Angiogenesis in human liver tumors

Angiogenesis is an important mode of tumor associated neovascularization to support tumor growth. For liver tumors, including hepatocellular carcinoma (HCC) which is one of the most common malignancies world wide, and a number of benign tumors, angiogenesis may represent an interesting target for therapy. The angiogenic status of human liver tumors is not investigated in-depth, and is the subject of this research.
The studies included three parts. In human HCC biopsies, we analyzed endothelial cell proliferation and apoptosis, microvascular density, and vessel maturation status, and correlated them with tumor vascularization on dynamic contrast enhanced CT and with prognosis. Furthermore, we determined both in HCC and in benign liver tumors the gene and protein expression levels of the angio-genes VEGF, Angiopoietins-1/-2, and their receptors. These molecules are currently considered to be essential for the initiation of angiogenesis. In the last part we examined the expression of Cyclooxygenase-2, that can stimulate angiogenesis and is associated with tumor growth, invasion and metastasis.
We demonstrated that in HCC originating in either cirrhotic or non-cirrhotic livers, tumor endothelial cells are predominantly quiescent, and that the tumor microvessels exhibit characteristics of mature vessels. HCCs and benign tumors furthermore do not exhibit robust angiogene expression, and also Cyclooxygenase-2 is likely not implicated in liver tumor vascularization. The observation that the vasculature of liver tumors is morphologically en phenotypically different from that in normal liver justifies further research, as it implies that vascular remodeling is taking place but that the molecular control is not via the conventional angio-genes.

	Titel en inhoudsopgave
	Afkortingen
	Hoofdstuk 1
	Hoofdstuk 2
	Hoofdstuk 3
	Hoofdstuk 4
	Hoofdstuk 5
	Summary, General Discussion and future perspectives
	Samenvatting
	Chinese samenvatting
	Acknowledgements
	Curriculum vitae
	Colour pictures
	Volledige dissertatie

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