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Expression of Survivin and Caspase-3 and Its Relationship to Apoptosis in Adenoma and Carcinoma of Human Large Bowel

Author: ZhengAiQiu
Tutor: ChenYunBo
School: Jilin University
Course: Clinical
Keywords: Colorectal cancer Apoptosis Survivin Caspase-3
CLC: R735.34
Type: Master's thesis
Year: 2006
Downloads: 113
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Abstract

Colorectal carcinoma is one of the commonest malignant tumors inalimetary canal.It has become the fifth death reasons of malignant tumorsin our country.The present study demonstrated that the occurrence ofmalignant tumors was not only related to the activation of oncogene andmutation or losing of the tumor suppressor gene,but also related to theinhibition of apoptosis of tumor cell.The main function of apoptosis intumorigenesis and development of malignant tumors is negativeregulation,it can inhibit the rapid growth of tumor cell.Caspase familyprotein is the core mechanism of apoptosis ,Caspase-3 palys a veryimportant role in apoptosis of tumor cell. It participates in apoptosisinduced by many factors .Survivin is the novelest member of IAPfamily,and it is a supreme inhibitor apoptotic gene founded currently.Itexpresses in many kinds of tumor tissue of human,which inhibits theactivity of caspase-3 and caspase-7 to cut off the process of apoptosis.We collected 93 pathologic specimen, 48 from colorectalcarcinoma,25 from colorectal adenoma,20 from normal colorectaltissues.All the patients clinical datas were from the second clinicalhospital of Jilin University.All the colorectal carcinoma patients were notthrough radiotherapy or chemotherapy before operation .The expressionof survivin and caspase-3 was investigated in colorectal adenoma andcarcinoma by immunohistochemical method,and tumor cell apoptosiswas examined by TUNEL method.We distributed the pathologicspecimen to different group with the histological grades and pathologicalstages. The result showed that the positive expression rate of survivin inthe process of colorectal adenoma-carcinoma sequence increasedgradually.Survivin was presented in cytoplasm or membrane ofcolorectal cancer cells,and it was not expressed in lymphocyte and nucleiof colorectal cancer cells.The positive expression of survivin in tubularadenomas was 10%,in villous adenoma or tubulovillous adenomas was33.3% and in colorectal carcinoma was 70.8%.The expression ofsurvivin had significant differences among different groups.The positiveexpression of caspase-3 decreased from normal colorectal mucosa tocarcinoma.Caspase-3 was mainly presented in cytoplasm and seldompresented in nuclei.Caspase-3 was expressed more obviously in normaltissues than in carcinoma tissues.Both of the expression of survivin andcaspase-3 had significant differences among different histologicalgrades,and were not associated with different Dukes stages. Theexpression of survivin in carcinoma was not directly related to that ofcaspase-3.Apoptosis index(AI) of positive survivin group was significantlower than negative survivin group. AI of positive caspase-3 group wassignificant higher than negative caspase-3 group.Patients with survivin(-)and caspase-3(+) had the maximum apoptosis index.Form our study, the positive expression rate of survivin in theprocess of colorectal adenoma-carcinoma sequence increasedgradually,and validated that the occurrence of colorectal carcinoma was amulti-step and gradualness process.Survivin plays an important role inthe early development of colorectal carcinoma,and it may become apotential early diagnostic marker.The expression intensity of survivinstrongly affected the malignace and it can clue us to the prognosis ofcolorectal carcinoma.AI with survivin(+) decreased from tubularadenoma to carcinoma and it was lower than survivin(-).The resultshowed that survivin allowed the overgrowth of mutation cell throughcanceled the checkpoint of apoptosis ,in order to promote the accurrenceand development of cancer. The positive expression of caspase-3decreased from normal colorectal mucosa to carcinoma.The lowerexpression of caspase-3 was related to the formation of colorectalcarcinoma.With the lowered histological grades of colorectalcarcinoma ,the expression of caspase-3 decreased .It was the result ofabnormal differentiation of tumor.The expression of survivin incarcinoma was negative related to that of caspase-3. It confirmed thatsurvivin could prevented the apoptosis of tumor cell through restrainedthe activation of caspase-3.Survivin may become one of the idealesttarget which promote the therapy of tumor cell.In a word,tumorigenesisprogression of malignant tumor is a complex and multi-step processinvolving ploygene tegulation, affection factors of its are very much,mechanism of its is not so clear. It will impel the development ofcolorectum surgery if we find out the mechanism and treatment methodscontinued.Our study provided the basis of experiment and theory forexpression of survivin and caspase-3 and its relationship to apoptosis inadenoma and carcinoma of human large bowel ,provide the thought ofscience for the further research that the action of survivin and caspase-3in colorectal carcinoma occurrence and development.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Intestinal neoplasms > Colorectal tumors
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