Xiao-Dan Huang

Fascin and cortactin expression is correlated with a poor prognosis in hepatocellular carcinoma.

Objectives The aim of this study was to investigate the relationship between fascin and cortactin protein expression and clinicopathological parameters and survival time in patients with hepatocellular carcinoma (HCC). Methods A total of 77 specimens of HCC and seven specimens of normal liver tissues were collected. The expressions of fascin and cortactin were examined by immunohistochemical staining. The patients from whom the HCCs were taken were also followed up. In these 74 patients, Kaplan–Meier was used to assess survival outcomes. Results The data revealed that fascin and cortactin expressions were upregulated in the HCC samples. The positive expression of fascin significantly correlated with histological differentiation and metastasis. The positive expression of cortactin significantly correlated with histological differentiation, metastasis, and T stage (International Union Against Cancer). Survival time of the patients with positive fascin expression and positive cortactin expression was significantly decreased, and the median survival duration was short. Conclusion Fascin and cortactin might be important indicators of the malignancy and metastasis of liver cancer, and may have predictive value in the prognosis of HCC.

Lentiviral-mediated Smad4 RNAi promotes SMMC-7721 cell migration by regulation of MMP-2, VEGF and MAPK signaling

Hepatocellular carcinoma (HCC) is a highly malignant cancer characterized by rapid progression, easy metastasis and frequent recurrence. Previous studies have shown that the Smad4 signaling pathway plays an important role in the cell growth and apoptosis of HCC. However, the effect of Smad4 signaling on the invasion and migration of HCC cells remains unclear. The present study aimed to examine the effects of the transforming growth factor (TGF)-β1-Smad4 signaling pathway on the migration of HCC cells. Lentiviral vectors expressing miRNA against Smad4 were constructed to block the expression of Smad4 in HCC cells, and transwell units were used to investigate the invasive potential of SMMC-7721 cells before and after TGF-β1 treatment. mRNA levels of matrix metalloproteinase (MMP)-2 and -9 were analyzed by reverse-transcription PCR, and concentrations of vascular endothelial growth factor (VEGF), p-JNK, p-p38 and p-Erk1/2 proteins were analyzed by Western blotting. The results indicate that TGF-β1 induced cellular invasion in the SMMC-7721 cells. These effects were almost completely blocked by the knockdown of Smad4. Reverse-transcription PCR and Western blot analysis revealed that MMP-2, VEGF, p-JNK and p-p38 were up-regulated by the silencing of Smad4, while the expression of MMP-9 and p-Erk1/2 was not affected by Smad4 silencing with or without TGF-β1 stimulation. These findings suggest that TGF-β1-induced SMMC-7721 cell invasion by the up-regulation of MMP-2 and VEGF is Smad4-dependent. The activation of MMP-2 and VEGF may be an important mechanism by which Smad4 is involved in metastasis. TGF-β1-Smad4 signaling may regulate SMMC-7721 cell migration through the activation of the MAPK pathway.

Natural compound oblongifolin C inhibits autophagic flux, and induces apoptosis and mitochondrial dysfunction in human cholangiocarcinoma QBC939 cells

The compounds, which are obtained from natural plants or microbes may offer potential as one of the strategies for the management of cholangiocarcinoma. Oblongifolin C (OC), a natural small molecule compound extracted and purified from Garcinia yunnanensis Hu, can activate the mitochondrial apoptotic pathway in human cervical cancer cells. However, the direct effects of OC on cholangiocarcinoma cells are not well defined. The effect of OC on cell apoptosis and its underlying mechanisms were investigated in cultured QBC939 cells by the methyl thiazol tetrazolium assay, mitochondrial membrane potential, ATP content and western blot analysis. The present study reported that the in vitro treatment of human cholangiocarcinoma QBC939 cells with different concentrations (5, 10, 20 and 40 μM) of OC decreased cell viability and induced apoptosis in a dose-dependent manner. The results of the present study also showed that OC-induced QBC939 cell apoptosis was mediated through the inhibition of autophagy and mitochondrial dysfunction (MtD). Additionally, inhibiting autophagy increased OC-induced apoptosis and MtD, whereas exposure to the autophagy inducer, rapmycin, attenuated these changes. Together, the results of the present study are the first, to the best of our knowledge, to identify OC as a chemotherapeutic agent against human cholangiocarcinoma QBC939 cells in vitro via the regulation of autophagy and MtD.

Cholecystectomy does not significantly increase the risk of fatty liver disease.

AIM To investigate the relationship between cholecystectomy and fatty liver disease (FLD) in a Chinese population. METHODS A total of 32428 subjects who had voluntarily undergone annual health checkups in the Second Affiliated Hospital of Nanjing Medical University from January 2011 to May 2013 were included in this study. Basic data collection, physical examination, laboratory examination, and abdominal ultrasound examination were performed. RESULTS Subjects undergoing cholecystectomy were associated with greater age, female sex, higher body mass index, and higher levels of systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, and triglycerides. However, no significant differences were found in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, albumin, and serum uric acid. The overall prevalence of FLD diagnosed by ultrasonography was high at 38.4%. The prevalence of FLD was significantly higher for subjects who had undergone cholecystectomy (46.9%) than those who had not undergone cholecystectomy (38.1%; χ(2) test, P < 0.001). Cholecystectomy was positively associated with FLD (OR = 1.433, 95%CI: 1.259-1.631). However, after adjusting for possible factors associated with FLD, multivariate regression analysis showed that the association between cholecystectomy and FLD was not statistically significant (OR = 1.096; 95%CI: 0.939-1.279). CONCLUSION According to our study results, cholecystectomy may not be a significant risk factor for FLD.

BCAT1 expression in hepatocellular carcinoma.

The branched chain amino acids (BCAAs), bearing an aliphatic side chain with a branch, account for up to 40% of the performed amino acid requirements of mammals [1]. Branched chain amino acid transaminase 1 (BCAT1), located at 12p12.1, is one of enzymes catabolizing BCAAs [2]. BCAT1 and its encoded protein have been analyzed in a variety of cancers, including gliomas [3], urothelial carcinoma [4], nasopharyngeal carcinoma [5], colorectal cancer [6], etc. However, limited studies have focused on the relationship between BCAT1 and liver disease. Reportedly, upregulation of BCAT1 was found in nonalcoholic steatohepatitis (NASH) [7], reflecting possible metabolic alterations of damaged hepatocytes. To investigate the relationship of BCAT1 and hepatocellular carcinoma (HCC), we analyzed BCAT1 expression in HCC and paired adjacent non-tumour tissues by immunohistochemistry using tissue microarray, and explored its correction with the survival of HCC patients. We analyzed 51 patients (45 men, age range from 38 to 72 years) who underwent curative resection at hospitals for histologically proven HCC that cooperated with National Engineering Center for Biochip at Shanghai during August 2006 to December 2008. All patients were followed up until September 2013 with an observation time of 4.8 to 7 years. Survival curves were estimated using the Kaplan—Meier method and compared by the log-rank test. A two-tailed P value of less than 0.05 was considered statistically significant. We found that 52.9% (27/51) of HCC samples were positive for BCAT1, which was observed primarily in the cytoplasm. In contrast, 78.4% (40/51) of the adjacent liver tissues expressed BCAT1 (P = 0.012, Fisher’s exact test). Segregation of these patients into the BCAT1-positive and BCAT1-negative groups did not reveal significant correlations with tumour number, maximal size, differentiation, pTNM