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

The immunohistochemical detection of multidrug resistance (MDR1) gene products and their mRNA within brain tumor cells has already been described by Fojo et al. 1987. 63 specimens of astrocytomas and glioblastomas were analysed in the present study (Grading type 1 to 4) by means of the monoclonal antibody JSB1. The endothelial cells were positive only in astrocytic tumors with a grading of 1. Increasing tumor grading resulted in more positive immunological reactions in tumor cells. The most impressive reaction could be found in anaplastic astrocytoma and glioblastoma (G3 and G4). Overexpression of this P-glycoprotein, a plasma membrane component of a relative molecular mass of 170 kDa was not only found in tumor cells of anaplastic astrocytomas, but also in endothelial cells and some non-neoplastic brain diseases. Positive immunological reactions in protoplasmatic astrocytes could be demonstrated in cases of phenylketonuria (1/1), tuberculous leptomeningitis (2/2), SSPE (3/4), X-ray necrosis (1/1) and necrotizing viral encephalitis (1/4). According to this, it seems that astrocytes are able to express P-glycoprotein under the influence of some special metabolic conditions. This underlines the detoxicating function of reactive astrocytes within the total number of cells in the CNS.
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PMID:[Expression of P-glycoprotein as a multidrug resistance gene product in human reactive astrocytes and astrocytoma]. 794 20

P-glycoprotein (P-gp) is a 170 kDa transmembrane glycoprotein which plays a significant role in modulating pleomorphic or multiple drug resistance (MDR) in a wide variety of human cancers like renal and colorectal carcinoma. However, its role in modulating drug resistance in other types of cancer is less well defined. The purpose of this review is to critically examine the evidence that P-gp plays an important role in producing drug resistance in astrocytic gliomas. Malignant astrocytoma is clinically resistant to most types of cytotoxic drugs, including those associated with the MDR phenotype and the cross-resistance patterns of short-term cultures derived from malignant glioma are consistent with this phenotype. Consequently, it might be expected that this tumor would express high levels of P-gp. However, immunohistochemical findings from a number of previous studies have provided conflicting data about the expression of P-gp in these tumors, although P-gp has been consistently detected in normal brain in the endothelial cells in cerebral blood vessels and is thought to contribute to the blood-brain barrier phenomena. In order to determine if P-gp contributes to drug resistance in malignant astrocytoma, we undertook a study of P-gp expression in a panel of short-term cultures derived from these tumors in which we determined the in vitro chemosensitivity. However, immunocytochemical studies with a panel of antibodies which recognize both internal and external epitopes of the P-gp molecule have consistently failed to show the characteristic membrane staining associated with MDR in any of the cultures, including those markedly cross-resistant to vincristine and doxorubicin. One antibody, JSB-1, showed heterogeneous granular cytoplasmic staining which was unrelated to a particular pattern of drug resistance. This is probably because this antibody cross-reacts with a widely distributed cytoplasmic antigen, pyruvate carboxylase, which is present in abundance in normal astrocytes. The unexpectedly poor specificities of many of the antibodies thought to be specific for P-gp is reviewed in the context of malignant astrocytoma. In conclusion, the role of P-gp in producing drug resistance in malignant astrocytoma is questionable and further studies might more profitably concentrate on the mechanisms of resistance to DNA-damaging agents like the nitrosoureas, methylating agents or platinum-based drugs.
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PMID:Does P-glycoprotein play a role in clinical resistance of malignant astrocytoma? 1063 Mar 53

Understanding and overcoming multidrug resistance (MDR) may be a promising strategy to develop more effective pharmacotherapies for malignant gliomas. In the present study, human malignant glioma cell lines (n=12) exhibited heterogeneous mRNA and protein expression and functional activity of the mdr gene-encoded P-glycoprotein (PGP) and MDR-associated protein (MRP). Correlation between mRNA expression, protein levels and functional activity was strong. Inhibition of PGP activity by verapamil or PSC 833 enhanced the cytotoxic effects of vincristine, doxorubicin, teniposide and taxol. Inhibition of MRP activity by indomethacin or probenecid enhanced the cytotoxic effects of vincristine, doxorubicin and teniposide. The human cerebral endothelial cell line, SV-HCEC, exhibited the strongest PGP activity of all cell lines. Five primary human glioblastomas and one anaplastic astrocytoma displayed heterogenous protein levels of PGP and MRP-1 in tumor cells and of PGP in biopsy specimens in vivo, but no functional activity of these proteins upon ex vivo culturing. These data suggest that the glioma cell line-associated MDR-type drug resistance is a result of long-term culturing and that cerebral endothelial, but not glioma cells, may contribute to MDR-type drug resistance of gliomas in vivo.
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PMID:P-glycoprotein and multidrug resistance-associated protein mediate specific patterns of multidrug resistance in malignant glioma cell lines, but not in primary glioma cells. 1465 54