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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1998-4-23
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pubmed:abstractText |
The overexpression of two membrane glycoproteins, P-glycoprotein and multidrug-resistance protein (MRP1) is a major cause of resistance to chemotherapeutic agents in the treatment of human cancers. Both proteins confer a similar multidrug-resistant (MDR) phenotype. 99mTc-MIBI, a myocardial imaging agent, which is also useful for the detection of a variety of tumours, has been shown to be a substrate for P-glycoprotein and MRP1. It thus may provide additional information about the P-glycoprotein and MRP1 status of tumour cells. In order to obtain information on the substrate specificity of these proteins, we have studied the transport kinetics of Tc-MIBI in two cell lines, K562/ADR and GLC4/ADR, which overexpress P-glycoprotein and MRP1, respectively. The mean active efflux coefficient ka, which is proportional to the ratio of maximal efflux rate VM to the apparent Michaelis-Menten constant Km, used to characterise the efficiency of the active efflux, was very similar being 1.9 +/- 0.6 x 10(-11) s(-1) x cells x ml and 1.3 +/- 0.5 x 10(-11) s(-1) x cells x ml for drug-resistant K562 and GLC4, respectively. These values are 50-100-times lower than for daunorubicin and other anthracycline derivatives, strongly suggesting that the efficiency of both transporters to pump Tc-MIBI is by far less than that to efflux anthracyclines. Our data show that (a) P-glycoprotein and MRP transporter efficiencies to wash out Tc-MIBI are similar, in spite of a different suspected mechanism of its transport and (b) that both transporters are less efficient to pump Tc-MIBI than to pump anthracyclines (the ka parameter is about 100-times lower for TC-MIBI than for anthracycline).
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Daunorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Multidrug Resistance-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Organotechnetium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Radiopharmaceuticals,
http://linkedlifedata.com/resource/pubmed/chemical/Valinomycin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0014-2956
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
252
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
140-6
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pubmed:dateRevised |
2007-7-23
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pubmed:meshHeading |
pubmed-meshheading:9523723-ATP-Binding Cassette Transporters,
pubmed-meshheading:9523723-Antibiotics, Antineoplastic,
pubmed-meshheading:9523723-Biological Transport,
pubmed-meshheading:9523723-Daunorubicin,
pubmed-meshheading:9523723-Drug Resistance, Multiple,
pubmed-meshheading:9523723-Humans,
pubmed-meshheading:9523723-Kinetics,
pubmed-meshheading:9523723-Membrane Potentials,
pubmed-meshheading:9523723-Multidrug Resistance-Associated Proteins,
pubmed-meshheading:9523723-Neoplasm Proteins,
pubmed-meshheading:9523723-Organotechnetium Compounds,
pubmed-meshheading:9523723-P-Glycoprotein,
pubmed-meshheading:9523723-Phenotype,
pubmed-meshheading:9523723-Radiopharmaceuticals,
pubmed-meshheading:9523723-Tumor Cells, Cultured,
pubmed-meshheading:9523723-Valinomycin
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pubmed:year |
1998
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pubmed:articleTitle |
Comparison of the kinetics of active efflux of 99mTc-MIBI in cells with P-glycoprotein-mediated and multidrug-resistance protein-associated multidrug-resistance phenotypes.
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pubmed:affiliation |
Laboratoire de Physicochimie Biomoléculaire et Cellulaire, Université Paris Nord, Bobigny, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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