Enhanced effect of combination chemotherapy based on induction of proliferative activity for advanceduro thelial cancers.

联合化疗治疗晚期膀胱癌已受到广泛关注。然而，化疗的效果仍然不尽人意。本研究旨在阐明理想的化疗药物计划及甲氨蝶呤联合化疗对膀胱癌细胞的作用机制。来源于膀胱癌的KU-7细胞被用作靶细胞。细胞在不同时间暴露于不同浓度的甲氨蝶呤（MTX）和长春花碱（VBL）。采用流式细胞术溴脱氧尿苷(BrdU) /脱氧核糖核酸（DNA）双变量分析评价肿瘤细胞的增殖活性。在裸鼠体内接种KU-7细胞，观察不同联合化疗方案的抗肿瘤作用。用浓度为5微克/毫升的MTX进行24小时的预孵育，随后暴露于VBL - 1 .与同时暴露于这些物质相比，浓度为0.05微克/毫升的MTX显示出50%的细胞毒性增加。MTX预孵育浓度在0.5 - 5 mcg/ml之间，通过brdu标记的细胞比例估计细胞的增殖活性显著增加。在体内研究中，VBL组在MTX治疗后，肿瘤体积减少了-20.5（]SY.+- 12.8%[）。另一方面，同时给药组肿瘤体积增加28.8(]SY.+-[)19.2%。差异有统计学意义（p<0.01）。这些数据表明，与MSX和VBL联合化疗同时治疗和/或相反的化疗方案相比，MTX预处理对膀胱癌细胞的抗肿瘤作用显著增强。在基础实验的基础上，局部浸润性膀胱癌的多模式治疗作为膀胱保留试验正在以不同的方案进行。合并和结合许多潜在的有效和补充疗法显示了改善治疗后生活质量和治愈率的可能性。我们现在计划使用经尿道切除术、全身改良M-VAC化疗和骨盆超分割照射作为局部晚期膀胱癌的保膀胱治疗。本研究共纳入27例经组织学证实的肌肉浸润性膀胱癌患者（临床分期为T3/T4）。所有患者均行经尿道切除术作为组织学诊断和肿块缩小的结果。对于局部浸润性膀胱癌的治疗，高分割放疗联合全身化疗可能是一种可接受的替代方案，而不是立即膀胱切除术。少

Considerable attention has been given to combination chemotherapy for the treatment of advanced bladder ancer. However the effectiveness of the chemotherapy still remains unsatisfactory. The present study was undertaken to clarify the ideal chemotherapertic drug scheduling and the mechanism of action of methotrexate in combination chemotherapy against bladder cancer cells. KU-7 cells derived from bladder cancer were utilized as the target. The cells were exposed to various concentrations of methotrexate (MTX) and vinblastine (VBL) in different time schedules. Flow cytometric bromodeoxyuridine (BrdU) /deoxyribonucleic acid (DNA) bivariate analysis was performed to evaluate the proliferative activity of tumor cells. Furthermore, KU-7 cells were inoculated in nude mice, and anti-tumor effects following different schedules of the combination chemotherapy were assesed as an in vivo study. Twenty-four-hour preincubation with MTX in a concentration of 5 mcg/ml and subsequent exposure of VBL i … More n a concentration of 0.05 mcg/ml demonstrated 50% increased cytotoxicity when compared with simultaneous exposure of these agents. MTX preincubation at the concentration ranging from 0.5 to 5 mcg/ml resulted in significantly increased proliferative activity of cells estimated by BrdU-labeld cell ratio. In the in vivo study, a -20.5(]SY.+-。[)12.8% tumor volume reduction was obtained in MTX petreatment with subsequent administraion to the VBL group. On the other hand, a 28.8(]SY.+-。[)19.2% increased tumor volume was observed for the simultaneous administration group. The difference was statistically significant (p<0.01). These data indicate that MTX pretreatment can significantly enhance the antitumor effects when compared with simultaneous treatment and/or the reversed schedule in combined chemotherapy with MSX and VBL against bladder cancer cells.Based on the fundamental experiments, multimodal treatment for locally invasive bladder cancer as a bladder reserving trials is being pursued in diverse protocols. Incorporating and combining with many potentially effective and complementary therapies demonstrate the possibility of improving the post-treatment quality of life and the curerate. We now planed the use of transurethral resection, systemic modified M-VAC chemotherapy and hyperfractionated pelvic irradiation as a bladder preserving treatment for locally advanced bladder cancer. A total of 27patients with histologically confirmed muscle-invasive bladder cancer (clinically stages T3/T4) were entered in this study. All patients underwent transurethral resection as a result of histological diagnosis along with mass reduction. Hyperfractionated radiotherapy in conjunction with systemic chemotherapymay be an acceptable alternative to immediate cystectomy for the management of locally invasive bladder cancer. Less