The inhibition of @entity5 angiogenesis could be an efficient therapeutic strategy for the treatment of @entity11 . Prominent @entity2295 is induced by these @entity5 , and microvascular proliferation is a malignancy grading criterion. However, @entity11 cells can also invade the brain diffusely over long distances without necessarily requiring angiogenesis. Experimentally, it was shown that especially during early stages of growth in rodent brain, @entity11 cells can coopt the preexistent host vasculature to recruit their blood supply in the @entity2048 . This phenomenon was only observed in orthotopic models in which the @entity5 cells were implanted into the brain which is a densely vascularized environment, but not in subcutaneous models in which @entity5 cells are implanted into a virtual space. Using an orthotopic @entity19 model, we analyzed whether systemic anti-angiogenic therapy with an antibody against the @entity11132 ( @entity11132 ) could inhibit intracerebral growth of xenografted @entity1 @entity463 cells and what effect this treatment had on @entity5 morphology and invasiveness. We found that anti-angiogenic therapy inhibited @entity5 growth by 80% compared to buffer-treated controls. The intratumoral microvessel density was reduced by at least 40% in treated animals compared to controls. However, in @entity19 treated with the anti- @entity11132 antibody, we noticed a striking increase in the number and total area of small satellite @entity5 clustered around the primary mass. These satellites usually contained central vessel cores, and @entity5 cells often had migrated along blood vessels over long distances to eventually reach the surface and spread in the subarachnoid space. Systemic anti-angiogenic therapy can thus apparently increase the invasiveness of @entity11 in the orthotopic model. @entity5 cell invasion was tightly associated with preexistent blood vessels, suggesting that increased cooption of the host vasculature could represent a compensatory mechanism that is selected for by inhibiting adequate @entity5 vascularization.

Invasion as limitation to anti-angiogenic XXXX therapy.

@entity1 :: ('9606', 'Species') :: ['human'] @entity11132 :: ('16542(Tax:10090)', 'Gene') :: ['VEGFR-2', 'vascular endothelial growth factor receptor-2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Tumor', 'tumors'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity2295 :: ('MESH:D015861', 'Disease') :: ['neovascularization'] @entity11 :: ('MESH:D005910', 'Disease') :: ['glioma', 'malignant gliomas', 'gliomas'] @entity2048 :: ('MESH:D004832', 'Disease') :: ['absence of neovascularization'] @entity463 :: ('MESH:D005909', 'Disease') :: ['glioblastoma']
@entity11 :: (MESH:D005910,Disease) :: ['glioma']
