Chemopreventive Efficacy of Broccoli Sprouts against BC

西兰花芽对 BC 的化学预防功效

• 批准号: 7726891
• 负责人: THOMAS A KENSLER
• 金额: $ 22.11万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 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/7726891
• 关键词: Activities of Daily Living; Animals; Anticarcinogenic Agents; Antioxidants; Biological Assay; Biological Markers; Blood; Brassica; Breast; Broccoli - dietary; Cabbage - dietary; Carcinogens; Cauliflower; Chemicals; Chemoprevention; Chemopreventive Agent; Clinical Research; Clinical Trials Design; Consumption; Controlled Clinical Trials; Correlative Study; Coupled; DNA; Data; Drug Kinetics; Edible Plants; Effectiveness of Interventions; End Point; Enzyme Induction; Enzymes; Epidemiologic Studies; Epithelial Cells; Estrogen Metabolism; Estrogens; Food; Food Safety; Gene Proteins; Gene Targeting; Genes; Genomics; Glucosinolates; Glutathione S-Transferase; Human; Hydrolysis; Intake; Intervention; Intestines; Isothiocyanates; Knockout Mice; Laboratory Finding; Lead; Malignant Neoplasms; Mammalian Cell; Mammary Gland Parenchyma; Mammary Tumorigenesis; Mammary gland; Mastectomy; Measures; Messenger RNA; Metabolism; Myrosinase; NAD(P)H Dehydrogenase (Quinone); NAD(P)H dehydrogenase (quinone) 1, human; NQO1 gene; Operative Surgical Procedures; Pattern; Pharmacodynamics; Phase; Phytochemical; Placebo Control; Placebos; Plants; Population; Preparation; Proteins; Proteome; Proteomics; Quinone Reductases; Randomized; Reactive Oxygen Species; Research Personnel; Risk; Risk Marker; Rodent; Safety; Serum; Sprague-Dawley Rats; Sulforaphane; Testing; Tissues; Transcript; Transferase; Translating; Urine; Vegetables; Water; Woman; cancer risk; cancer type; carcinogenesis; chemical carcinogenesis; cruciferous vegetable; day; detoxication; enzyme activity; fruits and vegetables; glucoraphanin; indexing; inhibitor/antagonist; mRNA Expression; malignant breast neoplasm; mammary epithelium; metabolomics; neoplastic; novel; preclinical study; prophylactic; transcription factor; urinary

PROVIDED. Epidemiological studies provide convincing evidence for an inverse relation between quantities of fruit and vegetables consumed and the risk of developing cancer. Cruciferous vegetable (e.g., broccoli) consumption has been recently associated with reduced risk for breast cancer. A major mechanism for protection against carcinogenesis involves induction of phase 2 detoxication enzymes that promote elimination of carcinogens and boost antioxidant capacity. Many edible plants, most notably 3-day-old broccoli sprouts, contain potent phase 2 enzyme inducer activity in the form of isothiocyanates or their glucosinolate precursors. In animals, sulforaphane, derived from the principal glucosinolate (glucoraphanin) of broccoli sprouts, is a very potent inducer of phase 2 enzyme activity and protects against chemical carcinogenesis. The objective of this study is to translate and evaluate these laboratory findings in a human population at elevated risk for breast cancer. Previous trials have afforded important information on the safety, metabolism, and urinary disposition of isothiocyanates, and on the activation of glucosinolates. Therefore, our aims are to 1) determine the pharmacodynamic action of a broccoli sprouts preparation, as well as pure sulforaphane and pure glucoraphanin, in the mammary epithelium of rodents to develop better biomarkers; 2) evaluate the pharmacokinetics and pharmacodynamic action of broccoli sprouts in 30 healthy women undergoing breast reduction surgery or prophylactic mastectomy by conducting a 10-day randomized placebo controlled clinical trial that measures isothiocyanate levels in blood, urine and mammary tissue as well as phase 2 inducer activity, mRNA transcript levels and estrogen metabolites in mammary tissue; and 3) test whether a 3 month intervention of a broccoli sprout preparation modulates a panel of breast cancer risk biomarkers (Ki67 expression, estrogen metabolite profiles, novel markers) compared to placebo in 126 women at increased risk for breast cancer using a Phase II randomized clinical trial design. These studies will provide a rigorous assessment of the usefulness of modulating expression of carcinogen detoxication enzymes and other sulforaphane target genes by means of a food containing a standardized level of a phytochemical as a general strategy for chemoprevention in humans.

假如。 流行病学研究提供了令人信服的证据，证明了数量的水果与 蔬菜消耗的癌症风险。十字花科蔬菜（例如，西兰花）的消费量 最近与乳腺癌风险降低有关。保护的主要机制 致癌作用涉及诱导2期解毒酶，以促进促进致癌物的消除 并提高抗氧化能力。许多可食用的植物，最著名的是3天大的西兰花芽 第2阶段的酶诱导剂活性，异硫氰酸盐或其葡萄糖苷酸前体的形式。在动物中 磺胺硫烷源自西兰花芽的主要葡萄糖苷（葡萄糖磷酸），是一种非常有效的 第2期酶活性的诱导剂，可预防化学癌发生。这个目的 研究是在人口中翻译和评估这些实验室发现的乳房风险较高 癌症。以前的试验提供了有关安全性，代谢和尿液的重要信息 异硫氰酸酯的处置和葡萄糖醇的激活。因此，我们的目标是1） 确定西兰花新芽制剂的药效动作，以及纯粹的硫素和 纯葡萄糖蛋白，在啮齿动物的乳腺上皮中，以形成更好的生物标志物； 2）评估 西兰花芽的药代动力学和药效动力作用在30位健康妇女的乳房中 通过进行为期10天的随机安慰剂控制临床，还原手术或预防性乳房切除术 测量血液，尿液和乳腺组织以及2期诱导剂中异硫氰酸酯水平的试验 乳腺组织中的活性，mRNA转录水平和雌激素代谢物； 3）测试是否3个月 西兰花发芽制剂的干预调节乳腺癌风险生物标志物（KI67） 表达，雌激素代谢产物谱，新颖的标记）与126名女性的安慰剂相比 使用II期随机临床试验设计患乳腺癌的风险。这些研究将提供严格的 评估调节致癌酶表达和其他其他 通过含有标准水平的植物化学水平的食物作为硫烷靶基因 人类化学预防的一般策略。