Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors
Yolanda Piña,1 Samuel K Houston,1 Timothy G Murray,1 Tulay Koru-Sengul,2,3 Christina Decatur,1 William K Scott,4 Lubov Nathanson,4 Jennifer Clarke,2 Theodore J Lampidis,51Bascom Palmer Eye Institute, 2Department of Epidemiology and Public Health, 3Sylvester Comprehensive Cancer Center...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Dove Medical Press
2012-05-01
|
Series: | Clinical Ophthalmology |
Online Access: | http://www.dovepress.com/retinoblastoma-treatment-impact-of-the-glycolytic-inhibitor-2-deoxy-d--a9995 |
id |
doaj-1046816bca3e4ac9a742a1934c9bb645 |
---|---|
record_format |
Article |
spelling |
doaj-1046816bca3e4ac9a742a1934c9bb6452020-11-24T23:07:58ZengDove Medical PressClinical Ophthalmology1177-54671177-54832012-05-012012default817830Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumorsPiña YHouston SKMurray TGKoru-Sengul TDecatur CScott WKNathanson LClarke JLampidis TJYolanda Piña,1 Samuel K Houston,1 Timothy G Murray,1 Tulay Koru-Sengul,2,3 Christina Decatur,1 William K Scott,4 Lubov Nathanson,4 Jennifer Clarke,2 Theodore J Lampidis,51Bascom Palmer Eye Institute, 2Department of Epidemiology and Public Health, 3Sylvester Comprehensive Cancer Center, 4Department of Molecular Genomics, 5Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL, USAPurpose: The purpose of this study was to evaluate the effect of 2-deoxy-D-glucose (2-DG) on the spatial distribution of the genetic expression of key elements involved in angiogenesis, hypoxia, cellular metabolism, and apoptosis in LHBETATAG retinal tumors.Methods: The right eye of each LHBETATAG transgenic mouse (n = 24) was treated with either two or six subconjunctival injections of 2-DG (500 mg/kg) or saline control at 16 weeks of age. A gene expression array analysis was performed on five different intratumoral regions (apex, center, base, anterior-lateral, and posterior-lateral) using Affymetrix GeneChip Mouse Gene 1.0 ST arrays. To test for treatment effects of each probe within each region, a two-way analysis of variance was used.Results: Significant differences between treatment groups (ie, 0, 2, and 6 injections) were found as well as differences among the five retinal tumor regions evaluated (P < 0.01). More than 100 genes were observed to be dysregulated by ≥2-fold difference in expression between the three treatment groups, and their dysregulation varied across the five regions assayed. Several genes involved in pathways important for tumor cell growth (ie, angiogenesis, hypoxia, cellular metabolism, and apoptosis) were identified.Conclusions: 2-DG was found to significantly alter the gene expression in LHBETATAG retinal tumor cells according to their location within the tumor as well as the treatment schedule. 2-DG's effects on genetic expression found here correlate with previous reported results on varied processes involved in its in vitro and in vivo activity in inhibiting tumor cell growth.Keywords: retinoblastoma, hypoxia, genetic expression, glycolytic inhibitor, 2-DGhttp://www.dovepress.com/retinoblastoma-treatment-impact-of-the-glycolytic-inhibitor-2-deoxy-d--a9995 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Piña Y Houston SK Murray TG Koru-Sengul T Decatur C Scott WK Nathanson L Clarke J Lampidis TJ |
spellingShingle |
Piña Y Houston SK Murray TG Koru-Sengul T Decatur C Scott WK Nathanson L Clarke J Lampidis TJ Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors Clinical Ophthalmology |
author_facet |
Piña Y Houston SK Murray TG Koru-Sengul T Decatur C Scott WK Nathanson L Clarke J Lampidis TJ |
author_sort |
Piña Y |
title |
Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors |
title_short |
Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors |
title_full |
Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors |
