Browsing by Author "IBANEZ, L"

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    ISOLATION OF PEROXISOMES FROM FROZEN HUMAN LIVER SAMPLES
    (1992) ALVAREZ, A; HIDALGO, U; KAWADA, ME; MUNIZAGA, A; ZUNIGA, A; IBANEZ, L; KOENIG, CS; SANTOS, MJ
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    MULTIDRUG RESISTANCE GENE AND P-GLYCOPROTEIN EXPRESSION IN GASTRIC ADENOCARCINOMA AND PRECURSOR LESIONS
    (1991) VOLLRATH, V; CHIANALE, J; GONZALEZ, S; DUARTE, I; ANDRADE, L; IBANEZ, L
    Overexpression of the Multiple Drug Resistance gene (MDR1) has been proposed as a major mechanism related to both intrinsic and acquired resistance to chemotherapeutic agents. The gene product is a membrane protein (P-glycoprotein), that acts as an energy-dependent drug efflux pump decreasing drug accumulation in resistant tumor cells. We have characterized MDR1 and P-Glycoprotein expression in human gastric adenocarcinoma and in precursor lesions. MDR1 mRNAs, analyzed by dot-blot technique, were detected in 9 of 10 non-tumoral gastric mucoase and in 8 of 10 gastric adenocarcinomas. Immunohistochemical analysis, using the MRK16 monoclonal antibody, revealed heterogeneous expression of P-Glycoprotein in individual cells. The P-Glycoprotein was found on the surface of cells of gastric areas with intenstinal metaplasia subtype III. This type of intestinal metaplasia, also called "colonic metaplasia", has been strongly associated with a high risk for the development of gastric cancer. The fact that the P-Glycoprotein was detected in this precursor lesion is consistent with the intestinal metaplasiadysplasia and carcinoma sequence proposed in the histogenesis of this tumor. The finding that P-Glycoprotein was heterogeneously expressed in malignant cells of some gastric adenocarcinomas also suggests that this transporter system probably contributes to primary and secondary multidrug resistance in this neoplasm.