Objective To investigate the combined effects of somatostatin (SST) and cisplatin (DDP) on proliferation and apoptosis in gallbladder cancer cells,and to investigate the mechanism of the combined effects.Methods We performed immunohistochemistry to detect the PTEN expression in gallbladder cancer.We then investigated the combined effects of SST and DDP on cell proliferation in vitro with CCK-8 assay and analyzed the interaction between these two drugs using isobologram analysis.We also investigated the combined effects on cell proliferation in vivo using a xenograft nude mouse model.FITC-Annexin V/PI assay and TUNEL staining assay were performed to detect the proportion of apoptosis after combined treatment in vitro and in vivo.Reactive oxygen species and mitochondrial membrane potential were detected with DCFH-DA assay and JC-1 staining assay after the combined treatment.We finally detected the PTEN and p-AKT associated proteins using western blotting after the combined treatment.Results PTEN was abnormally decreased in gallbladder cancer tissues.PTEN expression was negatively correlated with cancer differentiation and was positively correlated with patients'survival time.DDP treatment decreased while combined treatment with SST induced PTEN expression and inhibited AKT activation by reversing resistance to DDP.Isolated SST or DDP treatment inhibited gallbladder cancer GBC-SD and SGC996 cell proliferation which was dose-dependence.These two drugs synergistically inhibited gallbladder cancer cell growth in vivo and in vitro.Isolated SST or DDP treatment induced cell apoptosis and combined treatment induced cell apoptosis the most.SST inhibited AKT activation but did not induce ROS.DDP induced ROS resulting in increased cell apoptosis.Either SST or DDP alone increased the levels of cytoplasmic cytochrome C protein and activated caspase-3.Conclusions SST enhanced growth inhibition by cisplatin in gallbladder cancer cells through inducing PTEN expression.This study provides the theoretical basis for further combined clinical chemotherapeutic applications.

Objective To investigate the predictive value of preoperative serum tumor markers test for lymph node metastasis of intrahepatic cholangiocarcinoma (ICC).Methods The retrospecgtive cohort study was conducted.The clinicopathological data of 69 patients with ICC who were admitted to the Xinhua Hospital of Shanghai Jiaotong University between May 2006 and May 2016 were collected.Among 69 patients with pathological diagnosis,24 with lymph node metastasis were allocated into the lymph node metastasis group and 45 without lymph node metastasis were allocated into the non-lymph node metastasis group.Tumor markers of the 2 groups were preoperatively detected,including alpha-fetoprotein (AFP),carcinoembryonic antigen (CEA),prostate specific antigen (PSA),CA19-9,CA125,CA242,CA153,CA724,CA211,neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC).Receiver operating characteristic (ROC) curve was built,and critical value,sensitivity and specificity were calculated based on ROC curve.Coincident rate between significant indicators and results of pathological examination was calculated.Observation indicators:(1) overall positive rates of tumor markers;(2) comparison of tmmor markers levels in the 2 groups;(3) tumor markers predicted ROC curve of lymph node metastasis and coincident rate between ROC curve and results of postoperative pathological examination.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (Q25,Q75) and comparison between groups was analyzed using the Wilcoxon rank sum test.Comparison of count data was analyzed by the chi-square test and Fisher exact probability.The statistically significant indicators were analyzed by the ROC curve.Results (1) Overall positive rates of tumor markers:positive rates of AFP,CEA,PSA,CA19-9,CA125,CA242,CA153,CA724,CA211,NSE and SCC in 69 patients were 27.5％ (19/69),29.0％ (20/69),4.3％ (3/69),69.6％ (48/69),36.2％ (25/69),50.7％ (35/69),26.1％ (18/69),21.7％ (15/69),62.3％ (43/69),31.9％(22/69) and 21.7％(15/69),respectively.Positive rates of AFP,CEA,CA19-9,CA125,CA242,CA153,CA724,CA211,NSE and SCC were more than 20％,which became comparison indicators of 2 groups.(2) Comparison of tumor markers levels in the 2 groups:levels of CA19-9,CA125,CA242 and CA211 were 284.9 U/mL (42.5 U/mL,730.3 U/mL),63.6 U/mL (23.4 U/mL,172.1 U/mL),71.7 U/mL (25.6 U/mL,138.9 U/mL),6.7 μg/L (3.9 μg/L,17.5 μg/L) in the lymph node metastasis group and 58.0 U/mL (25.9 U/mL,405.9 U/mL),18.2 U/mL (11.7 U/mL,33.8 U/mL),11.0 U/mL (3.7 U/mL,41.7 U/mL),3.7 μg/L (2.7 μg/L,6.9 μg/L) in the non-lymph node metastasis group,respectively,with statistically significant differences between the 2 groups (Z=2.016,3.213,3.143,2.482,P＜0.05).(3) Tumor markers predicted ROC curve of lymph node metastasis and coincident rate between ROC curve and results of postoperative pathological examination:area under the ROC curve of CA19-9,CA125,CA242 and CA211 were respectively 0.648 [95％ confidence interval (C I):0.515-0.781,P＜0.05],0.736 (95％ CI:0.608-0.864,P＜0.05),0.731 (95％ CI:0.603-0.859,P＜0.05),0.714 (95％ CI:0.581-0.847,P＜0.05).The positive critical value,sensitivity and specificity of CA19-9,CA125,CA242 and CA21 were 150.6 U/mL,35.7 U/mL,43.4 U/mL,6.0 μg/L and 62.5％,66.7％,70.8％,62.5％ and 71.1％,82.2％,77.8％,75.6％,respectively.The coincident rate between ROC curve and results of postoperative pathological examination of CA 19-9,CA 125,CA242 and CA211 were 68.1％ (47/69),76.8％(53/69),75.4％(52/69),71.0％(49/69),respectively.Conclusion The levels of serum CA19-9,CA125,CA242 and CA211 can effectively predict lymph node metastasis of patients with ICC.

