Down-modulation of heat shock protein 70 and up-modulation of Caspase-3 during schisandrin B-induced apoptosis in human hepatoma SMMC-7721 cells

AIM: To investigate the effect of schisandrin B (Sch B) on proliferation and apoptosis of human hepatoma SMMC-7721 cells in vitro and regulation of Hsp70 and Caspases-3, 7, 9 expression by Sch B. METHODS: Human hepatoma cell line SMMC-7721 was cultured and treated with Sch B at various concentrations. Growth suppression was detected with MTT colorimetric assay. Cell apoptosis was confirmed by DNA ladder detection and flow cytometric analysis. The expression of Hsp70, Caspases-3, 7, 9 were analyzed by Western blot analysis. RESULTS: Sch B inhibited the growth of hepatoma SMMC-7721 cells in a dose-dependent manner, leading to a 50% decrease in cell number (LC50) value of 23.50 mg/L. Treatment with Sch B resulted in degradation of chromosomal DNA into small internucleosomal fragments, evidenced by the formation of a 180-200 bp DNA ladder on agarose gels. FCM analysis showed the peak areas of subdiploid at the increased concentration of Sch B. The results of Western bolt analysis showed that Hsp70 was down-regulated and Caspase-3 was up-regulated, while the activity of Caspases-7, -9 had no significant change. CONCLUSION: Sch B is able to inhibit the proliferation of human hepatoma SMMC-7721 cells and induce apoptosis, which goes through Caspase-3-dependent and Caspase-9-independent pathway accompanied with the down-regulation of Hsp70 protein expression at an early event.     

Effects of herbal compound 861 on human hepatic stellate cell proliferation and activation

AIM: To investigate the effects of herbal compound 861 (Cpd 861) on cell proliferation in human hepatic stellate cells (LX-2) and human hepatocellular liver carcinoma cells (HepG2), and expression of α-smooth muscle actin (α-SMA) in LX-2 cells.METHODS: LX-2 and HepG2 cells were incubated with various concentrations of Cpd 861 (0.1-0.003 mg/mL)for 1, 2, 3, 5 and 7 d. Cell proliferation was analyzed by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Effects of Cpd861on the expression of cc-SMA mRNA in LX-2 cells weremeasured by real-time quantitative PCR method using SYBRGreen I technology.RESULTS: Cpd 861, at 0.1 mg/mL, significantly inhibitedLX-2 cell proliferation (15% decrease relative to control,P<0.05) after 3 d of incubation. The inhibitory effects seemedto increase with the treatment time (25% decrease after5 d of incubation and 35% decrease after 7 d of incubation,P<0.01). However, Cpd 861 did not affect HepG2 cellproliferation at the same concentration used for I_X-2 cells.The expression levels of ~-SMA mRNA decreased significantlywhen LX-2 cells were exposed to Cpd 861 for 48 h (59%decrease relative to control, P<0.05) or 72 h (60% decreaserelative to control, P<0.01).CONCLUSION: Cpd 861 can significantly inhibit LX-2 cellproliferation in a dose-dependant manner, and reduce theexpression levels of o~-SMA mRNA in LX-2 cells. Since hepaticcell proliferation and high level of ~-SMA are associatedwith liver fibrosis, the results suggest that Cpd 861 may beuseful in the treatment of this disease.     

Percutaneous balloon angioplasty of inferior vena cava in Budd-Chiari syndrome-R1

This study was to evaluate the clinical effects of percutaneous balloon angioplasty of Budd-Chiari syndrome (BCS) caused by inferior vena cava (IVC) obstruction. Between 1993 and 1999, 28 men and 14 women with mean age of 44+/-12 years underwent percutaneous balloon angioplasty for primary BCS. Color Doppler ultrasound and venography showed membranous and segmental obstruction of IVC in 29 and 13 patients, respectively. Fourteen patients also had left- and/or mid-hepatic vein obstruction. Angioplasty of IVC was successful in 41 patients (97.6%), resulting in a reduction of pressure gradient between IVC and the right atrium from 15.0+/-2.5 to 5.5+/-0.8 mmHg (P<0.01). A stent was placed in the site of obstruction in the patient with unsuccessful balloon angioplasty. Patients with successful angioplasty or stent placement had significant improvement in clinical symptoms indicated by a reduction in hepatomegaly and the degree of ascites. No specific attempt was made to treat the occluded left- and/or mid-hepatic vein due to the presence of potent right hepatic vein. Over the follow-up period of 32+/-12 months, restenosis of IVC occurred in only one patient (2.4%), which was redilated successfully. Percutaneous balloon angioplasty is a safe and effective therapy for Budd-Chiari syndrome caused by IVC obstruction, therefore should be the first choice of treatment for this condition.     

Expression and Prognostic Roles of Eag1 in Resected Esophageal Squamous Cell Carcinomas

Expression of Eag1 was detected in resected esophageal squamous cell carcinomas tissues and matched tissues by immunohistochemistry and RT-PCR. Positive expression of Eag1 protein was 75% (51/68), and mRNA was 73% (8/11) in primary cancer tissues. Eag1 protein positively stained in all 10 metastatic lymph nodes. Eag1 protein and mRNA were negatively expressed in all non-cancerous matched tissues. Eag1 protein was associated with depth of penetration (P = 0.023), but not associated with other clinicopathological factors. Eag1 protein positive group had a significantly shorter survival time than the negative group (P = 0.005). Survival rates at each time-point for the positive group were lower than that for the negative group (P = 0.006), and Eag1 was identified as an independent prognostic factor of long-term survival (P = 0.016). In conclusion, Eag1 was aberrantly expressed in ESCC and correlated with poor prognosis after surgery.     

