Brien S E, Zagzag D, Brem S
Jewish General Hospital, Department of Neurology and Neurosurgery, School of Medicine, McGill University, Montreal, Quebec, Canada.
Neurosurgery. 1989 Nov;25(5):715-9. doi: 10.1097/00006123-198911000-00005.
The application of a monoclonal antibody to bromodeoxyuridine (BUdR) provides a rapid, reproducible, nontoxic, immunohistochemical method to measure cellular kinetics of intracerebral tumor angiogenesis. The rabbit brain tumor model of angiogenesis consists of tumor and endothelial cell populations with high proliferative rates that demonstrate the close interdependence between microvascular and neoplastic growths as well as topographic gradients, heterogeneity, and regional microdomains of cell proliferation. The labeling index (LI) of endothelial cells was 25.8% at the tumor periphery, compared to 1.7% in the tumor center (P less than 0.001). Concomitant with an increased turnover of neoplastic cells at the tumor periphery. LI was 26.6% with a LI of 7.7% in the center (P less than 0.01). Furthermore, labeled tumor cells tended to be organized around proliferating capillaries, with less DNA synthesis farther from the nearest blood vessel. The established normal microvessels of the brain, e.g., in the opposite tumor-free hemisphere, were mitotically inactive with a LI of less than 0.001%. Quantitation of vascular cytokinetics should be useful in further studies of the pathophysiology of brain tumor angiogenesis and the development of pharmacological approaches directed toward the microvasculature.
应用抗溴脱氧尿苷（BUdR）单克隆抗体提供了一种快速、可重复、无毒的免疫组织化学方法，用于测量脑肿瘤血管生成的细胞动力学。兔脑肿瘤血管生成模型由具有高增殖率的肿瘤细胞群和内皮细胞群组成，显示出微血管生长与肿瘤生长之间的密切相互依存关系，以及细胞增殖的地形梯度、异质性和区域微区。肿瘤周边内皮细胞的标记指数（LI）为25.8%，而肿瘤中心为1.7%（P<0.001）。与肿瘤周边肿瘤细胞更新增加相一致。周边LI为26.6%，中心为7.7%（P<0.01）。此外，标记的肿瘤细胞倾向于围绕增殖的毛细血管组织，离最近血管越远，DNA合成越少。例如，在对侧无肿瘤半球中，已建立的正常脑微血管有丝分裂不活跃，LI小于0.001%。血管细胞动力学的定量分析在脑肿瘤血管生成病理生理学的进一步研究以及针对微血管的药理学方法的开发中应具有重要作用。
