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Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice

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Title: Inhibition of Eph receptor A4 by 2,5-dimethylpyrrolyl benzoic acid suppresses human pancreatic cancer growing orthotopically in nude mice
Authors: Takano, Hironobu Browse this author
Nakamura, Toru Browse this author →KAKEN DB
Tsuchikawa, Takahiro Browse this author →KAKEN DB
Kushibiki, Toshihiro Browse this author
Hontani, Kouji Browse this author
Inoko, Kazuho Browse this author
Takahashi, Mizuna Browse this author
Sato, Shoki Browse this author
Abe, Hirotake Browse this author
Takeuchi, Shintaro Browse this author
Sato, Nagato Browse this author
Hiraoka, Kei Browse this author
Nishihara, Hiroshi Browse this author →KAKEN DB
Shichinohe, Toshiaki Browse this author →KAKEN DB
Hirano, Satoshi Browse this author →KAKEN DB
Keywords: EphA4
prognostic factor
2,5-dimethylpyrrolyl benzoic acid
human pancreatic cancer
orthotopic models
Issue Date: 19-Oct-2015
Publisher: Impact Journals
Journal Title: Oncotarget
Volume: 6
Issue: 38
Start Page: 41063
End Page: 41076
Publisher DOI: 10.18632/oncotarget.5729
Abstract: Ephrin receptor A4 (EphA4) is overexpressed in human pancreatic adenocarcinoma (PDAC) and activate cell growth. Recent studies have identified small molecules that block EphA4. In this study, we investigated the correlation between EphA4 expression and the prognosis of patients with PDAC. We also examined the cytostatic efficacy of 2,5-dimethylpyrrolyl benzoic acid (compound 1), a small molecule that blocks EphA4, in PDAC cells. Overall survival of patients with EphA4 positivity was significantly shorter than that of patients with EphA4 negativity (P = 0.029). In addition, multivariate analysis revealed that EphA4 expression was an independent prognostic factor in PDAC patients (P = 0.039). Compound 1 showed a cytostatic efficacy in PDAC cells expressing EphA4 in vitro and in vivo. Our study indicated that compound 1 suppressed both EphA4 and Akt phosphorylations, and induced apoptosis in PDAC cells expressing EphA4. In conclusion, compound 1 has a high potential as a therapeutic agent for patients with PDAC.
Type: article
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)

Submitter: 中村 透

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