Control of angiogenesis by attenuation of oxygen tension in the metastatic tumor of the lung

转移瘤的氧气和营养是通过肿瘤微循环提供的。如果能控制这种肿瘤微循环的血管生成，就有可能实现新的治疗方法。氧的供应取决于肿瘤微循环的流量、微循环血容量的含氧量和微循环的地理分布。为了控制肿瘤组织中的组织氧分压，肿瘤微循环的分布或肿瘤血管的生成是主要指标，因为血流和氧气含量较难干预。首先，为了了解肿瘤的微循环特征，我们分析了注入硅橡胶的管型模型。该方法虽然可见小静脉网密度增大，但不能很好地显示直径小于10微米的毛细血管网。我们使用FITC白蛋白活体显微镜，在背部皮肤折叠窗腔法下显示肿瘤微循环。我们用东丽大鼠和LY80同基因肿瘤对物种进行了检测。观察照射前后微血管密度、氧图及组织学微血管分布情况，发现肿瘤中心区氧分压较高，周边区氧分压较低。照射后微血管密度降低，肿瘤直径增大不明显。这种现象可能会降低肿瘤组织中的氧分压，进而导致生长迟缓。

Oxygen and nutrition for the metastatic tumor was supplied through tumor microcirculation. If angiogenesis of this tumor microcirculation could be controlled, we may achieve new therapy.Oxygen supply is determined by flow of tumor microcirculation, oxygen content of microcirculatory blood volume, and geographical distribution of microcirculation. To control tissue oxygen tension in tumor tissue, distribution of tumor microcirculation or tumor angiogensis is the main target because flow and oxygen content is more difficult to intervene.First, to understand the microcirculatory characteristics of tumor, we analyzed cast model infused with silicon rubber. Although dense increase of venule network was found out, capillary network less than 10micrometer in diameter couldn't be well identified in this method. We used intravital microscopy using FITC albumin to visualize tumor microcirculation under Dorsal Skin fold Window Chamber method. We used Donryu rat and LY80 syngenic tumor to the species. We checked the microvessel density, oxygen mapping, and histological microvessel distribution before and after irradiation.Oxygen tension was higher in central area of the tumor and lower in peripheral zone. After irradiation, microvessel density decreased while increase of tumor diameter is not evident. This phenomenon may decrease the oxygen tension in tumor tissue followed by growth retardation.