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

通过减弱肺转移性肿瘤中的氧张力来控制血管生成

• 批准号: 16591410
• 负责人: HORINOUCHI Hirohisa
• 金额: $ 2.37万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591410/
• 关键词: cancer; tumor microcirculation; angiogenesis; hypoxia; oxymetry; 放射線治療; 組織酸素分圧; 人工酸素運搬体; 腹水肝癌; 腫瘍内酸素分圧

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.

通过肿瘤微循环为转移性肿瘤提供氧气和营养。如果这种肿瘤微循环的血管生成能够得到控制，我们可能会获得新的治疗方法。供氧由肿瘤微循环流量、微循环血容量含氧量和微循环的地理分布决定。由于血流和氧含量较难干预，控制肿瘤组织内的组织氧张力，以肿瘤微循环分布或肿瘤血管生成为主要目标。首先，为了了解肿瘤的微循环特性，我们对注入硅橡胶的铸型模型进行了分析。虽然发现微静脉网络密集增加，但不能很好地识别直径小于10微米的毛细血管网络。应用FITC白蛋白活体显微镜观察背侧皮肤褶窗室法下肿瘤微循环。我们用东柳大鼠和LY80同基因肿瘤对该物种进行研究。我们检查了辐照前后微血管密度、氧定位和组织学微血管分布。氧张力在肿瘤中央区较高，外周区较低。照射后微血管密度降低，肿瘤直径增大不明显。这种现象可能使肿瘤组织的氧张力降低，从而导致生长迟缓。

项目成果

Systemic administration of hemoglobin vesicle elevates tumor tissue oxygen tension and modifies tumor response to irradiation.

• DOI: 10.1016/j.jss.2007.12.770
• 发表时间: 2009
• 期刊: The Journal of surgical research
• 作者: Manabu Yamamoto;Y. Izumi;H. Horinouchi;Y. Teramura;H. Sakai;M. Kohno;Masazumi Watanabe;M. Kawamura-M.-Kawa

Enhanced radiation response of a solid tumor with the artificial oxygen carrier 'albumin-heme'

人工氧载体“白蛋白-血红素”增强实体瘤的放射反应

• 发表时间: 2008
• 期刊: Cancer Sci.(Epub 2008 Apr 21.) 99(6)
• 作者: Horinouchi H ;Yamamoto H;Komatsu T;Huang Y;Tsuchida E;Kobayashi K.
• 通讯作者: Kobayashi K.