Manzone H, Billings P C, Cummings W N, Feldman R, Clark L C, Odell C S, Horan A M, Atiba J O, Meyskens F L, Kennedy A R
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104-6142, USA.
Cancer Epidemiol Biomarkers Prev. 1995 Jul-Aug;4(5):521-7.
It is essential to identify intermediate marker endpoints of carcinogenesis for the evaluation of the effectiveness of cancer-chemopreventive agents. We have observed that levels of proteolytic activities (as detected by 4 different substrates) are increased 2-3-fold (P < 0.003) in oral buccal mucosa cells of smokers and patients with oral leukoplakia or erythroplakia as compared to a nonsmoking comparison group. In addition, proteolytic activity levels in the buccal cells were increased nearly 3-fold in patients with oral trauma (P < 0.01) or diabetes (P < 0.02), as well as pregnant women (P < 0.04). Excluding these subgroups of patients in epidemiological studies increase the differences in levels of proteolytic activities between both the nonsmoking comparison group and smokers and between the comparison group and patients with oral leukoplakia or erythroplakia. Evaluation of prerandomization levels of proteolytic activities of patients in cancer chemoprevention trials will increase the statistical power by allowing stratified randomization based on levels of proteolytic activities. The observed increases in levels of proteolytic activities in tissues at higher than normal risk of cancer development suggest that levels of proteolytic activities should be used as immediate marker endpoints in human cancer prevention trials using protease inhibitors as potential anticarcinogenic agents.
识别致癌作用的中间标记终点对于评估癌症化学预防剂的有效性至关重要。我们观察到，与非吸烟对照组相比，吸烟者以及患有口腔白斑或红斑的患者的口腔颊黏膜细胞中的蛋白水解活性水平（通过4种不同底物检测）增加了2至3倍（P < 0.003）。此外，口腔创伤患者（P < 0.01）、糖尿病患者（P < 0.02）以及孕妇（P < 0.04）的颊细胞中的蛋白水解活性水平增加了近3倍。在流行病学研究中排除这些患者亚组会增加非吸烟对照组与吸烟者之间以及对照组与口腔白斑或红斑患者之间蛋白水解活性水平的差异。在癌症化学预防试验中评估患者随机分组前的蛋白水解活性水平，通过基于蛋白水解活性水平进行分层随机分组，将提高统计效能。在癌症发生风险高于正常水平的组织中观察到的蛋白水解活性水平升高表明，在使用蛋白酶抑制剂作为潜在抗癌剂的人类癌症预防试验中，蛋白水解活性水平应用作直接标记终点。
