ObjectiveTo investigate the effects of MMI-166 on the proliferation and apoptosis of human pancreatic cancer SW1990 cells.MethodsMMI-166 of different concentrations (25,50,100 μg/ml) were used to treat human pancreatic cancer SW1990 cell for 24,48 h.Effect of MMI-166 on cell proliferation wasdetected by 3- (4,5-dimethyl-2-thiazole) -2-5-biphenly-tetrazole bromide ( MTT ) method and effect on cell apoptosis was tested by Annexin V-PI method and flow cytometry (FCM).ResultsTwenty-four hours after MMI-166 treatment of different concentrations (25,50,100 μg/ml),the inhibitory rates of the cells were (34.23±3.87)％,(44.81 ±2.01)％,(53.91 ±1.74)％,and the corresponding values were (39.95 ± 1.83) ％,( 52.26 ± 3.46 ) ％,( 63.20 ± 2.48 ) ％ at 48 h,which suggested a time-and concentrationdependent manner.The cell's apoptosis rates were (11.19 ±0.47)％,(23.01 ±0.53)％,(28.10 ± 0.52) ％ at 24 h,and the corresponding values were ( 11.19 ± 0.47 ) ％,( 23.01 ± 0.53 ) ％,( 28.10 ± 0.52)％ at 48 h,which were significantly higher than those in control group [ (0.09 ±0.12)％,P ＜0.05].ConclusionsMMI-166 can inhibit proliferation and induce apoptosis of human pancreatic SW1990 cell in a time- and concentration-dependent manner.

Objective To study the expression of Survivin and COX-2 in ampullary carcinoma and their clinical significance.MethodsThe expression of Survivin and COX-2 proteins were tested by EnVision immunohistochemistry in 40 cases of ampullary carcinomas,and 8 cases of normal ampulla of vater as the controls.ResultsThe positive rate of Survivin in ampullary carcinonas was significantly higher than that of the controls(82.5％ vs 0,P ＜ 0.01 ). The expression of Survivin in ampullary carcinoma was correlated with duodenal invasion,pancreatic invasion and lymph node metastasis ( P ＜ 0.05 ).Significant difference was also observed in the expression rate of COX-2 between the patients with ampullary carcinoma and the normal controls (67.5％ vs 0,P ＜ 0.01 ).The expression of COX-2 in ampullary carcinoma was correlated with duodenal invasion,pancreatic invasion and lymph node metastasis (P ＜ 0.05). Significantly positive correlation was found between the expression of Survivin and COX-2 by using spearman correlation analysis ( r =0.383,P =0.015).ConclusionThe specific up-regulation of COX-2 gene and Survivin gene may play an important role in the genesis and development of ampullary carcinoma.COX-2 and Survivin may be used as early diagnosis markers and potential therapeutic targets in ampullary carcinoma.

Livin,as a novel member of human inhibitor of apoptosis protein family,is highly expressed in many malignant tumors.Livin plays critical role in apoptosis inhibition,regulating the cell cycle,participating in tumor angiogenesis.Livin is also significant to chemoresistance.The majority of the current data suggests that Livin expression in cancer appears to be associated with unfavorable clinico-pathological parameters,such as disease relapse and shorter patient survival.In recent years,immunotherapy and gene therapy for the targeting of Livin have become a hot research field,which provides new strategy and direction for tumor therapy.

