在 BALB/c小鼠的结肠肿瘤CT-26的生长，当植入到 结肠是一个营养反应部位（NR）， 膳食必需脂肪酸（EFA）。 这些影响是通过 通过环氧化酶途径合成前列腺素 (PG的）的1和2系列。 肿瘤生长的抑制 结肠和肺定植与抑制 花生四烯酸在环氧合酶途径中的代谢 膳食海洋油的成分，二十碳五烯酸（EPA） 和二十二碳六烯酸（DHA），其用于 3系列。 这些事件，如果确实与营养有关， 当CT-26植入肩胛骨中部区域时可能发生， 营养无反应位点（NNR）。 使用CT-26肿瘤 植入结肠（NR）和轻度肩胛骨（NNR）， 计划进行等热量营养脂质干预，包括 不同的EFA，有和没有不同的海洋石油。 推论 研究在CT-26细胞的组织培养中进行。 营养干预将根据肿瘤潜伏时间进行评价， 肿瘤生长、肺定植、转移潜能，以及 宿主的死亡。 EFA、EPA和吲哚美辛对 前列腺素合成和肿瘤及组织的脂质分布 评估。 这些研究应提供：1）了解 EFA与肿瘤生长和转移的关系，2） 对EPA和DHA抑制结肠的关系的见解 肿瘤，3）海洋石油与 其他饮食脂质作为结肠肿瘤抑制剂，4）指南 针对结肠肿瘤预防的营养干预， 结肠癌切除术后的管理 与放疗或化疗联合使用。