SRC-1 and Twist1 are prognostic indicators of liver cancer and are associated with cell viability, invasion, migration and epithelial-mesenchymal transformation of hepatocellular carcinoma cells.

BACKGROUND: Liver cancer is the second leading cause of worldwide cancer-related death, and it has an increasing incidence rate. To investigate the role of SRC-1 and Twist1 in liver cancer and determine their expression in terms of prognosis for patients with liver cancer and in general for hepatocellular carcinoma (HCC) cell lines. METHODS: The present study included a total of 70 patients who underwent liver transplantation or hepatic resection surgeries in our hospital from May 2011 to December 2012. Demographic data and clinical variables as well as alpha-fetoprotein (AFP) and hepatitis B virus (HBV) data were collected. The expression of SRC-1 and Twist1 was determined using immunohistochemistry (IHC). The expression of SRC-1 in different HCC cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Following SRC-1 silencing by sh-RNA, cell viability, invasion, migration and expression of epithelial-mesenchymal transformation (EMT)-related proteins as well as Twist levels were measured. RESULTS: The expression of SRC-1 and Twist1 was positively correlated in HCC patients. The expression of SRC-1 differed significantly based on patient tumor diameter, tumor-node-metastasis (TNM) grade, and state of liver cirrhosis, and it also differed in patients with dissimilar tumor metastasis conditions, while the expression of Twist1 in patients was significantly correlated with TNM grade and state of liver cirrhosis as well as by the conditions of tumor metastasis. Survival analysis showed that the expression of both SRC-1 and Twist1 were significantly associated with the overall survival (OS) time of HCC patients. Meanwhile, patients with both SRC-1 (+) and Twist1 (+) tissue had the lowest OS, while patients with both SRC-1 (-) and Twist1 (-) tissue had the highest OS. Cox univariate and multivariate analyzes showed that SRC-1 expression, tumor stage and liver cirrhosis were independent risk factors for OS time. SRC-1 was highly expressed in HCC cell lines, and inhibition of SRC-1 had a significantly negative impact on cell viability, invasion, migration and EMT; it also inhibited the expression of Twist. CONCLUSIONS: Expression of both Twist1 and SRC-1 were correlated with clinical outcomes and prognoses for HCC patients, and both Twist1 and SRC-1 were independent risk factors for HCC patient survival conditions. Inhibition of SRC-1 suppressed cell proliferation, invasion, migration and EMT of HCC cells, which might be the result of Twist inhibition.

Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV-; n = 100); MVI+ but did not undergo TACE (TACE-, n = 30); and TACE-/MVI- (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI- patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI- patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.

Advantages of laparoscopic common bile duct exploration in common bile duct stones.

OBJECTIVE: To compare the efficacy, safety, and surgical outcomes of laparoscopic common bile duct exploration, endoscopic retrograde cholangiopancreatography, and open common bile duct exploration for treatment of common bile duct stones. METHODS: In total, 210 patients were prospectively randomized into 3 groups: laparoscopic common bile duct exploration, endoscopic retrograde cholangiopancreatography, and open common bile duct exploration. The primary outcome measures were the common bile duct stone clearance rate and the complication rate. The secondary outcome measures were mortality, total costs, and length of hospital stay. RESULTS: The success rates in the laparoscopic common bile duct exploration group (97.14%, 68 out of 70) and open common bile duct exploration group (98.57%, 69/70) were significantly higher than that in the endoscopic retrograde cholangiopancreatography group (85.71%, 60/70, both p < 0.05). The complication rates in the laparoscopic common bile duct exploration group (2.86%, 2/70) and open common bile duct exploration group (1.43%, 1/70) were significantly lower than that in the endoscopic retrograde cholangiopancreatography group (14.29%, 10/70, both p < 0.05). The success rate and complication rate were not significantly different between the laparoscopic common bile duct exploration group and open common bile duct exploration group (both p > 0.05). CONCLUSION: Laparoscopic common bile duct exploration provides an alternative therapeutic approach that was safer and more reliable, allowed for earlier recovery, and provided more cost-effective treatment of common bile duct stones.

