When GBM-derived neurosphere cultures are grown in 1% oxygen, hypoxia-inducible factor 1alpha (HIF1alpha) protein levels increase dramatically, and mRNA encoding other hypoxic response genes, such as those encoding hypoxia-inducible gene-2, lysyl oxidase, and vascular endothelial growth factor, are induced over 10-fold.
We show that VEGF pathway blockade resulted in tumor growth retardation and inhibition of tumor vasculature in preclinical models of pediatric glioblastoma and breast cancer brain metastases, suggesting that multiparametric MRI can provide a powerful adjunct to accelerate the development of antiangiogenic therapies for use in these patient populations.
We investigated whether stem cell marker expression [CD133, CD34, and vascular endothelial growth factor (VEGF)] and IDH1 mutation correlate with clinical factors and prognosis in glioblastoma.
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.
We find that MMP-2 activity in human U251 GBM xenografts increases (*P=0.03) and collagen IV content decreases (*P=0.01) during vascular endothelial growth factor (VEGF-A) antibody neutralization.
We examined VEGF regulation in U87 MG human glioblastoma cells and in U87/T691 cells, a clonal derivative that contains a truncated erbB2/Neu receptor that interferes with EGFR signaling through the formation of nonfunctional heterodimeric receptor complexes.
We carried out microarray gene expression analysis and immunohistochemistry comparing 21 recurrent glioblastomas progressing during antiangiogenic treatment with VEGF neutralizing antibody bevacizumab to paired pretreatment tumors from the same patients.
We analyzed RNA from 132 primary human glioblastoma tissue samples by reverse-transcription polymerase chain reaction (RT-PCR) for the EGFRvIII and EGFR wild-type mutations and by quantitative RT-PCR for expression of vascular endothelial growth factor (VEGF).
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.
Using a panel of glioblastoma cell lines we found that Bevacizumab is able to block the secreted VEGF by the tumor cells and be internalized to the cytoplasm, inducing cytotoxicity <i>in vitro</i>.
Training and validation data confirmed that baseline ADC<sub>L</sub> was an independent predictive biomarker for OS in anti-VEGF therapies, but not in lomustine, after accounting for age and baseline enhancing tumor volume.<b>Conclusions:</b> Pretreatment diffusion MRI is a predictive imaging biomarker for OS in patients with recurrent GBM treated with anti-VEGF monotherapy at first or second relapse.<i></i>.
Thus, by introducing VEGF-overexpressing glioblastoma cells into the brain, we have established a reproducible and predictable in vivo model of tumor-associated intracerebral hemorrhage caused by the enhanced expression of single molecular species.
Through qPCR analysis of gene induction in primary endothelial cells, we provide evidence that increased VEGF-A and TGFβ2 signalling in the tumour microenvironment is sufficient to invoke many of the changes in gene expression noted in glioblastoma vessels.
This study aimed to address the biological importance of c-Myc in the development of gliomas, we downregulated the expression of c-Myc in the human glioblastoma cell line IN500 and studied the in vitro effect on cellular growth, proliferation, and apoptosis and the expression of VEGF and the in vivo effect on tumor formation in a xenograft mouse model.
These tumors exhibit a high degree of vascularization, and malignant progression from astrocytoma to glioblastoma is often accompanied by increased angiogenesis and the upregulation of vascular endothelial growth factor and its receptors.
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.
These results prove for the first time that over-expression of VEGF in human glioblastoma cells induces cathepsin L expression at the transcriptional level.
These observations shed light on the complex pro- and anti-angiogenic pathways involving the cross-talk between TGF-β and VEGF/PLGF signalling in glioblastoma which may involve parallel stimulation of angiogenesis and EndMT in distinct target cell populations.