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)

Two monoclonal antibodies, MRK16 and C219, both directed at the 170 kDa P-glycoprotein multidrug resistance agent, were applied to frozen sections or cytospin preparations from normal human tissues and 60 non-Hodgkin's malignant lymphomas. Adrenal gland, kidney, liver and pancreas were always stained by the reagents, albeit with slightly different patterns. Brain capillaries as well as macrophages and some elements of the bone marrow, peripheral blood, ovarian stroma and colonic, gastric and jejunal mucosa were positive in all examined preparations. There were differences in the staining patterns with the two antibodies. Among the 60 non-Hodgkin's lymphomas, 25 contained a number of positive cells, which ranged from 2% to 100%. No correlation was seen between the expression of P170 and histological type, stage, clinical symptoms or growth fraction. A close relationship was shown between the presence of P170 positive elements and the clinical course of the disease (P less than 0.001).
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PMID:Immunohistochemical detection of the multidrug transport protein P170 in human normal tissues and malignant lymphomas. 168 59

Monoclonal antibody MRK16 was used to determine the location of P-glycoprotein, the product of the multidrug-resistance gene (MDR1), in normal human tissues. The protein was found to be concentrated in a small number of specific sites. Most tissues examined revealed very little P-glycoprotein. However, certain cell types in liver, pancreas, kidney, colon, and jejunum showed specific localization of P-glycoprotein. In liver, P-glycoprotein was found exclusively on the biliary canalicular front of hepatocytes and on the apical surface of epithelial cells in small biliary ductules. In pancreas, P-glycoprotein was found on the apical surface of the epithelial cells of small ductules but not larger pancreatic ducts. In kidney, P-glycoprotein was found concentrated on the apical surface of epithelial cells of the proximal tubules. Colon and jejunum both showed high levels of P-glycoprotein on the apical surfaces of superficial columnar epithelial cells. Adrenal gland showed high levels of P-glycoprotein diffusely distributed on the surface of cells in both the cortex and medulla. These results suggest that the protein has a role in the normal secretion of metabolites and certain anti-cancer drugs into bile, urine, and directly into the lumen of the gastrointestinal tract.
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PMID:Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. 244 83

Multidrug resistance to anticancer drugs proved to be related to the MDR1 gene which encodes the P-glycoprotein, an energy-dependent drug-efflux pump for lipophilic drugs. We investigated the expression of the MDR1 gene in clinical samples by RT-PCR. The subjects were all resected cases of 14 colorectal cancers, five gastric cancers, two esophageal cancers, two gallbladder cancers and 20 lung cancers. Adrenal gland was used as a positive control. Total RNA was extracted from a fresh tissue sample. The cDNA was synthesized from 1 microgram of total RNA using reverse transcriptase. With the above cDNA as the template, amplification of the 157-bp fragment of the MDR1 gene was performed using PCR. The PCR product was polyacrylamide gel-electrophoresed and ethidium bromide-stained. In addition, a dot blot analysis was performed to quantify the amount of PCR product. Since PCR was performed simultaneously under the same conditions, the PCR product was quantified at four stages, from (3+) to (-), to indicate the degree of expression of MDR1 mRNA. Adrenal gland showed (3+)-(2+) and colorectal cancer exhibited mostly (2+)-(1+). Both cancerous and non-cancerous areas evidenced a similar degree of expression in the cases of colorectal cancer. The MDR1 gene was expressed at low levels in other digestive tract cancers and in lung cancer. The levels of MDR1 expression revealed no correlation to either histological type or clinical stage. The present method may contribute to designing anti-cancer protocols.
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PMID:[Analysis of MDR1 (multidrug resistance) gene expression by RT-PCR]. 838 54