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Expressions Of EphB4 Receptor In Pancreas Cancer And Their Relationship Of Clinical Pathology And Angiogenesis

Posted on:2010-10-24Degree:MasterType:Thesis
Country:ChinaCandidate:L ZhangFull Text:PDF
GTID:2144360278953226Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective: pancreatic cancer is a malignancy of the digestive system tumors, one of the highest, because of its hidden morbidity, rapid progress is not sensitive to radiotherapy and chemotherapy, the treatment of the difficulties, the mortality and morbidity ratio of 0.99:1. Although pancreatic surgery over the past 30 years significant progress has been made, but the treatment of pancreatic cancer is still not satisfactory, the data show that 5-year survival rate of pancreatic cancer is still lower than 5.0%, the tumor is one of the worst prognosis. And with the aging of the population, changes in diet and smoking groups increased over the past 30 years the incidence of pancreatic cancer at home and abroad were on the rise.Receptor tyrosine kinase (Receptor tyrosine kinases, RTKs) family, is currently the largest known gene family of cancer. Eph receptors and their ligands ephrins and RTK gene family is the largest branch of the family of EphB4 receptor and ephrinB2 in tumor angiogenesis research has drawn greater attention. EphB4 receptor signaling pathways through the two-way adjacent to the endothelial cells and the interaction between ligands and promoted the vascular endothelial cells sprouting, migration, proliferation and lumen formation. EphB4 receptor and ephrinB2 in the artery and vein on the specific distribution and the corresponding knock-out after the performance, suggesting their involvement in embryonic angiogenesis regulation in the process of differentiation of artery and vein, artery and vein that early endothelial cells, EphB4 receptor and ephrinB2 bi-directional signal transduction mediated rejection of orientation and the formation of blood vessels. At the same time, EphB4 receptor in colon cancer has beenproved; breast cancer; endometrial cancer; prostate cancer; expression, such as malignant mesothelioma. At present, tumor angiogenesis as a research hotspot of EphB4 receptor and angiogenesis of pancreatic cancer and how the association between, see the relevant reports to date have not yet. In this study, immunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) detection methods such as EphB4 receptor, EphB4 receptor are explored in pancreatic ductal cell carcinoma tissue and tumor microvessel density (MVD), clinical pathological stage, differentiation, the relationship between invasive.Methods: First Affiliated Hospital of Dalian Medical University Department of Pathology from 2002 to 2008, surgical resection of pancreatic ductal cell carcinoma 27 cases of paraffin-embedded specimens. 4μm serial sections. Using immunohistochemical SP method EphB4 receptor and at the same time to the known expression of the EphB4 receptor positive breast cancer as a positive control, normal pancreatic tissue as a negative control. Using immunohistochemical SP method CD34, microvessel density count (Micro vessel density, MVD).Collection of First Affiliated Hospital of Dalian Medical University in 2007 and 2008 surgical resection of pancreatic ductal cell carcinoma of fresh specimens in 5 cases (operating room to obtain samples in liquid nitrogen immediately after the release of frozen, after transfer to the refrigerator to preserve -80℃). Using reverse transcription polymerase chain reaction (RT-PCR) Detection of EphB4 receptor mRNA in the five cases of pancreatic ductal cell carcinoma of the expression of the fresh specimen to the known expression of EphB4 receptor-positive breast cancer cells as the ZL-1 positive control, normal pancreatic tissue as a negative control.Results: Immunohistochemical detection of EphB4 receptor, the results show that the experimental group in the positive expression rate was 66.7% (18/27), negative control group, no expression, there is significant difference between the two groups (P<0.05). EphB4 receptor mainly expressed in the cytoplasm or membrane of tumor cells, yellow, brown-yellow granules, which are unevenly distributed in the tumors were small pieces or distribution, staining intensity is also inconsistent. Part of the normal pancreatic tissue and pancreatic ductal carcinoma cell carcinoma. occasionally EphB4 receptor-positive islet staining alone, the exact cause was unclear, pending further study. Poorly differentiated group, the expression of EphB4 receptor, the well-differentiated group comparison between the EphB4 receptor expression was statistically significant (P <0.05). Clinical TNM staging,Ⅲ,ⅣEphB4 receptor expression during theⅠ,ⅡEphB4 receptor expression during the comparison between the statistical significance (P <0.05). EphB4 receptor and age, sex, tumor site, such as no significant difference between the comparison.Immunohistochemical detection of CD34, showed that pancreatic ductal cell carcinoma in a variety of forms of microvessel-rich than the normal pancreatic tissue, cancer tissue significantly increased the number of microvessels. 27 cases of pancreatic ductal cell carcinoma of the mean MVD of normal pancreatic tissue and the average MVD was significantly more (P <0.05). MVD pancreatic ductal cell carcinoma with clinicopa-thological factors of the relationship between the statistical analysis of MVD and differentiation can be seen, and poorly differentiated carcinoma with MVD in MVD between well-differentiated cancer was significantly more (P <0.05).Ⅲ,Ⅳstages of pancreatic ductal cell carcinoma of MVD with stageⅠ,Ⅱpancreatic ductal cell carcinoma of MVD was significantly more (P <0.05). Pancreatic ductal cell carcinoma in patients with MVD with age, sex, tumor site showed no significant difference between.Using RT-PCR detected 5 cases of pancreatic ductal cell carcinoma of fresh specimens EphB4 receptor mRNA, 5 specimens were seen to express, not the expression of negative control group. RT-PCR product agarose gel electrophoresis with the corresponding gray value between the MVD value of a positive correlation (P <0.05).Conclusion: EphB4 receptor in pancreatic ductal cell carcinoma in the high-expression and tumor angiogenesis and invasiveness are closely related, and its role in tumor angiogenesis further elucidate the mechanism, EphB4 receptor is expected to be a targeted anti-angiogenesis target .
Keywords/Search Tags:pancreatic neoplasms, EphB4 receptor, Micro vessel density
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