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作 者:尚伯杨[1] 吴淑英[1] 商悦[1] 李电东[1] 甄永苏[1]
机构地区:[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050
出 处:《中国新药杂志》2009年第21期2075-2080,共6页Chinese Journal of New Drugs
基 金:国家高科技研究发展计划(863计划)资助项目(2006AA02A255)
摘 要:目的:观察力达霉素与不同抗肿瘤药物在体内外联合应用的抗肿瘤作用。方法:采用克隆形成法观察力达霉素和抗肿瘤药物联合应用对肿瘤细胞的抑制作用。以小鼠移植性肿瘤肝癌22模型观察力达霉素与多种抗肿瘤药物分别联合应用在不同剂量下的治疗结果。结果:克隆形成实验表明力达霉素分别与5氟尿嘧啶、紫杉醇、阿霉素、诺维本/顺铂体外联合应用CDI值均小于0.7;体内实验表明力达霉素分别与5氟尿嘧啶、紫杉醇、诺维本/顺铂联合应用能有效抑制肿瘤生长,其最佳CDI值分别为0.92,0.89,0.96。结论:力达霉素与不同抗肿瘤药物联合应用表明,体外实验对肿瘤细胞杀伤有协同作用,体内试验有增效作用,显示有一定的临床应用前景。Objective:To investigate the synergistic anti-tumor effect of lidamycin (LDM) in combination with several clinical anti-tumor drugs including 5-fluorouracil (5Fu) , paclitaxel (TAX) , adriamycin (ADM) , navelbine (NVB) and cisplatin (CDDP) in vitro and in vivo. Methods: Cytotoxicity of drug combination toward various human tumor cell lines was determined by clonogenic assay in vitro. Tumor inhibitory effect in vivo was evaluated by using the model of subcutaneously transplanted hepatoma 22 in KM mice. The coefficient of drug interaction (CDI) was used to analyze the synergistic effect of drug combination. Results: LDM in combination with 5-Fu, NVB, TAX, ADM, or CDDP showed a significant synergistic anti-tumor effect in vitro as the CDI for each combination was less than 0.7. In the model of subcutaneously transplanted hepatoma 22 in vivo, LDM in combination with 5-Fu, TAX, and NVB/CDDP effectively inhibited the growth of H22 in mice ; the optimum CDI for each combination was 0.92, 0.89, and 0.96, respectively. Conclusion : Lidamycin shows a synergetic anti-tumor effect in combination respectively with several anti-tumor drugs in vitro and in vivo, which implies a clinical prospect of this combination treatment.
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