The U251 glioblastoma and a glioblastoma xenograft cell line transduced with a recombinant replication-defective adenovirus vector containing the cDNA of wild-type p16 and antisense RNA of uPAR significantly inhibited human mammary epithelial cell capillary formation and vascular endothelial growth factor (VEGF) expression.
Genetic ablation of interleukin-1 ligands or receptor in mice bearing RCAS/tv-a-induced platelet-derived growth factor B-overexpressing glioblastoma results in reduced oedema and partial restoration of the integrity of the blood-brain barrier, respectively; similar to results obtained with vascular endothelial growth factor neutralization.
Recently, we evaluated modular peptide carrier L1 bearing CXCR4 targeting ligand for its ability to condense siRNA and facilitate endosomal escape and VEGFA gene silencing in CXCR4-expressing endothelial and glioblastoma cells.
We have scrutinized the mechanism of transcriptional activation of vascular endothelial growth factor (VEGF) expression by IL-6 in the mouse brain and in glioblastoma cells.
Moreover, stellettin B blocks the expression and secretion of a major proangiogenic factor, vascular endothelial growth factor (VEGF), in glioblastoma cells.
The VEGF polymorphism rs833061 was strongly associated with increased risk for glioma (odds ratio = 164.85) and glioblastoma (odds ratio = 155.66), confirmed after Bonferroni correction.
Inhibition at the expression of VEGF RNA and protein levels was observed in glioblastoma-astrocytoma U-87 MG cells treated with exosome-delivered siRNAs.
These results suggest that HDAC inhibitors reduce VEGF secretion and modulate the expression of the other VEGF family members, and therefore may inhibit angiogenesis in glioblastoma tissues.
Proangiogenic cytokines such as VEGF and angiopoietin-2 (Ang-2) have high expression in glioblastoma in a cell-specific manner and not only drive tumor angiogenesis and vascular permeability but also negatively regulate T-lymphocyte and innate immune cell responses.
Bevacizumab (BEV), a humanized monoclonal antibody that blocks the effects of vascular endothelial growth factor A, has produced impressive response rates for recurrent GB and has been approved as second-line therapy.
Using three glioblastoma cell-lines (U87, U251, and SNB19), the adaptation of glioblastoma cells in a 1% (hypoxia) and 20% (normoxia) oxygen microenvironment on proliferation, metabolism, migration, neurosphere formation, CD133 and VEGF expression was investigated.
Following incubation of glioblastoma cell lines under hypoxic/anoxic conditions for 24-48 hours, Fas mRNA levels remained unchanged, whereas VEGF expression was markedly upregulated.
Bevacizumab (Bev), a humanized anti-VEGF antibody, is associated with the improvement of progression-free survival and performance status in patients with glioblastoma.
Finally, in situ hybridization on glioblastoma sections shows that the in vivo expression patterns of IL-8 and VEGF genes overlap, but are not identical.
The development of angiogenesis inhibitor therapy, including treatments targeting vascular endothelial growth factor (VEGF) in particular, raised new hopes for the treatment of GB, but no Phase III clinical trial to date has reported survival benefits relative to standard treatment.