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Intratumoral Microvessel Density And The Correlation With Expression Of PTEN And VEGF In Human Astrocytomas

Posted on:2004-05-27Degree:MasterType:Thesis
Country:ChinaCandidate:S H ZuoFull Text:PDF
GTID:2144360092499714Subject:Surgery
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Objective: Glioma is the most common tumor in central nervous svstem,holding 40-67% of the primary intracranium tumors. Glioblastoma multiforme has the highest malignancy among them and median survival time of patients with GM tumors has remained no more than one year. Malignancy of gliomas is mainly associated with its rapid and invasive growth, which makes it very difficult to resect them completely. Although comprehensive treatments in modern oncology have made rapid progress, but as one common tumor, patients' prognosis still remains very poor . With development of molecular biology and pathogenesis, people have focused their reseach in gene field.At present it is well-known that occurrence and progress of gliomas is because of disequilibrium of apoptosis and proliferation owing to activation of protooncogene and inactivation of anti-oncogene. It becomes hot spot to disclose pathogenesis of gliomas. PTEN gene is one anti-oncogene which was found in 1997 and is related to late phase of many kinds of tumor. Because of it ,PTEN gene was called gene which is mutated in multiple advanced cancer1 (MMAC1) .PTEN gene is the first anti-oncogene with phosphatase activity which has double specificity. Main function region of PTEN protein lies on N-termination which is composd of 403 amino acids and is encoded by 1209 nucleotides. The122-123rd Amino acid sequence coincidences with catalytic domain core motif of Protein- tyrosine-phosphatase and phosphatase with double-specificity. N-termination of PTEN protein has homology subsequence with tonus protein and adjuvant protein ,which is connected with connectin. N-termination of PTEN protein and Compound at this site take part in regulation of cell growth.Moreover, both of them play certain role in infiltration of tumor cell , vascularization and metastasis. Gene pointmutation and deletion are main types, which imply loss of PTEN gene function in astrocytoma. PTEN gene inactivation has firm correlation with progressive malignancy in astrocytoma. Because most of gene point-mutation and delection occur in the grade four astrocytoma, PTEN gene plays an important role in occurrence and malignancy in human gliomas. Most reseaches have been carried from the view of gene level ,but location of PTEN protein and its expression in tumors have seldom reported .Vascular endothelial growth factor is one kind of polypeptide polypeptide which was found in recent year. Importance has been attached to biological activity of VEGF in angiogenesis and promoting permeability gradully.Tumorgrowth and metastasis are based on Angiogenesis. VEGF can stimulate endothelial cellproliferation and play an important role in angiogenesis. It was found that VEGF is one kind of homology dimer glycoprotein with hepalean activity whose molecular weigh is 40-45Kd and is mitogen which has effects on endothelial cell. VEGF can not only aim directly at endothelial cell,but also increase vascular permeability ,so it is called vascular permeability factor(VPF).VEGF specificity receptoris expressed highly in gliomas and endothelial cell of tumor . Structural analysis of VEGF gene implys that total length of human VEGF gene is 14Kb ,which is composed of 8 exons an 7 introns .Coding region lies in the eight exons which are spliced and produce different mRNA. VEGF aims directly at endothelial cell ,but it has no effct on the other cells Which indicates that VEGF can connect with receptor on the surface of endothelial cell and produce a marked effect..VEGF hyper-expression has important significance in gliomas .It implys that VEGF has close correlation with noplasia. Glioma growth not only depends on proliferation of neoplasm cells ,but also angiogenesis in the tumor. Research makes clear that when diameter of the tumor surpasses 2 mm, it needs blood supply from neonate blood capillary. With augmentation of the tumor, it still harvests tumor growth promotive factor from endothelial cell. Eoplasm angiogenesis is a complicated pathophysiological process regulated by genes in which lots of...
Keywords/Search Tags:Astrocytoma, Vascularization, PTEN, VEGF, Immunohistochemistry
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