Antiangiogenesis with bevacizumab, an antibody against vascular endothelial growth factor (VEGF), has been used for devascularization to limit the growth of malignant glioma.
Determining the mechanism of treatment failure of the VEGF monoclonal antibody bevacizumab for malignant glioma would provide insight into approaches to overcome therapeutic resistance.
The expressions levels of VEGF and intracellular adhesion molecule-1 (ICAM-1) were increased in the migration-prone sublines as well as in samples from patients with high-grade glioma when compared to those with low-grade glioma.
In this study, we demonstrate the feasibility of combining adenovirus-mediated soluble VEGF receptor-1 anti-angiogenic gene therapy with AdHSV-tk/GCV suicide gene therapy to treat experimental MGs.
The vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) signaling cascade plays a critical role in tumor angiogenesis and metastasis and has been correlated with several poorly prognostic cancers such as malignant gliomas.
In this study we sought to determine whether hypoxia detected by (18)F-fluoromisonidazole (FMISO) PET accurately reflects the expression of HIF-1α and VEGF in the tumour and can be used as a biomarker of antiangiogenic treatment and as a prognostic factor in newly diagnosed and recurrent malignant gliomas.
Several antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) or its receptors are currently in clinical trials as therapy for high-grade glioma and bevacizumab was recently approved by the FDA for treatment of recurrent glioblastoma.
Using DNA microarray analysis, we examined VEGF and related gene expression in 71 newly diagnosed malignant gliomas and analyzed the relationship to edema and survival.
We found that these tumors expressed significant amounts of VEGF mRNA in comparison with other brain tumors, including malignant gliomas and meningiomas.
In conclusion, p38 MAPK and JNK pathways play an important role in VEGF secretion from malignant glioma cells under normoxic conditions, possibly contributing to VEGF-induced angiogenesis in malignant gliomas at vital tumor areas where there is no hypoxia.
Based on these results, we performed three different antiangiogenic experiments targeted to inhibit VEGF expression in a human malignant glioma (U87) mouse model: anti-VEGF neutralized antibody intraperitoneal injection; interferon-beta intramusclar injection; and transfection of an endogenous nonspecific angiogenesis inhibitor, thrombospondin-1, into glioma cells caused inhibition of VEGF secretion and/or mRNA expression and resulted in glioma growth inhibition of 70%, 84%, and 50%, respectively, compared with control.
Statistical analysis revealed that the Ang2 expression was negatively correlated with vessel maturation in malignant gliomas and that vascular endothelial growth factor expression was positively correlated with vessel maturation in low-grade gliomas (P < 0.05).