Chemopreventive Efficacy of Broccoli Sprouts against BC

提供了 流行病学研究提供了令人信服的证据，证明水果的数量与 蔬菜消费和患癌症的风险。十字花科蔬菜（例如，西兰花）消费 最近与降低乳腺癌风险有关。一个主要的保护机制， 致癌作用包括诱导2期解毒酶，促进致癌物的消除 增强抗氧化能力许多可食用的植物，最著名的是3天大的花椰菜芽，含有有效的 异硫氰酸酯或其芥子油苷前体形式的2相酶诱导剂活性。在动物中， 萝卜硫素，来自西兰花芽的主要芥子油苷（萝卜硫苷），是一种非常有效的 2相酶活性的诱导剂，并防止化学致癌作用。的目的 这项研究是在乳腺癌风险升高的人群中翻译和评估这些实验室发现 癌先前的试验提供了关于安全性、代谢和尿毒性的重要信息。 处置的异硫氰酸酯，并对芥子油苷的活化。因此，我们的目标是：1） 确定西兰花芽制剂的药效作用，以及纯莱菔硫烷， 纯萝卜硫苷，在啮齿类动物的乳腺上皮细胞，以开发更好的生物标志物; 2）评估 西兰花芽菜在30例健康妇女中的药代动力学和药效学作用 通过进行为期10天的随机安慰剂对照临床试验， 测量血液、尿液和乳腺组织中异硫氰酸酯水平以及II期诱导剂的试验 活性、mRNA转录水平和乳腺组织中的雌激素代谢物;以及3）测试3个月的 西兰花芽制剂的干预调节了一组乳腺癌风险生物标志物（Ki 67 表达，雌激素代谢产物谱，新的标志物）与安慰剂相比，在126名妇女中， 使用II期随机临床试验设计的乳腺癌风险。这些研究将提供一个严格的 评估调节致癌物解毒酶和其他 通过含有标准化水平的植物化学物质作为 人类化学预防的一般策略。

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.