Core B. Clinical & Biomarkers Core

核心 B. 临床

• 批准号: 10705704
• 负责人: DOROTHY K HATSUKAMI
• 金额: $ 64.27万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705704
• 关键词: 2-butenal; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; 7alpha hydroxylase; Acetylcysteine; Acrolein; African American population; Biological; Biological Markers; Blood; Cadmium; Clinical; Clinical Research; Clinical Trials; Collection; Conduct Clinical Trials; Cotinine; Data; Dose; Erythrocytes; Ethnic Origin; Ethnic Population; Exposure to; Genetic; Genotype; Goals; Hawaii; Hour; Human Resources; IL8 gene; Individual; Inflammation; Inflammatory; Inhalation; Inhalation Drug Administration; Interleukin-6; Japanese American; Laboratories; Linoleic Acids; Malignant neoplasm of lung; Measures; Metabolic; Metabolism; Minnesota; Native Hawaiian; Nicotine; Not Hispanic or Latino; Oral; Oral Administration; Oxidative Stress; Participant; Pathway interactions; Patient Recruitments; Peroxidases; Plasma; Procedures; Program Research Project Grants; Race; Research; Risk; Running; Sampling; Services; Site; Smoker; Stable Isotope Labeling; Time; Tobacco; Training; Urine; Variant; alpha Tocopherol; biomarker panel; blood-based biomarker; caucasian American; cigarette smoking; clinical biomarkers; clinical implementation; clinical trial participant; clinical trial recruitment; cohort; cost; cost effective; ethnic difference; former smoker; multi-ethnic; never smoker; non-smoking; phenanthrene; programs; propylene oxide; racial difference; racial population; recruit; sample collection; smoking cessation; urinary

ABSTRACT The Clinical and Biomarkers Core is critical for the studies in this program project renewal proposal. The Core will run clinical trials to collect biological samples and will carry out analyses of tobacco constituent biomarkers. The Clinical Trial component of this Core includes trained personnel with clinical research and implementation expertise that will be applied to conduct the clinical trials proposed in Projects 2 and 4. Both trials include the use of stable isotope-labeled constituents. Project 2 will use oral administration of [pyridyl-D4]-nicotine to develop a CYP2A6 genetic score that will allow to predict nicotine metabolism in smokers. This study will recruit 400 smokers (Native Hawaiians, Japanese Americans, Whites, and African Americans) in Hawaii and Minnesota. Project 4 will administer [D10]phenanthrene and [13C18]linoleic acid to 50 never smokers and 50 formers smokers, to investigate the potential contribution of metabolic and inflammatory pathways to the elevated risk for lung cancer in former smokers. The Biomarkers component of the Core will analyze a panel of biomarkers of exposure and effect. These will include total nicotine equivalents, cotinine, total 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanol, phenanthrene tetraol, and mercapturic acids of acrolein, crotonaldehyde, and propylene oxide, and urinary cadmium (Cd) in urine samples collected in clinical trials. Plasma nicotine metabolite ratio will be also measured. Results of these analyses will be used by Projects 2, 3, and 4. In addition, biomarkers of potential harm (urinary and blood-based biomarkers relevant to oxidative stress and inflammation) will be measured for Projects 3 and 4. The Core will also assess urinary Cd in 1000 samples from Project 1. The biological samples and biomarker results generated by this Core will be used by all projects.

摘要 临床和生物标志物核心对于本项目更新提案中的研究至关重要。核心 将进行临床试验以收集生物样本，并将对烟草成分生物标志物进行分析。 本核心的临床试验部分包括经过临床研究和实施培训的人员 将应用于开展项目2和4中提出的临床试验的专业知识。这两项试验都包括 使用稳定的同位素标记成分。项目2将使用口服[吡啶基-D4]-尼古丁来开发 CYP 2A 6遗传评分，可预测吸烟者的尼古丁代谢。这项研究将招募400名 在夏威夷和明尼苏达州的吸烟者（夏威夷土著人，日裔美国人，白人和非洲裔美国人）。 项目4将对50名从不吸烟者和50名既往吸烟者给予[D10]菲和[13 C18]亚油酸， 研究代谢和炎症途径对肺部疾病风险升高的潜在贡献， 吸烟者的癌症核心的生物标志物部分将分析一组暴露的生物标志物 及效果这些将包括总尼古丁当量、可替宁、总4-（甲基亚硝胺）-1-（3-吡啶基）-1-（甲基亚硝胺） 丁醇、菲四醇和丙烯醛、巴豆醛和环氧丙烷的巯基尿酸，和 在临床试验中收集的尿样中的尿镉（Cd）。血浆尼古丁代谢物比率也将 测定了这些分析的结果将用于项目2、3和4。此外，潜在的生物标志物 将测量伤害（与氧化应激和炎症相关的尿液和血液生物标志物）， 项目3和4。核心还将评估项目1的1000份样本中的尿镉。生物样品 由该核心生成的生物标志物结果将被所有项目使用。