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The Mechanism Of IDO And Foxp3Participating In Endometrial Cancer Immune Tolerance

Posted on:2015-02-15Degree:MasterType:Thesis
Country:ChinaCandidate:S S ZhangFull Text:PDF
GTID:2284330431474909Subject:Surgery
Abstract/Summary:PDF Full Text Request
Endometrial carcinoma, as one of gynecological tumor, is a group of epithelialprimary endometrial malignant tumor. With the change of medical conditions and dietary structure, its incidence and mortality is rising year by year, and is the third popular in the female cancer diseases,while second only to breast cancer and lung cancer. For early endometrial cancer,5year survival rate can reach77.6%, and early diagnosis, early treatment has become an important method of improving the prognosis of patients with endometrial cancer. But due to its slow growth and slow transfer, its clinical manifestations are not specific and often manifested as irregular uterine bleeding.But as a preoperative gold standard for diagnosis, also as orcurettage after uterine endometrial biopsy pathology, atypical complex hyperplasia and differentiation of EC in endometrial tissue biopsies are difficult to identify, and EC is better than near the bottom of the palace and the uterine body angle, no method could be used to obtain the lesion in curettage occasionally, and often leading to much misdiagnose. Compared with early endometrial cancer, advanced and recurrent endometrial cancer patients show little response to conventional chemotherapy and hormone treatment,5year survival rate is lower. So to explore the new diagnosis and treatment, and improve the survival rate of endometrial carcinoma has become the new direction of clinical attention.In recent years, with the development of cellular and molecular level, the related research related with tumor system has been paid more and more attention. Closely monitoring of the immune system is often affected by the tumor.and the tumor occurrence, development, metastasis and recurrence is due to tumor cells by gene mutation. Expression of "non self" material,have a variety of ways to escape the surveillance of the growth immune system. Indoleamine2,3-dioxygenase (IDO) has been proved to be closely related to a variety of important human diseases, such as Alzheimer’s disease,cataract. In the suppression of T cell immunity and antitumor immunity, inducing fetal immune tolerance and immune tolerance of grafts plays an important role in the regulation of metabolism and immunity, whether can IDO is an important target in the treatment of disease? Since the view of through inhibition of IDO induced tryptophan metabolism induced by IFN-r on tumor growth was proposed, much attention are paid to the research on the expression of IDO correlated with tumor. Through the study of the pathogenic mechanism and in vitro pharmacological tests, the clinical significance of IDO is observed in many specimens of extensive research, and that IDO in tumor cells and cause tumor escape from immune surveillance play an important role in the process is proved But in endometrial cancer occurrence,development and metastasis whether they are closely linked on clinical prognosis, currently there is no related reports.Objective:Through the research of IDO, Foxp3in endometrial tissue of different expression levels in the tumors, endometrial carcinoma and benignuterine body tissue, and explore its significance in endometrial carcinoma occurrence, progression; and through the comparison of patients with endometrial carcinoma, investigate related factors, clinical features and pathology, reveal the relationship between the between IDO, Foxp3and endometrial carcinoma; further clarify the relationship between IDO in clinical prognosis of endometrial cancer, offer a new method for endometrial cancer immune therapy. Methods:During2011-2013,57cases of patients specimens with endometrial cancer and benign tumor of body of uterus and30cases were included in Obstetrics and Gynecology of Jingzhou Central Hospital, respectively by RT-PCR (Polymerase Chain Reaction) semi quantitative detection of IDO mRNA expression and its relationship with clinical factors in patients with endometrial cancer and pathological factors in endometrial carcinoma,immunohistochemistry on IDO, Foxp3technique and semi quantitative analysis of the location, the detection of the expression levels of endometrial tissue IDO, Foxp3, and compared with age, clinical stage, pathological type,histological grade and lymph metastasis and the relationship between IDO,Foxp3expression in endometrial carcinoma, and statistical analysis was inducted.Results:(1) the expression of IDO in endometrial carcinoma was significantly h igher than that of benign uterine tumor, and there were significant difference st atistically (P<0.05). Expression of Foxp3in endometrial carcinoma was signifi cantly higher than the expression in benign uterine tumor, with significant diffe rence in Statistics (P<0,05)(2) For endometrial cancer, FIGO stage and histological grade were correlate d with the expression of IDO, and have statistical significance (P<0.05). The c orrelation was significant beteen expression of Foxp3and histological type (P <0.05). IDO, Foxp3showed positive expression and have significant differenc e with histological grade(P<0.05)(3)IDO mRNA expression is higher than the level of benign uterine tumor in e ndometrial carcinoma (P<0.5),and its expression is associated with the FIGO stage and histological grade (P<0.5). Conclusion:The positive expression of IDO was mainly detected in the endometrial carcinoma women with high histological grade and pathological types of endometrial adenocarcinoma. IDO expression was correlated with Foxp3. The experiments prove that IDO and Foxp3engage the occurrence and development of endometrial cancer, and IDO plays a key role in endometrial cancer immune tolerance.
Keywords/Search Tags:IDO, Foxp3, uterine body cancer, immune tolerance
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