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The Study Of Relation Between Genesis Of Human Glioma And Simian Virus 40 Infection

Posted on:2003-05-26Degree:MasterType:Thesis
Country:ChinaCandidate:X J WangFull Text:PDF
GTID:2144360065456160Subject:Neurosurgery
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Objective: Human brain glioma is the most common malignant tumor in the central neurous system,it accounts for 35-60% of all brain tumors.The prognosis is still very poor in most mtiertts with the highly malignant degree,especially for childhood glioma. For unknowing the pathogenesis,we could not interfere with the glioma. So,to cure this stubborn diease is still a worldwide problem. After American scholar discovered the first tumor virus.,Rous sarcoma virus (RSV),the occurrence of the tumors havebeen associated with the virus at the beginning of this century.Simian virus 40 (SV40) is a small DNA virus containing closed circular double stranded DNA.lt was discovered as a contaminant of poliovaccines propagated in rhesus monkey kidney cells in 1960. SV40 together with JC virus (JCV) and BK virus (BKV),belong to the group of polyomaviruses,these viruses have been cosidered as possible factors in the etiopathogenesis of human brain tumors,due to their neurotropism and oncogenic potential in experimental animals. Several studies found that SV40 is able to transform cells in culture and has a potent ability to induce some specific tumortypes in rodents,such as ependymomas, choroids plexuspapillomas, medulloblastomas, glioblastoma multiforme and mesotheliomas et al. SV40 oncogenicity and transforming ability are strictly dependent on the expression of the early region of the viral genome.encoding for the large tumor antigent (T-ag), a nuclear phosphoprotein of 96,000 molecular weght with multiple biological and biochemical properties. SV40 T-ag has ATPase and helicase activities, binds to viral and cellular DNA ,inducing their replication.SV40 encode oncogene proteins that may complex withcellar tumor suppressor gene products,such as p53, inactivate their functions and interfere with their negative regulation of cell growth.T-ag of SV40 is the major transforming protein of virus and when expressed alone,can alters the integrity and stability of the host cell genome,inducing numerical and structural chromosomal aberrations .Recently,about 15% of human cancer were found to involve SV40 infections, and SV40 sequences were detected by polymerase chain reaction (PCR) in ependymomas and choroid plexus papillomas of childhood,as well as in brain glioma tissues. The goal of this study is to explore the correlation between SV40 and glioma tissues and its role in the carcinogenesis of human glioma,Methods: The PCR ,Dot blot hybridization,in situ hybridization (ISH) and immunohistochemical staining method were used to detect the SV40 DNA sequences in 97 human brainglioma cell lines:BT325. T-ag expression and T-ag-p53 complexes were investigated by immunoprecipitation and Western blot in SV40 DNA positive cases.Results: (1) The presence of SV40 DNA sequence was investigated in human glioma tissues. The SV40 DNA PCR sequences were present in 46/97 (47.4%) in gliomas and 1/20 (5%) innormal brain tissues. The SV40 DNA sequences were also present in BT325 cell lines. The positive rates of SV40 DNA in glioma group was significantly higher than those in human normal brain tissues (P<0.01). There were relationship between SV40 infection and pathological grade of glioma(p<0.01). (2) By using ISH and Dot bolt, the SV40 DNA were detected only in 43 human brain tumor tissues out of 46 SV40 DNA PCR positive cases,1 human normal brain tissues and the BT325 cell lines were also positive. Hybridization signals were present within the nuclei of tumor cells and the positive cells distributed diffusively or focally. {3) T-ag expression was found in 38 human glioma tissues out of 43 SV40 DNA positive cases. And a significant correlation was found between T-ag expression and pathological grading (Pearson contingency coefficent p=0.71, p<0.01) .Tag-p53 specific complex was found in 38 Tag positive cases.Conclusion: (1) The results of this study indicate that thehuman brain glioma tissues could be infected with SV40, and latent infection of Sv40 could be implicated in the glioma,and there is a close correlation between...
Keywords/Search Tags:Simian Virus 40, Glioma, Large tumor antigen, p53 Tumor suppressor gene
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