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Experimental chemotherapy and radiotherapy for metastatic mouse bladder cancer

小鼠转移性膀胱癌的实验性化疗和放疗

基本信息

批准号：
03670754
负责人：
USUI Tsuguru
金额：
$ 1.34万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

Combination chemotherapies such as M-VAC (Methotrexate, Doxorubicin, Vinblastine, Cis-platin) were administered to the patients with advanced urothelial cancer. On the outcome of M-VAC regimen, overall response rate of approximately 60% was high, but short duration of response and low response rate in the bone of less than 20% were remained to be studied. To solve these problems we studied on (1) In in vitro experiment using MTT assay, whether effectiveness of anticancer agents is promising or not, (2) In in vivo experiment using C3H/He mice, how to manage the regimen in the combination chemotherapy. All of 4 drugs containing in the M-VAC regimen had a significant anti-tumor activity. On the in vivo experiment, we confirmed the tumor formation in the lung which were induced by injecting the MBT-2 tumor cells into the tail vain of C3H/He mice. Growth inhibition rate of the tumors was higher in the group treated with M-VAC at 2 days after the injection of MBT-2, but not in the group at 7 days after that. Does escalation including double does of M-VAC did not improved the growth inhibition rate. These results may indicate that to improve the duration of response anti-cancer regimen should be started at the period of micro-metastasis of the tumor. Bone metastasis in MBT-2 injected C3H/He mice was occured by clumping of inferior vena cava, and the same regimen in the combination chemotherapy was performed. There was no response in the bone tumor, even by double does of M-VAC.This result coincided with the clinical one and might indicate that does escalation of M-VAC regimen might induce a further toxicity.

采用甲氨蝶呤、阿霉素、长春新碱、顺铂等联合化疗方案治疗晚期尿路上皮癌。关于M-VAC方案的疗效，总体有效率约为60%，但持续时间短，骨内有效率低于20%仍有待研究。为了解决这些问题，我们在以下方面进行了研究：(1)采用四甲基偶氮唑盐比色法进行体外实验，研究抗癌药物的疗效是否有希望；(2)在体内实验中，以C3H/He小鼠为实验对象，研究联合化疗中的化疗方案。M-VAC方案中的4种药物均具有显著的抗肿瘤活性。在体内实验中，我们证实了将MBT-2肿瘤细胞注射到C3H/He小鼠的尾腔内，在肺内形成了肿瘤。M-VAC治疗组在注射MBT-2后2天肿瘤生长抑制率较高，而在注射MBT-2后7天治疗组肿瘤生长抑制率较低。剂量增加，包括两倍剂量的M-VAC，并没有提高生长抑制率。提示应从肿瘤微转移期开始抗癌治疗，以提高疗效。C3H/He小鼠注射MBT-2后，下腔静脉结节形成骨转移模型，联合化疗采用相同方案。在骨肿瘤中，即使双倍剂量的M-VAC也没有反应。这一结果与临床结果一致，可能表明M-VAC方案的升级可能会引起进一步的毒性。