| Study on the expression of Fas/FasL in human gliomas and the inhibitory effect of FasL cDNA on the growth of glioma cellsi/i vitro as well as in vivoPh.D. Student: Zheng Yu Supervisor: Professor Pu PeiyuAbstractGlioma is the most common type of primary intracranial tumors. It has been reported that malignant glioma accounted for about 60% of gliomas. Although the currently available multi-modalities of therapies, such as microsurgical operation, radiotherapy and chemotherapy, have been improved, the median survival time of patients with malignant glioma is only 52 weeks. So glioma is still a refractory disease in the neurosurgical field. In order to improve the unfavorable prognosis of patients with malignant gliomas, the mechanism of the development and progression of gliomas as well as the new strategies for the treatment of malignant gliomas should be studied necessarily.In multi-cellular organisms, cells comprise a complicated society, in which cell proliferation and cell death are strictly regulated. Recently, apoptosis was found to exert an important role in keeping the stabilization of cell number in the process of self renewel. When the DNA of cells is damaged and could not be repaired, the process of apoptosis is initiated to avoid passing the wrong information down to the next generation. Any pathogenesis interfering with proliferation-death mediating mechanism will induce excessive proliferation and/or inhibition of apoptosis, result in abnormal cell accumulation and tumor formation. Excessive proliferation and inhibition of apoptosis are common characteristics of transforming cells and key events of rumorigenesis. So the study on the molecular mechanisga of apoptosis and the induction of apoptosis of gliomacells is one of the hotspot of glioma research. By now the known genes that mediating apoptosis are : CD95/Fas/APO-l, bcl-2, c-myc, p53, caspases, etc. Fas is one of death receptor, when integrating with its ligand, it can pass the death signal to its downstream molecules.Up to date, although there have been some reports on the expression of Fas and FasL genes in gliomas, but these results were obtained from a small number of brain tumors or glioma cell lines, the relationship among Fas genes expression, histopathological type, proliferation activity and biological behavior of gliomas has not been reported. The inhibitory effect of FasL gene on the growth of glioma cells in vitro as well as in vivo has rarely been reported. In the present study, the expression of Fas and FasL genes in gliomas and the relationship among Fas genes expression , the rumor grade and rumor proliferation activity were investigated in order to elucidate the role of Fas/FasL genes in the pathogenesis of gliomas. The feasibility of using Fas/FasL genes as targets for gene therapy of gliomas was also studied by in vitro and in vivo experiments.Part I : Study on the gene expression of Fas and FasL and their relationship to proliferation activity of human gliomasThe gene expression of Fas, FasL in 64 human gliomas, 2 malignant human glioma cell lines and 6 normal brain tissues were studied by Northern blot hybridization and immunohistochemical staining, and their expression level correlated with glioma grade and Ki-67LI was analysed.1. Expression of Fas, FasL in human gliomasIt was found that 6 normal brain tissues and one of 2 malignant human glioma cell lines did not express Fas mRNA or Fas protein; whereas 45of 64 human brain tumors (70%) expressed Fas mRNA and 53 of 64 (83%) expressed Fas protein respectively. The positive rate and expression level of Fas and its mRNA is increased with the ascending of WHO tumor grade. (Fas mRNA: r=0.636, P<0.01, r=0.712, PO.01; Fas: x ^ 10.47, PO.05, , r=0.643 P<0.01). The difference of7positive rate and expression level of Fas and its mRNA between the low and high-grade tumors was statisticaly significant. So,Fas genes, may play an important role in the malignant progression in gliomas. The expression level of Fas gene also provides...
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