Experimental chemotherapy and radiotherapy for metastatic mouse bladder cancer

联合化疗，如M-VAC（甲氨蝶呤，阿霉素，长春碱，顺铂）给予晚期尿路上皮癌患者。在M-VAC方案的结局方面，总体有效率约为60%，但缓解持续时间短和骨缓解率低于20%仍有待研究。针对这些问题，我们进行了以下研究：（1）MTT法体外实验，探讨抗癌药物的有效性;（2）C_3H/He小鼠体内实验，探讨联合化疗方案的选择。M-VAC方案中所含的4种药物均具有显著的抗肿瘤活性。在体内实验中，我们证实了通过将MBT-2肿瘤细胞注射到C3 H/He小鼠尾静脉中诱导的肺中的肿瘤形成。注射MBT-2后第2天，M-VAC治疗组的肿瘤生长抑制率较高，但在注射MBT-2后第7天，M-VAC治疗组的肿瘤生长抑制率则不高。剂量递增（包括双倍剂量的M-VAC）并未改善生长抑制率。这些结果可能提示，为了提高缓解持续时间，应在肿瘤微转移期间开始抗癌方案。C3 H/He小鼠注射MBT-2后，通过下腔静脉成块形成骨转移，联合化疗采用相同的方案。M-VAC剂量加倍对骨肿瘤无明显疗效，这与临床结果一致，提示剂量递增可能引起进一步的毒性反应。

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.