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Expression And Significance Of GRIM-19and STAT3in Human Glioma

Posted on:2014-02-17Degree:MasterType:Thesis
Country:ChinaCandidate:S H SunFull Text:PDF
GTID:2234330398478417Subject:Surgery
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Background and PurposeGlioma is the most easily approached tumor in the encephalic.It almost exacerbates as infiltrating type. So far it mainly depends on surgery cutting to treat and it should be maintained with the help of radiotherapy,chemotherapy, genetherepy, immuno therapy and so on after the surgery. Although there has been great improvement in treatment methods, malignancy features by rapid growth,strong invasion and easy recurrence. So it is not satisfying after surgery. The median survival time of people who are afflicted with GBM(glioblastoma multiforme) is merely12-15months. Thereafter,the study of the beginning, deteriorating, and treatment is an important subject in the medical and some relative areas, In recent years, with the development of the molecular biology in the cancer research,the study of molecular mechanism and withering had been further explored,but the occurrence mechanism of glioma is not clear.GRIM-19(Gene associated with retinoid-IFN-induced mortality) which is induced by interferon/retinoic acid and can make cells deteriorate is a new gene chosen in the study of interferon-β; IFN-β and all-trans-retinoic acid, RA inducing cells to apoptosis by the way of delating opposite elements. GRIM-19is not belonged to any of the already known apoptosis gene.eg:Bcl-2,death recepor and caspase family. So far as concerned, GRIM-19participates in the process of cell proliferation and repoptosis,and the reduction of expression and site mutation may lead to the cell proliferation and vicious transformation. STAT3signal transduction pathway is a recently discovered cancer gene and it works as an important member in the gene family of transducing and transcribing the activator. The constant activating associates closely to the beginning and developing of tumor. It is discovered that the constitutive activation of STAT3plays a important role in the survival, proliferation, vasculogenesis, invasion and transferring, Immune escape.The suppression of STAT3signal Signal transduction pathway in and out of the body can restrain the cell proliferation and survival as well as inducing cells to apoptosis. GRIM-19is considered as a new negative regulator to express and activate STAT3. The study of GRIM-19in glioma is rare, and we can see no relative papers reporting GRIM-19and STAT3together. This research is to study its function in the beginning and developing of the glioma by the way of RT-PCR technical testing for the expression of GRIM-19mRNA and STAT3mRNA in the glioma tissues and non-neoplastic brain tissue so as to provide new idea in the clinic treatment for glioma.Materials and Methods45samples is got from the neurosurgery of the second Affiliated Hospital of Zhengzhou University. All the tumor samples are got from the parenchyma of the tumor, not including the central necrosis and Tumor border area,and they are through the diagnosis of the pathologist.All the samples are attacked for the first time,and they are not treated with radiotherapy and chemotherapy. Among them,there are28men and17women whose age is2-73years old,and the average age is37.23±16.35years old. The samples are stored in the liquid nitrogen after they are obtained and then transferred into the refrigerator of-80℃. They are strictly classified according to the the classification standard of the central nervous system tumors which is released by WHO in2007. Among them,there are5Ⅰ,18Ⅱ,12;,10Ⅳ. Ⅰ~Ⅱ belong to the lower malignancy group, the amount is23; Ⅲ-Ⅳ belong to the higher malignancy group,number22.Besides,13normal cerebral tissue samples of brain injury or cerebral hemorrhage patients are picked as normal control.After the RT-PCR test for the expression of GRIM-19mRNA、 STAT3gene mRNA in the45glioma tissues and the13tumor tissues. The result were analyzed with the statistics software of SPSS17.0. Probabiilty values a=0.05were considered statistically significant.Results1. The expression of GRIM-19mRNA in different grade gliomaGRIM-19mRNA presents low expression in glioma tissue specimens; high expression in the non-tumor brain tissue. The expression of GRIM-19mRNA in the non-tumor brain tissue,glioma tissue, low-grade malignant tumor tissues,highly malignant glioma group is respectively1.091、0.025、0.923、.076、0.986±040、0.856±0.040. The differences were significant between non-tumor brain tissue and glioma tissues, as well as between any two of the non-tumor brain tissue, low-grade malignant gliomas and high-grade gliomas.(P<0.05)2.The expression in different grade gliomaSTAT3mRNA presents high expression in glioma tissue specimens; low expression in the non-tumor brain tissue. The expression of STAT3mRNA in the non-tumor brain tissue,glioma tissue, low-grade malignant tumor tissues,highly malignant glioma group is respectively:0.671±0.020、0.818±0.049、0.786±0.030、0.843±0.041. The differences were significant between non-tumor brain tissue and glioma tissues, as well as between any two of the non-tumor brain tissue, low-grade malignant gliomas and high-grade gliomas.(P<0.05)3.The relevancy between GRIM-19and STAT3According to statistics,the expression of GRIM-19mRNA and STAT3mRNA is negative correlation,their expression is tend to opposite sides. The pearson relation is r=-0.618, P<0.05, and it makes sense in statistics.Conclusions1.The mRNA expression of GRIM-19gene in the glioma is obviously weakened which is compared to non-tumor brain tissue.As the pathological grade rises, the expression reduces gradually.2.The mRNA expression of STAT3gene in the glioma is obviously strengthened which is compared to non-tumor brain tissue. As the pathological grade rises, the expression promotes gradually.3.The expression of GRIM-19and STAT3presents negative correlation. GRIM-19and STAT3are expected to become the target spot in the diagnosis and treatment of glioma gene.
Keywords/Search Tags:Glioma, GRIM-19, STAT3, RT-PCR
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