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vascular_endothelial_growth_factor

Vascular endothelial growth factor

In contrast with the prevailing view that most tumors and metastases begin as avascular masses, evidence is presented here that a subset of tumors instead initially grows by coopting existing host vessels. This coopted host vasculature does not immediately undergo angiogenesis to support the tumor but instead regresses, leading to a secondarily avascular tumor and massive tumor cell loss. Ultimately, however, the remaining tumor is rescued by robust angiogenesis at the tumor margin. The expression patterns of the angiogenic antagonist angiopoietin-2 and of pro-angiogenic vascular endothelial growth factor (VEGF) suggest that these proteins may be critical regulators of this balance between vascular regression and growth 1)

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 2) 3).

In glioblastoma, tumor progression appears to be triggered by expression of VEGF, a regulator of blood vessel permeability.

Vascular endothelial growth factor (VEGF) is the major proangiogenic factor in many solid tumors. Vascular endothelial growth factor receptor (VEGFR) is expressed in abundance in pediatric patients with medulloblastoma and is associated with tumor metastasis, poor prognosis, and proliferation.

Bevacizumab is a monoclonal antibody that inhibits angiogenesis by clearing circulating VEGF, resulting in a decline in the contrast-enhancing tumor, which does not always correlate with treatment response.

Malignant glioma treated with anti-vascular endothelial growth factor (VEGF) bevacizumab show progression patterns that vary with different mechanisms of resistance.

Angiopoietin is part of a family of vascular endothelial growth factors that play a role in embryonic and postnatal angiogenesis.

Vascular endothelial growth factor A (VEGF-A)

Vascular endothelial growth factor A (VEGF-A), also known as Vascular Permeability Factor or VEGF165, is a potent mitogenic and angiogenic disulfide-linked homodimer responsible for angiogenesis in several organs including the CNS. VEGF-A has been shown to increase extravasation of proteins from tumor associated capillaries, thus the monicker Vascular Permeability Factor. VEGF-A is part of the VEGF family of proteins which includes VEGF-B, VEGF-C, VEGF-D, and placental growth factor.

VEGF-A expression is increased by reduced blood flow and ischemia, and is involved in the growth and expansion of tumors in a cycle where tumor growth results in ischemia, which increases VEGF-A expression resulting in angiogenesis and further tumor growth. Furthermore, VEGF-A is secreted from tumors, which has made it a primary objective for development of the VEGF-A antagonist bevacizumab (Avastin, Roche). Bevacizumab is used as an adjuvant chemotherapeutic agent in the treatment of metastatic colon cancer, advanced non-squamous, non-small cell lung cancer, metastatic kidney cancer, and glioblastoma. VEGF-A has also been shown to play an integral part in exudative age-related macular degeneration, where choroidal neo-vascularization results in blood and protein leakage below the macular and subsequent vision loss. Exudative age-related macula degeneration is also treated with anti-VEGF-A.

see Vascular Endothelial Growth Factor in chronic subdural hematoma

1)
Holash J, Maisonpierre PC, Compton D, Boland P, Alexander CR, Zagzag D, Yancopoulos GD, Wiegand SJ. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science. 1999 Jun 18;284(5422):1994-8. PubMed PMID: 10373119.
2)
Sweet JA, Feinberg ML, Sherman JH. The role of avastin in the management of recurrent glioblastoma. Neurosurg Clin N Am. 2012;23:331–41.
3)
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.
vascular_endothelial_growth_factor.txt · Last modified: 2018/11/12 16:01 by administrador