ObjectiveTo investigate the effectiveness of epidermal growth factor receptor antagonist (AG-1478) on chronic proliferative cholangitis (CPC), so as to investigate new treatment approach for hepatolithiasis associated with CPC. MethodsForty-six SD rats were divided into 5 groups: CPC model group (n=10), only made models. AG-1478 treatment group (divided into 3 mg/kg， 6 mg/kg， and 12 mg/kg groups, n=10 per group), the common bile ducts in CPC animal model received an intralumenal administration of AG-1478 at the meantime of modeling, followed by intraperitoneal AG-1478 injection of 1.5 mg/(kg·d) for 7 days. Sham operation group (SO group, n=6). Subsequently, histopathological observation, immunohistochemistry, real time PCR， and Western blot were used to evaluate the mRNA expression and influence of AG-1478 on the hyperplasia （EGFR， ki-67， BrdU， collagen Ⅰ protein） and lithogenic potential (Mucin 5AC) of CPC. ResultsCompared with CPC model group, the expressions of EGFR, ki-67， and BrdU were obviously decreased in the AG-1478 treatment group. Also, the inhibition of hyperplasia of biliary epithelium and collagen fibers were confirmed by histopathological observation. Additionally, the expressions of Mucin 5AC mRNA and collagen Ⅰ protein remarkable decreased in the AG-1478 treatment group (Plt;0.05). Conclusions EGFR inhibitor (AG-1478) could shows inhibitory effectivenss on the CPC-mediated hyperplasia and lithogenic potential, and therefore holds promise as the new treatment approach for CPC.
ObjectiveTo summarize progression of growth factor receptor (GFR) signaling pathway in endocrineresistant breast cancer. Method Literatures about mechanisms of GFR signaling pathway in the development of endocrineresistant breast cancer were reviewed. ResultsThe crosstalk between GFR and estrogen receptor (ER) signaling pathway had been reported to be involved in the development of endocrine-resistant breast cancer. Interrupting this signaling pathway could overcome endocrine therapy resistance. Many clinical trails had shown that the utilizing endocrine therapy combined with GFR inhibitors could obviously increase the survival rate of patients with breast cancer. ConclusionSeveral agents targeting GFR signaling pathways show a great potential for treatment of patients with breast cancer.