体外药物敏感实验为依据的恶性脑胶质瘤个体化化疗初步研究

目的:建立胶质瘤细胞体外原代培养模型,利用MTT法进行体外药物敏感实验,为临床化疗方案的设计提供理论指导,实施个体化化疗。方法:32例术后病理证实为胶质瘤(WHOⅢ级)的新鲜标本,制备肿瘤单细胞悬液进行体外原代培养,与7种抗肿瘤药物在临床血浆峰值浓度(PPC)条件下作用72小时,MTT法标记存活的肿瘤细胞,用酶标仪检测光密度值(OD),计算出抑制率(IR),检测不同肿瘤个体对化疗药物的敏感和耐药情况,从而指导临床个体化化疗方案的制定。另选取同期符合上述入选标准的20例间变型星形细胞瘤患者作为对照组,按照VM-26加DDP方案经验化疗,化疗4个疗程结束后,复查影像学,按照WHO肿瘤疗效评价标准评价治疗效果,分为稳定(SD),进展(PD),缓解(PR)。结果:32例临床标本的原代培养及药敏试验,其PPC下的抑制率(IR%)>50%者,DDP有20例;VCR有9例;VM-26有12例;VP-16有17例;Procarbazine有7例;BCNU有6例;Taxol有3例;其敏感性依次为:DDP>VP-16>VM-26>VCR>Procarbazine>BCNU>Taxol。根据体外药物敏感实验结果制定个体化化疗方案治疗29例,肿瘤缓解率为47.2%,对照组为29.4%,2组x2检验统计P<0.05。结论:7种常用的抗肿瘤药物均有耐药的情况,进行化疗药物的敏感测定可以避免耐药药物的使用。根据体外药物敏感实验结果制定个体化化疗方案化疗与对照组相比近期疗效较满意。

Preliminary Study on Individualized Chemotherapy Based on DrugSensitivity and Resistance Assay in Patients with Malignant Glioma

Objective: To establish neurogliocytoma cells ex-vitro primary culture model and carry out chemosensitivity experi-ment by the MTT assay.To provide theory guidance for designing and optimizing clinical chemotherapy regimen,to practice individual-ization chemotherapy.Methods: Using 32 fresh specimen which were proved to be neurogliocytoma(WHO grade 3) to produce mono-plast suspension and carry out vitro primary culture,add 7 antineoplastic drugs with peak plasma concentration to primary culture glioma cells,after 72 hours measure the survival tumor cell with the MTT colorimetric assay,get the optical density and the inhibition ratio,then judge the sensitiveness and drug fast of every drugs to every tumors,to guide the clinical individual Chemotherapy.Another 20 patients with anaplastic glioma received VM-26 and DDP regimen chemotherapy.Radiology evaluation of 2 groups is done in the light of WHO malignant tumor treatment effect assessment following 4 periodic of chemotherapy.Results: 32 clinical gliomas specimen were subject to primary culture and susceptibility test.The rank of sensitivity from high to low is: DDP> VP-16> VM-26>VCR >procarbazine>BCNU> paclitaxe.Based on the ex-vivo chemotherapy sensitivity and resistance assay,individualized chemotherapy is implemented in 29 pa-tients.Glioma remission ratio in individualized chemotherapy is 47.2%,in comparision with contral group the difference is significant.Conclusion: MTT colorimetric assay is convenient,objective and simple method with good repeatability.Every one of 7 drugs commonly used has the situation of drug resistance.Chemosensitivity assay can avoid using the resistant drugs and provide guidance to improve the clinical chemotherapy effect.Individualized chemotherapy on the basis of vitro sensitivity and resistance assay for patients with malig-nant glioma could improved treatment efficacy.