AIM:To perform a comparative analysis of clinicopathological correlations of cyclooxygenase2 (COX2) expression in pancreatic cancer, examined by monoclonal and polyclonal antibodies.METHODS: The COX2 expression in 85 ...AIM:To perform a comparative analysis of clinicopathological correlations of cyclooxygenase2 (COX2) expression in pancreatic cancer, examined by monoclonal and polyclonal antibodies.METHODS: The COX2 expression in 85 resection specimens of pancreatic ductal adenocarcinoma was immunohistochemically examined using both monoclonal and polyclonal antibodies. The final immunoscores were obtained by multiplying the percentage of positive cells with the numeric score reflecting the staining intensity.COX2 expression levels were classified into three categories (0, 1+, and 2+) and the clinicopathological correlations were statistically evaluated and analyzed.RESULTS: The positive tumor expression rates of COX2 were 80.5% using monoclonal antibody and 69.4% using polyclonal antibody. In the KaplanMeier analysis, no significant correlations were found between levels of COX2 expression and overall survival (OS), but trends to longer OS were found in COX2 negative cases using monoclonal antibody. Significantly longer disease free survival was revealed in COX2 negative cases using monoclonal antibody (P = 0.019). No correlations between COX2 expression levels and grade (G), tumor (T) status and nodal (N) status were demonstrated. Low histological grade showed a strong association with a longer OS (P < 0.001). Correlation of survival and T status revealed a shorter OS in T3 tumors, but the results reached only marginal statistical significance (P = 0.070). In the multivariate Cox proportional hazards regression model, histological grade, T and N status remained valuable predictors of a worse survival with borderline significance for T [hazards ratio (HR) = 4.18 for G (if G = 3, P < 0.001); HR = 1.64 for T (if T = 3, P = 0.065); HR = 2.53 for N (if N = 1, P = 0.006)]. Higher grade, T or N status was associated with a worse OS. CONCLUSION: The immunohistochemically assessed level of COX2 expression does not seem to represent a valuable independent prognostic factor and is not superior to the conventional prognostic factors.展开更多
AIM: To study the effect of 5-lipoxygenase/cyclooxy- genase-2 (5-LOX/COX-2) dual inhibitor 7-tert-butyl-2, 3-dihydro-3, 3-dimethyl substituted dihydrofuran 30 (DHDMBF30) on proliferation and apoptosis of the pancreati...AIM: To study the effect of 5-lipoxygenase/cyclooxy- genase-2 (5-LOX/COX-2) dual inhibitor 7-tert-butyl-2, 3-dihydro-3, 3-dimethyl substituted dihydrofuran 30 (DHDMBF30) on proliferation and apoptosis of the pancreatic cancer cell line Capan-2 and the effect of DHDMBF30 on human pancreatic cancer in a nude mouse model. METHODS: Investigate the effect of 5-LOX/COX-2 dual inhibitor DHDMBF30 on proliferation and apoptosis of the pancreatic cancer cell line Capan-2 by RT-PCR, MTT assay, FCM and electron microscope. Cell line Capan-2 was inoculated percutaneously on the outer thigh of 12 nude mice. The VEGF mRNA of transplantation tumor was detected by RT-PCR. RESULTS: DHDMBF30 inhibits the proliferation of cell line Capan2, reduces the expression of 5-LOX, COX-2 and VEGF. After Capan2 was treated with DHDMBF30, we found that the apoptosis peak of the experimental group was significantly higher than that of the contrast group (3.08 ± 1.89 vs 27.67 ± 0.52, P < 0.001). The tumor weight of the DHDMBF30 group was significantly lower than PBS control groups (1.35 ± 0.47 vs 2.92 ± 0.73, P < 0.01). Expression of VEGF in the DHDMBF30 group was significantly decreased. CONCLUSION: DHDMBF30 inhibits the proliferation ofthe pancreatic cell line Capan2, and induces apoptosis and inhibits the growth of pancreatic cancer in nude mice.展开更多
基金Supported by A Grant from the Ministry of Health (IGA), No. NR 9295-3, Czech Republic
文摘AIM:To perform a comparative analysis of clinicopathological correlations of cyclooxygenase2 (COX2) expression in pancreatic cancer, examined by monoclonal and polyclonal antibodies.METHODS: The COX2 expression in 85 resection specimens of pancreatic ductal adenocarcinoma was immunohistochemically examined using both monoclonal and polyclonal antibodies. The final immunoscores were obtained by multiplying the percentage of positive cells with the numeric score reflecting the staining intensity.COX2 expression levels were classified into three categories (0, 1+, and 2+) and the clinicopathological correlations were statistically evaluated and analyzed.RESULTS: The positive tumor expression rates of COX2 were 80.5% using monoclonal antibody and 69.4% using polyclonal antibody. In the KaplanMeier analysis, no significant correlations were found between levels of COX2 expression and overall survival (OS), but trends to longer OS were found in COX2 negative cases using monoclonal antibody. Significantly longer disease free survival was revealed in COX2 negative cases using monoclonal antibody (P = 0.019). No correlations between COX2 expression levels and grade (G), tumor (T) status and nodal (N) status were demonstrated. Low histological grade showed a strong association with a longer OS (P < 0.001). Correlation of survival and T status revealed a shorter OS in T3 tumors, but the results reached only marginal statistical significance (P = 0.070). In the multivariate Cox proportional hazards regression model, histological grade, T and N status remained valuable predictors of a worse survival with borderline significance for T [hazards ratio (HR) = 4.18 for G (if G = 3, P < 0.001); HR = 1.64 for T (if T = 3, P = 0.065); HR = 2.53 for N (if N = 1, P = 0.006)]. Higher grade, T or N status was associated with a worse OS. CONCLUSION: The immunohistochemically assessed level of COX2 expression does not seem to represent a valuable independent prognostic factor and is not superior to the conventional prognostic factors.
基金Supported by Grant No. 30600603 from the National Natural Science Foundation of China and Grant No. 2005BS03003 from the Department of Science and Technology of Shandong Province of China
文摘AIM: To study the effect of 5-lipoxygenase/cyclooxy- genase-2 (5-LOX/COX-2) dual inhibitor 7-tert-butyl-2, 3-dihydro-3, 3-dimethyl substituted dihydrofuran 30 (DHDMBF30) on proliferation and apoptosis of the pancreatic cancer cell line Capan-2 and the effect of DHDMBF30 on human pancreatic cancer in a nude mouse model. METHODS: Investigate the effect of 5-LOX/COX-2 dual inhibitor DHDMBF30 on proliferation and apoptosis of the pancreatic cancer cell line Capan-2 by RT-PCR, MTT assay, FCM and electron microscope. Cell line Capan-2 was inoculated percutaneously on the outer thigh of 12 nude mice. The VEGF mRNA of transplantation tumor was detected by RT-PCR. RESULTS: DHDMBF30 inhibits the proliferation of cell line Capan2, reduces the expression of 5-LOX, COX-2 and VEGF. After Capan2 was treated with DHDMBF30, we found that the apoptosis peak of the experimental group was significantly higher than that of the contrast group (3.08 ± 1.89 vs 27.67 ± 0.52, P < 0.001). The tumor weight of the DHDMBF30 group was significantly lower than PBS control groups (1.35 ± 0.47 vs 2.92 ± 0.73, P < 0.01). Expression of VEGF in the DHDMBF30 group was significantly decreased. CONCLUSION: DHDMBF30 inhibits the proliferation ofthe pancreatic cell line Capan2, and induces apoptosis and inhibits the growth of pancreatic cancer in nude mice.