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• W4361948799 abstract "<div>Abstract<p><b>Purpose:</b> Focal adhesion kinase (FAK) regulates integrin and growth factor–mediated signaling pathways to enhance cell migration, proliferation, and survival, and its up-regulation correlates malignant grade and poor outcome in several types of cancer. In this study, we aimed to raise a potential therapeutic strategy using a FAK inhibitor for Barrett's esophageal adenocarcinoma.</p><p><b>Experimental Design:</b> The expression status of FAK in clinical Barrett's esophageal adenocarcinoma tissues was determined by immunohistochemistry. Cultured esophageal adenocarcinoma cells were treated with TAE226, a specific FAK inhibitor with an additional effect of inhibiting insulin-like growth factor-I receptor (IGF-IR), to assess its anticancer effect <i>in vitro</i>. Western blot was carried out to explore a participating signaling pathway for TAE226-induced cell death. Furthermore, TAE226 was orally administered to s.c. xenograft animals to investigate its anticancer effect <i>in vivo</i>.</p><p><b>Results:</b> Strong expression of FAK was found in 94.0% of Barrett's esophageal adenocarcinoma compared with 17.9% of Barrett's epithelia, suggesting that FAK might play a critical role in the progression of Barrett's esophageal adenocarcinoma. When esophageal adenocarcinoma cells were treated with TAE226, cell proliferation and migration were greatly inhibited with an apparent structural change of actin fiber and a loss of cell adhesion. The activities of FAK, IGF-IR, and AKT were suppressed by TAE226 and subsequent dephosphorylation of BAD at Ser¹³⁶ occurred, resulting in caspase-mediated apoptosis. <i>In vivo</i> tumor volume was significantly reduced by oral administration of TAE226.</p><p><b>Conclusions:</b> These results suggest that TAE226, a dual tyrosine kinase inhibitor for FAK and IGF-IR, could become a new remedy for Barrett's esophageal adenocarcinoma.</p></div>" @default.
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• W4361948799 date "2023-03-31" @default.
• W4361948799 modified "2023-10-16" @default.
• W4361948799 title "Data from Dual Tyrosine Kinase Inhibitor for Focal Adhesion Kinase and Insulin-like Growth Factor-I Receptor Exhibits Anticancer Effect in Esophageal Adenocarcinoma <i>In vitro</i> and <i>In vivo</i>" @default.
• W4361948799 doi "https://doi.org/10.1158/1078-0432.c.6517002.v1" @default.
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