【作者】 孙铁梁；

【导师】 张平；

【作者基本信息】 吉林大学 ， 外科学， 2010， 硕士

【摘要】 本实验主要采用免疫组织化学方法(SP法)检测Ku70在人不同胆管组织中的表达及意义。取临床手术切除胆管组织,经病理科明确诊断病例共70例,其中恶性胆管组织50例,正常胆管组织20例。在本实验中,50例胆管癌组织细胞中Ku70阳性率为92%(46/50),其中Ku70表达呈强阳性的有20例,大部分都为低分化肿瘤组织,另26例阳性表达大部分为中分化或高分化肿瘤组织,4例阴性表达,全部为高分化癌。20例正常胆管组织中Ku70阳性率为40%(8/20),说明Ku的表达与肿瘤的恶性程度呈正相关,且与组织分化程度呈负相观,即分化越低表达越强。有统计学意义,P<0.05。结论:(1)Ku70蛋白在正常胆管组织组、胆管癌组均有不同程度的表达,说明Ku70在生物体细胞中普遍发挥生物学功能。(2)Ku70蛋白的表达量在胆管癌组中明显高于正常胆管组,说明胆管癌中Ku70的表达增加是其发生、发展过程中的关键因素。(3)Ku70蛋白的表达量在低分化胆管癌组织中明显高于高分化的胆管癌组织。(4)胆管癌患者的年龄和性别对Ku70的表达无明显影响。相信通过对Ku70的进一步研究可以指导对胆管癌的治疗以及疾病预后提供了一条新途径。更多还原

【Abstract】 There is a Ku proteins in cells DNA binding proteins end, it is a kind of evolution in different species, conservative proteins are found to have homologous Ku protein. It is mainly participated in the same end connections (NHEJ) way to DNA double chain rupture (DBS), a key component of the repair of the existing in human, mammals, nematodes, insects, yeast, prokaryotes and plant body. In DNA double chain rupture repair DNA genetic replication, and transcription, telomere maintenance structure of biological activities, Ku protein plays an important role. Ku70 and Ku80 two Ku protein subunits composed with different source dimers form in living organisms. Ku protein is in the 1980s by autoantibodies in the form of multiple muscle inflammation in patients with scleroderma-overlap syndrome were first discovered, its name is originated from the first two letters before the patient Ku. Then in sle patients with nuclear collagen calm Ku also found the antibodies.Life is the most important in DNA, the genetic material susceptible to all sorts of endogenous and exogenous factors and the effect of genetic integrity, is the main threat, if not be repaired, can cause damage to cells and body, which causes the cell death. A study shows that the DSB defects, especially the same end connections (NHEJ) repair function defect may and the pathogenesis of tumor. NHEJ repair in mammalian chromosome in way of genomic instability and tumors on the key role. The key factor of any defect may cause DNA double chain rupture, repair the dysfunction of DNA damage induced apoptosis or through direct blocking DNA duplicate, transcription and cause cell death, Or damage accumulation degree and cause tumors. The tumor is a kind of disease, is the genes in the endogenous and exogenous etc. Various carcinogenic factor, under the action of the cells in the gene level of genetic disorders, making the cell is excessive proliferation and differentiation of abnormal or new creatures. All sorts of endogenous and exogenous factors, such as the function can cause DNA damage and mutation, when the DNA damage cannot be repaired in time or repair failure can cause chromosomal appear translocation and displacement, further development will lead to cancer.Bile duct carcinoma is a originated in the bile duct of epithelial cells of malignant tumor, surgical treatment is currently the most effective treatment, but the resection rate is low, most 25% to 50% in between, prognosis is poor, of chemotherapy and radiation, nor sensitive, so a new treatment approach is very necessary. Currently the treatment of malignant tumor basically has 3 kinds include: surgical treatment, chemical drug therapy and radiation therapy. In the therapy of cancer of 3 kinds of means, mutual complement each other, achieve comprehensive treatment. In some cannot radiotherapy of tumor resection has important significance.Research has found that cancer cells and drug resistance of tumor radiation treatment resistance and Ku protein expression, and may through Ku knockout, improve tumor cells to drugs and radiation therapy. With the recent studies of protein and found it Ku close relations with tumor development, affects the development of tumors, treatment and prognosis in basic and clinical aspects has extensive prospect, may become the new target cancer treatment, believe to further research Ku to society and mankind tremendous benefit.This experiment mainly using immunohistochemistry (SP Ku70 detection method) in different meaning and expression of bile duct organization. Take resection bile duct, the organization department diagnosis cases were malignant bile duct, including 70 cases of 50 cases of normal tissue, bile duct organization 20 cases. In this experiment, 50 cases cholangiocarcinoma cells Ku70 positie for 92% (46/50), which is strong positive Ku70 expression of 20 cases, mostly for low differentiated cancer tissue, another 26 cases were positive in most of the expression of differentiation, or well-differentiated tumors, 4 cases, all negatie for well-differentiated cancers. 20 cases of normal tissues Ku70 positie for duct (40%), 20 Ku expression and the degree of malignant tumor, and positively correlated with the organization differentiation negatively in lower expression, differentiation. A statistically significant, P< 0.05. Conclusion (1) Ku70 protein in normal bile duct organization, cholangiocarcinoma group has different levels of expression that Ku70 in biological cells in biological function display. (2) Ku70 protein expression in cholangiocarcinoma group was obviously higher than normal, bile duct group Ku70 expression of bile duct carcinoma is its occurrence, development process of key factors. (3) Ku70 protein expression in low differentiated cholangiocarcinoma organization is obviously higher than high differentiation cholangiocarcinoma organization. (4) cholangiocarcinoma patient age and gender Ku70 to express no obvious effect. Believe Ku70 through to the further study of cholangiocarcinoma may guide the treatment of the disease outcomes and offers a new approach.更多还原