Retinoblastoma treatment: Impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LH BETAT AG retinal tumors

Yolanda Piña, Samuel K. Houston, Timothy G. Murray, Tulay Sengul, Christina Decatur, William K Scott, Lubov Nathanson, Jennifer Clarke, Theodore Lampidis

Research output: Contribution to journalArticle

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Abstract

Purpose: 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 LH BETAT AG retinal tumors. Methods: The right eye of each LH BETAT AG 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 LH BETAT AG 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.

Original languageEnglish
Pages (from-to)817-830
Number of pages14
JournalClinical Ophthalmology
Volume6
Issue number1
DOIs
StatePublished - May 27 2012

Fingerprint

Retinal Neoplasms
Retinoblastoma
Genomics
Deoxyglucose
Glucose
Cell Hypoxia
Injections
Apoptosis
Genes
Gene Expression
Neoplasms
Therapeutics
Growth
Transgenic Mice
Analysis of Variance
Appointments and Schedules

Keywords

  • 2-DG
  • Genetic expression
  • Glycolytic inhibitor
  • Hypoxia
  • Retinoblastoma

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Retinoblastoma treatment : Impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LH BETAT AG retinal tumors. / Piña, Yolanda; Houston, Samuel K.; Murray, Timothy G.; Sengul, Tulay; Decatur, Christina; Scott, William K; Nathanson, Lubov; Clarke, Jennifer; Lampidis, Theodore.

In: Clinical Ophthalmology, Vol. 6, No. 1, 27.05.2012, p. 817-830.

Research output: Contribution to journalArticle

Piña, Yolanda ; Houston, Samuel K. ; Murray, Timothy G. ; Sengul, Tulay ; Decatur, Christina ; Scott, William K ; Nathanson, Lubov ; Clarke, Jennifer ; Lampidis, Theodore. / Retinoblastoma treatment : Impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LH BETAT AG retinal tumors. In: Clinical Ophthalmology. 2012 ; Vol. 6, No. 1. pp. 817-830.
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abstract = "Purpose: 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 LH BETAT AG retinal tumors. Methods: The right eye of each LH BETAT AG 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 LH BETAT AG 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.",
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