| Gliomas are the most common primary brain tumors. The prognosis of the patients with malignant glioma has not been improved in recent twenty years, even though combined therapeutic modalities including surgical resection, radiotherapy and chemotherapy are currently available. As the knowledge of tumor biology and molecular genetics increased, it has been shown that the development of gliomas, just the same as the tumors in the other site of the body, results from the activation of proto-oncogenes and inactivation of tumor suppressor genes, and multiple genetic alterations are involved.It is commonly suggest from the reports of the European countries and The United ststes that EGFR overexpression and/or amplification are early and major event of primary GBM, while p53 mutation or inactivation is the primary molecular event in the low grade gliomas, progressing to secondary GBM. They considered that there are two different isolated molecular pathways for the development of primary and secondary GBM; even some author consider these two pathways are mutually exclusive,and constitute distinct disease entities which develop throuth the acquisition of different genetic alterations.However ,our previous studies on the EGFRexpression and p53 mutation of gliomas separately showed quite different situation.We found that p53 gene mutation was seen in low grade gliomas(5.3%),but more frequently occurred in primary GBM(45.5%).On the other hand, EGFR overexpression was common in primary GBM(72%), but also found in 33.3% cases of low grade gliomas. This result suggests that maybe both of these two molecular pathways contribute to the pathogenesis of primary and secondary GBM ,that can't be separated from ecth other so clearly, at least in the glioma patients from our country.Therefore, the aim of this study is to further investigate the role of EGFR and p53 in pathogenesis of gliomas , so as to correlate the overexpression and/or amplification of EGFR with the expression and mutation of p53 , as well as tumor proliferation activity. In addition,the feasibility of using p53 combined with antisense EGFR as a target for improving the efficacy of gene therapy of gliomas was also studied by in vitro well as in vivo experiments.Part I : Study on the gene expression of p53 and EGFR and their mutualrelationship in gliomas 1. The gene expression of EGFR and amplificationThe gene expression of EGFR in 50 fresh resected human gliomas, 2 malignant human glioma cell lines and 6 normal brain tissues were studied by RT-PCR ,immunohistochemical staining ,and Southern blot analysis. It was found that in high-grade gliomas EGFR was overexpressed in 70.59% (24/34) of cases, while in low grade gliomas EGFR overexpression rate was 50%(8/16),both 2 malignant human cell lines overexpressed EGFR, and 6 normal brain samlies had no EGFR expression. EGFR expression was significantly increased in ascending order from low to high grade gliomas.( r=0. 542, p<0. 001), The EGFRmRNA expression was coincidence with that of EGFR expression (r=0.812 , p<0. 001).EGFR gene amplification was found in only 1 case of low grade gliomas(l/16) and one human malignant glioma cell line (l/2).However,it was found in 12 cases of high grade gliomas(12/34),There is discrepancy between EGFR expression and EGFR amplification as found in 14 cases of EGFR overexpression without gene amplification. The results suggest that EGFR gene may play an important role in the development of low grade gliomas or high grade gliomas.2. P53 gene mutation and expression in human gliomasUsing immunohistochemical staining, PCR-SSCP, and DNA sequencing, The p53 gene mutations at the highly conservative region exon 5-8, and p53 protein expression were studied in 50 fresh resected human gliomas. 26 of 50 in gliomas were immunopositive as p53 protein accumlation, P53 mutation were found in 11 of 50(22%)gliomas, including 6 of 8 glioblatomas(75%), 4 of 23 anaplastic astrocytomas(17.4%), 1 of 16 I - II astrocytomas(6.25%).These results indicate that p53 gene mutation is a common geneti...
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