Alberts D S, Einspahr J, Aickin M, Hixson L, Earnest D, Roe D, Powell M
Department of Medicine, College of Medicine, University of Arizona, Tucson 85724.
J Cell Biochem Suppl. 1994;19:76-83.
During the 1990s, research interest in the use of chemopreventive agents to reverse human colon carcinogenesis increased exponentially. In parallel, there has been an increase in the need for putative surrogate endpoint biomarkers (SEBs) of cancer risk. Since the hallmark studies of Lipkin et al. and Terpstra et al., among others, the rate and patterns of rectal mucosal proliferation have been established as intermediate biomarker endpoints for colon cancer risk, modulated by potential chemopreventive agents including calcium, wheat bran fiber, and nutritional stress diets. Researchers rely heavily on these rectal mucosal proliferation indices as surrogate endpoints to evaluate the relative efficacy of various chemopreventive intervention strategies. Standardization through quality control/quality assurance (QC/QA) programs which continuously validate the accuracy, reproducibility, and variability of these indices is increasingly needed. Along with many others, we have attempted to validate 3H-thymidine and bromodeoxyuridine labeling indices in rectal mucosal biopsies as reliable SEBs. In this manuscript we outline a series of QC/QA steps that can be followed in the validation process for new as well as "old" biomarkers prior to their use as primary efficacy surrogate endpoints for chemopreventive agent intervention trials.
在20世纪90年代，对使用化学预防剂逆转人类结肠癌发生的研究兴趣呈指数级增长。与此同时，对癌症风险的假定替代终点生物标志物（SEB）的需求也在增加。自Lipkin等人和Terpstra等人的标志性研究以来，直肠黏膜增殖的速率和模式已被确立为结肠癌风险的中间生物标志物终点，受包括钙、麦麸纤维和营养应激饮食在内的潜在化学预防剂调节。研究人员严重依赖这些直肠黏膜增殖指数作为替代终点，以评估各种化学预防干预策略的相对疗效。越来越需要通过质量控制/质量保证（QC/QA）计划进行标准化，该计划不断验证这些指数的准确性、可重复性和变异性。与许多其他人一样，我们试图在直肠黏膜活检中验证3H-胸腺嘧啶核苷和溴脱氧尿苷标记指数作为可靠的SEB。在本手稿中，我们概述了一系列QC/QA步骤，在新的和“旧的”生物标志物用作化学预防剂干预试验的主要疗效替代终点之前，可在其验证过程中遵循这些步骤。
