Prevention of colon cancer and modulation of aberrant crypt foci, cell proliferation, and apoptosis by retinoids and NSAIDs.
Prevention of colon cancer and modulation of aberrant crypt foci, cell proliferation, and apoptosis by retinoids and NSAIDs.
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通过类维生素A和非甾体抗炎药预防结肠癌并调节异常隐窝病灶、细胞增殖和细胞凋亡。
DOI：
10.1007/978-1-4615-4149-3_6
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发表时间：
1999
影响因子：
--
通讯作者：
Pereira,MA
中科院分区：
文献类型：
--
作者：
Pereira,MA
癌症是一个多阶段的过程，涉及多个罕见事件，每个事件都表明突变或染色体改变。在癌症进展的沿着不同步骤中，细胞积累选择性生长优势，其可通过细胞增殖的增加和/或细胞凋亡和终末分化的减少来表现。因此，促进癌症进展可能涉及药剂、生长因子、原癌基因等，其增强细胞增殖同时减少细胞凋亡。另一方面，化学预防剂将是降低细胞增殖同时增强细胞凋亡导致癌前病变的选择性生长优势降低的试剂。Bird描述和回顾的异常隐窝病灶（ACF）是一种公认的早期结肠癌前病变。1细胞增殖增加似乎导致上皮细胞在隐窝腔积聚，因此异常隐窝外观变大。在实验室动物中，ACF由化学致癌物诱导，并且可能含有癌前细胞，这些癌前细胞具有与结肠肿瘤共同的许多特征，包括在一些言语障碍和激活的K-ras癌基因中。2- 4K-ras和APC突变也已在人类结肠中的ACF中被证实。5 -7ACF被提出进一步发展为腺瘤并最终癌症。在此进展过程中，细胞增殖水平增加，细胞凋亡增加较少，导致病变的总体生长。
Cancer is a multistage process involving multiple rare events with each suggesting a mutational or chromosomal alteration. At the different steps along the progression to cancer, the cells accumulate selective growth advantage that could be manifested by an increase in cell proliferation and/or a decrease in apoptosis and terminal differentiation. Promotion of the progression to cancer could therefore involve agents, growth factors, proto-oncogenes, etc., which enhance cell proliferation while decreasing apoptosis. Chemopreventive agents, on the other hand, would be agents that decrease cell proliferation while enhancing apoptosis resulting in a decrease in the selective growth advantage of precancerous lesions. A putative early precancerous lesion in the colon is the aberrant crypt focus (ACF) described and reviewed by Bird.1Increased cell proliferation appears to result in the accumulation of epithelial cells at the lumina of the crypts and hence the larger appearance of the aberrant crypts. In laboratory animals ACF are induced by chemical carcinogens and presumably contain precancerous cells that have many characteristics in common with colon tumors including in some dysphasia and an activated K-rasoncogene.2–4K-rasand APC mutations have also been demonstrated in ACF in human colon.5–7ACF are proposed to progress further to adenomas and finally cancer. During this progression, there is an increase in the level of cell proliferation with less of an increase in apoptosis, resulting in the overall growth of the lesions.