Vascular Endothelial Growth Factor is a Predictor of Relapse and Stage Progression in Superficial Bladder Cancer

Abstract

Tumor development is angiogenesis dependent, and vascular endothe 11*1 growth factor (VEGF) is a key growth factor in this process. We demonstrate that high expression of VEGF mRNA in 55 superficIal blad der cancers was associated with earlier recurrence (P = 0.001; hazard ratio, 3.09) and progression to a more invasive phenotype (P = 0.02; hazard ratio, 533). VEGF mRNA expression correlated with protein although in cases without high p53 protein expression, high VEGF mRNA also predicts a poor prognosis. The relationship between VEGF and early twnor recurrence suggests that seeding via angiogenesis may be a major mechanism in the pathogenesis of recurrence. These studies indicate that VEGF can predict the behavior of superfidal bladder tumors and is a therapeutic target for intravesical therapy.

Dual Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 in Angiogenesis and Invasion of Human Urinary Bladder Cancer

“…Furthermore, Crew et al (27,28) showed that enhanced expression of VEGF in superficial bladder cancers is associated with tumor progression to a more invasive phenotype. Because VEGF expression was affected by neither CEACAM1 overexpression nor CEACAM1 silencing in bladder cancer cell lines, the interaction of epithelial CEACAM1 with VEGF-C and VEGF-D might be an additional mechanism contributing to the vascularization and invasion of bladder cancer.…”

Cooperative stimulation of vascular endothelial growth factor expression by hypoxia and reactive oxygen species: the effect of targeting vascular endothelial growth factor and oxidative stress in an orthotopic xenograft model of bladder carcinoma

“…One consequence of TP activity in this cell line is increased expression of the angiogenic factor vascular endothelial growth factor (VEGF) (Brown et al, 2000). Increased VEGF expression has been shown to correlate with recurrence and progression in bladder tumours (Crew et al, 1997). Transcription of the VEGF gene is known to be driven by the hypoxia-inducible factor HIF-1a, and recent evidence has suggested that cellular HIF-1a levels are raised not only by hypoxia but are also increased in the presence of reactive oxygen species (ROS) (Page et al, 2002;Gao et al, 2002).…”

Eukaryotic initiation factor-4E in superficial and muscle invasive bladder cancer and its correlation with vascular endothelial growth factor expression and tumour progression

“…Following electrophoresis in a 6% polyacrylamide/urea-sequencing gel the protected fragments ( Figure 1) were analysed using the ImageQuant, Phosphorimager (Version 3.3, Molecular Dynamics Inc., Sunnyvale, CA, USA). Analysis was performed in a blinded fashion prior to determining patient outcome.To control against losses during the assay signals were normalized to the external control formed by hybridization of the sense and antisense GAPDH riboprobes (Crew et al, 1997). In addition, to allow accurate comparisons between ribonuclease protection assays a positive control was run on all electrophoresis gels.…”

“…The positive control was given the value of 100 arbitrary mRNA units and all other signals were expressed relative to this. A breast cancer specimen known to express large quantities of eIF-4E mRNA was used as the positive control for eIF-4E (Scott et al, 1997) whilst a bladder cancer specimen known to express large quantities of VEGF mRNA was used as the positive control for VEGF (Crew et al, 1997). …”