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Characterization of Vegf-C and Its Clinical Relevance in Lymphangiogenesis of Papillary Thyroid Carcinoma



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Characterization of Vegf-C and Its Clinical Relevance in Lymphangiogenesis of Papillary Thyroid Carcinoma by Xiaomin Yu
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This dissertation, "Characterization of VEGF-C and Its Clinical Relevance in Lymphangiogenesis of Papillary Thyroid Carcinoma" by Xiaomin, Yu, 虞曉敏, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Characterization of VEGF-C and its Clinical Relevance in Lymphangiogenesis of Papillary Thyroid Carcinoma Submitted by XIAOMIN YU for the degree of Doctor of Philosophy at The University of Hong Kong in August 2007 Papillary thyroid carcinoma (PTC), the most common variety of thyroid malignancy, is characterized with a high incidence of lymph node metastases. The key molecular pathogenesis for nodal metastases is lymphangiogenesis, a process in which new lymphatic vessels sprout from preexisting ones to facilitate the shedding of tumour cells into surrounding lymphatic vessels. Vascular endothelial growth factor C (VEGF-C) is one of the most potent directly acting lymphangiogenic factors, inducing proliferation and enlargement of lymphatic endothelium. However, the expression and clinical relevance of 1VEGF-C in PTC with reference to the high incidence of lymph node metastases have not been addressed. This study aimed to investigate the role of VEGF-C in the lymphangiogenesis of PTC and possibly provide insight of clinical relevance in facilitating the management of lymph nodes in PTC patients. The expression pattern of VEGF-C in relation to lymphangiogenesis of PTC was evaluated. Tissue expression of VEGF-C was quantified by Western blot and the interaction with its receptor flt-4 was evaluated by immunohistochemistry. The study revealed that VEGF-C protein was over-expressed in PTC lesions and correlated with the presence of lymph node metastases. Positive immunostaining for VEGF-C was confirmed in PTC tumour tissues and metastatic lymph nodes with positive correlation to flt-4 vessel density, suggesting that VEGF-C might have a role in cascading lymphangiogenesis of PTC by activating flt-4. VEGF-C is a secretory cytokine and if its circulating level correlates with tissue VEGF-C, measurement of serum VEGF-C can be of potential clinical applications. To validate whether circulating serum VEGF-C reflects tumour expression, serum VEGF-C levels were measured by enzyme-linked immunosorbent assay in primary PTC patients and correlated quantitatively with their corresponding tumour expression levels. It was found that serum VEGF-C was pronouncedly elevated, correlated quantitatively with tumour expression levels and decreased significantly after surgical treatment in PTC patients, 2suggesting that the majority of elevated serum VEGF-C originated from the tumours. Both serum and tissue VEGF-C levels demonstrated a similar correlation with clinicopathological features. Thus, in comparison to tumour tissues VEGF-C, measurement of circulating VEGF-C in PTC patients could be a surrogate with more readily applied features. The association between serum VEGF-C and tumour clinicopathological features was evaluated and compared with another circulating angiogenic factor, serum VEGF. Preoperative serum samples from 85 primary PTC patients and 44 control subjects with benign thyroid diseases were measured for serum VEGF and VEGF-C levels. Serum VEGF-C level, but not VEGF, was elevated in the presence of lymph node metastases and advanced tumour profiles. An increased preoperative serum VEGF-C level was shown to be an independent risk factor for predicting nodal metastases in PTC. In conclusion, VEGF-C has an important role in lymphangiogenesis of PTC. Its expressi
Release date NZ
January 27th, 2017
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Country of Publication
United States
colour illustrations
Open Dissertation Press
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