Suppression of cancer recurrence by intercepting tumor blood flow after X-ir radiation

本研究的目的是观察单次X射线照射对吉田肉瘤LY80的肿瘤微环境(肿瘤血流量、血管通透性、清晰度和间质液体压)的动态影响，探讨阻断肿瘤血流量(TBF)的治疗意义。麻醉大鼠肿瘤局部给予10Gy射线照射。静脉注射一种截留TBF并破坏肿瘤血管的comretataatin衍生物AC7700。(10 mg/kg/ml)。照射后24 h，肿瘤血流量开始增加，72~96 h增加2~2.5倍，所有用于评价肿瘤微环境的参数均显示肿瘤微循环得到改善。显然，这种肿瘤微循环的改善有助于癌症复发。在照射后的所有观察时间内，AC7700完全且不可逆地停止了TBF。AC7700照射后给药明显增强抗肿瘤作用。这种组合可能具有重要的治疗益处，即使在对任何一种治疗都不敏感的肿瘤中也是如此。我们认为，照射后肿瘤微循环功能的破坏是抑制肿瘤生长的重要因素。它特别用于预防癌症复发。

The purpose of this study was to investigate dynamic changes in the tumor microenvironment (tumor blood flow, vascular permeability, clearance, and interstitial fluid pressure) induced after a single dose of X-ray irradiation in a variant of Yoshida sarcoma, LY80, and to clarify the therapeutic significance of intercepting tumor blood flow (TBF) after irradiation. Radiation (10 Gy) was administered locally to tumors of anesthetized rats. A combretastatin derivative which intercepts TBF and disrupts tumor vessels, AC7700, was administered i.v. (10 mg/kg/ml). At 24 h after irradiation, TBF began to increase and showed an increase of 2-2.5 times at 72-96 h. All parameters used to assess the tumor microenvironment consistently showed improvement of tumor microcirculation. Apparently, improvement of this tumor microcirculation contributes to cancer recurrence. At all investigated times after irradiation, AC7700 stopped TBF completely and irreversibly. AC7700 administration after irradiation markedly enhanced of antitumor efficacy. Such a combination might have important therapeutic benefit, even in tumors which are insensitive to either treatment alone. We conclude that destruction of tumor microcirculatory function after irradiation is important for suppressing tumor growth. It is particularly for preventing cancer recurrence.