Hepatosplenic γδ T-cell lymphoma

AIM: To investigate the clinicopathologic characteristics, immunophenotype and TCR gene rearrangements of hepatosplenic T-cell lymphoma in eight Chinese patients. METHODS: Eight Chinese patients with hepatosplenic 76 T-cell lymphomas were studied. Hematoxylin-eosin-stained slides and clinical histories were reviewed. We also carried out immunohistochemical staining for CD3, CD4, CD8, CD20, CD43, CD56, CD79a, UCHL-1, and TCR γδ. Rearrangements of TCR gamma and delta chain genes were also studied. RESULTS: The spleens were enlarged and the cut surfaces were homogeneous and red-purple in color without identifiable gross lesions or enlarged hilar lymph nodes. Histologically, lymphoma cells infiltrated the cords of Billroth and often packed the sinuses. Liver biopsy showed lymphoma cell infiltrations in the sinusoids, and three cases showed involvements of the portal tracts. Immunohistochemically lymphoma cells were positive for CD3, CD43, and CD56 in all cases. Four of eight cases were positive for CD8, and all cases were negative for CD4 (6/6). Monoclonal rearrangements of TCR y gene were demonstrated by PCR analysis in five out of the eight cases. TCR δ gene rearrangements were detected in six out of the eight cases, which demonstrated single bands on PAGE gel, and the amplification products in two cases were confirmed by sequencing. CONCLUSION: The clinicopathology of hepatosplenic γδ T-cell lymphoma in Chinese patients is similar to what was previously reported except that the splenomegaly is not so massive, and CD8 is positive.     

Barrett＇s esophagus and its correlation with gastroesophageal reflux in Chinese

AIM- To study the prevalence of Barrett‘s esophagus in Chinese and its correlation with gastroesophageal reflux. METHODS: This study was carded out in a large prospective series of 391 patients who had undergone upper endoscopy. The patients were divided into 3 groups according to the position of squamocolumnar junction (SC3). Reflux esophagitis (RE) and its degree were recorded. Intestinal metaplasia (IM) in biopsy specimen was typed according to histochemistry and HE and alcian blue (pH2.5) staining separately. Results correlating with clinical, endoscopic, and pathological data were analysed. RESULTS: The prevalence of IM endoscopically appearing Long-segment Barrett‘s Esophagus (LSBE) was 26.53%, Short-segment Barrett‘s Esophagus (SSBE) was 33.85% and gastroesophageal junction (GEJ) was 34.00%. IM increased with age of above 40 years old and no difference was found between male and female. Twelve were diagnosed as dysplasia (7 low -grade, 5 high-grade), 16 were diagnosed as cardiac adenocarcinoma and 1 as esophageal adenocarcinoma. The more far away the SCJ moved upward above GEJ, the higher the prevalence and the more severe the RE were. CONCLUSION: There was no difference of the prevalence of IM in different places of SCJ, and IM increased with age of above 40 years old. It is important to pay attention to dysplasia in the distal esophagus and gastro-esophageal junction, and adenocarcinoma is more common in cardia than in esophagus. BE is a consequence of gastroesophageal reflux disease.     

Diagnosis and surgical treatments of hepatocellular carcinoma with tumor thrombosis in bile duct： Experience of 34 patients

AIM: Hepatocellular carcinoma (HCC) with bile duct tumor thrombosis (BDT) is a rare event. The prognosis of this type of patients is very dismal. The aim of this study was to share the experience in the diagnosis and treatment of HCC with BDT, to further improve the prognosis of these patients.METHODS: Thirty-four patients of HCC with BDT received surgical treatment in authors‘ institute from July 1987 to January 2003 were reviewed retrospectively. The experience in the diagnosis and treatment, and the outcome of this type of HCC patients were summarized.RESULTS: Thirty of the 34 patients (88.2%) were positive for alpha-fetoprotein (AFP) (&gt;20 μg/L), and 12 patients (35.3%) were found having obstructive jaundice before operation, 18 cases were suspected of “obstruction of bile duct“ preoperatively. The primary tumors were frequently located at the left medial (13 cases) or right anterior lobe(14 cases). Thirty-one patients received liver resections and removal of BDT, while the other 3 patients received removal of BDT combined with hepatic artery ligation and cannulation(HAL+HAI), or only removal of BDT because their liver function reservation and general condition could not tolerate the primary tumor resection. The 1-year survival rate was 71.4%(20/28). The longest disease-free survival was over 15 years. The intrahepatic tumor recurrence within 1 year after operation was found in 14 patients (14/28, 50.0%).CONCLUSION: Surgical removal of primary tumors and BDT is safe and beneficial to the HCC patients with BDT. Early detection, diagnosis, and surgical treatment are the key points to prolong the survival time of patients.