Aotake T, Lu C D, Chiba Y, Muraoka R, Tanigawa N
Second Department of Surgery, Fukui Medical University, Yoshida-Gun, Japan.
Clin Cancer Res. 1999 Jan;5(1):135-42.
Activation of the angiogenic process occurs during tumorigenesis, as does disturbance of cell proliferation and apoptosis. Seeking a potential correlation, we investigated tumor cell apoptosis, proliferation, and angiogenesis in the adenoma-carcinoma sequence of colorectal carcinogenesis using an in situ apoptosis detection kit and MIB-1 and anti-CD34 antibodies in 27 adenomas with low dysplasia, 17 adenomas with high dysplasia, and 26 carcinomas in adenoma, as well as assessed p53 and bcl-2 expressions. The results showed that the potential for apoptosis was augmented, paralleling the increment of proliferation, in adenomas with low dysplasia but diminished when adenomas progressed from low dysplasia to high dysplasia and cancer. A gradual increment of microvessel density was observed during the progression with an increase during transition from low dysplasia to high dysplasia and cancer. Correlation coefficient test showed an inverse correlation between apoptotic index and microvessel density when all of the lesions were taken into account. No apparent impact of aberrant p53 on angiogenesis or bcl-2 on apoptosis was observed in this study. These results suggest that the angiogenesis initiates during transition from low dysplasia to high dysplasia and cancer, which may, in turn, contribute to the reduction of tumor cell apoptosis during colorectal carcinogenesis.
血管生成过程的激活发生在肿瘤发生过程中，细胞增殖和凋亡的紊乱也是如此。为了寻找潜在的相关性，我们使用原位凋亡检测试剂盒、MIB-1和抗CD34抗体，对27例低级别异型增生腺瘤、17例高级别异型增生腺瘤、26例腺瘤癌变以及评估p53和bcl-2表达情况，研究了结直肠癌发生过程中腺瘤-癌序列中的肿瘤细胞凋亡、增殖和血管生成情况。结果显示，低级别异型增生腺瘤中凋亡潜能增强，与增殖增加平行，但当腺瘤从低级别异型增生发展为高级别异型增生和癌变时，凋亡潜能减弱。在进展过程中观察到微血管密度逐渐增加，从低级别异型增生过渡到高级别异型增生和癌变时增加。当考虑所有病变时，相关系数检验显示凋亡指数与微血管密度呈负相关。本研究未观察到异常p53对血管生成或bcl-2对凋亡有明显影响。这些结果表明，血管生成在从低级别异型增生过渡到高级别异型增生和癌变的过程中开始，这反过来可能有助于结直肠癌发生过程中肿瘤细胞凋亡的减少。
