Tailor-made chemotherapy against malignant gliomas based on chemosensitivity test and analysis of drug resistance gene

不同的恶性胶质瘤对不同的抗癌药物有不同的作用。其机制可能与耐药基因的表达有关。体外抗肿瘤药物的作用通过化疗敏感性试验进行检测。恶性胶质瘤的个体化化疗以胶原凝胶基质法药敏试验为基础。采用RT-PCR方法检测耐药基因mRNA的表达。对53例恶性胶质瘤（间变性星形细胞瘤、胶质母细胞瘤）手术切除的肿瘤组织进行体外培养，用胶原凝胶基质法对6 ~ 9种抗癌药物进行药敏试验。根据药物敏感性，选择两种抗癌药物，经动脉途径注射。提取总RNA，采用RT-PCR方法检测MDR、Topo II等耐药基因。药敏试验结果与耐药基因表达进行比较。化疗敏感性试验中，CBDCA、CDDP、ACNU和VCR的平均肿瘤生长抑制率分别为42.7%、37.9%、30.8%和3.2%。这一结果表明铂类药物的敏感性较高。耐药基因表达与化疗敏感性无显著相关性（p=0.1）。此外，接受基于化疗敏感性试验的定制化疗的患者的平均生存期与接受常规化疗的患者的平均生存期无显著差异（p=0.07）。尽管检查的病例数不多，但应进一步研究针对性化疗。

Each malignant glioma shows different effect of anti-cancer drug. This mechanism could be related to expression of drug resistance gene. Effect of anti-cancer drug in vitro is examined with chemosensitivity test. Tailor made chemotherapy for malignant glioma was based on chemosensitivity test with collagen gel matrix method. In addition, mRNA expression of drug resistance gene was analyzed with RT-PCR method. Fifty-three cases of malignant gliomas (anaplastic astrocytoma, glioblastoma) were examined Tumor tissues obtained at surgery were cultured for 8 days for chemosensitivity test with collagen gel matrix method for 6 to 9 anti-cancer drugs. According to chemosensitivity, tow anti-cencer drugs were selected and injected through intra-arterial route. In addition, total RNA was extracted and RT-PCR method was performed for drug resistance genes such as MDR and Topo II. The result of chemosensitivity test was compared with expressions of drug resistance genes. Mean inhibition rate of tumor growth in chemosensitivity test showed 42.7% in CBDCA, 37.9% in CDDP, 30.8% in ACNU, and 3.2% in VCR. This result revealed high sensitivity in platinum drugs. Drug resistance gene expression was not significantly correlated with chemosensitivity (p=0.1). In addition, mean survival period of patients undergone with tailor made chemotherapy based on chemosensitivity test was not significantly different from mean survival period of patients undergone with conventional chemotherapy (p=0.07). In spite of small number of examined cases, tailor made chemotherapy should be further investigated.