Background and purpose:Gallbladder carcinoma, lacks of specific clinical manifestations,and is usually diagnosed at advanced stages of the diseases and even fewer can be resected.Chemotherapy has not shown significant activity in gallbladder carcinoma,so new agents should be applied to its treatment.Arsenic trioxide,verified as a breakthrough in the management of acute promyelocytic leukemia,has been applied in the research of a variety of solid tumors.This study is to investigate the biological effect of As_(2)O_(3) on human gallbladder carcinoma cell GBC cells and its mechanism.Methods:Hoechest33258 staining,DNA gel electrophoresis and flowcytometric were used to determine apoptosis.Western blot was performed to analysis apoptotic proteins expression.Results:The treatment of As_(2)O_(3) in gallbladder carcinoma cells could induce apoptosis in a dose-dependent manner and downregulate the expression of anti-apoptotic protein Bcl-2.Moreover,Bcl-2 overexpression could protect gallbladder carcinoma cells from As_(2)O_(3)-induced apoptosis.Conclusions:As_(2)O_(3) induces gallbladder carcinoma cell apoptosis via down regulation of Bcl-2.

Purpose: To study the mechanism of chemoprevention of colorectal cancer by aspirin. Methods: Different concentrations of aspirin have been used in the culture of colonic cell-Caco-2, its proliferation and apoptosis was observed during the culture and the expression of Fas/FasL mRNA was assayed by RT-PCR. Results: Major portion of cells died in the culture medium that was added high concentration of aspirin, but the lower concentration promoted apoptosis. The Fas mRNA was expressed in cells added with 25 mmol/L aspirin, but not in that of 1640. The FasL mRNA expressed in 25mmol/L aspirin was lower than in 1640. Conclusions: The lower concentration of aspirin can promote apoptosis of coloniccell, the mechanism has correlation with induction of the expression of Fas, and down-regulation of the expression of FasL.

Background and purpose:Arsenic trioxide,verified as a breakthrough in the management of acute promyelocytic leukemia,has been applied to a variety of solid tumors.Gall bladder carcinoma,lacking specific clinical manifestations,is usually diagnosed at advanced stages of the diseases and few cases can be resected by operation.Chemotherapy has not shown significant activity in gall bladder carcinoma.This study was to investigate the biological effect of As2O3 on the growth of human gall bladder carcinoma cell and its mechanism.Methods:GBC cells were cultured with different concentrations of As2O3,the proliferative activity of the cells was detected by MTT methods,and the cell cycle status was carried out by flow cytometry(FCM).Western blot and RT-PCR were performed to analyse the expression of cyclin D1,D2,D3,CDK4 and CDK6.GBC cells were transient transfected with cyclin D1 promoter construct pGL3 and then treated by different doses of As2O3.The luciferase activity was measured.Results:The treatment of As2O3 in gall bladder carcinoma cells could inhibit the growth of cells in a time and dose dependent manner,make cells arrest in G1 phase and down regulate the expression of cyclin D1.In addition,the activity of cyclin D1 promoter was down-regulated by As2O3 in a dose-dependent manner and decreased about 70 percent when treated with 4 ?mol/L As2O3.Conclusions:As2O3 can significantly inhibit the growth of human gall bladder carcinoma cells as well as down-regulate the expression of cyclin D1 in vitro.

Purpose:To evaluate the role of COX 2 in the carcinogenesis and progression of human colorectal neoplasms. Methods:The expression level of COX 2 in 122 colorectal neoplasm tissues(including 35 colorectal adenomas, 67 colorectal carcinoma and 23 colorectal cancer with synchoronous hepatic metastasis) was assayed by immunohistochemical methods. All specimens was analyzed by Conformation quantitative assay system, their stain strength was calculated.Results:Conformation quantitative assay showed the mean stain strength is 704.5 131.8 in colorectal adenoma, 1197.2 204.3 in colorectal cancer without hepatic metastasis and 1901.2 324.8 in colorectal cancer with synchoronous hepatic metastasis, there are significant differences among them statistically. According to the Dukes stages, mean stain strength is 1145.3 187.0 in B stage,1237.0?298.7 in C stage,1901.2 in D stage. There is statistic difference between Dukes stage D and B, C. Also our study indicated there was no relationship between age, sex, tumor location, tumor differentiation or tumor size with the level of COX 2 protein expression.Conclusions:In our test,higher COX 2 expression is seen in colorectal cancer than colorectal adenomas, colorectal cancer with synchoronous hepatic metastasis than colorectal cancer without hepatic metastasis,and Dukes D stage than the B?C. Thus COX 2 responses is important in the carcinogenesis and progression of colorectal cancer. NSAIDs or the others may play a role in the chemoprevention strategies of colorectal neoplasm as the COX 2 inhibitor.

ObjectiveTo provide clues to find a biomarker for early diagnosis, prognosis and therapy, as well as to understand the molecular mechanisms governing cancer progression. Methods Surgical specimens were obtained from 87 patients with histopathologically proven malignant or benign lesions. The differential protein profiles of these malignant and benign specimens were detected using two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). Western blotting and immuno-histochemistry were used to validate the results. RT-PCR was used to detect the gene expression in the tissues. ResultsMrp14 was found to be overexpressed in the tumor tissues of gallbladder cancer and extra-hepatic bile duct cancer, and in the bile of patients with malignant biliary tract tumours. The result was further verified using Western blot and immuno-histochemistry. RT-PCR confirmed the overexpression of Mrpl4 at the gene level. Mrp14 is a potential biomarker for biliary tract neoplasms. ConclusionsThis is the first report which described the overexpression of Mrp14 in biliary tract neoplasms and further studies are needed to confirm our findings. Mrp14 may be a potential hiomarker for biliary tract neoplasms. It may provide important clues on the molecular mechanisms governing cancer progression.