title_fullStr |
Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors |
title_full_unstemmed |
Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors |
title_sort |
retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in lhbetatag retinal tumors |
publisher |
Dove Medical Press |
series |
Clinical Ophthalmology |
issn |
1177-5467 1177-5483 |
publishDate |
2012-05-01 |
description |
Yolanda Piña,1 Samuel K Houston,1 Timothy G Murray,1 Tulay Koru-Sengul,2,3 Christina Decatur,1 William K Scott,4 Lubov Nathanson,4 Jennifer Clarke,2 Theodore J Lampidis,51Bascom Palmer Eye Institute, 2Department of Epidemiology and Public Health, 3Sylvester Comprehensive Cancer Center, 4Department of Molecular Genomics, 5Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL, USAPurpose: The purpose of this study was to evaluate the effect of 2-deoxy-D-glucose (2-DG) on the spatial distribution of the genetic expression of key elements involved in angiogenesis, hypoxia, cellular metabolism, and apoptosis in LHBETATAG retinal tumors.Methods: The right eye of each LHBETATAG transgenic mouse (n = 24) was treated with either two or six subconjunctival injections of 2-DG (500 mg/kg) or saline control at 16 weeks of age. A gene expression array analysis was performed on five different intratumoral regions (apex, center, base, anterior-lateral, and posterior-lateral) using Affymetrix GeneChip Mouse Gene 1.0 ST arrays. To test for treatment effects of each probe within each region, a two-way analysis of variance was used.Results: Significant differences between treatment groups (ie, 0, 2, and 6 injections) were found as well as differences among the five retinal tumor regions evaluated (P < 0.01). More than 100 genes were observed to be dysregulated by ≥2-fold difference in expression between the three treatment groups, and their dysregulation varied across the five regions assayed. Several genes involved in pathways important for tumor cell growth (ie, angiogenesis, hypoxia, cellular metabolism, and apoptosis) were identified.Conclusions: 2-DG was found to significantly alter the gene expression in LHBETATAG retinal tumor cells according to their location within the tumor as well as the treatment schedule. 2-DG's effects on genetic expression found here correlate with previous reported results on varied processes involved in its in vitro and in vivo activity in inhibiting tumor cell growth.Keywords: retinoblastoma, hypoxia, genetic expression, glycolytic inhibitor, 2-DG |
url |
http://www.dovepress.com/retinoblastoma-treatment-impact-of-the-glycolytic-inhibitor-2-deoxy-d--a9995 |
work_keys_str_mv |
AT piampntildeay retinoblastomatreatmentimpactoftheglycolyticinhibitor2deoxydglucoseonmoleculargenomicsexpressioninlhbetatagretinaltumors AT houstonsk retinoblastomatreatmentimpactoftheglycolyticinhibitor2deoxydglucoseonmoleculargenomicsexpressioninlhbetatagretinaltumors AT murraytg retinoblastomatreatmentimpactoftheglycolyticinhibitor2deoxydglucoseonmoleculargenomicsexpressioninlhbetatagretinaltumors AT korusengult retinoblastomatreatmentimpactoftheglycolyticinhibitor2deoxydglucoseonmoleculargenomicsexpressioninlhbetatagretinaltumors AT decaturc retinoblastomatreatmentimpactoftheglycolyticinhibitor2deoxydglucoseonmoleculargenomicsexpressioninlhbetatagretinaltumors AT scottwk retinoblastomatreatmentimpactoftheglycolyticinhibitor2deoxydglucoseonmoleculargenomicsexpressioninlhbetatagretinaltumors AT nathansonl retinoblastomatreatmentimpactoftheglycolyticinhibitor2deoxydglucoseonmoleculargenomicsexpressioninlhbetatagretinaltumors AT clarkej retinoblastomatreatmentimpactoftheglycolyticinhibitor2deoxydglucoseonmoleculargenomicsexpressioninlhbetatagretinaltumors AT lampidistj retinoblastomatreatmentimpactoftheglycolyticinhibitor2deoxydglucoseonmoleculargenomicsexpressioninlhbetatagretinaltumors |
_version_ |
1725616082600853504 |