ABSTRACT
Cholangiocarcinoma (CCA) is a fatal disease with increasing morbidity and poor prognosis due to poor response to conventional chemotherapy or radiotherapy. Neurotensin (NTS) has long been recognized as an important factor in the central nervous system and as an endocrine agent in the peripheral circulation via NTS receptor (NTSR) mediated actions. In recent years, NTS has been implicated in the carcinogenesis of numerous cancers; however, its role in cholangiocarcinoma remains obscure. Here, we observed the expression of NTS in cholangiocarcinoma vs. non-cancerous tissues and found that up-regulation of NTS facilitated cholangiocarcinoma cell metastasis and down-regulation of NTS inhibited their migration ability. Mechanistically, NTS drove cholangiocarcinoma cell metastasis via the EGFR/AKT pathway. Both the PI3-K inhibitor LY294002 or EGFR inhibitor Erlotinib stopped the discrepant metastatic capacity between NTS-depleted cholangiocarcinoma cells and control cells, further confirming that EGFR/AKT was required in NTS-promoted cholangiocarcinoma cell metastasis. More importantly, overexpression of NTS predicted poor prognosis of CCA patients. In summary, NTS could promote cholangiocarcinoma cells metastasis by amplifying EGFR/AKT signaling and may therefore be useful to predict patient prognosis.
Subject(s)
Bile Duct Neoplasms/pathology , Biomarkers, Tumor/metabolism , Cholangiocarcinoma/secondary , Neoplasm Recurrence, Local/pathology , Neurotensin/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Apoptosis , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/metabolism , Biomarkers, Tumor/genetics , Case-Control Studies , Cell Movement , Cell Proliferation , Cholangiocarcinoma/genetics , Cholangiocarcinoma/metabolism , ErbB Receptors/genetics , ErbB Receptors/metabolism , Follow-Up Studies , Humans , Lymphatic Metastasis , Neoplasm Invasiveness , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Neurotensin/genetics , Prognosis , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction , Survival Rate , Tumor Cells, CulturedABSTRACT
Objective:To explore clinical and fistula origin characteristics of congenital coronary artery fistula (CAF).Methods:Clinical and coronary angiographic (CAG)data of 37 congenital CAF patients,who were treated in our hospital from Apr 2011 to Aug 2016 and diagnosed by CAG,were retrospectively analyzed.Chief complaint symptoms were analyzed.According to fistula origin location,patients were divided into left anterior descending (LAD)group (n=23),right coronary artery (RCA)group (n=6),LAD & RCA group (n=2),left circumflex (LCX)group (n=5)and left main (LM)group (n=1).Characteristics of fistula origin and drainage location dis-tribution were analyzed.Results:Among the chief complaints of 37 congenital CAF patients,there were 24 cases (64.9%)of chest tightness and short of breath,six cases (16.2%)of chest pain,five cases (13.5%)of palpitations and two cases (5.4%)of heart murmur in physical examination.Compared with RCA group,LAD & RCA group, LCX group and LM group,there was significant rise in percentage of LAD fistula origin (16.2%,5.4%,13.5%, 2.7% vs.62.2%),P <0.01 all,but there were no significant difference among other groups,P >0.05 all.The 23 cases of LAD fistula origin included 22 cases of pulmonary artery fistulas (PAF)and one case of bronchial artery fis-tulas (BAF);the six cases of RCA fistula origin included three cases of PAF,two cases of right atrial fistulas (RAF) and one case of left ventricular fistulas (LVF);the five cases of LCX fistula origin included two cases of RAF,and one case of PAF,LVF and RVF respectively.Conclusion:Coronary angiography is the gold standard to diagnose congenital CAF.Percentage of congenital CAF originated from left coronary artery is significantly more than that of right coronary artery.
ABSTRACT
Objective:To explore clinical and fistula origin characteristics of congenital coronary artery fistula (CAF).Methods:Clinical and coronary angiographic (CAG)data of 37 congenital CAF patients,who were treated in our hospital from Apr 2011 to Aug 2016 and diagnosed by CAG,were retrospectively analyzed.Chief complaint symptoms were analyzed.According to fistula origin location,patients were divided into left anterior descending (LAD)group (n=23),right coronary artery (RCA)group (n=6),LAD & RCA group (n=2),left circumflex (LCX)group (n=5)and left main (LM)group (n=1).Characteristics of fistula origin and drainage location dis-tribution were analyzed.Results:Among the chief complaints of 37 congenital CAF patients,there were 24 cases (64.9%)of chest tightness and short of breath,six cases (16.2%)of chest pain,five cases (13.5%)of palpitations and two cases (5.4%)of heart murmur in physical examination.Compared with RCA group,LAD & RCA group, LCX group and LM group,there was significant rise in percentage of LAD fistula origin (16.2%,5.4%,13.5%, 2.7% vs.62.2%),P <0.01 all,but there were no significant difference among other groups,P >0.05 all.The 23 cases of LAD fistula origin included 22 cases of pulmonary artery fistulas (PAF)and one case of bronchial artery fis-tulas (BAF);the six cases of RCA fistula origin included three cases of PAF,two cases of right atrial fistulas (RAF) and one case of left ventricular fistulas (LVF);the five cases of LCX fistula origin included two cases of RAF,and one case of PAF,LVF and RVF respectively.Conclusion:Coronary angiography is the gold standard to diagnose congenital CAF.Percentage of congenital CAF originated from left coronary artery is significantly more than that of right coronary artery.
