Analysis of apoptotic related gene in malignant glioma and development of the gene therapy

通过对凋亡相关基因(bax、bcl2、bclxl)的分析，发现EGFR异常表达与bclxl表达密切相关。使用这些实验模型的结果与使用我们的操作案例的研究得到了类似的结果。恶性胶质瘤过度表达异常的EGFR，肿瘤的增殖能力(MIB-1阳性率)较高，临床上发现其倾向于抑制细胞凋亡，也倾向于过度表达bclxl。但在手术病例中，也有bclxl过度表达而出现细胞凋亡的病例。在这种情况下，Bax的表达已经被识别。恶性胶质瘤中细胞凋亡的出现与bax/bclxl的比值有关。Bcl-xl在恶性胶质瘤细胞凋亡中起抑制作用，而bax则作为诱导基因。研究发现，EGFR异常与bclxl的表达有关。分析60例手术标本中Bax的表达和P53的突变型。结果显示，预测P53与Bax关系的方式有趋势性。总之，野生型P53促进Bax的表达，突变型P53抑制Bax的表达。然后，将外源p53基因或p130基因插入四种基因重组细胞系中。检测P53家族和Bax蛋白在体外的表达。然而，P53家族与Bax之间的关系尚不能得到我们所预期的结果。根据这些结果，我们可以推测P53家族通过一个新的基因向Bax传递信号。但是，我们无法确定这种新的基因。

From the analysis of Apoptosis relation gene (bax, bcl-2, bcl-xl), it was discovered that the expression of abnormal EGFR was related to the expression of bcl-xl. The result using these experimental models got the similar result from the research using our operation cases. The tumor proliferation capability (the MIB-1 positive rate) was high in malignant glioma over expressing abnormal EGFR, and it was clinically discovered that it tended to suppress apoptosis and tended to also over express bcl-XL. However, there were the cases in which apoptosis occurred in spite of over expression of bcl-xl in the operation cases. In such case, the expression of bax has been recognized. The appearance of apoptosis was related to the ratio of bax/bcl-XL in malignant glioma. Bcl-XL in apoptosis of malignant glioma, it was made to be an inhibitor, and bax was related as an induction gene. It was found that abnormal EGFR was related the expression of bcl-XL. We analyzed the expression of bax and mutation type of p53 in the sixty operation cases. In the result, there was a tendency of the way which anticipated the relationship between p53 and bax. In short, wild type p53 makes the bax expression promote, and mutant type p53 does suppress the bax expression. Then, we insert exogenous p53 gene or p130 gene in four kinds of gene recombination cell line. Then, we examined the expression of p53 family and bax in vitro. However, we could not have the results of the relationship between p53 family and bax, which we expected. From these results, we could estimate that p53 family send a signal via a new gene to bax. But, we could not determine this new gene.