Schmidt, Katharina and Moser, Christian and Hellerbrand, Claus and Zieker, Derek and Wagner, Christine and Redekopf, Julia and Schlitt, Hans J. and Geissler, Edward K. and Lang, Sven A. (2015) Targeting Fibroblast Growth Factor Receptor (FGFR) with BGJ398 in a Gastric Cancer Model. ANTICANCER RESEARCH, 35 (12). pp. 6655-6665. ISSN 0250-7005, 1791-7530
Full text not available from this repository. (Request a copy)Abstract
Aim: To assess the efficacy of targeting fibroblast growth factor receptor (FGFR) with the pan-FGFR inhibitor BGJ398 in a gastric cancer (GC) model. Materials and Methods: Expression of FGFRs was determined in GC cell lines (KKLS, MKN-45, TMK-1). Impact of the FGFR inhibitor BGJ398 on growth, motility, signaling, expression of transcription factors and secretion of vascular endothelial growth factor-A (VEGFA) was determined in vitro. Results were validated in subcutaneous tumor models. Results: In vitro, FGFR inhibition was most effective in KKLS cells (high FGFR1, FGFR2IIIc, no FGFR2IIIb expression) with inhibition of growth, motility, signaling, c-MYC expression and VEGFA secretion. BGJ398 showed some activity in MKN-45 cells (intermediate FGFR1, high FGFR2IIIb, low FGFR2IIIc expression), while TMK-1 cells (low FGFR1, no FGFR2IIIb and FGFR2IIIc expression) did not respond. Results were confirmed in vivo with strongest efficacy on growth in KKLS tumors and only minor impairment of TMK-1 lesions. Conclusion: Efficacy of FGFR inhibition is dependent on FGFR1 and FGFR2IIIc expression in GC models.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLORECTAL-CANCER; TYROSINE KINASE; K-SAM; ANGIOGENESIS; INHIBITION; NVP-BGJ398; EXPRESSION; CARCINOMA; CELLS; FGFR; angiogenesis; gastric cancer |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 May 2019 11:14 |
| Last Modified: | 02 May 2019 11:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4359 |
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