In previous study, the 150-ku oxygen-regulated protein(ORP150) was identified as a candidate glycoprotein related to hepatocellular carcinoma.In order to further validate the expression level of ORP150 in hepatocellular carcinoma, protein expression was determined by Western blot and cell immunochemistry, and messenger RNA(mRNA) expression was detected by quantitative real-time polymerase chain reaction.The effect of ORP150 on apoptosis and invasive potential of hepatocellular carcinoma cells was evaluated using the small interference RNA(siRNA) technique.Both the protein and mRNA expression levels of ORP150 were significantly upregulated in hepatocellular carcinoma cell lines compared with a non-tumor human liver cell line.After transfection with the specific siRNA of ORP150, significantly greater apoptosis of hepatocellular carcinoma cells was induced compared with untransfected cells.However, no significant effect on invasive potential was found.Overexpression of ORP150 was associated with hepatocellular carcinoma, and ORP150 might promote the proliferation of hepatocellular carcinoma cells by inhibiting apoptosis.ORP150 could be a potential therapeutic target for hepatocellular carcinoma.

ObjectiveTo explore the diagnostic value of computed tomography (CT) value for perihepatic lymph node metastasis of primary liver cancer (PLC).MethodsClinical data of 14 patients undergoing PLC resection + lymph node dissection in Xin Hua Hospital Afifliated to Shanghai Jiao Tong University School of Medicine between October 2001 and January 2015 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among the patients, 8 were males and 6 were females with the age ranging from 36 to 73 years old and the median of 51 years old. Fifteen groups of suspicious positive lymph nodes of the 14 patients were detected by enhanced CT scan before operation, and were divided into the positive group (n=8) and the negative group (n=7) according to the postoperative pathological examination. The differences in plain CT value, arterial phase CT value and coefficient of variation (CV) of arterial phase CT value of the lymph nodes between two groups were compared. And the diagnostic accuracy of the lymph node metastasis by these indexes was analyzed. The observation indexes of two groups were compared usingt test and the analysis on the diagnostic accuracy of lymph node metastasis was conducted using receiver operating characteristic (ROC) curve. ResultsThe plain CT value, arterial phase CT value and CV of arterial phase CT value were respectively (30±4) HU, (45±10) HU and (30±10)% in the positive group, and were respectively (43±5) HU, (65±18) HU and (17±6)% in the negative group, and signiifcant differences were observed between two groups (t=-5.400,-2.660, 2.990;P<0.05). ROC curve analysis showed that the cut-off value of plain CT value, arterial phase CT value and CV of arterial phase CT value was respectively 38 HU, 54 HU and 22%, and the diagnostic accuracy was respectively 100%, 80% and 80%.ConclusionsCT value has certain diagnostic value for perihepatic lymph node metastasis of PLC. Perihepatic lymph node metastasis is likely to occur when plain CT value<38 HU, arterial phase CT value<54 HU and CV of arterial phase CT value>22%.