Dexamethasone Effect on the Expression of Transforming Growth Factor-ß1/Smads Signaling Pathway in Benign Biliary Stricture Fibroblasts in Rodent.

OBJECTIVE: To investigate the effects of dexamethasone on transforming growth factor (TGF)-ß1/Smads signaling pathway in benign biliary stricture (BBS) fibroblasts. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Guizhou Medical University, Guiyang, Guizhou, China, from January to August 2016. METHODOLOGY: Fibroblasts derived from rabbit BBS model were cultured and identified, then treated by different concentration of dexamethasone (0.02, 0.1 and 0.5 mg/ml). Dexamethasone-treated cells and non-treated control groups were incubated respectively for 48 hours. Cell proliferation was assessed using cell counting kit-8. Relative mRNA expression of TGF-ß1, Smad4 and Smad7 were assessed by quantitative RT-PCR. Protein expression of TGF-ß1 and Smad4 were investigated by Western blotting. RESULTS: Treatment with dexamethasone significantly inhibited the proliferation of BBS fibroblasts, significantly attenuated both the mRNA and protein expression of TGF-ß1 and Smad4, and significantly up-regulated the mRNA expression of Smad7 in BBS fibroblasts (all p<0.05, 0.1-0.5 mg/ml), and exhibited in a dose-dependent manner. CONCLUSION: TGF-ß1/Smads signaling pathway may play an important role in BBS progression; dexamethasone significantly altered the expression of TGF-ß1/Smads signaling pathway and significantly inhibited cell proliferation in rabbit BBS fibroblasts. Therefore, dexamethasone may be a therapeutic option for the prevention of BBS.

Tetramethylpyrazine Effects on the Expression of Scar-Related Genes in Rabbit Benign Biliary Stricture Fibroblasts.

OBJECTIVE: To investigate the effects of tetramethylpyrazine (TMP) on transforming growth factor-ß1 (TGF- ß1), α-smooth muscle actin (α-SMA), and neuronal regeneration related protein (P311) in benign biliary stricture fibroblasts of rabbit. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Guizhou Medical University, Guiyang, Guizhou, China, from April to December 2015. METHODOLOGY: Fibroblasts isolated from rabbits following benign biliary stricture were cultured and treated with different concentrations of TMP(0.08, 0.4, and 2.0 mg/ml). TMP-treated cells and non-treated control groups were incubated for 48-hours, and proliferation was assessed using the cell counting kit-8 assay. The mRNAexpressions of TGF-ß1, α-SMA, and P311 were assessed by quantitative RT-PCR. Protein expressions of TGF-ß1 and α-SMAwere investigated by Western blotting. RESULTS: Treatment with TMPsignificantly reduced the proliferation of benign biliary stricture fibroblasts, and significantly attenuated both the mRNAand protein expressions of TGF-ß1, α-SMA, and P311 (p < 0.05) in a dose-dependent manner. CONCLUSION: TMPsignificantly reduced the proliferation of benign biliary stricture fibroblasts, and significantly downregulated the mRNA/protein expression of TGF-ß1, α-SMA, and P311. Therefore, TMPmay be a therapeutic option for the prevention of benign biliary stricture.

[Analysis of 216 cases of total laparoscopic hysterectomy].

