CHOLECYSTOKININ EFFECT ON PANCREATIC GROWTH & TUMORS

胆囊收缩素对胰腺生长的影响

• 批准号: 3187593
• 负责人: THOMAS E ADRIAN
• 金额: $ 11.47万
• 依托单位: CREIGHTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 1993-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3187593
• 关键词: DNA; DNA repair; Leguminoseae; alkylation; autoradiography; benzopyrenes; bioassay; chemical carcinogen; chemical carcinogenesis; cholecystokinin; colon neoplasms; dietary lipid; food processing /preparation; gastrointestinal hormones; hormone receptor; immunocytochemistry; inhibitor /antagonist; intestines; nutrition related neoplasm /cancer; nutrition related tag; ornithine decarboxylase; pancreas neoplasms; pancreatic islet hyperplasia; protein kinase C; radioimmunoassay; trypsin inhibitors; tumor promoters

Feeding a variety of animals with trypsin inhibitors results in a marked hypertrophy and hyperplasia of the pancreas, which predisposes the animals to the development of tumors when challenged with carcinogens. Raw soya, which contains a heat labile trypsin inhibitor has been shown to promote spontaneous tumors, in long-term studies. We have previously shown that the pancreatic growth in response to feeding raw soya in the rat is accompanied by a rise in plasma cholecystokinin (CCK). Infusion of CCK at a dose which mimics this response causes similar pancreatic growth. More recently we have shown that the pancreatic growth resulting from feeding of either raw soya flour or a high fat diet in the hamster is blocked by a potent and specific CCK receptor antagonist. Dietary fat is a potent releaser of CK and the increasing incidence of pancreatic cancer in man is thought to be related to high fat intake, so CCK could be a contributing factor. In addition, pancreatic tumor cells have receptors for this trophic hormone. We postulate that CCK receptor blockade will reverse the potentiating effects of raw soya or high fat diets on pancreatic cancer in the hamster and that it will reduce the effect of carcinogens even in animals fed normal diets. The purpose studies will firstly investigate the effect of CCK receptor blockade (L364,718) on the promoting effect of raw soya and high fat diets on chemical carcinogen (BOP) induced carcinoma in the hamster. Because preliminary studies demonstrated growth in the large and small bowel following both raw soya and high fat feeding, we will investigate the release of trophic hormones, tissue growth and CCK receptor blockade in these areas too. Secondly the effect of the same antagonist on carcinogenesis in animals on normal diet (low fat and cooked soya) will be assessed. Thirdly we will examine the mechanism of initiation and post-initiation of carcinogenesis by examining DNA alkylation and the key enzymes of tissue growth, respectively. These studies may show how fat contributes to pancreatic carcinogenesis.

用胰蛋白酶抑制剂喂养各种动物， 胰腺肥大和增生，这使动物 与肿瘤的发展有关。 生大豆， 含有热不稳定的胰蛋白酶抑制剂， 自发性肿瘤，在长期研究中。 我们之前已经证明， 在大鼠中，胰腺对喂食生大豆的反应是 并伴有血浆胆囊收缩素（CCK）升高。 CCK输注， 模拟这种反应的剂量引起类似的胰腺生长。 更 最近，我们已经表明，胰腺生长所造成的喂养， 无论是生大豆粉或高脂肪饮食的仓鼠是阻止由一个 有效和特异性CCK受体拮抗剂。 膳食脂肪是一种有效的 肌酸激酶激酶的抑制剂与胰腺癌发病率的增加有关， 被认为与高脂肪摄入有关，因此CCK可能是一种贡献 因子 此外，胰腺肿瘤细胞具有这种受体， 营养激素 我们假设CCK受体阻断剂将逆转增强的 生大豆和高脂饮食对仓鼠胰腺癌的影响 而且它还能减少致癌物质的影响， 正常饮食 本研究的目的是首先探讨CCK受体在心肌细胞凋亡中的作用 阻断（L364，718）对生大豆和高脂肪饮食的促进作用 对化学致癌物（BOP）诱发仓鼠癌的影响。 因为 初步研究表明大肠和小肠的生长 在喂食生大豆和高脂肪饲料后，我们将调查 营养激素的释放，组织生长和CCK受体阻断， 这些地区也是。 第二，同一拮抗剂对动物致癌作用的影响， 将评估正常饮食（低脂和熟大豆）。 第三，我们将研究启动和启动后的机制， 通过检测DNA烷基化和组织的关键酶， 增长，分别。 这些研究可能会显示脂肪如何促进胰腺癌的发生。