ABSTRACT
Dysregulation of mTORC1/mTORC2 pathway is observed in many cancers and mTORC1 inhibitors have been used clinically in many tumor types; however, the mechanism of mTORC2 in tumorigenesis is still obscure. Here, we mainly explored the potential role of mTORC2 in esophageal squamous cell carcinoma (ESCC) and its effects on the sensitivity of cells to mTOR inhibitors. We demonstrated that RICTOR, the key factor of mTORC2, and p-AKT (Ser473) were excessively activated in ESCC and their overexpression is related to lymph node metastasis and the tumor-node-metastasis (TNM) phase of ESCC patients. Furthermore, we found that mTORC1/ mTORC2 inhibitor PP242 exhibited more efficacious anti-proliferative effect on ESCC cells than mTORC1 inhibitor RAD001 due to RAD001-triggered feedback activation of AKT signal. Another, we demonstrated that down-regulating expression of RICTOR in ECa109 and EC9706 cells inhibited proliferation and migration as well as induced cell cycle arrest and apoptosis. Noteworthy, knocking-down stably RICTOR significantly suppresses RAD001-induced feedback activation of AKT/PRAS40 signaling, and enhances inhibition efficacy of PP242 on the phosphorylation of AKT and PRAS40, thus potentiates the antitumor effect of RAD001 and PP242 both and . Our findings highlight that selective targeting mTORC2 could be a promising therapeutic strategy for future treatment of ESCC.
ABSTRACT
Objective@#To observe the endoscopic morphology of gastric varices of patients with portal hypertension type one isolated gastric varices (IGV-1) and to explore the etiology, treatment and prognosis of portal hypertension IGV-1.@*Methods@#From January 2006 to June 2018, at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and North Branch of Ruijin Hospital, 54 patients with portal hypertension IGV-1 were retrospectively analyzed. The varices were classified according to the endoscopic morphology and the etiology treatment, therapeutic efficacy and prognosis were also analyzed. Descriptive method was used for statistical analysis.@*Results@#Among the 54 patients with portal hypertension IGV-1, the endoscopic morphology of varices were tuber type in 24 patients (44.4%), grape string type in nine patients (16.7%), strip type in five patients (9.3%), dendritic type in three patients (5.6%) and mixed type in 13 patients(24.1%). Etiological analysis showed that the primary disease of 34 cases (63.0%) were hepatogenic, 11 cases (20.4%) were pancreatic origin, and nine cases (16.7%) were from other diseases. As to treatment, three cases (5.6%) were treated with adhesive, two cases (3.7%) were treated with sclerotherapy, and 49 cases (90.7%) were treated with combination of adhesive and sclerotherapy. Therapeutic efficacy evaluation showed that 46 cases (85.2%) were significantly effective, eight cases were effective, 0 case was ineffective, and all the 54 cases (100.0%) were improved. The prognostic analysis showed that 35 cases (64.8%) had no bleeding in five years and eight cases (14.8%) had no bleeding in 10 years. Nine patients (16.7%) died, including six cases of pancreatic cancer, two cases of liver failure and one case of gastrointestinal bleeding.@*Conclusions@#The endoscopic morphology of IGV-1 portal hypertension in mainly tuber type. The main cause is hepatogenic and the combination of adhesive and sclerotherapy is beneficial to the regression of gastric varices.
ABSTRACT
Objective To observe the endoscopic morphology of gastric varices of patients with portal hypertension type one isolated gastric varices (IGV-1) and to explore the etiology,treatment and prognosis of portal hypertension IGV-1.Methods From January 2006 to June 2018,at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and North Branch of Ruijin Hospital,54 patients with portal hypertension IGV-1 were retrospectively analyzed.The varices were classified according to the endoscopic morphology and the etiology treatment,therapeutic efficacy and prognosis were also analyzed.Descriptive method was used for statistical analysis.Results Among the 54 patients with portal hypertension IGV-1,the endoscopic morphology of varices were tuber type in 24 patients (44.4％),grape string type in nine patients (16.7％),strip type in five patients (9.3％),dendritic type in three patients (5.6％) and mixed type in 13 patients(24.1％).Etiological analysis showed that the primary disease of 34 cases (63.0％) were hepatogenic,11 cases (20.4％) were pancreatic origin,and nine cases (16.7％) were from other diseases.As to treatment,three cases (5.6％) were treated with adhesive,two cases (3.7％) were treated with sclerotherapy,and 49 cases (90.7％) were treated with combination of adhesive and sclerotherapy.Therapeutic efficacy evaluation showed that 46 cases (85.2％) were significantly effective,eight cases were effective,0 case was ineffective,and all the 54 cases (100.0％) were improved.The prognostic analysis showed that 35 cases (64.8％) had no bleeding in five years and eight cases (14.8％) had no bleeding in 10 years.Nine patients (16.7％) died,including six cases of pancreatic cancer,two cases of liver failure and one case of gastrointestinal bleeding.Conclusions The endoscopic morphology of IGV-1 portal hypertension in mainly tuber type.The main cause is hepatogenic and the combination of adhesive and sclerotherapy is beneficial to the regression of gastric varices.