OBJECTIVE: To investigate the effectiveness and safety of total laparoscopic hysterectomy (TLH). METHODS: A retrospective study of laparoscopic hysterectomy was conducted in this setting. From March 2002 through March 2004, 216 women were subjected to TLH. The average age of the patients was 45.5 years (38-60 years). Out of the 216 patients, 24 had dysfunctional uterine bleeding, 5 atypical endometrial hyperplasia, 139 uterine fibroid, 46 adenomyosis, 2 cervical carcinoma in situ and 36 had a previous lower abdominal surgery. The TLH was carried out using ultrasonic scalpel and the amputated uterus was removed transvaginally. The vagina and peritoneum were closed under laparoscopy. RESULTS: Of the 216 cases who underwent TLH, 23 had bilateral adnexectomy, 36 had ovarian cystectomy, and 54 had adhesiolysis simultaneously. No case was converted to laparotomy. The mean operating time was (103 +/- 35) min. The average amount of blood loss was 83 +/- 45 ml (60-320 ml) during operation. The average hospital stay after operation was (5.3 +/- 1.9) days. There were 4 patients with urinary tract injury in this study population. One bladder perforation was found during operation and repaired under laparoscopy. Two patients had vesicovaginal fistula formation. One ureteral-vaginal fistula was found after operation. The fistula was all closed spontaneously with a prolonged catheter drainage. CONCLUSIONS: TLH appears a safe, effective and reproducible procedure. It is an alternative method for those women who need hysterotomy.

Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study

ABSTRACT BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV−; n = 100); MVI+ but did not undergo TACE (TACE−, n = 30); and TACE−/MVI− (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI− patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI− patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.

Effects of p16 gene on biological behaviours in hepatocellular carcinoma cells.

AIM: To investigate the effects of p16 gene on biological behaviours in hepatocellular carcinoma cells. METHODS: HCC cell lines SNU-449 and HepG2.2.15 were infected respectively by a replication defective, recombinant retrovirus capable of producing a high level of p16 protein expression (pCLXSN-p16). G418 resistant stable P16 protein expression cell lines were selected. And the biological behaviours of the p16 gene transfected HCC cells were observed. RESULTS: Initial in vitro experiments in HCC cell line SNU-449 with loss of p16 protein expression demonstrated the pCLXSN-p16 treatment significantly inhibited cell growth. But there was no treatment effect when the pCLXSN-p16 was used in another HCC cell line HepG2.2.15 which has positive p16 protein expression. Subsequent study in a nude mouse model demonstrated that the p16 gene transfected SNU-449 had a lower succeeding rate in the first time establishment of tumors and grew more slowly in the nude mice when compared with non-transfected SNU-449. Moreover, the nude mice inoculated with transfected SNU-449 had a longer surviving time than those inoculated with non-transfected SNU-449. CONCLUSION: Our results show that the p16INK4a gene transfer can inhibit the proliferation and reduce the invasion ability of hepatocellular carcinoma.

[Influence of p16 gene on the biological behavior of human hepatocellular carcinoma].

BACKGROUND & OBJECTIVE: Inactivation of the tumor suppressor gene p16INK4a is one of the most common genetic alterations in human hepatocellular carcinomas (HCC), making it an ideal target gene for treatment of HCC. The objective of this study was to investigate the influence of wild p16 gene on the biological behavior of HCC. METHODS: HCC cell strains SNU-449 (loss of p16 protein expression) and HepG2.2. 15 (positive p16 protein expression) were respectively infected by a retrovirus expression vector of p16 gene (pcLXSN-p16). The stable p16 protein expression cell strains were selected. The biological behaviors of the p16 gene transfected HCC cells were observed. RESULTS: SNU-449 with negative p16 protein expression demonstrated that pcLXSN-p16 treatment significantly inhibited cell growth (the amount of cells at G0-G1 phase increased). However, there was no treatment effect when pcLXSN-p16 was transfected in HepG2.2. 15 which has positive p16 protein expression. Subsequent study in a nude mouse model demonstrated that the p16 gene transfected SNU-449 had a lower succeeding rate of first time establishment of tumors and grew more slowly in the nude mice as compared with non-transfected SNU-449. Moreover, the nude mice inoculated with transfected SNU-449 had a longer survival time than those inoculated with non-transfected SNU-449. CONCLUSION: The transfer of wild p16 gene can inhibit the proliferation and reduce the invasion ability of HCC cells with p16 negative expression, but can not affect the HCC cells with p16 positive expression.