Downregulation of growth differentiation factor-15 in trichostatin A-induced apoptosis could play a role in progression of gastric cancer.

AIM: To investigate the effect of trichostatin A (TSA) on gastric cancer cell line BGC-823, and identify the differentially expressed genes induced by TSA, which might participate in the progression of gastric cancer. METHODS: MTT, fluorescence microscopy, and flow cytometry were used to detect the effect of TSA on growth inhibition and apoptosis of BGC-823 cells. Using gene microarray, we analyzed the changes in gene expression. Change in growth differentiation factor-15 (GDF-15) was verified by qRT-PCR and Western blotting. The expression of GDF-15 in gastric cancer and adjacent normal tissues was detected by immunohistochemistry. RESULTS: Apoptosis of BGC-823 cells induced by TSA (75 ng/mL for 48 h) was demonstrated by flow cytometry. There were significant variations between TSA treated groups and control groups (P = 0.02). Nuclear chromatin condensation and fluorescence intensity were observed by fluorescence microscopy. GDF-15 gene expression and protein level were significantly reduced in the TSA treated group (75 ng/mL for 48 h). Immunohistochemistry demonstrated that the expression of GDF-15 in gastric adenocarcinoma was significantly higher than in the surrounding normal tissues (P < 0.05). CONCLUSION: Lower GDF-15 gene expression due to TSA-induced apoptosis was found in gastric cancer cell line BGC-823. Higher GDF-15 gene expression was seen in gastric adenocarcinoma tissues.

Differential expression of glycoprotein non-metastatic melanoma protein B (GPNMB) involved in trichostatin A-induced apoptosis in gastric cancer.

In this study, we investigated the effect of trichostatin A (TSA) on the gastric cancer cell line BGC-823. The effect of TSA on growth inhibition and apoptosis of BGC-823 cells was examined. The gene expression profile was determined by microarray. Western blotting was used to study the levels of acetylated histone H4 and Glycoprotein non-metastatic melanoma protein B (GPNMB) proteins. GPNMB gene expression was measured by real-time PCR. GPNMB protein levels in gastric adenocarcinoma tissues and adjoining normal tissues were detected by immunohistochemistry. The results showed that a significant decrease in cell population following treatment with 75 ng/mL TSA for 48 h (0.87 ± 0.04) as compared to control (1.14 ± 0.06) (P = 0.02). Apoptotic cells were increased in TSA (75 ng/mL for 48 h) treated group as compared to the control group (from 2.02% to 19.74%) by flow cytometry. The expression of acetylated histone H4 was increased in TSA treated (75 ng/mL for 48 h) group (from 1.00 ± 0.26 to 1.87 ± 0.33, F = 5.862, P = 0.0038) as compared to the control group by Western blotting. After 48 h TSA treatment (75 ng/mL), BGC-823 cells showed decrease in GPNMB gene expression (from 1.00 ± 0.21 to 0.59 ± 0.11, F = 6.214, P = 0.0018). Immunohistochemistry showed that GPNMB expression in gastric adenocarcinoma was significantly higher than the adjoining normal tissues (P = 0.000). To conclusion, our results support that TSA can induce apoptosis, and increase acetylated histone H4 in BGC-823 cells. GPNMB expression is decreased in BGC-823 cells after TSA treatment. GPNMB is overexpressed in gastric adenocarcinoma tissue. GPNMB involved in TSA-induced apoptosis might participate in gastric cancer.

Experience of congenital choledochal cyst in adults:treatment, surgical procedures and clinical outcome in the Second Affiliated Hospital of Harbin Medical University.

This study was undertaken to analyze and evaluate the diagnosis and principal treatment methods for congenital choledochal cyst, focusing on various surgical procedures and clinical outcome. A comprehensive, retrospective study was conducted on 72 adult patients who presented with choledochal cyst from 1985 to 2002. Surgical procedures were cyst excision with hepaticojejunostomy in 25 cases for type I or type IV-B, extrahepatic cyst excision with hepaticojejunostomy in 8 cases for type IV-A, extrahepatic cyst excision with modified hepaticojejunostomy in 2 cases for type IV-B, non-cyst excision with or without hepaticojejunostomy in 27 cases for types I, II, IV-A, IV-B. The early postoperative morbidity and mortality rate were 16.1% (9/62) and 6.5% (4/62) respectively, and the complication rate related to surgical procedure was 30.6% (19/62). The incidence of cholangiocarcinoma with non-cyst excision or non-operated congenital choledochal cyst was 10.8% (4/37). One patient died of primary hepatocellular carcinoma after cyst excision with hepatojejunostomy. In conclusion, our results showed that complete excision of choledochal cyst for types I, II, and IV-B and complete excision of extrahepatic choledochal cyst from the hepatic hilum in type IV-A with hepaticojejunostomy or modified hepaticojejunostomy are the treatment of choice for choledochal cyst in adult patients.