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Survivin MRNA Expression And Its Correlation With Cell Apoptosis And Proliferation And Clinicopathology In Hepatocellular Carcinoma

Posted on:2004-05-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:J F PanFull Text:PDF
GTID:1104360092990625Subject:Surgery
Abstract/Summary:PDF Full Text Request
Survivin is a recently described inhabitor of apoptosis by Ambrosini,since reported in Nature Medicine,it was gained extensive attention. It is expressed in several fetal tissues,but not in adult differential tissues except thymus.It is abundantly expressed in transfected cells and almost all of the human cancers,including melanoma, neuroblastoma,breast cancer,Iung cancer,and malignant tumor of digestive system, urogenital system and blood.In contrast,all the neighboring nontumor tissues were completely negative for survivin expression.Survivin is expressed in the Gi/M phase of the cell cycle,associates with microtubules of the mitotic spindle and regulates cell gene transcription.Overexpression of survivin in cancer cells may overcome this apoptosis-related cell cycle checpoint and cause the increase of cell proliferation and decrease of apoptosis,unbalance of proliferation and apoptosis,and cause the occurrence and development of cancer.Ito reported that all the HCC cell lines expressed survivin mRNA,and there is a high expression in HCC tissues,but not in nontumor tissues. After survivin transfection, survivin expression decreased in Go/Gi phase and increased in S phase in HCC cell lines. Survivin promotes cell proliferation and play an important role in carcinogenesis and progession of HCC.Previous investigation showed that the apoptosis-related genes are significantly correlated with carcinogenesis andprogession,clinicopathology and MDR in cancer.Survivin is an inhibitor of apoptosis,so we hypotheses that it may also play an important role in carcinogenesis and progression of HCC and correlate with clinicopathology and MDR in HCC.This experiment studyed the relations of survivin mRNA,cell apoptosis and proliferation,clinicopatholoy and MDR in HCC, evaluated the role of inhibitor of apoptosis survivin in carcinogenesis and progession,and the evaluation of invasion and prognosis and MDR in HCC.Part 1: The Experimental study of relationship between survivin mRNA expression and apoptosis and proliferation in HCCObjectiverTo study a novel apoptosis inhabitor survivin mRNA expression,and the cell apoptosis and proliferation in HCC.Evaluate the relationship between survivin mRNA expression and apoptosis and proliferation in HCC.Method:Reverse transcription polymerase chain reaction (RT-PCR),TUNEL and SABC-IHC were used to detect the expression of survivin mRNA in 31 cases of HCC tissues,and cell apoptosis and the ki-67 expression in 28 HCC respectively.Analyzing the relationship between survivin mRNA expression and apoptosis and proliferation in HCC.ResultThe positive survivin mRNA expression was observed in 22 out of 31(71%) cases of HCC,in contrast the negative was 9 out of 3 l(29%);and all the neighboring nontumor and cirrhotic tissues were completely negative for survivin mRNA expression.The apoptosis index(Al) was ranging from 0.4%-15%,and the overall average was 4.24±3.92%.The average of Al in cases of survivin mRNA positive was 4.64± 4.30%, and the negative was 3.36±2.98%,and no significant diference between the two groups(p>0.05). The ki-67 proliferation indexPI) was ranging from 2%-80%,and the overall average was 26.21±14.9%.The average of PI in the cases of survivin mRNA positive was 30.32±15.43%, and the negative was 17.56±9.44%.The PI showed a significant positive correlation with the survivin mRNA expression(p<0.05).Conclusion:The result show a high expression of survivin in HCC,it suggest that survivin may play a important role in the occurrence and progression of HCC.There is no significant difference between survivin mRNA expression and AI,whereas PI showed a significant positive correlationwith the survivin mRNA expression.Though survivin is em apoptosis inhibitor^ doesn't significant influence cell apoptosis in HCC;and it plays an important role in the progression and development of HCC by promoting cell proliferation.Survivin will be a potential new target of gene therapy in HCC by control cell proliferation.Part2:The relationship of survivin mRNA expressio...
Keywords/Search Tags:hepatocellular carcinoma, survivin, apoptosis, proliferation clinical pathology, multiple drug resistance, MDR-1
PDF Full Text Request
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