Chemosensityivity and drug resistance in urogenital carcinoma

1.肾细胞癌(RCC)对顺铂、阿霉素(ADM)、长春新碱耐药，与睾丸肿瘤或尿路移行细胞癌的药敏试验(琥珀酸脱氢酶抑制试验)比较，能较好地反映其临床特征。结论：1.多药耐药(MDR)1基因编码的P-糖蛋白的表达被认为是RCCs固有MDR表型的主要原因。金属硫蛋白的表达被认为是膀胱癌顺铂耐药的重要因素之一。3.多药耐药相关蛋白过表达和/或DNA拓扑异构酶II表达降低可能导致非P-糖蛋白介导的非典型多药耐药。4.顺铂耐药的机制是多因素的，参与了细胞内顺铂浓度降低、细胞内谷胱甘肽脱毒增加或谷胱甘肽S转移酶pi基因表达增加等多种因素。丁硫氨酸亚磺胺通过降低顺铂耐药膀胱癌细胞内GSH，提高顺铂敏感性。5.采用前瞻性随机对照试验，比较ADM联合维拉帕米膀胱内灌注预防浅表性膀胱癌术后复发的疗效，并提出维拉帕米的临床意义。

1.Renal cell carcinoma(RCC)was resistant to cisplatin, adriamycin(ADM)and vinblastine as compared with testicular tumor or transitional cell carcinoma of the unrinary tract on chemosensitivity test (succinate dehydrogenase inhibition test), reflecting the clinical features well. The expression of P-glycoprotein, encoded by the multidrug resistance(MDR)1 gene was considered to be mainly responsible for the intrinsic MDR phenotype of RCCs.2. The expression of metallothionein was considered to be one of the important factors responsible for the cisplatin resistance of bladder carcinoma.3.Not only P-glycoprotein-mediated classical MDR but also non-P-glycoprotein-mediated atypical MDR,which may be induced by the overecpression of multidrug resistance-associated protein(MRP)and/or decreased expression of DNA topoisomerase II,may develop in bladder carcinoma treated with chemotherapy including ADM.4.The mechanism of cisplatin resistance in bladder carcinoma is multifactorial and many factors including decreased intracellular concentration of cisplatin, increased detoxification associated with increased intracellular level of glutathione(GSH)or increased ecpression of glutathione S-transferase pi mRNA were considered to be involved. Buthionine sulfoximine increased the cisplatin sesitivity of cisplatin-resistant bladder cancer by decreasing the inatracellular GSH.5.A prospective randomized trial was conducted to compare the prophylactic effect of intravesical instillation of ADM plus verapamil with that of ADM alone for postoperative recurrrence of superficial bladder cancer, and the significance of verapamil was suggested.