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Study On Methy Latron And Mutation And Protein Expression Of Hmlh1 Gene With Miscrosatellite Instability In Sporadic Colonic Carcinomas

Posted on:2007-05-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:F ChenFull Text:PDF
GTID:1104360185954724Subject:Surgery
Abstract/Summary:PDF Full Text Request
Colorectal cancer are the most common malignant tumors in humanbeing,which account for 40% of humanbeing tumors.There is a trend of rise in somehig cities in our coumtry, meaningwhile, The trend towards Younger andproximal Colon,in recent year,there is a obvious rise in diagnosis and treatmentof colon Cancer,but the prognosis is still poor,It is a urgent question to solve.Colon cancer is divided into heredity and non-heredity,The former includeFap and Hnpcc, non-heredity Colon cancer is what we Call sporadic coloncancer.With development of molecular-biology,The tumors are kmown is amore-steps process, involving a lot of genes There is evidence to suggest anassociation between colon cancer and diets containing a high proportion of fatand meat.The process of colon cancer include three parts(1)oncogenes andSuppressed genes,(2)actives of MMR,(3)Methylation of DNA.We detected mutation of Hmlh1 gene in 57 Sporadic colon Cancers by usingPCR-sscp.There is six mismatching repair gene Hmlh1 happern,We alsodetected the erpression of Hmlh1 gene protein in colon Cancers ,indictingmutation Can bring about the erpression of protein.We also detected theerpression of MSI colon Cancers and analysed the correlation among MSI andHmlh1 protein and clinical pathological characteristics,There is a highsignificant correlation between MSI and mechanism of colon cancers. We alsodetected Hmlh1 methylation in colon cancers There is a high significantcorrelation among methylation and MSI+and Hmlh1 protein,SugestingHmlh1-hymethylation is the reason to bring about colon cancers. Age-ralatedhypermethylation is found in patients with spordadic colon cancers,Which mayCause MSI+ and might be the mechanisms in development of colon cancers ofelderly people.We also analysed the expression of Hmlh1 protein by usingWestern-blot, The low expression of Hmlh1 protein is 17。5%,there was asigmificient correlation between the observed Hmlh1 protein and clinicalpathylogical characteisitic,such as right-sided location and low-differentiated.Proved by medline retrieve,The study on methylantion MSI+ and Hmlh1mutation in colon cancers is a creative study at home and abroad.The researchachieves international advanced level and the leading level in our country.Westudy the mechanism of colon cancers is helpful to provided evidences ofdiagnosis and treatment of colon cancers.
Keywords/Search Tags:Miscrosatellite
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