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Study On The Regulatory Mechanism Of Angiogenesis In Esophageal Carcinoma And The Effects Of Angiogenic Factors On The Structural Vessels And Perfused Vessels

Posted on:2003-02-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:M GuoFull Text:PDF
GTID:1104360065456114Subject:Digestive medicine
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Study on the Regulatory Mechanism of Angiogenesisin Esophageal Carcinoma and the Effects of Angiogenic Factors on theStructural Vessels and Perfused VesselsPostgraduate student: Min Guo Adivisors: Li Dong Wang1, Ivan Ding21. Laboratory for Cancer Reseach, College of Medicine, Zhengzhou University,Zhengzhou, Henan, China 4500522. Department of Radiation Oncology, University of Rochester Medical Center,Rochester, NY, U.S.A. 14642Esophageal carcinoma (EC) is one of the six most common malignant diseases worldwide. The dramatic geographic distribution is the striking characteristic for EC, the ratios for EC incidence between the high- and low-risk areas could be as great as 500:1. Moreover, EC has a very poor prognosis, the five-year survival rate for the late or advanced stage is only 10%. Linzhou (formerly Linxian) and Huixian of Henan province, Northern China, have been well recognized as the highest incidence area for EC in the world, with a morbidity of 161/100,000 for male and 103/100,000 for female, EC remains a leading cause of cancer-related deaths in these areas, and probably because of that: the exact etiological factors for EC have not been identified; the mechanism of esophageal multiple-step carcinogenesis is still not clear; thus lack of effective preventive target and early diagnostic biomarkers. Lack of specific and sensitive methods for treatment is another key factor for poorly prognosis of EC. It was noteworthy that the five-year survival rate for EC patients at early-stage could be improved up to 90%, mass survey for the high-risk population is strategies to find early stage EC patients. However, intermediate and late stage patients are still dominant in clinic. Recent studies in tumor angiogenesis have demonstrated that tumor angionenesis are closely related with tumor growth, invasion and metastases. Therefore, it is of great importance to elucidate the regulatory mechanism of tumor angiogenesis to design new strategies and establish more effective way for tumor therapy and to improve the survival rate of EC patients.Angiogenesis is the formation of new blood vessels from preexisting micro-vasculature. The proliferative rate of avascular tumor is similar with vascular tumor, yet the survival rate and death rate maintain balance, thus tumor mass can keep very small. Most primaably maintain a prolonged state of avascular, and apparently dormant. Without blood vessels, tumor couldn't grow beyond l~2mm3 in diameter due to diffusion limit for oxygen and nutrient supply, however, these micro-scopic tumor mass can, in some way, eventually switch on angiogenesis by recruiting surrounding mature host blood vessel to begin sprouting capillaries which grow and infiltrate the tumor mass. Thus, tumor obtain the potent for relentless expansion and hematogenouse metastatic spread as well. Angiogenesis process includes the following steps: dissolution of vascular endothelial basal membrane; migration of endothelium to tumor tissue; proliferation of endothelium on the tips of migration; tubulization of endothelium and formation of capillary; formation of new basal membrane. This complex process involves the interaction of tumor cells, endothelial cell and extracellular matrix microenviroment and its regulation depends on a fine balance of angiogenic and angiostatic factors that promote or inhibit neovascularization respectively. It has been shown that tumor vessel is an immature vessel system which is initiated and maintained by high level growth factors and lack surrounding pericytes, the tumor vessel will stop growing and the immature vessel will disappear if the angiogenic factors are removed. Much attention has been raised on mechanism of tumor angiogenesis and anti-angiogenesis therapy in recent years. However, there is little knowledge on angiogenesis mechanism in esophageal carcinoma patients from high-risk areas. The present study was undertaken to systematically determine the mRNA levels of angiogenic factors and angiogenesis-related chemokines and cytokines in EC using...
Keywords/Search Tags:primary esophageal squamous cell carcinoma, angiogenesis, angiogenic factors, angiostatic factors, multiple-probe RNase protection assay, immunohisto-chemical staining, animal model.
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