miR-194 inhibits liver cancer stem cell expansion by regulating RAC1 pathway.

Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver CSCs remains unclear. Herein, we observed low expression of miR-194 in chemoresistant HCC cells. A remarkable decrease of miR-194 was detected in EpCAM or CD133-positive liver CSCs and CSC-enriched hepatoma spheres. Interference miR-194 facilitated liver CSCs expansion by enhancing the self-renewal of liver CSCs. While up-regulating miR-194 inhibited liver CSCs expansion by suppressing the self-renewal of liver CSCs. Furthermore, hepatoma cells with miR-194 overexpression performed more sensitivity to sorafenib treatment. Mechanistically, functional studies found that Ras-related C3 botulinum toxin substrate 1 (RAC1) was a direct target of miR-194. Overexpression of miR-194 inhibited the expression of RAC1 in liver CSCs. Special RAC1 siRNA diminished the discrepancy in liver CSC proportion and the self-renewal capacity between miR-194 overexpression hepatoma cells and control cells, which further confirmed that RAC1 was required in miR-194-inhibited liver CSCs expansion. More importantly, downregulated expression of miR-194 was a predictor of poor prognosis of HCC patients.

Small molecule metabolite biomarkers for hepatocellular carcinoma with bile duct tumor thrombus diagnosis.

Hepatocellular carcinoma with bile duct tumor thrombus (BDTT) is a malignant disease. The most commonly used diagnosis methods for BDTT are MRCP/ERCP, ultrasonic diagnosis or CT scan. However, BDTT is often misdiagnosed as other bile duct diseases, such as extrahepatic cholangiocarcinoma (EHCC), choledochal cyst (Cyst) and common bile duct stone (Stone). Diagnostic methods, which are more accurate and less destructive, are urgently needed. In this paper, we analyzed the small molecule metabolites in the serum of BDTT, Stone, Cyst and EHCC patients and normal people using untargeted GC-MS, and identified 21 metabolites that show different levels among different samples. Using targeted UHPLC-QQQ-MS analysis, we found that several metabolites are significantly changed. ROC curve analysis revealed two metabolites, L-citrulline and D-aspartic acid, as potential biomarkers that can distinguish BDTT from other bile duct diseases.

Risk factors of intra-abdominal bacterial infection after liver transplantation in patients with hepatocellular carcinoma.

OBJECTIVE: To explore the risk factors of intra-abdominal bacterial infection (IAI) after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). METHODS: A series of 82 HCC patients who received LT surgeries in our department between March 2004 and April 2010 was recruited in this study. Then we collected and analyzed the clinical data retrospectively. Statistical analysis system (SPSS) software was adopted to perform statistical analysis. Chi-square test, t-test and Wilcoxon rank sum test were used to analyze the clinical data and compute the significance of the incidences of early-stage IAI after LT for HCC patients. Binary logistic regression was performed to screen out the risk factors, and multiple logistic regression analyses were performed to compute the independent risk factors. RESULTS: A series of 13 patients (13/82, 15.9%) had postoperative IAI. The independent risk factors of postoperative intra-abdominal bacterial infections after LT for HCC patients were preoperative anemia [Hemoglobin (HGB) <90 g/L] and postoperative abdominal hemorrhage (72 hours >400 mL), with the odds ratios at 8.121 (95% CI, 1.417 to 46.550, P=0.019) and 5.911 (95% CI, 1.112 to 31.432, P=0.037). CONCLUSIONS: Postoperative IAI after LT in patients with HCC was a common complication. Preoperative moderate to severe anemia, as well as postoperative intra-abdominal hemorrhage more than 400 mL within the first 72 hours might independently indicate high risk of IAI for these patients.

Sorafenib extends the survival time of patients with multiple recurrences of hepatocellular carcinoma after liver transplantation.

AIM: to determine the efficacy and toxicities of sorafenib in the treatment of patients with multiple recurrences of hepatocellular carcinoma (HCC) after liver transplantation in a Chinese population. METHODS: twenty patients with multiple recurrences of HCC after liver transplantation were retrospectively studied. They received either transarterial chemoembolization (TACE) or TACE combined with sorafenib. RESULTS: the median survival times (MST) after multiple recurrences was 14 months (TACE+sorafenib group) and 6 months (TACE only group). The difference was significant in MST between the two groups (P=0.005). The TACE + sorafenib group had more stable disease (SD) patients than the TACE group. The most frequent adverse events of sorafenib were hand-foot skin reaction and diarrhea. In the univariate analysis, preoperative bilirubin and CHILD grade are found to be significantly associated with tumor-free survival time, the survival time after multiple recurrences and overall survival time. TACE+sorafenib group showed a better outcome than single TACE treatment group. In the multivariate COX regression modeling, the preoperative high CHILD grade was found to be a risk factor of tumor-free survival time. In addition, the preoperative high bilirubin grade was also found to be a risk factor of survival time after recurrence and overall survival time. Furthermore, survival time after recurrence and overall survival time were also associated with therapeutic schedule, which was indicated by the GROUP. CONCLUSION: Treatment with TACE and sorafenib is worthy of further study and may have more extensive application prospects.