Dietary Intervention in the Gallus Domesticus Model of Ovarian Cancer

卵巢癌鸡内金模型的饮食干预

• 批准号: 7473514
• 负责人: DALE B HALES
• 金额: $ 7.85万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-02 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7473514
• 关键词: 2 year old; Age; Aging; Animal Model; Antineoplastic Agents; Attention; Broccoli - dietary; Carcinogens; Carotenoids; Chemicals; Chemoprevention; Chemopreventive Agent; Chickens; Clinical Trials; Consumption; Development; Diet; Diet Modification; Dietary Intervention; Disease; Effectiveness; Enzymes; Epithelial ovarian cancer; Estradiol; Estrogen Metabolism; Estrogens; Folate; Food; Foundations; Freeze Drying; Glucosinolates; Goals; Histopathology; Homologous Gene; Hormonal Carcinogenesis; Human; Hydrolysis; Incidence; Individual; Indole-3-Carbinol; Life; Liver; Longevity; Malignant Neoplasms; Malignant neoplasm of ovary; Medical; Metabolism; Modeling; Numbers; Ovarian Carcinoma; Ovary; Plants; Plasma; Play; Potassium; Prevention; Role; Selenium; Sulforaphane; Testing; Validation; Vitamin A; Woman; bioactive food component; cancer risk; cancer therapy; carcinogenesis; cost; cruciferous vegetable; dietary supplements; feeding; human disease; improved; interest; lifestyle intervention; mortality; nutrition; ovarian cancer prevention; ovarian neoplasm; polyphenol; preclinical study; prevent; tumor progression

DESCRIPTION (provided by applicant): The proposed studies will test the effectiveness of a broccoli-enriched diet, and examine the mechanism of action of broccoli and indole-3-carbinol using the laying hen as a model of ovarian carcinoma. With the exception of the aging hen, there are no other animal models of spontaneous epithelial ovarian cancer that mimic the human disease. We hypothesize that increasing the consumption of broccoli may be a nontoxic way to prevent ovarian cancer, augment cancer therapy and to significantly increase life span. There is growing evidence that estrogens may play a role in ovarian tumor progression. Cruciferous vegetables such as broccoli contain a vast array of potentially bioactive compounds, including glucosinolates that can be hydrolyzed to metabolites with known anticarcinogenic activity, particularly sulforaphane and indole-3-carbinol (I3C). Broccoli also contains bioactive components including folate, potassium, selenium, vitamins A, C, E, carotenoids, and polyphenols. Individual components of broccoli have been studied as anticancer agents. I3C has been studied extensively has protective activity against hormonal carcinogenesis attributed to its ability to induce enzymes that alter estrogen metabolism in addition to facilitating metabolism and elimination of carcinogens. The first goal of this application is to establish the parameters for feeding broccoli to hens. The ultimate goal of the proposed studies will be to determine the effectiveness of a broccoli-enriched diet in the prevention and suppression of ovarian cancer in the aging hen, which will provide the foundation for developing a clinical trial in humans. Whereas cancer biologists have typically approached nutrition and cancer risk by examining specific chemical components derived from plants, examination of whole foods in chemoprevention studies has received less attention. The proposed studies will examine a single bioactive food component, I3C, and the whole food from which it's derived, broccoli, to determine their effectiveness in the prevention of ovarian cancer. The hypotheses to be tested are that 1) I3C and broccoli enriched diets will alter estrogen metabolism in favor of reducing carcinogenesis; and 2) feeding hens a diet enriched with broccoli or I3C will result in a reduction in the incidence of ovarian cancer. Two specific aims are proposed: Aim 1) Evaluate a 10% freeze-dried broccoli vs. 500, 1000 and 2500 mg/kg (mass per kg food) indole-3-carbinol (I3C) supplemented diets in 2 year old white Leghorn hens. Aim 2) Determine if a broccoli supplemented vs. I3C supplemented diets prevent the development of ovarian cancer in chickens.

描述（由申请人提供）： 拟议的研究将测试富含西兰花的饮食的有效性，并使用蛋鸡作为卵巢癌模型来研究西兰花和吲哚-3-甲醇的作用机制。除了老年母鸡之外，没有其他自发性上皮性卵巢癌动物模型可以模仿人类疾病。我们假设增加西兰花的摄入量可能是预防卵巢癌、增强癌症治疗和显着延长寿命的无毒方法。越来越多的证据表明雌激素可能在卵巢肿瘤的进展中发挥作用。西兰花等十字花科蔬菜含有大量潜在的生物活性化合物，包括芥子油苷，它们可以水解成具有已知抗癌活性的代谢物，特别是萝卜硫素和吲哚-3-甲醇 (I3C)。西兰花还含有生物活性成分，包括叶酸、钾、硒、维生素 A、C、E、类胡萝卜素和多酚。西兰花的各个成分已被研究作为抗癌剂。 I3C 已被广泛研究具有针对激素致癌的保护活性，这归因于其除了促进代谢和消除致癌物之外还能够诱导改变雌激素代谢的酶的能力。该应用程序的第一个目标是建立向母鸡饲喂西兰花的参数。拟议研究的最终目标是确定富含西兰花的饮食在预防和抑制老年母鸡卵巢癌方面的有效性，这将为开展人体临床试验奠定基础。尽管癌症生物学家通常通过检查源自植物的特定化学成分来研究营养和癌症风险，但化学预防研究中对天然食品的检查却很少受到关注。拟议的研究将检查单一生物活性食物成分 I3C 及其来源的天然食物西兰花，以确定它们在预防卵巢癌方面的有效性。要测试的假设是 1) 富含 I3C 和西兰花的饮食将改变雌激素代谢，有利于减少致癌作用； 2) 给母鸡饲喂富含西兰花或 I3C 的饮食将降低卵巢癌的发病率。提出了两个具体目标： 目标 1) 评估 2 岁白来航母鸡添加 10% 冻干西兰花与添加 500、1000 和 2500 mg/kg（每公斤食品质量）吲哚-3-甲醇 (I3C) 的日粮。目标 2) 确定添加西兰花的饮食与添加 I3C 的饮食是否可以预防鸡患卵巢癌。