Anti-angiogenic gene therapy of malignant glioma.
Glioblastoma, one of the best vascularized tumours in humans, appears well suited for an antiangiogenic therapy. VEGF (vascular endothelial growth factor), the most important angiogenesis factor identified to date, is highly expressed in glioblastoma. VEGF is particulary upregulated in palisading cells adjacent to necroses and has subsequently been shown to be hypoxia-inducible in glioma cells in vitro. VEGF-receptor tyrosine kinases, VEGF-R1 (flt-1) and VEGF-R2 (flk-1), are induced in a tumour stage dependent manner during glioma progression and are exclusively expressed in tumour vascular endothelial cells. These observations suggest that VEGF-receptors are promising targets for tumour endothelial cell specific therapy. The ability to block VEGF-signalling by the VEGF-R2 dominant-negative mutant identifies the VEGF/VEGF-R2 system as a major regulator of glioma angiogenesis. Several experimental approaches demonstrate that in rat gliomas tumour growth can be prevented by the inhibition of angiogenesis. These findings are of pivotal importance for the development of anti-angiogenic therapies in glioblastoma patients.
Stratmann
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A
Department of Neuropathology, University of Freiburg Medical School, Federal Republic of Germany.
Machein
M R
MR
Plate
K H
KH
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000235:genetics / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005909:Glioblastoma / Q000098:blood supply / Q000235:genetics / Q000628:therapy*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D040262:Receptors, Vascular Endothelial Growth Factor
D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor