الملخص
Objective To explore the efficacy, safety, and factors that might influence the efficacy of antiPD-1 antibody-based therapy in advanced hepatocellular carcinoma in the real world. Methods The clinical features, efficacy, and safety in patients with advanced hepatocellular carcinoma who received anti-PD-1 antibody-based therapy were retrospectively analyzed. The survival status was followed-up. Results The objective response and the disease control rate were 21.8% and 76.4%, respectively. The overall incidence of adverse events during treatment was 81.8%, of which the incidence of grade 3/4 adverse events was 14.5%. The incidence of immune-related adverse events was 58.2% and the incidence of grade 3/4 immune-related adverse events was 3.6%, and no treatment-related death was observed. The median PFS of the 55 patients was 5.0 (95%CI: 3.9-6.1) months, and the median OS was 11.4 (95%CI: 6.5-16.3) months. Univariate and multivariate analyses showed that liver function Child-Pugh scores and performance status ECOG score were the influencing factors of the objective response rate and survival. Conclusion In the real world anti-PD-1 antibody-based therapy is safe and effective in patients with advanced hepatocellular carcinoma, in which the performance status ECOG score and liver function Child-Pugh score before treatment are independent prognostic factors influencing survival.
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ObjectiveTo compare liver pathology changes of patients with Budd-Chiari syndrome (BCS) and intrahepatic portal hypertension (IPH) after portosystemic shunt surgery. MethodsFrom January 2010 to December 2011,liverbiopsy was taken during shunt surgery (9 BCS patients,4 IPH patients),and 6-9 months after surgery on follow-up.Collagen type Ⅳ ( Col Ⅳ ),procollagen m (PC Ⅲ ),matrix metalloproteinase (MMP-1),tissue inhibitors of metalloproteinase(TIMP-1) were tested using SABC (immuonohistochemistry) method,and HE staining to observe the morphology of liver tissue.Free portal vein pressure before and after shunt was measured. ResultsIn BCS group,Col Ⅳ,PC 1Ⅲ and TIMP-1expression downregulated after surgery (127 ±15) vs.(137 ±16),t =4.896,P-0.013; (115.2 ± 10.6) vs.(127.3±9.5),t=4.877,P=0.003; (119.2±11.3) vs.(131.2±l9.6),t=2.841,P=0.023.MMP-1expression did not change ( P ＞ 0.05 ),while MMP-1/TIMP-1was not significantly correlated with liver fibrosis (0.95 ±0.16) vs.(0.98 ±0.15),t =-0.710,P =0.504.In IPH group,the expression of Col Ⅳ,PCⅢ,MMP-1,and MMP-1/TIMP-1did not change significantly after surgery (P ＞0.05).Compared with that in IPH group the expression of PC Ⅲ,Col Ⅳ and TIMP-1downregulated significantly in BCSgroup (127±15) vs.(150 ±12),U=3.000,P=0.038; (115.2 ±10.6) vs.(128.1±2.8),U=2.000,P=0.023; (119.2 ± 11.3) vs.(131.4 ±2.5),U=3.000,P =0.038.By HE staining in BCS group there was significant intrahepatic congestion which alleviated after surgery.While in PHT group liver pathology did not change significantly after surgery.FPP in BCS and IPH patients significantly decreased after shunt surgery (25 ±8) vs.(41±8) cmH20,t=17.816,P=0.000;(31±8) vs.(45 ±9) cmH20,t =5.745,P =0.010 ). Drop of FPP of BCS group plays a key role in reversal of liver fibrosis.ConclusionsIn BCS group liver pathology improved after shunt surgery probably by removing the intrahepatic obstruction,but in IPH group liver pathology remained unchanged after shunt.
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Objective To investigate the effect of LI-cadherin- SiRNA protein on the growth and metastatic potentials of transplanted human hepatocellular carcinoma cell lines (Hep3B) in nude mice.Methods We transfected LI-cadherin- SiRNA to Hep3B cells,Hep3B cell suspension (transfected or control ) was injected subcapsullaryly into the spleen of nude mice,hepatic metastasis was observed by naked eye and immunohistochemistry.In addition,Western-blot was used to detect the level of LI-cadherin in different metastatic site.Results (1) Hep3B was green after successful transfect interference vector under fluorescence inverted microscope,in this study,the transfect rate was 80％.(2) Hep3B liver metastasis model in nude mice was established.The metastasis rates in the empty plasmid carrying group,the control group and the SiRNA transfect group were 50％,60％ and 80％,respectively.The number of metastasis caner nodules in the SiRNA transfect group was 26,significantly higher than other two groups.(3) The level of protein expression for LI-cadherin in the SiRNA transfect group is significantly lower than the control group and the empty plasmid carrying group.Conclusions LI-cadherin is crucial and important for the adhension capability of HCC in its migration.SiRNA transfected LI-cadherin increases the metastasis in a nude mouse model inoculated with human hepatocellular carcinoma cell lines.
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Objective To investigate the expressions of p53,p16 protein and the clinical significance in advanced gastric carcinoma. Methods The expressions of p.53 ,p16 were detected by using immunohistochemistry in 24 specimens of normal gastric mucosa and 55 specimens of gastric carcinoma. Results The positive rate of p53 ,p16 in normal gastric mucosa and gastric carcinoma tissues were 0,100% ;67.3% ,30. 9%, respectively (P <0. 05). The positive rate of p53, p16 in non-differentiated、low- differentiated and moderate- differentiated 、high- differentiated gastric carcinoma tissues were 80. 0% ,56.7% and 48. 0% ,56. 0% ,respectively(P <0. 05). Conclusions The abnormal expressions of p53 and p16 play an important role in the course and prognosis of gastric carcinoma. The positive expression of p53 was correlated with the degree of defferentiation of gastric carcinoma. No correlation between the expression of p16 and grade of differentiation was observed.
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Objective To study the expression of RhoA protein in colorectal carcinoma. Methods The expression of RhoA protein in 92 cases of colorectal ccarcinoma and 30 cases of normal rectal tissue was detected by SP immunohistochemical technique. Results RhoA protein were negative in 40 cases of normal colorectal tissue. In 92 cases of colorectal carcinoma, the positive rate of RhoA protein was 70.7%. It was significantly higher than that in the normal colorectal tissue. The positive rate of RhoA protein in high-differentiated 、moderate-differentiated and lowdifferentiated rectal carcinoma were 43.5% 、74.4% and 86.7% ,respectively(P ＜0.05). The positive rates of RhoA in phase Ⅰ、phase Ⅱ、phase Ⅲ and phase Ⅳ were 48.6% 、77.3% 、83.3% and 94.1%, respectively (P ＜ 0.05).The positive rate of RhoA protein in patients with lymphnode mestastasis and non-lymphnode mestastasis were 82% and 57.1% (P ＜ 0.05). Conclusion RhoA protein could be related with the differentiation、invasion、metastatsis and prognosis of colorectal carcinoma.