Phase 1 and phase 2 proliferative lesions of colonic epithelial cells in diseases leading to colonic cancer
Phase 1 and phase 2 proliferative lesions of colonic epithelial cells in diseases leading to colonic cancer
复制标题
导致结肠癌的疾病中结肠上皮细胞的第一期和第二期增殖性病变
作者：
M. Lipkin
人的结肠上皮细胞开始发展出恶性细胞的某些特征，而它们在常规形态学检查中仍然表现正常。细胞通过特定的阶段，在此期间，它们表达越来越异常的增殖特征。随着1期增殖性病变的发展，结肠上皮细胞在其成熟期间不抑制DNA合成，并且开始发展增强的增殖能力。细胞增殖的总体动力学保持正常，粘膜中没有细胞的净滞留或积聚。随着2期增殖性病变的形成，细胞开始发展出使其能够以越来越多的数量保留在粘膜中的特性。细胞增殖的总体动力学变得异常，并且开始观察到细胞的净保留和积累。这些变化伴随着分化特异性分子错误，导致代谢途径的异常持续性，导致DNA合成增强。这些增生性细胞病变出现在人类遗传性家族性息肉病、发展为孤立性结肠肿瘤的普通人群个体以及给予化学致癌物后的啮齿动物中，表明它们是导致恶性转化的最终共同分子途径上的主要步骤。它们的表达在家族性息肉病中加速。在家族性息肉病中，可以筛查增生性病变和日益严重的细胞增生程度，筛查程序的实用性正在研究中。导致持续DNA合成的分子病变、导致模型系统中出现上述变化的可疑致癌物的相互作用以及针对导致增强DNA合成的反应的更有效的化疗和免疫疗法的开发是目前重要的主题。
Colonic epithelial cells in man begin to develop some of the characteristics of malignant cells while they still appear normal on conventional morphological examination. The cells pass through specific phases during which they express increasingly abnormal proliferative characteristics. As a Phase 1 proliferative lesion develops, colonic epithelial cells do not repress DNA synthesis during their maturation, and begin to develop an enhanced ability to proliferate. The over‐all kinetics of cell proliferation remain normal, without a net retention or accumulation of cells in the mucosa. As a Phase 2 proliferative lesion forms, the cells begin to develop properties that enable them to be retained in the mucosa in increasing numbers. The over‐all kinetics of cell proliferation become abnormal, and net retention and accumulation of cells begin to be observed. These changes are accompanied by differentiation‐specific molecular errors, resulting in the abnormal persistence of metabolic pathways leading to enhanced DNA synthesis. These proliferative cellular lesions arise in hereditary familial polyposis in man, in individuals in the general population who develop isolated colonic neoplasms, and in rodents after a chemical carcinogen is given, suggesting that they are major steps on a final common molecular pathway leading to malignant transformation. Their expression is accelerated in familial polyposis. The proliferative lesions and increasingly severe degrees of cellular atypia can be screened in familial polyposis, the utility of the screening procedure is being studied. The molecular lesions leading to persistent DNA synthesis, the interaction of suspected carcinogens leading to the appearance of the above changes in model systems, and the development of more effective chemotherapy and immunotherapy against the reactions leading to enhanced DNA synthesis are topics of importance at the present time.