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459 Inhibition of the Secretin/Secretin Receptor Axis Attenuates Biliary Fibrosis During Cholestasis
- Source :
- Gastroenterology. 148:S-980
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- A S L D A b st ra ct s BGJ398, a pan-FGFR inhibitor currently being employed in human trials, resulted in a significant increase in cellular apoptosis. Tumor tissue from mice sacrificed 10 weeks after biliary oncogene transduction of AKT and YAP also demonstrated increased expression of FGFR 1-4. BGJ398 treatment resulted in a significant reduction in tumor burden and increase in tumor cell apoptosis as assessed by the TUNEL assay in our mouse model of CCA. In Conclusion, YAP is a critical oncogene in CCA and promotes biliary carcinogenesis, in part, via upregulation of FGFR. In a murine genetic model of CCA, the FGFR specific inhibitor BGJ398 significantly reduces tumor burden by inducing apoptosis. Thus, inhibition of FGFR represents a promising therapeutic approach in YAP-driven human CCA.
Details
- ISSN :
- 00165085
- Volume :
- 148
- Database :
- OpenAIRE
- Journal :
- Gastroenterology
- Accession number :
- edsair.doi...........ab230d5c8644fe1d6bb8f94309256c2f