Source:http://linkedlifedata.com/resource/pubmed/id/19925494
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2010-2-23
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pubmed:abstractText |
Lapatinib is a small molecule inhibitor of both HER2 and the epidermal growth factor receptor (EGFR). We investigated the effect of treatment with lapatinib alone or in combination with a fluoropyrimidine derivative S-1 against pancreatic cancer. The HER2/EGFR expression in each of the four pancreatic cancer cell lines MiaPaca-2, PANC-1, Capan-1 and Capan-2 was measured by flow cytometry. The anti-tumor effects of lapatinib (30 mg/kg) and/or S-1 (10 mg/kg) were evaluated using female BALB/c nude mice xenografts generated using these four cell lines. Synergy between lapatinib and S-1 was examined by median effect analysis in vitro. Resected pancreatic cancer tissues from 137 patients were immunohistochemically stained with anti-human HER2 and EGFR antibodies. The administration of lapatinib as a single agent substantially suppressed tumor growth in vivo of all pancreatic cancer cell lines examined. A strong correlation was observed between HER2 expression and the anti-tumor effect of lapatinib in vivo. Lapatinib synergized with S-1 to inhibit the tumor growth of MiaPaca-2 and PANC-1 xenografts. When used as a single agent in vitro, lapatinib barely inhibit the cell growth of any cell line. However, lapatinib synergized with the anti-tumor activity of the S-1 components 5-fluorouracil and 5-chloro-2,4-dihydrogenase against all cell lines. Immunohistochemical staining demonstrated that 70% of the pancreatic cancers overexpressed HER2 and/or EGFR. Both lapatinib monotherapy and combined treatment with S-1 may be promising treatments for patients with pancreatic cancers; the majority these cancers express lapatinib target molecules.
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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/Drug Combinations,
http://linkedlifedata.com/resource/pubmed/chemical/Oxonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines,
http://linkedlifedata.com/resource/pubmed/chemical/S 1 (combination),
http://linkedlifedata.com/resource/pubmed/chemical/Tegafur,
http://linkedlifedata.com/resource/pubmed/chemical/lapatinib
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1349-7006
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
468-73
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pubmed:meshHeading |
pubmed-meshheading:19925494-Animals,
pubmed-meshheading:19925494-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:19925494-Cell Line, Tumor,
pubmed-meshheading:19925494-Drug Combinations,
pubmed-meshheading:19925494-Female,
pubmed-meshheading:19925494-Humans,
pubmed-meshheading:19925494-Mice,
pubmed-meshheading:19925494-Mice, Inbred BALB C,
pubmed-meshheading:19925494-Oxonic Acid,
pubmed-meshheading:19925494-Pancreatic Neoplasms,
pubmed-meshheading:19925494-Quinazolines,
pubmed-meshheading:19925494-Tegafur,
pubmed-meshheading:19925494-Xenograft Model Antitumor Assays
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pubmed:year |
2010
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pubmed:articleTitle |
In vitro and in vivo evidence that a combination of lapatinib plus S-1 is a promising treatment for pancreatic cancer.
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pubmed:affiliation |
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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