Objective To investigate of the MMI-166 on the expression of MMP-2,MMP-9 and the cell apoptosis of nude mouse xenografts of SW1990 human pancreatic cancer cells.Methods Establishment of control and experimental groups,randomly,the human pancreatic cancer xenograft model of SW1990 was constructed.The control group was treated with normal saline,and experimental group was treated with MML-166 (200 mg · kg-1 · d-1).The tumor volume and tumor inhibition rate was measured by vernier caliper through length and short diameter.The expression of MMP-2 and MMP-9 protein was observed using immunohistochemistry in the tumor tissues.Apoptosis index was detected by deoxynucleotidyl transferase-mediated nick end labeling (TUNEL method).Results The tumor volume of MMI-166 group (1252.30± 464.84) mm3 was less than the control group (2241.82±208.06) mm3,significantly.The inhibition rate was 34.47％ between the experimental groups (treat with MMI-166) (1.42±0.15) g and control group (2.17±0.20) g.The expression of MMP-2 (2.80 ± 1.10) ％ and MMP-9 (2.60 ± 1.52) ％ protein was significantly downregulated in MMI-166 group,compared with the control group.Apoptotic index in the experimental group (75.60±9.71) ％ was higher than the control group (17.40 ± 10.14) ％,significantly.Conclusion The mechanism of MMI-166 inhibiting pancreatic tumor growth and inducing apoptosis may be related to the suppression of MMP-2 and MMP-9 protein expression.

ObjectiveTo study the expression of matrix metallopro-teinase-2 (MMP-2),matrix metalloproteinase-9 (MMP-9) in the pancreatic carcinomas. Methods MMP-2,MMP-9 expression were detected by immunohistochemistry in surgically resected specimens ( cancer tissues,cancer-adjacent tissues and normal tissues) from 30 PC patients,11 pancreatitis patients and 6 normal patients.the results were analyzed combined with clinical pathologic characteristics.The data was analyzed by Chi-Square test.ResultsThere was no expression of MMP-2,MMP-9 in normal pancreatic tissues.Both of MMP-2 and MMP-9 expressions were 18.2％ in chronic pancreatitis titssues.Expression of MMP-2,MMP-9 were higher in cancer tissues than in cancer-adjacent tissues(63.3％ vs 23.3％,56.7％ vs 40.0％,P ＜0.05).There were positive correlation between MMP-2,MMP-9 expression and lymph nodal metastasis,tumor sizes,clinical stage and differentiation of tumor(P ＜0.05).Conclusions The expression of MMP-2 and MMP-9 was high,and linked to its unfavorable prognosis.

Objective To investigate the expression of TROP2 and MMP-9 protein expression in cholangiocarcinomas and their relationship between the pathological behavior and prognosis.Methods A total of 54 patients who were diagnosed with cholangiocarcinoma in the People's Hospital of Binzhou,were retrospectively reviewed.Immunohistochemical staining and Log rank test were used to detect the expression of TROP2 and MMP-9 protein in 54 cases of cholangiocarcinomas and 18 cases of normal bile duct tissues achieved by partial hepatectomy of hepatolithiasis.Results The positive expression rate of TROP2 in cholangiocarcinoma tissues (55.6％) was higher than that of normal bile duct tissues (5.6％).The positive expression rate of MMP-9 in cholangiocarcinoma tissues (51.9％) was higher than that of normal bile duct tissues (11.1％).The differences of the expression of TROP2 and MMP-9 in cholangiocarcinoma of TNM stage,lymph node metastasis and neural invasion were significant(all P ＜ 0.05).There was significant positive correlation between TROP-2 and MMP-9 expression by using spearman correlation analysis (r =0.555,P ＜ 0.001).Survival analysis showed that TROP2 expression was an independent prognostic factor in cholangiocarcinoma.Conclusions TROP2 plays a important role in the development and metastasis of cholangiocarcinoma.Thus,TROP2 may be a prognostic indicator for cholangiocarcinoma.

