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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2010-9-29
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pubmed:abstractText |
The combination therapy of CPT-11, a prodrug of SN-38, with S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, shows a high clinical response rate in non-small cell lung cancer (NSCLC). However, this combination causes severe toxicities such as diarrhea. Here, we investigated the advantages of treatment with the SN-38-incorporating polymeric micelles NK012 over CPT-11 in combination with S-1 in mice bearing a NSCLC xenograft in terms of antitumor activity and toxic effects, particularly intestinal toxicity. In vitro cytotoxic effects were examined in human NSCLC cell lines (A549, PC-9, PC-14, EBC-1 and H520). In vivo antitumor effects were evaluated in PC-14- and EBC-1-bearing mice after NK012 or CPT-11 administration on Days 0 and 7 and S-1 administration on Days 0-13. Pathological changes in the small intestine were also investigated. The in vitro growth inhibitory effects of NK012 were 56.8- to 622-fold more potent than those of CPT-11. NK012/S-1 treatment showed significantly higher antitumor activity both in PC-14-bearing (p = 0.0007) and EBC-1-bearing mice (p < 0.0001) than CPT-11/S-1 treatment. The deformity and decrease in the density of intestinal villi were more severe in CPT-11/S-1-treated mice than in NK012/S-1-treated mice. NK012/S-1 combination is a promising candidate regimen against NSCLC without inducing toxicities such as severe diarrhea and therefore warrants clinical evaluation.
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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/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Dihydrouracil Dehydrogenase (NADP),
http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations,
http://linkedlifedata.com/resource/pubmed/chemical/Micelles,
http://linkedlifedata.com/resource/pubmed/chemical/Oxonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/S 1 (combination),
http://linkedlifedata.com/resource/pubmed/chemical/Tegafur,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidylate Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/irinotecan
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1097-0215
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
127
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2699-706
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pubmed:meshHeading |
pubmed-meshheading:20198621-Animals,
pubmed-meshheading:20198621-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:20198621-Camptothecin,
pubmed-meshheading:20198621-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:20198621-Cell Line, Tumor,
pubmed-meshheading:20198621-Dihydrouracil Dehydrogenase (NADP),
pubmed-meshheading:20198621-Drug Combinations,
pubmed-meshheading:20198621-Drug Delivery Systems,
pubmed-meshheading:20198621-Drug Synergism,
pubmed-meshheading:20198621-Female,
pubmed-meshheading:20198621-Humans,
pubmed-meshheading:20198621-Intestinal Mucosa,
pubmed-meshheading:20198621-Lung Neoplasms,
pubmed-meshheading:20198621-Mice,
pubmed-meshheading:20198621-Mice, Inbred BALB C,
pubmed-meshheading:20198621-Mice, Nude,
pubmed-meshheading:20198621-Micelles,
pubmed-meshheading:20198621-Oxonic Acid,
pubmed-meshheading:20198621-RNA, Messenger,
pubmed-meshheading:20198621-Tegafur,
pubmed-meshheading:20198621-Thymidylate Synthase,
pubmed-meshheading:20198621-Xenograft Model Antitumor Assays
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pubmed:year |
2010
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pubmed:articleTitle |
Synergistic antitumor activity of the SN-38-incorporating polymeric micelles NK012 with S-1 in a mouse model of non-small cell lung cancer.
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pubmed:affiliation |
Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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