Vascular endothelial growth factor in children with neuroblastoma: a retrospective analysis

Abstract

BackgroundDespite aggressive therapy, advanced stage neuroblastoma patients have poor survival rates. Although angiogenesis correlates with advanced tumour stage and plays an important role in determining the tumour response to treatment in general, clinical data are still insufficient, and more clinical evaluations are needed to draw conclusions. The aim of this study was to evaluate vascular endothelial growth factor (VEGF) expression in patients with neuroblastoma, determine whether it correlates with other prognostic factors and/or therapeutic response, and to assess should VEGF be considered in a routine diagnostic workup.Materials and methodsVEGF expression was determined by immunohistochemistry using anti-VEGF antibody in paraffin embedded primary tumour tissue from 56 neuroblastoma patients. Semiquantitative expression of VEGF was estimated and compared with gender, age, histology, disease stage, therapy, and survival. Statistical analyses, including multivariate analysis, were performed.ResultsVEGF expression correlated with disease stage and survival in neuroblastoma patients. Combination of VEGF expression and disease stage as a single prognostic value for survival (P-value = 0.0034; odds ratio (OR) (95%CI) = 26.17 (2.97-230.27) exhibited greater correlation with survival than individually. Hematopoietic stem cell transplantation significantly improved survival of the advanced stage patients with high VEGF expression.ConclusionVEGF expression should be considered in a routine diagnostic workup of children with neuroblastoma, especially in those more than 18 months old and with advanced disease stage. High VEGF expression at the time of disease diagnosis is a bad risk prognostic factor, and can be used to characterize subsets of patients with an unfavourable outcome.

Targeted Delivery to Neuroblastoma of Novel siRNA-anti-GD2-liposomes Prepared by Dual Asymmetric Centrifugation and Sterol-Based Post-Insertion Method

“…VEGF-A, a growth factor for tumour angiogenesis, plays an important role in highly vascularised neuroblastoma tumours (23) and has been chosen as a target for siRNAbased therapeutics. Anti-GD2-DDAB-liposomes loaded with siRNA specific for VEGF-A successfully reduced expression of this gene in neuroblastoma cell lines by 30%, supporting our strategy of using anti-GD2-liposomes as potential carriers for the specific delivery of siRNA to neuroblastoma cells.…”

“…This molecule is well known as a pro-angiogenic factor which stimulates growth of new blood vessels in the tumour and therefore promotes the development of the tumour mass (22). Recent data showed its relevance in neuroblastoma progression (23). Anti-GD2-DDAB-liposomes were chosen as delivery particles for VEGF-A siRNA, because they showed higher siRNA encapsulation efficiencies compared to HSPC-liposomes (Table I).…”

Expression of Ki-67, p53 and VEGF in Pediatric Neuroblastoma

“…Previous studies have shown that high-risk NB with advanced-stage is resistant to various therapeutic approaches resulting in poor survival rates (Ishola and Chung, 2007;Jakovljevic et al, 2009, Cheung, 2012. Therefore, finding new molecular markers in NB is essential to improve targeted therapy via appropriate approach and to increase the survival rates of children.…”

Prostaglandin receptor EP2 is a novel molecular target for high-risk neuroblastoma

“…The activation of EP2 receptor can induce a myriad of tumor-promoting cytokines, chemokines, growth factors, and responding receptors, thereby amplifying inflammation, strengthening the tumor microenvironment, and promoting the growth of tumors in skin, colon, prostate, and brain (14,16,(21)(22)(23)(24). We next examined the expression relationships between EP2 receptor and a number of well-known tumor-associated factors via analyzing the Versteeg-88 dataset ( Table 2) (43), TGF-β1/TGFBR1 (44,45), and VEGF/VEGFR (46). Conversely, none of currently known anti-neuroblastoma factors (0 out of 5), including CSF-2, IFN-γ, IL-2, IL-27, and TNF-α (34,47,48), correlated with EP2 receptor in neuroblastoma tumors (P = 0.001) ( Table 2).…”