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

转移瘤的氧和营养是通过肿瘤微循环提供的。肿瘤微循环中的氧供应取决于肿瘤微循环的流量、微循环血容量中的氧含量以及微循环的地理分布。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生成是主要目标，因为流量和氧含量更难干预。首先，为了了解肿瘤的微循环特性，我们分析了灌注硅橡胶的铸型模型。该方法虽然能观察到微静脉网的密集增加，但不能很好地识别直径小于10 μ m的毛细血管网。我们使用FITC白蛋白活体显微镜在背侧皮褶窗室法下显示肿瘤微循环。我们使用了Donryu大鼠和LY80同源肿瘤的物种。照射前后分别检测肿瘤微血管密度、氧分压图及组织学微血管分布，肿瘤中心区氧分压较高，周边区氧分压较低。照射后肿瘤微血管密度下降，肿瘤直径增加不明显。这种现象可能会降低肿瘤组织中的氧分压，继而导致生长迟缓。

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.