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The Study Of Tumor Suppressor Gene -ARHI/NOEY2 And Its Hypermethylation In Pathogenesis And Mechanism Of Treatment Of Pancreatic Cancer

Posted on:2005-04-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:H YangFull Text:PDF
GTID:1104360185973270Subject:Digestive medicine
Abstract/Summary:PDF Full Text Request
Pancreatic cancer is associated with high malignancy and poor prognosis. It is the reason that overall 5-year survival rate of pancreatic cancer does not exceed 5% in most studies, because it is diagnosed too late to have the chance of surgery, which is still considered as curative therapy for pancreatic cancer today. The incidence of pancreatic cancer is steadily increased in recent years .The reported,adjusted and age-standardized mortality rate of pancreatic cancer increased by 5.53%,6.41% and 4.57% annually .Pancreatic cancer accounted for 1.83% of all deaths due to tumor in 1991 and 2.26% in 2000 in China. And also, the recognition of molecular mechanisms involved in pancreatic carcinogenesis is much less than other tumors such as colorectal cancer.ARHI/NOEY2 is a maternally imprinted tumor suppressor gene that maps to a site on chromosome 1p31. ARHI is expressed in normal ovarian and breast epithelial cells, but majority of ovarian and breast cancers lost expression of ARHI. ARHI expression from the paternal allele can be down-regulated by multiple mechanisms including DNA methylation. Hypermethylation of CpG islands located in promoter region serves as an important mechanism for gene inactivation. So methyltransferase inhibitors have been developed as strategies of tumor therapy. The aim of this study was to explore the association of hypermethylation of ARHI with pancreatic carcinoma, and to identify the effect and the possible mechanisms of demethylating agent on pancreatic cell lines and pancreatic carcinoma xenografted in Nude Mice. l.The association of ARHI/NOEY2 and its hypermethylation of CpG island inhuman pancreatic carcinoma tissues.Methods: Human pancreatic cancer tissue and normal pancreatic tissue were collected. 1. The expression of ARHI/NOEY2 protein was investigated by immunohistochemistry using a specific antibody in 24 tissues. 2.To analyze the association of ARHI/NOEY2 with tumor stage, size, location, sex, age, smoking,...
Keywords/Search Tags:ARHI/N0EY2, pancreatic carcinoma, methylation, apoptosis, cell cycle, nude mice
PDF Full Text Request
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