GENE THERAPY FOR MALIGNANT BRAIN TUMORS USING HSV/EBV HYBRID AMPLICONS.

在此之前，我们评估了5-氟胞嘧啶(5-FC)/胞嘧啶脱氨酶(CD)基因治疗等病毒介导的化疗敏感性基因转导和前体药物治疗恶性胶质瘤的疗效。首先，我们研究了放射治疗对恶性胶质瘤5-氟胞嘧啶(5-FC)/胞嘧啶脱氨酶(CD)+尿嘧啶磷酸核糖转移酶(UPRT)基因治疗的促进作用。这种联合治疗可能是可行的，尽管为了防止副作用，应该减少辐射剂量和辐射面积(癌症基因治疗9：840-845,2002)。其次，我们研究了5-FC/CD基因治疗人脑胶质瘤细胞的凋亡诱导和半胱氨酸氨基转移酶的作用。这些结果表明，5-FC/CD基因治疗可诱导人恶性胶质瘤细胞发生凋亡，而细胞的凋亡是通过激活caspase 3和9的线粒体caspase级联通路来实现的(《神经肿瘤学杂志》66：117-127,2004)。最近，我们正在建立新的HSV/EB杂合扩增载体系统用于转基因传递，并利用核磁共振成像技术利用工程转铁蛋白受体对转基因表达进行体内成像。

Previously, we evaluated the therapeutic efficacy of the virus-mediated transduction of the chemosensitivity genes and prodrugs for malignant gliomas such as 5-fluorocytosine (5-FC)/cytosine deaminase (CD) gene therapy.Firstly, we investigated the ability of radiation therapy to enhance 5-fluorocytosine (5-FC)/cytosine deaminase (CD) plus uracil phosphoribosyltransferase (UPRT) gene therapy in malignant gliomas. This combination therapy may be feasible for the treatment of gliomas, although the radiation dose and area should be reduced in order to prevent side effects (Cancer Gene Therapy 9 : 840-845, 2002).Secondly, we examined the induction of apoptosis and the role of caspases in 5-FC/CD gene therapy using human malignant glioma cells. These results indicate that 5-FC/CD gene therapy induces apoptosis in human malignant glioma cells and that the apoptotic cell death is mediated by the activation of mitochondrial caspase cascades involving caspases 3 and 9 (J of Neuro-Oncology 66 : 117-127, 2004).Recently, we are making new HSV/EB hybrid-based amplicon vector system for transgene delivery and developing the use MRI for in vivo imaging of transgene expression employing engineered transferrin receptor.