| 1.Correlation analysis between preoperative serum alpha-fetoprotein level and early recurrence of hepatocellular carcinoma after hepatectomyBackground and objective At present,hepatectomy is the most effective treatment for hepatocellular carcinoma,especially in the early stage of HCC,but the high recurrence rate after resection is still a common cause of failure for HCC treatment.Some studies have found that the patients with late recurrence of HCC had a better prognosis than those with early recurrence.Therefore,the early detection of risk factors and prediction for early recurrence of HCC became the key to the further study.Serum alpha-fetoprotein(AFP)which associated with recurrence and metastasis of HCC,is a specific tumor marker of hepatocellular carcinoma.It has significant predictive value in the prognosis of patients with hepatocellular carcinoma.However,there are few reports on the relationship between preoperative serum AFP level and early recurrence after HCC resection.Therefore,the purpose of this study was to investigate the relationship between preoperative serum AFP levels and early recurrence of HCC patients and to evaluate the clinical value of preoperative serum AFP levels in predicting the early postoperative recurrence of HCC.Method 1.385 cases of patients who were confirmed hepatocellular carcinoma after hepatectomyfrom January 2010 to March 2016 in the Department of Hepatobiliray and Pancreatic Spleen Surgery of Xijing Hospital were collected.These cases include 316 males and 69 females with an average age of 51.52±10.28.The patientswere divided into three groups based on the preoperative serum AFP level: AFP <20 ng / m L,20 ng / m L≤AFP <400 ng / m L and 400 ng / m L≤AFP.Then analyze the relationship between preoperative serum AFP levels and early postoperative recurrence among the three groups by retrospective case-control study and study the risk factors which influence preoperative serum AFP levels from multivariate.2.Analyze the 385 patients of hepatocellular carcinoma by retrospective case study and divide them into two groups based on the time of recurrence after resection: early recurrence and non-early recurrence.Contrastively analyzed the clinical data,surgical data and pathological data of two groups and analyze the risk factors that affect the early postoperative recurrence of hepatocellular carcinomafrom multivariate.Result 1.385 cases of patients were collected in total,of which 136 cases in the group of AFP <20ng / m L,100 cases in the group of 20 ng / m L≤AFP<400ng / m L and 149 cases inthe group of 400 ng / m L≤AFP.The results showed that there were significant differences among the three groups in total hepatic vascular exclusion,Child-Pugh grading,portal vein tumor thrombus,diameter of tumor,tumor size,with or without cirrhosis,tumor tissue differentiation,adjacent tissue invasion and early postoperative recurrence.The group of AFP <20 ng / m L had higher tumor tissue differentiation than patients withelevated preoperative serum AFP,while the rate of total hepatic blood flow occlusion,the proportion of portal vein tumor thrombus,tumor size,degree of liver cirrhosis,adjacent were lower the other two group(P <0.05).Survival analysis showed that there was a significant difference among three groups in the 1-year and 2-year free-recurrence survival rates and 2-year survival rate.The 1-year,2-year disease-free survival rate and 2-year survival rate of AFP <20 ng / m L group were significant higher than the other two groups.Cox regression model analysis showed that portal vein tumor thrombus,ascites,diameter of tumor,tumor tissue differentiation,adjacent tissue invasion and early postoperative recurrence of HCC were independent risk factors for the elevated preoperative serum AFP levels.2.Compared with the non-early recurrence group,the early recurrence group was significantly higher in the HBV infection rate,the proportion of portal vein tumor thrombus,the number of tumors,the diameter of tumor and the preoperative serum AFP level.COX Multivariate analysis showed that portal vein tumor thrombus,preoperative serum AFP levels,HBs Ag positive,diameter of tumor and tumor differentiation were independent risk factors for early postoperative recurrence of HCC.The survival time of patients with early recurrence was apparently lower than those non-early recurrences.Conclusion Preoperative serum AFP level has an important predictive value for the early recurrence of patients with primary hepatocellular carcinoma after hepatectomy.Preoperative serum AFP levels in HCC patients were related to portal vein thrombosis,ascites,diameterof tumor,tumor differentiation,adjacent tissue invasionand early recurrence of hepatocellular carcinoma.Patients with early recurrence have a worse prognosis.2.Gal and PEI-modified Superparamagnetic iron oxide nanoparticles delivery si RNA as a targeted therapy of hepatocellular carcinomaBackground and objective At present,RNA interference(RNAi)has become a promosing treatment for HCC.However,how to increase the targeting and specificity of RNAi to liver cancer is a scientific problem that needs to be solved.Therefore,the purpose of this study was to investigate the role of galactose(GAL)and polyethyleneimine(PEI)-modified magnetic nanoparticles as carriers for targeting si RNA to hepatoma cells and their therapeutic effects on HCC.Method Gal and PEI-modified magnetic nanoparticles were synthesized at first,and the characteristics of the nanoparticles were analyzed.The transfection efficiency of Gal-PEI-SPIO/si RNA complexes and the biological effects on hepatoma cells was verified by in vitro experiments.Meanwhile the therapeutic effect of therapeutic effects on liver cancer was verified in mice.Results 1.In an agarose gel electrophoresis assay,Gal-PEI-SPIO with si RNA formed a mixture at an Fe: si RNA weight ratio of over 4,which indicated that the si RNA duplexes were tightly bound to Gal-PEI-SPIO.2.Flow cytometry revealed that Gal-PEI-SPIO nanoparticles can effectively carry si RNA into cells.At the same time in vitro q PCR and Western blot experiments found that Gal-PEI-SPIO/si-c Met nanocomplexes can effectively reduce the expression level of c-Met.3.In vivo detection of the distribution of si RNA in mice revealed that the presence of si RNAs bound to Gal-PEI-SPIO nanoparticles was significantly longer in vivo.Further in vivo experiments demonstrated that Gal-PEI-SPIO/si-c Met nanocomplexes cansignificantly inhibit tumor growth.Conclusion 1.Gal and PEI-modified magnetic nanoparticles can bind si RNA tightly,protect the si RNA from nuclease degradation and extend the half-life of the si RNA in vivo.2.Gal and PEI-modified magnetic nanoparticles can targetly carry si RNA into hepatoma tissue and play a role in inhibiting tumor growth. |
