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The Expression Of Hypoxia-inducible Factor-1α And Glucose Transport-3 In Human Gliomas

Posted on:2009-11-22Degree:MasterType:Thesis
Country:ChinaCandidate:X XuFull Text:PDF
GTID:2144360245984516Subject:Surgery
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Gliomas are most common primary malignant brain tumors. Rapid proliferation is one of the important features of malignant tumors. During the development of tumors, the excessive proliferation of tumor cells results that oxygen and glucose in tumor microenvironment are relative deficient. Changes of microenvironment can trigger tumors producing a series of protective reaction in the stress lest tumor cells be injured or killed in hypoxia environment, and cells of the tumors obtain nutrient more effectively. Glucose is one of the most important nutrients in tumor cells, it can provide through energy metabolism and carbon skeleton through material metabolism. Energy is essential for the growth of tumor cells, and carbon skeleton can be used to synthesize some important nutrients such as protein,lipids and so on. glucose transporters(GLUTs) are the main transporters of glucose transmembrane transportation in mammal cells. Compared with the normal cells,the uptake and metabolism of glucose in malignant cells are all significantly increased.Accordingly, glucose transporter,in charge of glucose uptake,was highly expressed in malignancy tissues. Up to now,14 members were found in GLUT s family. GLUT3 is one of the transporters which have high transporting capacity.There are some studies indicated that GLUT3 was not expressed in nomal glial cells., but highly expressed in glioma cells. hypoxia inducible factor-1(HIF-1) is one of regulators of GLUT3, it can regulate the expression of GLUT3 in many nomal tissuses.Objective: Our study is to investigate the expressions of HIF-1a and GLUT3 in human gliomas and to analyze the relation among them under the pathological condition.Methods:1. From Mar.2006 to Aug.2007, We collected 47samples of human gliomas and 5 samples of normal brain tissues from the patients, who recived operation in the second hospital of hebei medical university. The study was focused on the expression of HIF-1αand GLUT3 in these samples.2. Expression of the HIF-1αand GLUT3 was investigated by immunohistochemistry in 52 specimens. The relationship between HIF-1a expression level and GLUT3 expression level were analyzed. After that, The relationship between their expression levels and the glioma grades were analyzed respectively through the same methods.3. Statistical analysis: the data were analyzed by statistical software spss11.0 and cs2000. Difference of equal data was compared with Kruskal-Wallis H test and Nemenyi test. Correlation analysis was evaluated by spearman correlation analysis. The significant different level in statistics was p<0.05. Results: this experiment altogether examined 47 samples of human gliomas and 5 samples of normal brains, the expression of them as follow:1. The expression of HIF-1αin the gliomas: 5 samples of normal brains does not have HIF-1αto express.The expression levels of HIF-la was increased corresponding to the ascending of the glioma grades,the level of HIF-1αwas 0% in normal brains,52.6% in glioma gradeⅡ,81.3% in glioma gradeⅢ,100% in glioma gradeⅣ. There are significant differences in statistics between low grade glioma(Ⅱ) and high grade glioma(Ⅲ,Ⅳ).2. The expression of GLUT3 in the gliomas: 5 samples of normal brains does not have GLUT3 to express.The expression levels of GLUT3 was increased corresponding to the ascending of the glioma grades,the level of GLUT3 was 0% in normal brains,36.8% in glioma gradeⅡ,75% in glioma gradeⅢ,100% in glioma gradeⅣ. There are significant differences in statistics between low grade glioma(Ⅱ) and high grade glioma(Ⅲ,Ⅳ).3. The expression of HIF-1αwas also positively correlated with GLUT3 expression at protein level. The expression level GLUT3 were increased corresponding to the ascending of the HIF-1a expression level.Conclusion:1. The expression level of HIF-1αwas increased corresponding to the ascending of the glioma grades. 2. The expression level of GLUT3 was increased corresponding to the ascending of the glioma grades.3. The expression of HIF-1αwas also positively correlated with GLUT3 expression. HIF-1αand GLUT3 may play a critical role in the malignant progression of the gliomas regarding their role in glycolysis. It also suggested they may be two candidate targets or prognostic markers for the glioma therapy.
Keywords/Search Tags:HIF-1α, GLUT-3, glioma, glycolysis, immunohistochemistry
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