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

晚期膀胱癌的联合化疗已引起人们的高度重视。然而，化疗的效果仍然不令人满意。本研究旨在阐明甲氨蝶呤联合化疗对膀胱癌细胞的理想化疗方案及其作用机制。以膀胱癌来源的KU-7细胞为靶细胞。细胞暴露于不同浓度的甲氨蝶呤(MTX)和长春花碱(VBL)不同的时间安排。采用流式细胞仪BrdU/DNA双变量分析评价肿瘤细胞的增殖活性。此外，将KU-7细胞接种于裸鼠体内，观察不同联合化疗方案的体内抗肿瘤作用。与浓度为5微克/毫升的甲氨蝶呤预先孵育24小时，然后暴露于VBLI…当浓度超过0.05微克/毫升时，细胞毒性比同时暴露时增加50%。用BrdU-Labeld细胞率测定，0.5~5微克/毫升的MTX预孵育可显著增强细胞的增殖活性。在体内研究中，a-20.5(]sy.+-.[]MTX组肿瘤体积缩小12.8%，VBL组肿瘤体积缩小12.8%。另一方面，28.8(]sy.+-.[]同时给药组肿瘤体积增加了19.2%。差异有统计学意义(p&lt；0.01)。这些数据表明，与MSX和VBL联合化疗中的同步治疗和/或逆转方案相比，MTX预处理可以显著提高抗肿瘤效果。在基础实验的基础上，多模式治疗局部浸润性膀胱癌作为一种保留膀胱的试验正在以不同的方案进行。结合和结合许多潜在有效和互补的治疗方法，证明了改善治疗后生活质量和疗效的可能性。我们现在计划使用经尿道电切术、全身改良的M-VAC化疗和超分割盆腔放疗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期)。根据组织学诊断和肿块缩小，所有患者均接受了经尿道电切术。对于局部浸润性膀胱癌的治疗，超分割放射治疗联合全身化疗可能是一种可接受的替代立即膀胱切除术的方法。较少

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