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Chemopreventive Efficacy of Broccoli Sprouts against BC

西兰花芽对 BC 的化学预防功效

基本信息

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
项目类别：
财政年份：
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

项目摘要

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.

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