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The Significance And Mechanism Of Lymphangiogenesis In Human Colorectal Carcinoma

Posted on:2005-08-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z X LiFull Text:PDF
GTID:1104360125958233Subject:Human Anatomy and Embryology
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Colorectal cancer is a common type of malignant tumors in human beings. Its incidence rate has been increased gradually in the past few years. Lymphatic system is the primary pathway of metastasis for gastrointestinal malignace including colorectal cancer. The extent of lymph node involvement is a key prognostic factor for the patient's outcome, and is a major basis for operation or radiotherapy. Clinical and pathologic data point to the spread of solid tumor via the lymphatics is an important early event in many malignant tumors. In the past 10 years, however, almost all studies about metastasis focused on the angiogenesis, and very few scholars paid attention to the lymphangiogenesis, the gowth of new lymphatic vessels. This has in part been due to difficulty in studing lymphatic vessels because of their morphology and a lack of lymphatic-specific markers. So far, the exact mechanism of lymphatic vessels remains unclear.From 2-3 years ago, identification of molecular markers of lymphatic vessels has made it possible to accurately differentiate lymphatic endothelial cells from blood endothelial cells. Councequently, lymphangiogenesis in tumors attracted more and more attention, and has been becoming a new hot spot in this field. Using the novel molecular markers, lymphatic vessels have so far been observed in many different experimental tumor models, in human breast cancers, and in head and neck squamous cell carcinoma. No evidence for intratumoral lymphatics has been found in human liver cancer and melanomas. Future studies are required to determine whether intratumoral lymphtics are restricted only to certain types of tumor and whether their presence has any prognostic significance.Vascular endothelial growth factor-C (VEGF-C) and VEGF-D , novel members of the VEGF family of growth factors are the two lymphangiogenesis promoting factors. Structurally, these protein growth factors differ from the angiogenic growth factor VEGF because of the presence of amino- and carboxyl- terminals propeptides, but retain the central VEGF homology domain containing the cystine knot motif that is conserved in all VEGF family members. VEGF-C is the first lymphangiogenic factor identified and is capable of binding its receptor VEGFR-2(KDR) and VEGFR-3(Flt-4). VEGFR-2 mainly expressed in blood endothelial cells, and VEGFR-3 presents in lymphatic endothelial cells of adult body. VEGF-C drives lymphangiogenesis through VEGFR-3 signal pathway. Up to now, there is ample evidence for expression of VEGF-C in many kind of human tumors. Moreover, a correlation between VEGF-C expression and rate of metastasis to lymph nodes has been found in breast, gastric, thyroid, lung, and colorectal cancers. However, very few studies discussed the role of VEGF-C expression on lymphangiogenesis in tumors, as well as the relationship between VEGF-C expression and lymphatic microvessel density(LMVD). The aim of this study was to research whether lymphangiogenesis take placed or not in human colorectal carcinoma, and the relationship between lymphatic microvessel density(LMVD) and lymph node involvement, and finally to analysis the role of VEGF-C/VEGFR-3 expression in promoting lymphangiogenesis and lymphatic metastasis. The results are as follows:Partâ…  Relationship between lymphangiogenesis and lymph node metastasis in colorectal carcinomasObjective: To investigate the lymphangiogenesis in colorectal carcinomas, and to analyze the relationship between the LMVD and lymph nodes metastasis.Methods: Fifty-six patients with colorectal cancer and ten adenomas were sdutied. Lymphatic vessels and blood vessels were stained by 5'-Nase-ALPase double staining method, the lymphatic vessels were also observed by transmission electron microscope(TEM) and backscattered electron images-scanning electron microscope(BEI-SEM). Results: 1.1 Morphologic characteristic of lymphatic vessels 1.1.1 Enzyme histochmistry staining for 5'-Nase in normal mucosa and adenomaLymphatic vessels were 5'-Nase positive (brown) and blood vessels were A...
Keywords/Search Tags:colorectal carcinoma, lymphangiogenesis, lymph node metastasis, vascular endothelial growth factor-C(VEGF-C), vascular endothelial growth factor receptor-3(VEGFR-3)
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