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angiogenesis

Angiogenesis

The process by which new arteries and veins form from preexisting blood vessels. Angiogenesis proceeds through sprouting, endothelial cell migration, proliferation, and vessel destabilization and stabilization. They are responsible for assembling and disassembling the endothelial lining of blood vessels.

Angiogenesis is necessary for sustained neoplastic development. The angiopoietin 1 and angiopoietin 2 have been implicated in the regulation of this process; reports have suggested that a net gain in Ang-2 activity may be an initiating factor for tumor angiogenesis.

Vascular endothelial growth factor (VEGF) is a member of the VEGF/platelet-derived growth factor gene family. The binding to the tyrosine kinase VEGF receptor-2 stimulates tumor progression producing angiogenesis, vascular permeability and mitogenesis 1) 2).

Neo-angiogenesis is a hallmark of glioblastoma (GBM) and is sustained by autocrine and paracrine interactions between neoplastic and nonneoplastic cells.

Malignant gliomas are characterized by increased angiogenesis, which is a marker of the histological grading system 3).

The currently available treatment approaches acting against angiogenesis are mainly directed toward three pathways: VEGF pathway, VEGF-independent pathways and inhibition of vascular endothelial cell migration. It has been demonstrated that antiangiogenic therapy can produce a rapid radiological response and a decrease of brain edema, without significantly influencing survival. Future studies should consider that: animal models are inadequate and cells used for animal models (mainly U87) are deeply different from patient GBM cells; GBM cells may become resistant to antiangiogenic therapy and some cells may be resistant to antiangiogenic therapy ab initio; and angiogenesis in the peritumor tissue has been poorly investigated. Therefore, the ideal target of angiogenesis is probably yet to be identified 4).

Recently, endocan has emerged as a new marker of vascular endothelial cells from cancers in other organs.

1)
Sweet JA, Feinberg ML, Sherman JH. The role of avastin in the management of recurrent glioblastoma. Neurosurg Clin N Am. 2012;23:331–41.
2)
Pope WB, Lai A, Mehta R, Kim HJ, Qiao J, Xue X, et al. Apparent diffusion coefficient histogram analysis stratifies progression-free survival in newly diagnosed bevacizumab-treated glioblastoma. AJNR Am J Neuroradiol. 2011;32:882–9.
3)
Plate K. H., Breier G., Weich H. A. & Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359, 845–848, 10.1038/359845a0 (1992).
4)
De Bonis P, Marziali G, Vigo V, Peraio S, Pompucci A, Anile C, Mangiola A. Antiangiogenic therapy for high-grade gliomas: current concepts and limitations. Expert Rev Neurother. 2013 Nov;13(11):1263-70. doi: 10.1586/14737175.2013.856264. Review. PubMed PMID: 24175724.
angiogenesis.txt · Last modified: 2016/04/02 15:46 (external edit)