Epidermal growth factor receptor as a target for anti-proliferative treatment of proliferative cholangitis in hepatolithiasis

The Journal of Surgical Research
Fu Yu LiTimothy M Pawlik

Abstract

In recent years, with a deeper understanding of pathologic changes in hepatolithiasis, more and more attention has been paid to the relationship of postoperative remnant proliferative cholangitis (PC) with stone recurrence and biliary restenosis, but effective management strategies have not yet been developed. Thus, the aim of this study was to determine whether epidermal growth factor receptor inhibitor (AG-1478) could inhibit hyperplasia and lithogenic potentiality of PC. The PC animal model was established via retrograde insertion of a 5-0 nylon thread into the common bile duct through Vater's papilla. The common bile duct in the therapeutic group received a single intraluminal administration of AG-1478, followed by weekly intraperitoneal injections of AG-1478. Subsequently, influence of EGFR inhibitor on hyperplasia, apoptosis, and lithogenic potential of PC were evaluated via histology, expression changes of EGFR, BrdU, Ki-67, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Fas, mucin 5 AC, and collagen I. EGFR inhibitor AG-1478 was effective not only in inhibiting the mRNA and protein expression of EGFR, BrdU, and Ki-67, but also in increasing Fas mRNA expression and TUNEL-positive cells, as a result...Continue Reading

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Citations

Sep 13, 2013·BioMed Research International·Zipei LiuShuguang Wang
Jul 4, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anna PellatLaura Fouassier
May 23, 2019·International Journal of Molecular Medicine·San-Hu LiuJie Zhou

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