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

基于化疗敏感性试验和耐药基因分析的恶性胶质瘤个体化化疗

基本信息

批准号：
14571325
负责人：
HAYASHI Akimune
金额：
$ 2.18万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

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.

不同的恶性胶质瘤表现出不同的抗癌药物作用。这一机制可能与耐药基因的表达有关。体外药敏试验检测抗癌药物的体外作用。恶性胶质瘤的个体化化疗建立在胶原凝胶基质法药敏试验的基础上。用RT-PCR方法分析耐药基因的mRNA表达。对53例恶性胶质瘤(间变性星形细胞瘤、胶质母细胞瘤)进行检测，取肿瘤组织培养8d，用胶原凝胶基质法检测6~9种抗癌药物的敏感性。根据化疗药物敏感性，选择两种抗癌药物经动脉内注射。提取总RNA，用RT-PCR方法检测耐药基因mdr、Topo II，并将药敏试验结果与耐药基因表达结果进行比较。药敏试验显示CBDCA、CDDP、ACNU、VCR对肿瘤生长的平均抑制率分别为42.7%、37.9%、30.8%、3.2%。这一结果表明，铂类药物具有很高的敏感性。耐药基因表达与化疗敏感性无明显相关性(p=0.1)。此外，根据药敏试验进行个体化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)。尽管检查病例数量较少，但仍需进一步研究量身定制化疗方案。