Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multidrug resistance (MDR) in tumor cells is commonly associated wich the over-expression of P-glycoprotein (Pgp), the product of the MDR1 gene. In this study, we investigated whether over-expression of Pgp in natural killer (NK) cells would influence their granule- as well as fas-mediated cytolytic activities. YT-INDY, a human NK-like cell line, was transfected with the MDR 1 gene, then tested for Pgp activity the presence of various concentrations of R-verapamil, a potent Pgp inhibitor. We showed that, unlike control YT-INDY, the Pgp activity of the transfectants (YT-mdr(+)) was only partially inhibited by R-verapamil. We also showed that Fas lytic activity was unaltered and that the loss of granule-mediated cytotoxicity was not due to reduced LFA-1 expression or to a decrease in target cell (TC) binding. Our data indicate that Pgp may be involved in the release of cytotoxic molecules.
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PMID:Over-expression of multidrug resistance P-glycoprotein inhibits NK granule-mediated lytic ability without affecting the Fas lytic pathway. 1032 58

P-glycoprotein (P-gp) is often expressed (40-50%) on leukemic cells at diagnosis in acute myelogenous leukemia (AML), and is even more frequently present after treatment failure. Several large cohorts of newly diagnosed AML patients treated with a classical anthracycline + standard doses of cytosine arabinoside were tested for the prognosis value of MDR1 phenotype, and demonstrated an high correlation between a significant increase of MDR1 gene expression and treatment failure (or, better, drug resistance). This P-gp(+) drug resistance could be due either to a particular phenotype of bad prognosis AML, as it is suggested by the association of myelodysplasia, complex karyotype and advanced age with MDR1 phenotype, or due primarily to the active efflux of anthracyclines and VP16 in P-gp(+) leukemic cells. Several observations tend to confirm the functional role of the P-gp in clinical drug resistance; (i) using multivariate analysis, MDR1 phenotype appears to be an independent variable, as potent (or higher) as karyotype and age for predicting in vivo drug resistance; (ii) the prognostic value is limited to the CD34(+)/P-gp(+) phenotype, wich is linked to a functional P-gp; (iii) the in vitro sensitivity to anthracyclines and VP16 is highly correlated with P-gp expression. All these data argue for an early use of P-gp modifier agents in the treatment of AML. The role of the MDR1 gene in ALL resistance is controversial and marginal compared to the sensitivity of ALL blasts to glucocorticoids, and the frequency of MDR1 phenotype is low at diagnosis, and is increasing only after repetitive chemotherapies.
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PMID:MDR1/P-GP expression as a prognostic factor in acute leukemias. 1050 Jul 74