Experimental chemotherapy and radiotherapy for metastatic mouse bladder cancer

晚期尿路上皮癌患者采用M-VAC（甲氨蝶呤、阿霉素、长春花碱、顺铂）联合化疗。关于M-VAC方案的结果，大约60%的总有效率是很高的，但反应持续时间短和低于20%的骨反应率仍有待研究。为了解决这些问题，我们进行了(1)体外MTT实验，研究抗癌药物的疗效是否有希望；(2)C3H/He小鼠体内实验，研究如何在联合化疗中管理方案。M-VAC方案中包含的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小鼠尾静脉后，可诱导肺内形成肿瘤。注射MBT-2后2天M-VAC组肿瘤生长抑制率较高，注射MBT-2后7天M-VAC组肿瘤生长抑制率较低。包括双剂量M-VAC在内的剂量递增并没有提高生长抑制率。这些结果可能提示，为了延长反应时间，应从肿瘤微转移期开始进行抗癌治疗。MBT-2注射C3H/He小鼠发生骨转移的方式为下腔静脉结块，联合化疗方案相同。在骨肿瘤中，即使使用两次M-VAC也没有反应。该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。

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.