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Activation of p38 mitogen-activated protein kinase is necessary for gemcitabine-induced cytotoxicity in human pancreatic cancer cells

https://asahikawa-med.repo.nii.ac.jp/records/208
https://asahikawa-med.repo.nii.ac.jp/records/208
6da40d70-cfd4-477b-9b93-df2e17919a4f
名前 / ファイル ライセンス アクション
249.pdf 249.pdf (513.7 kB)
Item type 学術雑誌論文 / Journal Article_02(1)
公開日 2007-02-27
タイトル
タイトル Activation of p38 mitogen-activated protein kinase is necessary for gemcitabine-induced cytotoxicity in human pancreatic cancer cells
言語 en
言語
言語 eng
資源タイプ
資源タイプ journal article
著者 小泉, 一也

× 小泉, 一也

小泉, 一也

ja-Kana コイズミ カズヤ

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Tanno, S

× Tanno, S

Tanno, S

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Nakano, Y

× Nakano, Y

Nakano, Y

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Habiro, A

× Habiro, A

Habiro, A

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Izawa, T

× Izawa, T

Izawa, T

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Mizukami, Y

× Mizukami, Y

Mizukami, Y

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Okumura, T

× Okumura, T

Okumura, T

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Kohgo, Y

× Kohgo, Y

Kohgo, Y

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著者 ローマ字
Koizumi Kazuya
書誌情報 ANTICANCER RESEARCH

巻 25, 号 5, p. 3347-3353, 発行日 2005-09-01
ISSN
収録物識別子タイプ ISSN
収録物識別子 0250-7005
リンクURL
内容記述タイプ Other
内容記述 http://www.ncbi.nlm.nih.gov/pubmed?term=Activation%20of%20p38%20mitogen-activated%20protein%20kinase%20is%20necessary%20for%20gemcitabine-induced%20cytotoxicity%20in%20human%20pancreatic%20cancer%20cells | http://www.ncbi.nlm.nih.gov/pubmed?term=Activation%20of%20p38%20mitogen-activated%20protein%20kinase%20is%20necessary%20for%20gemcitabine-induced%20cytotoxicity%20in%20human%20pancreatic%20cancer%20cells
抄録
内容記述タイプ Abstract
内容記述 Background: Gemcitabine is a pyrimidine nucleoside analogue that is clinically active against pancreatic cancer. We have recently demonstrated that p38 MAPK is specifically activated by gemcitabine and pharmacological blockade of p38 MAPK signaling prevented gemcitabine-induced apoptosis in human pancreatic cancer cells. In this study, we further investigated to clarify that p38 MAPK is implicated in the cytotoxic action of gemcitabine. Materials and Methods: Cells expressing a dominant-negative mutant of p38 MAPK were generated. Clonogenic assay was used to assess the long-term effect on cancer cell viability in the human pancreatic cancer cells, PK1 and PCI43. The p38 MAPK activation level was assessed using an antibody specific to the phosphorylated form. Results: Gemcitabine increased the activation level of p38 MAPK in a dose-dependent manner and induced apoptosis in tested two human pancreatic cancer cells lines. The selective p38 MAPK inhibitors, SB203580 and SB202190, reduced gemcitabine-induced activation of p38 MAPK, prevented the gemcitabine-induced apoptosis and increased long-term clonogenic survival. Overexpression of a dominant-negative p38 mutant in cells resulted in the reduction of gemcitabine-induced p38 MAPK activation and apoptosis, and increases in clonogenic survival. Conclusions: These results strongly suggest that the activation of p38 MAPK signaling is necessary for gemcitabine-induced cell death in human pancreatic cancer cells. Based upon these results, we would suggest that molecules of p38 MAPK signaling pathways should be listed as novel targets for gemcitabine-based therapy.
注記
内容記述タイプ Other
注記 International Institute of Anticancer Research, Koizumi, K; Tanno, S; Nakano, Y; Habiro, A; Izawa, T; Mizukami, Y; Okumura, T; Kohgo, Y, ANTICANCER RESEARCH, 25(5), 3347-3353, 2005.
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資源タイプ text
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小泉, 一也, Tanno, S, Nakano, Y, Habiro, A, Izawa, T, Mizukami, Y, Okumura, T, Kohgo, Y, n.d., Activation of p38 mitogen-activated protein kinase is necessary for gemcitabine-induced cytotoxicity in human pancreatic cancer cells: 3347–3353 p.

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