Objective To investigate the expressions of cancerous inhibitor of protein phosphatase2A (CIP2A),phosphatidylinositol 3-kinase(PI3K),and survivin in pancreatic carcinomas and their clinical significance.Methods The expressions of CIP2A,PI3K,and survivin proteins were tested by immunohistochemistry in 64 cases of pancreatic carcinomas and adjacent paracancerous tissues.Results The positive rate of CIP2A in pancreatic carcinomas was significantly higher than adjacent paracancerous tissues (70.3％ vs 5.6％,P ＜0.05).Significant difference was observed in the expression rate of PI3K between the patients with pancreatic carcinomas and paracancerous tissues (73.4％ vs 8.3％,P ＜0.05).Significant difference was also observed in the expression rate of survivin between the patients with pancreatic carcinomas and paracancerous tissues (75.0％ vs 2.8％,P ＜0.05).CIP2A,PI3K,and survivin were significantly differentially expressed in pancreatic carcinoma among different tumor differentiation,tumor node metastasis (TNM) stage,and neural invasion and lymph node metastasis (all P ＜ 0.05).Spearman correlation analysis showed significantly positive correlation between the expressions of CIP2A and the others (PI3K and survivin) (both P ＜0.05),and between the expressions of PI3K and surviving (P ＜0.05).Conclusions CIP2A was involved in the development of pancreatic carcinomas and might activate the PI3K/Akt/survivin pathway.Our data identified CIP2A as a critical oncoprotein involved in cell proliferation,invasion,and metastasis.It could serve as a therapeutic target for pancreatic carcinomas.

Objective To investigate the relationship of Twist induced epithelial mesenchymal transitions (EMT) during pancreatic carcinoma progression.Methods The expressions of Twist,N-cadherin and Vimentin proteins were tested by immunohistochemistry in 42 cases of pancreatic carcinomas and 26 cases of adjacent paracancerous tissues.Results The positive rates of Twist,N-cadherin and Vimentin in 42 cases of pancreatic carcinomas were 76.2％,59.5％ and 57.1％,respectively.The positive rate of Twist,N-cadherin and Vimentin were all significant between pancreatic carcinomas and paired tumor-adjacent paracancerous tissues (all P ＜0.001).The differences of the expression of Twist,N-cadherin and Vimentin in pancreatic carcinoma of tumor differentiation,TNM stage,neural invasion and lymph node metastasis were significant (all P ＜ 0.05).Significantly positive correlation was found between the expression of Twist and the others (N-cadherin and Vimentin) by using spearman correlation analysis (r =0.506,P =0.001 ; r =0.417,P =0.006).Significantly positive correlation was found between the expression of N-cadherin and Vimentin by using spearman correlation analysis(r =0.462,P =0.002).Conclusions Twist signaling pathway activation might mediate pancreatic epithelial cells to EMT and then promote pancreatic carcinoma invasion and metastasis.

Objective To investigate the expressions of Livin and vascular endothelial growth factor (VEGF)in pancreatic carcinoma and their cilinical significances.Methods The expressions of Livin and VEGF proteins were tested by immunohistochemistry in 68 cases of pancreatic carcinomas and 44 cases of adja-cent paracancerous tissues.Results The positive rates of Livin in pancreatic carcinomas and adjacent paracan-cerous tissues were 73.5% and 4.5% respectively,and the difference was statistically significant (χ2 =48.137,P<0.001).The positive rates of VEGF in pancreatic carcinomas and adjacent paracancerous tissues were 69.1% and 13.6% respectively,and the difference was statistically significant (χ2 =29.147,P <0.001).The expressions of Livin and VEGF were related with tumor differentiation (χ2 =6.061,P=0.014;χ2 =6.592,P=0.010),TNMstage (χ2 =4.175,P=0.041;χ2 =9.992,P=0.002),lymph node metasta-sis (χ2 =11.731,P=0.001;χ2 =12.002,P=0.001)and neural invasion (χ2 =9.950,P=0.002;χ2 =7.433,P=0.006).Significantly positive correlation was found between the expressions of Livin and VEGF by using Spearman correlation analysis (r=0.320,P=0.008).Survival analysis showed that the expressions of Livin and VEGF were independent prognostic factors in pancreatic carcinoma.Conclusion Livin and VEGF involve in the development,migration and metastasis of pancreatic carcinoma.Livin may upregulate the expres-sion of VEGF,which may lead to the angiogenesis and migration in pancreatic carcinoma.