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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
1998-11-3
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pubmed:abstractText |
To evaluate the concept that transfer of the human carboxylesterase (CE) gene will overcome the drug resistance of a solid tumor to CPT-11 (irinotecan), we used an adenovirus vector (AdCMV.CE) carrying human CE cDNA to infect CPT-11-resistant A549 human adenocarcinoma cells (A549/CPT) in vitro and in vivo and evaluated cell growth over time. The A549/CPT cells, selected by stepwise and continuous exposure of parental A549 cells to CPT-11 over 10 months, had a 6-fold resistance to CPT-11 and 42% CE activity in comparison with parental A549 cells. AdCMV.CE infection resulted in an increase in functional CE protein in resistant cells in vitro that was sufficient to convert CPT-11 to its active metabolite, SN-38, and effectively suppressed resistant cell growth in vitro in the presence of CPT-11. When AdCMV.CE was directly injected into established s.c. resistant A549-based tumors in nude mice receiving CPT-11, there was a 1.8-fold reduction in tumor size at day 20 compared to that of controls (P < 0.05). These observations suggest that adenovirus-mediated gene transfer of the human CE gene and concomitant administration of CPT-11 may have potential as a strategy for local control of acquired CPT-11 resistance of solid tumors.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Carboxylesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Carboxylic Ester Hydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/irinotecan
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
58
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4368-74
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9766666-Adenocarcinoma,
pubmed-meshheading:9766666-Adenoviruses, Human,
pubmed-meshheading:9766666-Antineoplastic Agents,
pubmed-meshheading:9766666-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:9766666-Camptothecin,
pubmed-meshheading:9766666-Carboxylesterase,
pubmed-meshheading:9766666-Carboxylic Ester Hydrolases,
pubmed-meshheading:9766666-Cell Division,
pubmed-meshheading:9766666-Cell Survival,
pubmed-meshheading:9766666-Clone Cells,
pubmed-meshheading:9766666-DNA, Complementary,
pubmed-meshheading:9766666-DNA Topoisomerases, Type I,
pubmed-meshheading:9766666-Drug Resistance, Neoplasm,
pubmed-meshheading:9766666-Genetic Vectors,
pubmed-meshheading:9766666-Humans,
pubmed-meshheading:9766666-Lung Neoplasms,
pubmed-meshheading:9766666-Recombinant Proteins,
pubmed-meshheading:9766666-Transfection,
pubmed-meshheading:9766666-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
Reversal of CPT-11 resistance of lung cancer cells by adenovirus-mediated gene transfer of the human carboxylesterase cDNA.
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pubmed:affiliation |
Division of Pulmonary and Critical Care Medicine, The New York Hospital-Cornell Medical Center, New York 10021, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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