Core B. Clinical & Biomarkers Core

核心 B. 临床

• 批准号: 10411518
• 负责人: DOROTHY K HATSUKAMI
• 金额: $ 57.33万
• 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/10411518
• 关键词: 2-butenal; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; Acetylcysteine; Acrolein; African American population; Biological; Biological Markers; Blood; Cadmium; Clinical Research; Clinical Trials; Collection; Conduct Clinical Trials; Cotinine; Data; Dose; Erythrocytes; Ethnic Origin; Ethnic group; Exposure to; Genetic; Genotype; Goals; Hawaii; Hour; Human Resources; IL8 gene; Individual; Inflammation; Inflammatory; Inhalation; 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; cohort; cost; cost effective; former smoker; multi-ethnic; never smoker; non-smoking; phenanthrene; programs; propylene oxide; racial and ethnic; racial difference; 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.

抽象的 临床和生物标志物核心对于该计划项目更新建议的研究至关重要。核心 将进行临床试验以收集生物样品，并将进行烟草组成生物标志物的分析。 该核心的临床试验组成部分包括训练有素的临床研究和实施人员 将应用于项目2和4中提出的临床试验的专业知识。这两个试验包括 使用稳定的同位素标记成分。项目2将使用[吡啶基-D4] - 尼古丁的口服给药 CYP2A6遗传评分将允许预测吸烟者中的尼古丁代谢。这项研究将招募400 夏威夷和明尼苏达州的吸烟者（夏威夷原住民，日裔美国人，白人和非裔美国人）。 项目4将对50名从未吸烟者和50名吸烟者施用[D10]菲和[13C18]亚油酸， 研究代谢和炎症途径对肺风险升高的潜在贡献 前吸烟者的癌症。核心的生物标志物成分将分析一组暴露的生物标志物 和效果。这些将包括总尼古丁当量，可替宁，总4-（甲硝基氨基氨基）-1-（3-吡啶基）-1- 丁香醇，二烷二醇，蛋白酶，克罗托醛醛和氧化丙烷的苯坦二醇和苏联酸，以及 临床试验中收集的尿液样品中的尿镉（CD）。血浆尼古丁代谢物比率也将 测量。这些分析的结果将由项目2、3和4使用。此外，潜在的生物标志物 将测量与氧化应激和炎症有关的伤害（尿和基于血液的生物标志物） 项目3和4。核心还将评估项目1的1000个样品中的尿CD。生物样品 所有项目都将使用该核心产生的生物标志物结果。