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A Research On The Connection Between COX-2Expression In Resectable Pancreatic Ductal Adenocarcinoma And Its Bio-parameters

Posted on:2013-03-26Degree:MasterType:Thesis
Country:ChinaCandidate:X SunFull Text:PDF
GTID:2234330374966279Subject:Oncology
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Backgroun and Aim:Pancreatic ductal adenocarcinoma (PDAC), a highly agressive pancreatic malignancy, is the most common pancreatic neoplasm and has very a poor prognosis. Surgery is the primary selection for the treatment, however, most patients are not surgery candidate when being diagnosed. The benefits of chemotherapy has been very limited, even combined with the latest molecular targeted drugs. Therefore, seeking new ways of treating pancreatic cancer has become our urgent task. In recent years, a great number of laboratory and clinical researches associated with pancreatic have been carried out world wide, unfortunately no inspiring outcomes have been seen. It has been confirmed that the carcinogenesis proliferation and metastasis of digestive malignancies are closed correlated with inflammation and its cytokines, such as esophageal cancer, gastric cancer, colorectal cancer and hepatic cancer. In that case,to inhibit inflammation has become a new breakthrough in pancreatic cancer treatment. In our research, we are dedicated to interpret the link between the expression of COX-2,a major inflammatory cytokine, in pancreatic cancer specimen and its clinicopathology diameters, aiming at paving the way for a new way of therapeutic strategy.Material and Method:A total of32PDAC patients who had undergone a Pancreatectomy, all32patients were followed till early2012,and their clinicopathological parameters were documented in detail. The COX-2, ki-67,Bcl-2,VEGF expression in32resection specimens of pancreatic cancer were immunohistochemically examined using monoclonal antibody and the final immunoscores were obtained by multiplying the percentage of positive cells with the numeric score reflecting the staining intensity. These procedures were carried out under the guidance of pathologists, and all32specimen were confirmed as pancreatic ductal adenocarcinoma pathologically. Tumor angiogenesis were scored as Ⅰ,Ⅱ and Ⅲ by means of Microvascular Density (MVD), extracellular matrix(ECM) was evaluated following roughly the same pattern. The expression scores of COX-2was later compared with the expression of Ki-67,Bc1-2,VEGF,and MVD,ECM. SPSS17.0was used for statistical analysis, statistical methods include Spearman correlation analysis, kappa consistency test,Chi-square test, Fisher’s exact test and Kaplan-Meier analysis, P<0.05was considered statistically significant.Results:Of all32specimen,22were positive stained for COX-2by means of immunohistology, the positive rate was68.7%. COX-2expression was significantly correlated with a shorter OS(0.648vs1.073Year, Log-rank test P=0.029<0.05). COX-2expression in PDAC is significantly correlated with tumor size, but other clinicopathological parameters, including tumor stage,differientiation,ascites, were not significantly correlated. And the intensity of COX-2expression was significantly correlated with Ki-67,Bc1-2,VEGF,MVD and ECM scores. Namely, a higher COX-2expression in PDAC indicates a higher tumor cell proliferation, less apoptosis,higher MVD and more ECM production.Conclusion:COX-2expression in PDAC resected specimen was significantly correlated with a poorer clinical prognosis.COX-2may facilitates PDAC growth in ways of promoting tumor proliferation,apoptosis inhibition; increasing tumor angiogesis and ECM abundance. Inhibition of COX-2could had shown potential as a new therapeutic strategy of PDAC.
Keywords/Search Tags:Chronic inflammation, Pancreatic cancer, Cyclooxygenase-2COX-2, Immunohistochemistry
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