Scalmati A, Lipkin M
Irving Weinstein Laboratory for Gastrointestinal Cancer Prevention, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
J Cell Biochem Suppl. 1992;16G:65-71. doi: 10.1002/jcb.240501113.
Intermediate biomarkers of abnormal cell growth and development have recently been used in chemoprevention trials in attempts to identify the efficacy of chemopreventive agents in human subjects. Measurements carried out include those related to cell proliferation, differentiation, and gene structure and expression in the colon. Among modified patterns of cell proliferation identified by microautoradiographic or immunoperoxidase assays, a characteristic expansion in the size of the proliferative compartment has been observed in normal-appearing colorectal mucosa of human subjects with disease increasing cancer risk; the same patterns have been induced by chemical carcinogens in rodents. Moreover, this intermediate biomarker has been modulated by chemopreventive agents in both rodents and humans. Newer intermediate biomarkers being studied for application to human chemopreventive programs include normal and abnormal patterns of expression of mucins, intermediate filaments and cytoskeletal proteins, and the structure and expression of a variety of genes associated with normal and abnormal cell development. The application of these various intermediate biomarkers to chemoprevention studies is increasing the ability of investigators to analyze the effects of novel chemopreventive agents in the colon and in other organs.
异常细胞生长和发育的中间生物标志物最近已用于化学预防试验，旨在确定化学预防剂在人体中的疗效。所进行的测量包括与结肠中细胞增殖、分化以及基因结构和表达相关的测量。在通过微放射自显影或免疫过氧化物酶测定法确定的细胞增殖改变模式中，在癌症风险增加的疾病患者外观正常的结直肠黏膜中观察到增殖区室大小的特征性扩大；在啮齿动物中，化学致癌物也诱导出了相同的模式。此外，这种中间生物标志物在啮齿动物和人类中均受到化学预防剂的调节。正在研究用于人类化学预防计划的更新的中间生物标志物包括粘蛋白、中间丝和细胞骨架蛋白的正常和异常表达模式，以及与正常和异常细胞发育相关的多种基因的结构和表达。这些各种中间生物标志物在化学预防研究中的应用正在提高研究人员分析新型化学预防剂对结肠和其他器官影响的能力。
