skip to content
Dovepress - Open Access to Scientific and Medical Research
View our mobile site

8852

Novel retinoblastoma treatment avoids chemotherapy: the effect of optimally timed combination therapy with angiogenic and glycolytic inhibitors on LHBETATAG retinoblastoma tumors

Original Research

(2189) Views  (490) Full article downloads

Authors: Samuel K Houston, Yolanda Piña, Timothy G Murray, et al

Published Date January 2011 Volume 2011:5 Pages 129 - 137
DOI: http://dx.doi.org/10.2147/OPTH.S15179

Samuel K Houston1, Yolanda Piña1, Timothy G Murray1, Hinda Boutrid1, Colleen Cebulla2, Amy C Schefler1, Wei Shi1, Magda Celdran1, William Feuer1, Jaime Merchan3, Ted J Lampidis4
1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Ophthalmology, The Ohio State University, Columbus, OH, USA; 3Division of Hematology/Oncology, Department of Medicine, 4Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL, USA

Purpose: The purpose of this study was to evaluate the effect of optimally timed combination treatment with angiogenic and glycolytic inhibitors on tumor burden, hypoxia, and angiogenesis in advanced retinoblastoma tumors.
Methods: LHBETATAG mice (n = 30) were evaluated. Mice were divided into 5 groups (n = 6) and received injections at 16 weeks of age (advanced tumors) with a) saline, b) anecortave acetate (AA), c) 2-deoxyglucose (2-DG), d) AA + 2-DG (1 day post-AA treatment), or e) AA + 2-DG (1 week post-AA treatment). Eyes were enucleated at 21 weeks and tumor sections were analyzed for hypoxia, angiogenesis, and tumor burden.
Results: Eyes treated with 2-DG 1 day post-AA injection showed a 23% (P = 0.03) reduction in tumor burden compared with 2-DG alone and a 61% (P < 0.001) reduction compared with saline-treated eyes. Eyes treated with 2-DG 1 week post-AA injection showed no significant decrease in tumor burden compared with 2-DG alone
(P = 0.21) and a 56% (P < 0.001) decrease in comparison with saline-treated eyes. 2-DG significantly reduced the total density of new blood vessels in tumors by 44% compared to saline controls (P < 0.001), but did not affect the density of mature vasculature.
Conclusions: Combination therapy with angiogenic and glycolytic inhibitors significantly enhanced tumor control. Synergistic effects were shown to be dependent on the temporal course of treatment, emphasizing optimal timing. 2-DG was shown to reduce the density of neovessels, demonstrating an antiangiogenic effect in vivo. As a result, angiogenic and glycolytic inhibitors may have significant potential as alternative therapies for treating children with retinoblastoma.

Keywords: retinoblastoma, adjuvant therapies, angiogenic inhibitors, glycolytic inhibitors




 

Other articles by Professor Timothy G Murray



Readers of this article also read:

Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors
ABO and rhesus blood group distribution in Kurds
From antiangiogenesis to hypoxia: current research and future directions
Radiation therapy for neovascular age-related macular degeneration
Improvement of adenoviral vector-mediated gene transfer to airway epithelia by folate-modified anionic liposomes
Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer for antiangiogenic vascular endothelial growth factor tumor-targeted therapy
Nanotherapeutics in angiogenesis: synthesis and in vivo assessment of drug efficacy and biocompatibility in zebrafish embryos
Nanoparticles of carbon allotropes inhibit glioblastoma multiforme angiogenesis in ovo
Inhibition of angiogenesis as a new therapeutic target in the treatment of lepromatous leprosy
The effect of anti-VEGF drugs (bevacizumab and aflibercept) on the survival of patients with metastatic colorectal cancer (mCRC)