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Study On The Expression Of Survivin In Human Gastric Cancer And Precancerous Lesion

Posted on:2004-12-11Degree:MasterType:Thesis
Country:ChinaCandidate:Y YuFull Text:PDF
GTID:2144360092490689Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Gastric cancer is one of the most common malignant tumors and is a leading cause of the death in neoplasms worldwide. For a tumor to become established, compromises in the control of cell proliferation, differentiation as well as in the control of cell death are necessary. Apoptosis is a course of programmed DNA strand breaking and of physiology or pathology consuming energy, which leads to cell death. Some researches indicated that apoptosis of gastric cancer cell was closely related with expression of some genes, such as bcl-2, P53, c-myc, Fas, survivin, Rb, Ras, et al. Recently, designated survivin, a novel member of the IAP (inhibitor of apoptosis protein) gene family was identified. These proteins are characterized by Cys/His baculovirus IAP repeats and a COOH terminal ring finger. Survivin is separated by EPR-1cDNA filtrating from human gene bank, which is a protein of 142 amino acids, containing only one copy of a baculovirus IAP repeat (BIR), without ring finger. Survivin can restrain inducement of apoptosis in G2/M of cell cycle, overexpress to get over the checkpoint of apoptosis in carcinoma and promote transformed cells proliferate abnormally. Survivin binds actived caspase-3 and -7, and inhibits caspase activity in human cells exposed to apoptotic stimuli. Caspases are the core mechanism of cell apoptosis.The signaling cascades induced by many factors converge into a common apoptotic pathway characterized by the activation of a family of cysteine proteases,the caspases.Activated effector caspase cleave then alimited set of cellular proteins,whose activation/inactivation results in the typical apoptotic morphology.Survivin is found in embryonic and fetal development, completely down-regulated and undetectable in normal adult tissue and became prominently reexpressed in all of the most common human cancers,including cancers of the stomach, liver, lung, colon, pancreas, prostate, and breast,in vivo. Abundunce researches indicated that survivin function importently in tumor production and development, which represented an "intermediate biological change identifying histologically normal mucosa at risk of neoplastic transformation."This study was conducted to investigate a potential distribution of survivin in gastric cancer, and relationship of survivin overexpression and the tumor progression and metastasis.Materials and MethodsA total of 46 gastric cancer tissue with their corresponding normal mucosa was obtained from surgury during Mar, 2001 and Feb, 2002 in the 1st affiliacted hospital of Zhejiang university. Among 46 cases of gastric cancer, 30 male, 16 female, mean 54.2 years old, 33 had lymph-node metastasis, 14 had distant metastasis. 114 gastritis and precancerous lesion tissue was obtained from the specimen biopsied at gastroscopy, 30 superficial gastitis, 34 medial-hyper-atrophic gastritis, 30 hyper-intestinal metaplasia, 20 gastric dysplasia. In the present study, 46 cases of gastric cancer with corresponding normal gastric mucosa was detected survivin mRNA expression using reverse transcription-polymerase chain reaction (RT-PCR). Survivin protein expression was examinded immunohistochemically in 43 gastric cancer tissue and 114 gastritis and precancerous lesion tissue. The volumes of survivin protein was quantitatively determined by ELISA among 30 gastric carcinoma cases and 34 normal gastric tissue cases. Observing the relationship between survivin expression and sex, diameter of tumors, the position of tumor occurrenc, gross type, the level of differentiation, vein invasion, tumor depth, lymph nodes metastasis, distant metastasis, TMN staging.ResultsSurvivin mRNA overexpression was detected in 32.6% gastric carcinomas (15 of 46 cases), and 10.87% corresponding normal tissue of theses cancer cases. There was significant difference between gastric carcinomas and corresponding normal tissue (P<0.05). But survivin mRNA expression was independent of sex, diameter of tumors, the position of tumor occurrenc, gross type, the level of d...
Keywords/Search Tags:Gastric neoplasms, Survivin gene, Immunohistochemistry, Reverse transcriptase-polymerase chain reaction
PDF Full Text Request
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