Combretastatin A-4 disodium phosphate: A vascular targeting agent that improves the anti-tumor effects of hyperthermia, radiation, and mild thermoradiotherapy
Combretastatin A-4 disodium phosphate: A vascular targeting agent that improves the anti-tumor effects of hyperthermia, radiation, and mild thermoradiotherapy
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DOI：
10.1016/s0360-3016(01)01742-4
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发表时间：
2001-11-15
影响因子：
7
通讯作者：
Horsman, MR
中科院分区：
文献类型：
--
作者：
Murata, R;Overgaard, J;Horsman, MR
目的：探讨血管靶向药物康泰素A-4磷酸二钠(CA4DP)联合热疗、放疗或亚低温热疗对C3H型小鼠乳腺癌移植瘤的治疗作用。方法：C3H型乳腺癌生长于雌性CDF1小鼠足后部，直径200 mm(3)。将CA4DP溶解于生理盐水中，腹腔注射。对受限制的非麻醉小鼠肿瘤进行局部热疗和/或放射治疗。肿瘤反应通过肿瘤生长或肿瘤对照试验进行评估。结果：CA4DP明显增强了肿瘤模型的热损伤作用。这种效应与25-400 mg/kg的药物剂量无关，但强烈依赖于注射药物和加热之间的时间间隔，当CA4DP比加热早1h或更小时时，改善最大。也有人提出温度依赖性，在42.5摄氏度时，热损伤增加1.9倍，在41.5和40.5摄氏度时增加2.6倍。CA4DP与热疗联合应用也能增强热致正常组织损伤，但增强程度不如肿瘤。CA4DP(25 mg/kg)可显著提高放射诱导的肿瘤局部控制率，CA4DP与温热(41.5℃，60min)联合应用可进一步增强CA4DP的抗肿瘤作用。结论：CA4DP可提高热疗的抗肿瘤效果，尤其是在温热条件下。更重要的是，它还增加了肿瘤对亚高温和放射的反应，这表明CA4DP最终可能在临床热放射治疗中有重要的应用。(C)2001年爱思唯尔科学公司。
Purpose: To investigate the effect of combining the vascular targeting drug combretastatin A-4 disodium phosphate (CA4DP) with hyperthermia, radiation, or mild thermoradiotherapy in a transplanted C3H mouse mammary carcinoma.Methods and Materials: The C3H mammary carcinoma was grown on the rear foot of female CDF1 mice and treated when at 200 mm(3) in size. CA4DP was dissolved in saline and injected i.p. Hyperthermia and/or radiation were locally given to tumors in restrained nonanesthetized mice. Tumor response was assessed using either a tumor growth or a tumor control assay. Mouse foot skin was used to assess normal tissue damage.Results: CA4DP significantly enhanced thermal damage in this tumor model. This effect was independent of drug doses between 25-400 mg/kg, but was strongly dependent on the time interval between drug injection and heating, with the greatest improvement seen when CA4DP preceded the heating by I h or less. There was also a suggestion of a temperature dependency with a 1.9-fold increase in heat damage at 42.5 degreesC and a 2.6-fold increase at 41.5 and 40.5 degreesC. Heat-induced normal tissue damage was also enhanced by combining CA4DP with heat, but the degree of enhancement was less than that seen in tumors. CA4DP (25 mg/kg) significantly increased radiation-induced local tumor control and this was further enhanced by combining CA4DP with mild temperature (41.5 degreesC, 60 min) heating.Conclusions: CA4DP improved the anti-tumor effect of hyperthermia, especially at mild temperatures. More importantly, it also increased the tumor response to mild hyperthermia and radiation, which suggests that CA4DP may ultimately have an important application in clinical thermoradiotherapy. (C) 2001 Elsevier Science Inc.