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The Expression And Clinical Significance Of Ku70 In The Tissue Of Human Pancreatic Tumor

Posted on:2012-08-01Degree:MasterType:Thesis
Country:ChinaCandidate:X ZhangFull Text:PDF
GTID:2154330332999455Subject:Surgery
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Ku protein is a DNA-binding protein, which is a heterologous dimers composed of Ku70 and Ku80, constituting the DNA-PKcs with DNA-PK. It is evolutionarily conserved and generally existing in the human body and a variety of plants and animals. In the nineteenth century to the eighties it was first found in the body of a polymyositis-scleroderma overlap syndrome patient in the form of antibodies, which is derived from the two letters of Ku in the first patient's name. As a DNA repair protein, Ku protein plays an important role in the pathway of DSBs. In addition, it is of great significance in main taining the telomere structure and the lack and the change of its activity make a differrence in the generation and development of tumors.DSBs is a kind of fatal DNA damage and a normal endogenous process,which can be triggered by drugs,radiation and other factors. As the mo st important genetic material of life in body,the damaged DNA can bring harm to body cells and cause cancer when not repaired or repaired improperly. NHEJ is the major repair mechanism in mammalian cells, when DSBs is repaired by this means, the binding of Ku protein and DNA end and DNA-PK can initiate the kinase activity. Studies showed that Ku protein may act as the regulator of DNA-PK by regulating the DNA-PK to complete DNA repair.Telomeres play a critical role in maintaining chromosomal stability and integrity of DNA genetic information, in recent years, many experiments indicated that changes of telo mere are related to the gene mutations,tumor formation and the aging of indi vidual organisms.ku protein can directly interact with hTERT to adjust the len gth of telomere and can play a key role in the maintenance and regulation of telomere structure when interacting with TRF2.In addition,ku protein can maintain the stability of telomere by pathways of Rad3 and Rad26.Cells ap optosis play its special role in processes such as embryonic development, reg eneration of mature cells and formation and development of tumors. Ku pro teins can participate in apoptosis by combining with the pro-apoptotic gene Bax, inhibiting the induction of DSBs and activation of DNA-Pkcs.Pancreatic cancer is one kind of common malignant tumors in the dige stive tract and one of the worst prognosis,ranking the fourth in causes of death from cancers. Surgical treatment is the most effective way,but the rate of surgical cure is low and that of postoperative 5-year after surgery is less than 5%,so it is quite necessary to explore a new therapeutic approach. Previous experiments have confirmed that the expression of Ku protein have a certain relation with resistances to drug and radiation therapy of tumor cells and we can enhance sensitivity of tumor cell to drugs and radiation therapy by inhibiting the expression of Ku protein. I believe that we can find new ways to treat malignant tumors through deepening research of Ku protein to increase the tumor sensitivity to radiotherapy and chemotherapy and improve the cure rate of malignant tumors.This experiment used immunohistochemistry (SP method) to detecte the expression of Ku70 in different human pancreatic tissues and investigate its significance. We obtained 80 cases of pancreatic tumor tissues,which were neither treated by radiotherapy nor chemotherapy before surgery.Each patient has detailed clinical data and surgical records.56 cases of pancreatic cancer tissue samples and 24 cases of benign pancreatic tissue samples are selected in random for experiments.The pathology were confirmed by the pathological sections after surgery.The results are:positive rates of Ku70 in pancreatic benign and malignant tumors were respectively 41.67% and 92.86%(p<0.05) which were statistically significant, there is a significant difference in expression of ku(P<0.05)between the well-differentiated or moderately-differentiated and poorly-differentiated pancreatic cancers. Conclusion:(1) Ku70 protein expresses in the benign and malignant pancreatic tumors in various degrees. Its expression in the pancreatic cancer is significantly higher than that of benign pancreatic tumor (P<0.05) indicating that as a DNA repair protein, Ku70 protein generally performs its function in DNA damage repair in both benign and malignant tumors. (2) The expression of Ku70 protein in pancreatic tumor has a positive correlation to the malignancy, which in poorly differentiated tumor is higher than that of moderate or well-differentiated tissues, while patient's age and gender have no remarkable effect on the expression of Ku70 (P> 0.05). (3) The high expression of Ku70 protein in pancreatic cancer tissues is relevant to their resistance to chemotherapy and radiation, which will make a significance to diagnosis, treatment and prognosis assessment of the tumor.
Keywords/Search Tags:Ku70, pancreatic Cancer, immunohistochemistry, expression
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