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The Expression Of Efflux Pumps Related To Resistance To Anticancer Drugs(Pgp, MRP, LRP) In Human SCLC Cancer Specimens And Modulation Of Multidrug Resistance In Human SCLC Cell Line GLC4/ADR By Inhibition Of MRP With Antisense MRP RNA

Posted on:2001-10-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:X H PengFull Text:PDF
GTID:1104360185469345Subject:Chemotherapy of malignant tumors
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Multidrug Resistance (MDR) is one of the major obstacles for the chemotherapeutic treatment of malignancies,and its major mechanism is resulted from over-expressing efflux pumps.It is known that P-glycoprotein(PgP), the Multidrug Resistance-associated Protein(MRP) and Lung Resistance Protein(LRP) are major componets of these bumps, by which cells pump out anticancer drugs from the cytoplasm or mediate intracelluar transportation between the cytoplasm and nucleus. There may be correlation between the overexpression of PgP ,MRP and the resistant to chemotherapy in cell lines derived from human SCLC .There are few studies about the expression of these pumps in human SCLC cancer specimens.In recent years, researchers have extensively studied the molecular basis of antisense RNA and defined them as specific modulator of gene expression. It has been demonstrated that these antisense RNAs are potential therapeutic agents in future for reversing the MDR phenotype .We use two antisense RNAs targeting 5' and 3' regions of MRP mRNA to study the effect of antisense MRP RNA on MDR of human SCLC cell line GLC4/ADR in which high expression of MRP gene was found.In the present study, we detected the expression of Pgp. MRP and LRP in 35 formalin-fixed paraffin-embeded specimens from 35 SCLC patients who had not received prior chemotherapy by immunohistochemistry.The positive rates of Pgp, MRP and LRP in 35 specimens were 34.3% (12/35), 14.3%(5/35), 5.7%(2/35), respectively. From 15 patients received chemotherapy with residual tumor, 3 of 4 patients with positive staining for PgP showed resistance to chemotherapy, but 8 out of 11 patients with negative staining for...
Keywords/Search Tags:Expression
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