Chemopreventive Efficacy of Broccoli Sprouts against BC

西兰花芽对 BC 的化学预防功效

• 批准号: 7902236
• 负责人: THOMAS A KENSLER
• 金额: $ 38.44万
• 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/7902236
• 关键词: Abbreviations; Activities of Daily Living; Animals; Anticarcinogenic Agents; Antioxidants; Biological Assay; Biological Markers; Blood; Brassica; Breast; Broccoli - dietary; Cabbage - dietary; Carcinogens; Catechol Estrogens; Cauliflower; Chemicals; Chemoprevention; Chemopreventive Agent; Clinical Research; Clinical Trials Design; Consumption; Controlled Clinical Trials; Correlative Study; Coupled; DNA; Data; Dose-Limiting; Drug Kinetics; Edible Plants; Enzyme Induction; Enzymes; Epidemiologic Studies; Epidemiology; Epithelial Cells; Estrogen Metabolism; Estrogens; Food; Food Safety; Gene Proteins; Gene Targeting; Genes; Genomics; Glucosinolates; Glutathione S-Transferase; High Pressure Liquid Chromatography; 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; Microarray Analysis; Myrosinase; NAD(P)H dehydrogenase (quinone) 1, human; NF-E2-related factor 2; NQO1 gene; Operative Surgical Procedures; Pattern; Pharmacodynamics; Phase; Phytochemical; Placebo Control; Placebos; Plants; Population; Preparation; Proteins; Proteome; Proteomics; Quinone Reductases; Randomized; Randomized Clinical Trials; Raphanus; Reactive Oxygen Species; Relative Risks; Reproduction spores; Research Personnel; Risk; Risk Marker; Rodent; Safety; Serum; Sprague-Dawley Rats; Sulforaphane; Testing; Tissues; Toxic effect; Transcript; Transferase; Translating; Two-Dimensional Gel Electrophoresis; Urine; Vegetables; Water; Woman; cancer risk; cancer type; carcinogenesis; chemical carcinogenesis; cruciferous vegetable; detoxication; enzyme activity; fruits and vegetables; glucoraphanin; indexing; inhibitor/antagonist; intervention effect; mRNA Expression; malignant breast neoplasm; mammary epithelium; metabolomics; neoplastic; novel; novel marker; preclinical study; prophylactic; transcription factor; urinary

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

流行病学研究提供了令人信服的证据，证明水果数量和 食用蔬菜和罹患癌症的风险。十字花科蔬菜(如西兰花)消费 最近与降低乳腺癌风险有关。一种主要的防范机制 致癌涉及诱导第二相解毒酶促进致癌物的消除 并增强抗氧化能力。许多可食用植物，尤其是3天大的西兰花芽，都含有强效成分 第二阶段酶以异硫氰酸酯或其硫代葡萄糖苷前体的形式诱导活性。在动物身上， 萝卜硫素，来源于西兰花芽中的主要硫代葡萄糖苷(硫代萝卜素)，是一种非常有效的 2相酶活性诱导剂，防止化学致癌。这样做的目的是 这项研究是在乳腺癌高危人群中翻译和评估这些实验室发现。 癌症。以前的试验已经提供了关于安全性、新陈代谢和尿液的重要信息。 异硫氰酸盐的处置，以及硫代葡萄糖苷的活化。因此，我们的目标是1) 测定西兰花芽制剂以及纯萝卜硫素的药效作用 在啮齿动物的乳腺上皮中，开发出更好的生物标志物；2)评估 西兰花芽在30名乳房健康女性体内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研究，进行乳房缩小手术或预防性乳房切除术 测量血液、尿液和乳腺组织中异硫氰酸酯水平的试验以及第二阶段诱导剂 乳腺组织的活性、mRNA转录水平和雌激素代谢产物；3)检测3个月后 干预西兰花芽制剂调节一组乳腺癌风险生物标记物(Ki67 表达，雌激素代谢物分布，新的标记物)与安慰剂相比，126名妇女在增加 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 调节致癌物解毒酶和其他基因表达的有效性评估 萝卜硫素靶基因通过含有标准化水平植物化学物质作为 人类化学预防的一般策略