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The Study for Non-cross Resistant Alternating Chemotherapy for Bladder Cancer

膀胱癌非交叉耐药交替化疗的研究

基本信息

批准号：
01570894
负责人：
TSUSHIMA Tomoyasu
金额：
$ 1.41万
依托单位：
Okayama University Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570894/
关键词：
Bladder Cancer Chemotherapy CDDP Resistance Cross Resistance・T24 ヒト膀胱癌培養細胞株 CDDP耐性

项目摘要

A cis-diamminedichloroplatinum(CDDP)-resistant cell line, CL-7/CDDP, has been established by chronic exposure of a parent human bladder cancer cell line, T24(CL-7), to CDDP at progressively increaced concentration for twenty months. CL-7 /CDDP was 2.7-fold more resistant to CDDP than CL-7 as determined by colony formation assay. Biological and biochemical characteristics were examined in CL-7/CDDP to compare with CL-7. There were no differences in doubling time and plating efficiency between the two cell lines, but a small one in the mode of chromosome numbers. Intra-cellular CDDP concentration after CDDP exposure showed no difference between the two cell lines, but CL-7/CDDP showed a higher glutathione(GSH)and metallothionein(MT)level. It is suggested that the mechanism of acquired resistance to CDDP is attributed to intra-cellular detoxication, but not to the efflux.The sensitivity of CL-7/CDDP for other anticancer drugs were examined by colony formation assay to compare with the par … More ent cell line, CL-7. Consequently, these drugs could be classified into 3 groups according to the degree of resistance ; drugs with an equal degree of resistance to that of CDDP(CDDP derivatives, MMC, VP-16), drugs for which the cells showed no resistance(ADM, CTX, IFO, VLB), and drugs whose cytocidal effects were enhanced(5-FU, MTX). The degree of resistance in the CDDP derivatives was the highest in DWA-2114R, decreesing in the following order in CBDCA, NK-121, and 254-S.An in vivo study was also performed. To determine the anti-tumor effects of anti-cancer drugs in nude mice, CL-7 and CL-7/CDDP cells of 10^7/body each were inoculated subcutaneouly, and the anti-cancer drug was administered intraperitoneally, when estimated tumor weight reached 100mg. Each dose of 2mg/kg, 4mg/kg, or 8mg/kg of CDDP was administered 3 times every 5 days. The inhibition of tumor growth was observed in the CDDP 8mg/kg group with the CL-7 and CL-7/ CDDP tumor, but the resistance to CDDP in the CL-7/CDDP tumor was not clear. Concerning the CL-7/CDDP tumor, the tumor growth was very slow and the dispertion of tumor weight among individual animals was large, which had to be improved.These results indicated the possibility of non-crosss resistant alternating chemotherapy using these three groups of drugs. Less

以人膀胱癌细胞系T24（CL-7）为亲本细胞，用递增浓度的顺铂（CDDP）慢性染毒20个月，建立了一个耐顺铂的细胞系CL-7/CDDP。集落形成试验表明，CL-7 /CDDP对CDDP的耐药性是CL-7的2.7倍。对CL-7/CDDP的生物学和生化特性进行了检测，并与CL-7进行了比较。两株细胞的倍增时间和平板接种效率无明显差异，但染色体数目模式差异较小。细胞内CDDP浓度在两种细胞系之间没有差异，但CL-7/CDDP显示出更高的谷胱甘肽（GSH）和金属硫蛋白（MT）水平。结果表明，CL-7/CDDP细胞对顺铂的获得性耐药机制可能与细胞内解毒作用有关，而与细胞外排无关。 ...更多信息 ent细胞株CL-7。因此，根据耐药程度，这些药物可分为3组：与CDDP耐药程度相同的药物（CDDP衍生物、MMC、VP-16）、细胞未显示耐药的药物（ADM、CTX、IFO、VLB）和杀细胞作用增强的药物（5-FU、MTX）。CDDP衍生物中的抗性程度在DWA-2114 R中最高，在CBDCA、NK-121和254-S中依次降低。还进行了体内研究。为了确定抗癌药物在裸鼠中的抗肿瘤作用，将CL-7和CL-7/CDDP细胞各以10^7/个体皮下接种，并且当估计的肿瘤重量达到100 mg时，腹腔内施用抗癌药物。CDDP 2 mg/kg、4 mg/kg或8 mg/kg各剂量每5天给药3次。CDDP 8 mg/kg组对CL-7和CL-7/ CDDP肿瘤的生长有抑制作用，但CL-7/CDDP肿瘤对CDDP的耐药性不明显。CL-7/CDDP肿瘤生长缓慢，个体间瘤重离散度大，有待改善，提示三组药物交替化疗无交叉耐药的可能性。少