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Detection Of The Receptor For Urokinase-type Plasminogen Activator And Its Clinical Application

Posted on:2002-01-19Degree:MasterType:Thesis
Country:ChinaCandidate:W Q GaoFull Text:PDF
GTID:2144360032452165Subject:Internal medicine (blood)
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Background The urokinase-type plasniinogen activator (uPAR) is a 5 5-60 kDa membrane glycoprotein, which anchors on cell membrane via a glycosyle phosphatidylinositol (GPL) moiety. A number of cell types has been identified express uPAR in vM. Binding of uPAR strongly stimulates the activation of pro-uPA and, hence, of plasminogen, resulting in localized production of the broad-spectrum serine protease, plasmin, which can digest extracelleular matrix proteins or activate other matrix-degrading enzymes such as metalloproteinases. In addition, uPAR can influence cell adhesion and migration by interacting with vitronectin (VN), integiins, and caveolin. All of these fimctions of uPAR are contribute to cell division, development and tissue remodeling and so forth. In the past few years, numerous reports have demonstrated that uPAR had overexpressed on some pathological cells during the condition of tumor and inflan抜matoiy, but been deficient on blood cells in patients with paroxysmal nocturnal hemoglobinuria (PNH). And uPAR could release into blood as soluble uPAR (suPAR) from the membrane of those cells. Therefore~ uPAR may play a certain role in the pathogenesis of some diseases. Objective To establish a specific inimunoradiometric assay (iRMA) for human soluble receptor for umkinase-type plaszninogen activator (suPAR) and to investigate uPAR levels in normal adults and some pathological conditions. Methods Two monoclonal antibodies (McAb) were used and one of them was labeled with 憕I by using Chloramine-T method to set up the IRMA for suPAR. Serum or plasma levels of norma] adults, patients suffered from benign and malignant tumors and from PNH were measured. The association of suPAR level with tumor invasion, metastasis and its alteration after treatment in patients with malignant tumor were also studied. The suPAR levels in pleural effusion of 26 cancer patients, 10 inflamniatoiy patients were detected by this assay. uPAR were measured on granulocytes by using flow cytometiy (FCM) in normal adults and PNH patients. Results The detectable limit of this suPAR IRMA was 0.70 Ii g/L. The mean levels of suPAR were (2.71 ?.12) ii g/L in serum of 62 nonnaladultsand(1.73?.96) ii g/L in plasma of 21 normal adults, while that in serum of 30 benign tumor patients were (3.71?.69) i,i g/L and (5.82?27) L?g/L in serum of 124 malignant tumor patients. The serum suPAR level of two types of tumor patients was increased in comparison with that of normal adults. And its increasing extend in malignant tumors was much greater than in 3 o~u~ I~kr~m* benign tumors. The sennn suPAR level of patients with malignant tumors was correlated with tumor invasion, metastasis and surgical intervention. The suPAR levels were (4.36? 2.12) ii g/L, (2.64 ?1.05) ~ g/L in cancerous pleural effusion and inflammatory pleural effusion, respectively. The suPAR level in cancerous pleural effusion was higher than that of inflammatory pleural effusion, and the latter was also elevated compared with that of normal plasnia. Moreover, the suPAR level was shown to be inversely associated with the survival time of cancer patients. In PNH patients, both mean fluorescence intensity and positive percent of fluorescence-activated granuiocytes of uPAR were remarkably decreased in comparison with those of the normal adults. In addition, some peak shape abnormalities (double peaks and/or peak ta...
Keywords/Search Tags:Urokinase-type plasminogen activator receptor, Immunoradiometric assay, Tumor, Flow cytomefly, Paroxysmal nocturnal hernoglobimnia
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