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Assessment of early changes in H-3-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression
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| Title: | Assessment of early changes in H-3-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression |
| Authors: | Zhao, Songji Browse this author →KAKEN DB | | Kuge, Yuji Browse this author →KAKEN DB | | Zhao, Yan Browse this author | | Takeuchi, Satoshi Browse this author | | Hirata, Kenji Browse this author →KAKEN DB | | Takei, Toshiki Browse this author | | Shiga, Tohru Browse this author →KAKEN DB | | Dosaka-Akita, Hirotoshi Browse this author | | Tamaki, Nagara Browse this author →KAKEN DB |
| Keywords: | H-3-FLT | | Gefitinib | | Molecular-targeted therapy | | A431 | | Athymic nude mice |
| Issue Date: | 6-Nov-2013 |
| Publisher: | Biomed central |
| Journal Title: | BMC cancer |
| Volume: | 13 |
| Start Page: | 525 |
| Publisher DOI: | 10.1186/1471-2407-13-525 |
| PMID: | 24191959 |
| Abstract: | Background: The purpose of this study was to evaluate whether early changes in 3'-deoxy-3'-H-3-fluorothymidine (H-3-FLT) uptake can reflect the antiproliferative effect of gefitinib in a human tumor xenograft, in comparison with the histopathological markers, Ki-67 and phosphorylated EGFR (phospho-EGFR). Methods: An EGFR-dependent human tumor xenograft model (A431) was established in female BALB/c athymic mice, which were divided into three groups: one control group and two treatment groups. Mice in the treatment groups were orally administered a partial regression dose (100 mg/kg/day) or the maximum tolerated dose of gefitinib (200 mg/kg/day), once daily for 2 days. Mice in the control group were administered the vehicle (0.1% Tween 80). Tumor size was measured before and 3 days after the start of treatment. Biodistribution of H-3-FLT and F-18-FDG (%ID/g/kg) was examined 3 days after the start of the treatment. Tumor cell proliferative activity with Ki-67 was determined. Immunohistochemical staining of EGFR and measurement of phospho-EGFR were also performed. Results: High expression levels of EGFR and Ki-67 were observed in the A431 tumor. After the treatment with 100 and 200 mg/kg gefitinib, the uptake levels of H-3-FLT in the tumor were significantly reduced to 67% and 61% of the control value, respectively (0.39 +/- 0.09, 0.36 +/- 0.06, 0.59 +/- 0.11% ID/g/kg for 100 mg/kg, 200 mg/kg, and control groups, respectively; p < 0.01 vs. control), but those of F-18-FDG were not. After the treatment with 100 and 200 mg/kg gefitinib, the expression levels of Ki-67 in the tumor were markedly decreased (4.6 +/- 2.4%, 6.2 +/- 1.8%,and 10.4 +/- 5.7% for 100 mg/kg, 200 mg/kg, and control groups, respectively, p < 0.01 vs. control). The expression levels of the phospho-EGFR protein also significantly decreased (29% and 21% of the control value for 100, and 200 mg/kg, respectively p < 0.01 vs. control). There was no statistically significant difference in tumor size between pre- and post-treatments in each group. Conclusion: In our animal model, H-3-FLT uptake levels significantly decreased after the treatment with two different doses of gefitinib before a significant change in tumor size was observed. These results were confirmed by the immunohistochemical staining of Ki-67 and phospho-EGFR protein immunoassay. Thus, it was indicated that early changes in H-3-FLT uptake may reflect the antiproliferative effect of gefitinib in a mouse model of a human epidermoid cancer. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/54550 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 趙 松吉
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