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The Expression Of Multidrug Resistance-associated Protein 1 And Lung Resistance Protein In Human Glioma And Its Clinical Sigificance

Posted on:2005-10-20Degree:MasterType:Thesis
Country:ChinaCandidate:C F DuFull Text:PDF
GTID:2144360125950309Subject:Surgery
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Multidrug resistance (MDR) is the major reason of chemo- therapy failure.There are many reasons resulting in MDR, including MRP,LRP,PKC,TNF-α,glutathione and its associated enzyme. The recent researches mainly focus on the gene of MDR and its associat- ed production and its reversion.This research dissuss the expression of MRP1 and LRP in human glioma and its association with clinical characteristics.We detect the expression of MRP1 and LRP in 61 human glioma patients with immunohistochemistry, which includes 16 relapse after 4 to 6 courses of chemotherapy.Then take 11 normal brain tissues as comparison.After specimen got, make continuous slices of 5 micrometers with microtome. Glassslides are made into tissue slices after dealed with L-polylysine, then specimen are dyed with MRP and LRP antibodies, reading with microscope. Select 5 high diploid visual fields, take count of the numbers of sum of the tumor cells and positively dyed cells, and then get the percentage of positive cells. х2 test and Fisher precise probability were used to test the difference of positive percentage of the two groups. х2 test and Fisher precise probability were used to test the difference of positive percentage of the two groups.In normal brain tissues and glioma,the positive expression of MRP1 was 9.1%(1/11)and 68.9%(42/61), and in primary glioma and secondary glioma,was 57.8%(26/45)and 100%(16/16); the positive expression of LRP in normal brain and in glioma was 9.1%(1/11),75.4%(46/61)respectively,and in primary glioma and secondary glioma was 66.7%(30/45)and 100%(17/17)respectively. Statistics analysis indicate that the expression of MRP1 in human glioma was much higher than that in normal brain tissues,and in secondary glioma was much higher than in primary glioma,which showed significant difference(p<0.01).So does LRP. The expression of MRP1 in 4 pathologic grades was grade I45.5%(5/11),grade Ⅱ55.6%(10/18),grade Ⅲ78.3%(18/23) and grade Ⅳ100%(9/9), respectively;and the expression of LRP was 27.3%(3/11), 66.7%(12/18), 95.7%(22/23), 100%(9/9)respectively. Hc test indicate that the expression of MRP1 and LRP was increased with the pathologic grades increasing(p<0.05).The expression of MRP1 and LRP showed no correlationship with age, sex, location, diameter and cystoid transformation(p>.05),while had correlation with the pathologic grade(p<0.05). So we could get conclusions:1. MRP1 and LRP had somewhat expression in normal brain tissues, and had higher expression in giloma than in normal brain tissues, which indicate that MRP1 and LRP were objective factors associated with chemotherapy resistance.2.The expression of MRP1 and LRP were much higher in secondary glioma than in primary glioma,which suggested that physical stimulation such as chemotherapy and or operation could increase the expression of MRP1 and LRP in glioma and were important basises of malignancy secondary resistance. 3.The expression of MRP1 and LRP in 4 grades of glioma had correlation with cell differentiation. 4.The expression of MRP1 and LRP in glioma had no correlation with age,sex,location,diameter and cystoid transformation.5.MRP1 and LRP had certain co-expression in glioma,combination detection could increase the prognostic value of chemotherapy sensitivity. In order to forecast the treatment effect,we could detect MRP1 and or LRP value in the patient vein with radioimmunity before chemotherapy and compared with last time.If the value decreased,which suggested that it was effective ,we could continue the regimen;if the value had no change or rising contrarily,which indicated cells produced drug resistance,and we must change the regimen.This not only alleviated the economic burden of the patient, but also with replacing sensitive drugs in time could kill cancer cells furthest and prolonged the survival time of the patients.
Keywords/Search Tags:multidrug resistance associated, protein 1, lung resistance protein, multidrug resistance, glioma, immunohistochemitry
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