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The Relation Between The Invasion And Metastasis Of Esophageal Squamous Cell Carcinoma And Heparanase, The Experimental Study On Inhibiting The Expression Of Heparanase In Vivo And In Vitro

Posted on:2005-02-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:K S ChenFull Text:PDF
GTID:1104360125457316Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Heparan sulfate(HS) is a biological macromolecules of entracellular matrix (ECM) and cell surface. It is a main element of basement membrane (BM). Heparanase is a kind of endoglycosidase , it can degrade the glycosidic bond between the side -line of heparan sulfate and core protein , damage the EC and BM directly, release and stimulate the biological active factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) .The studies have indicated that the heparanase is mainly distributed in the immuological tissues and cells . Such as placenta, spleen, lymph nodes, thymus, bore marrow and the activated T, B cells. It has a fundamental physiological function in the process of the period of the embryo growth, the cure of wound, tissue restore and the inflammation process. In the course of the tumor formation and development the tumor cells "hijack" the physiologicalfunction of the above cells effectively. Perhaps releasing the heparanase sulfate from the activated platelet as the vessel were in inflammation reaction, furthmore, making the inflammatory cells exude and stimulating vascular endothelial cellular split, in this way, the heparanase could induce the invasion, metastasis and the new vessel growth of tumor.Recently there were some reports about the expression of heparanase in the breast carcinoma colon carcinoma, liver carcinoma, prostategland carinoma and lymphoma back and forth finding, high expression of heparanase in the invasive or metastatic tumors and high metastatic carcinoma cell lines. On the animals with metastasis carcinoma and the melanoma patients with brain metastasis , the activity , contents and expression of heparanase also increases. After heparanase whole-gene sequence were transfected into the non-invasive lymphoma EbT cells, then inoculate to liver of nude mice, It was found the ability of invasion and metastasis increased significanfly .Otherwise, It was verified that laminarin sulfate could inhibit the expression of heparanase and the invasion ,metastasis of tumor by using heparanase antisense oligodeoxynucleotide and its inhibitor laminarin sulfare to cure breast carcinoma.Esophageal carcinoma is a kind of common diseases in our country, especially in Henan province. The most cases that caused the death of esophageal carcinoma are its invasion and metastasis. So the explore about the invasion and metastasis of esophageal carcinoma has become a focus. In despiteof there have been a lot of reports about the relation between the heparanase and the invasion and metastasis of tumor , there was only one report about the relation between the heparanase and invasion and metastasis of esophageal carcinoma. This report only used one way, that is RT-PCR, to indicate the expression of heparanase on the carcinoma tissue and normal mucosa. In order to explore farther the relation of expression heparanase surfate and the invasion and metastasis of esophageal carcinoma, to find the early defective markers of invasion and metastasis of esophageal carcinoma and to research the useful ways to repress the invasion and metastasis of esophageal carcinoma.This article detect integrally the expression of heparanase in the 54 cases of esophageal squamous cell carcinoma in the high occurred place, 22 cases of tumor-adjacentive atypical hyperplasia tissues and 54 cases of normal mucosa by the immunohistochemistry ways, in situ hybridization and reverse transcriptase-polymerase chain reactiion .Detecting the heparanase gene in serum of before and after operation by the way of PCR. Measuring the expression of heparanase of before and after operation on the 54 cases of esophageal squarmons carcinoma by the way of RT-PCR. Detecting the expression of heparanase protein and mRNA on the human esophageal carcinoma EC9706 cell line by the way of immunohistochemistry and whole-cell in situ hybrdization, at the same time to study the efficiency of the inhibition of heparanase sulfate, laminarin sulfate and the antisease oligodeoxynudeotide of heparanase on the expression...
Keywords/Search Tags:esophageal squamous cell carcinoma, atypical hyperplasia, heparanase, antisense oligodeoxynucleotide, laminarin sulfate, human esophageal EC9706 cell line, nude mice, uPA, VEGF
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