ID | 30755 |
JaLCDOI | |
FullText URL | |
Author |
Doihara, Hiroyoshi
Kaken ID
researchmap
Oota, Tetsuya
Hara, Fumikata
Takahashi, Hirotoshi
Yoshitomi, Seiji
Ishibe, Youichi
Shimizu, Nobuyoshi
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Abstract | Human esophageal cancers have been shown to express high levels of epidermal growth factor receptor (EGFR) and a relationship between high EGFR expression and local advance, the number of lymph node metastases, life expectancy, and sensitivity to chemo-radiotherapy has been demonstrated. We examined the use of gefitinib, an orally active EGFR-selective tyrosine kinase inhibitor, as a new strategy for treatment of esophageal carcinoma. The effects of gefitinib were evaluated in monotherapy and in combination with radiotherapy in human esophageal carcinoma cell lines. Gefitinib produced a dose-dependent inhibition of cellular proliferation in all of the 8 esophageal carcinoma cell lines examined, with IC50 values ranging from 5.7 microM to 36.9 microM. In combination, gefitinib and radiotherapy showed a synergistic effect in 2 human esophageal carcinoma cell lines and an additive effect in 5 cell lines. Western blotting demonstrated that gefitinib blocked activation of the EGFR-extracellular signal-regulated kinase (Erk) pathway and the EGFR-phosphoinositide-3 kinase (PI3K)-Akt pathway after irradiation. These results suggest that further evaluation of EGFR blockade as a treatment for esophageal cancer should be performed, and that radiotherapy combined with EGFR blockade may enhance the response of esophageal carcinoma to therapy. |
Keywords | gefitinib
esophageal cancer
radiosensitivity
epidermal growth factor receptor
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Amo Type | Article
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Publication Title |
Acta Medica Okayama
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Published Date | 2006-02
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Volume | volume60
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Issue | issue1
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Publisher | Okayama University Medical School
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Start Page | 25
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End Page | 34
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ISSN | 0386-300X
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NCID | AA00508441
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Content Type |
Journal Article
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language |
English
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File Version | publisher
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Refereed |
True
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PubMed ID | |
Web of Science KeyUT |