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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1985-8-5
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pubmed:abstractText |
Resistance to methotrexate was developed by continuous exposure of P388 murine leukemia cells in vitro to increasing concentrations of methotrexate up to 1 X 10(-7) M. Once established, the resistance to methotrexate was stable. This was also found in methotrexate-resistant cells that were maintained in methotrexate-free medium for more than 4 months. The sensitivity of the methotrexate-resistant P388 cells to doxorubicin was comparable to the sensitivity measured in the parental cell line. Another methotrexate-resistant cell line was developed, in a similar way, from doxorubicin-resistant P388 cells. This methotrexate-resistant cell line maintained its original resistance to doxorubicin. In methotrexate-sensitive cells, the dimethyl and dibutyl esters of methotrexate were 18.3- and 2.7-fold less active, respectively, than the free methotrexate in inhibiting cell growth. In methotrexate-resistant cells, the inhibitory effect of the methotrexate dimethyl ester was similar to its effect on the methotrexate-sensitive cell line. The activity of the methotrexate dibutyl ester was 3.3-fold lower than its activity in the parental cell line. However, both esters of methotrexate were much more active than free methotrexate in the methotrexate-resistant cell line. In the doxorubicin-resistant cell line, the activity of free methotrexate was comparable to its activity in the doxorubicin-sensitive parent cell line. However, this cell line was remarkably resistant to the ester analogs of methotrexate. The clinical implications of these findings are discussed.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0344-5704
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
31-4
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:4006047-Animals,
pubmed-meshheading:4006047-Cell Survival,
pubmed-meshheading:4006047-Cells, Cultured,
pubmed-meshheading:4006047-Doxorubicin,
pubmed-meshheading:4006047-Drug Resistance,
pubmed-meshheading:4006047-Esterification,
pubmed-meshheading:4006047-Leukemia, Experimental,
pubmed-meshheading:4006047-Leukemia P388,
pubmed-meshheading:4006047-Methotrexate,
pubmed-meshheading:4006047-Mice
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pubmed:year |
1985
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pubmed:articleTitle |
Cross resistance to esters of methotrexate in a doxorubicin-resistant subline of P388 murine leukemia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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