Retinoblastoma treatment: Utilization of the glycolytic inhibitor, 2-deoxy-2-fluoro-d-glucose (2-FG), to target the chemoresistant hypoxic regions in LH BETAT AG retinal tumors

Yolanda Piña, Christina Decatur, Timothy G. Murray, Samuel K. Houston, Milena Lopez-Cavalcante, Eleut Hernandez, Magda Celdran, Nikesh Shah, William J Feuer, Theodore Lampidis

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

PURPOSE. To analyze the effect of the glycolytic inhibitor 2-deoxy-2-fluoro-D-glucose (2-FG) on tumor burden, hypoxia, and blood vessels in LH BETAT AG retinal tumors. METHODS. Seventeen-week-old LH BETAT AG retinal tumor eyes (n = 36) were treated with 2-FG and analyzed at 1 day and 1 week post a single treatment, and 1 day post a biweekly treatment for 3 weeks. Tumor sections were analyzed for hypoxia, tumor burden, and vasculature. To assess tumor burden, sections were processed for standard hematoxylin-eosin (H&E) staining. Immunofluorescent techniques were used to stain for new and mature blood vessels. RESULTS. Hypoxia and tumor burden reduction are significantly different between the treatment schedules used (P < 0.001). Eyes treated with 2-FG for 3 weeks showed a significant decrease in hypoxia (P = 0.001) and tumor burden (P = 0.009); whereas those treated with one injection and evaluated at 1 day and 1 week postinjection did not show a decrease in either hypoxia (P = 0.373 and P = 0.782, respectively) or tumor burden (P = 0.203 and P = 0.836, respectively). When evaluating the spatial distribution of hypoxic regions in the different areas of the tumor, 2-FG showed a differential effect on hypoxia depending on the area. Hypoxia was most decreased in the base of the treated eyes with a 95% reduction (P <lt; 0.001). CONCLUSIONS. This is the first study to elucidate that 2-FG treatment in retinoblastoma produces an impact on hypoxia and a concomitant decrease on tumor burden. In this study, the authors validate their previous studies by revealing that glycolytic inhibitors effectively target hypoxia in retinoblastoma tumors. The future application of 2-FG as an adjuvant treatment to standard chemotherapy may enhance the treatment of retinoblastoma.

Original languageEnglish
Pages (from-to)996-1002
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume53
Issue number2
DOIs
StatePublished - Feb 1 2012

Fingerprint

Retinal Neoplasms
Retinoblastoma
Tumor Burden
Glucose
Therapeutics
Blood Vessels
Neoplasms
Hypoxia
Fluorodeoxyglucose F18
Hematoxylin
Eosine Yellowish-(YS)
Appointments and Schedules
Coloring Agents
Staining and Labeling
Drug Therapy

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Retinoblastoma treatment : Utilization of the glycolytic inhibitor, 2-deoxy-2-fluoro-d-glucose (2-FG), to target the chemoresistant hypoxic regions in LH BETAT AG retinal tumors. / Piña, Yolanda; Decatur, Christina; Murray, Timothy G.; Houston, Samuel K.; Lopez-Cavalcante, Milena; Hernandez, Eleut; Celdran, Magda; Shah, Nikesh; Feuer, William J; Lampidis, Theodore.

In: Investigative Ophthalmology and Visual Science, Vol. 53, No. 2, 01.02.2012, p. 996-1002.

Research output: Contribution to journalArticle

Piña, Yolanda ; Decatur, Christina ; Murray, Timothy G. ; Houston, Samuel K. ; Lopez-Cavalcante, Milena ; Hernandez, Eleut ; Celdran, Magda ; Shah, Nikesh ; Feuer, William J ; Lampidis, Theodore. / Retinoblastoma treatment : Utilization of the glycolytic inhibitor, 2-deoxy-2-fluoro-d-glucose (2-FG), to target the chemoresistant hypoxic regions in LH BETAT AG retinal tumors. In: Investigative Ophthalmology and Visual Science. 2012 ; Vol. 53, No. 2. pp. 996-1002.
@article{ccd6d4f815fb4e8ca47915a5ccd9660b,
title = "Retinoblastoma treatment: Utilization of the glycolytic inhibitor, 2-deoxy-2-fluoro-d-glucose (2-FG), to target the chemoresistant hypoxic regions in LH BETAT AG retinal tumors",
abstract = "PURPOSE. To analyze the effect of the glycolytic inhibitor 2-deoxy-2-fluoro-D-glucose (2-FG) on tumor burden, hypoxia, and blood vessels in LH BETAT AG retinal tumors. METHODS. Seventeen-week-old LH BETAT AG retinal tumor eyes (n = 36) were treated with 2-FG and analyzed at 1 day and 1 week post a single treatment, and 1 day post a biweekly treatment for 3 weeks. Tumor sections were analyzed for hypoxia, tumor burden, and vasculature. To assess tumor burden, sections were processed for standard hematoxylin-eosin (H&E) staining. Immunofluorescent techniques were used to stain for new and mature blood vessels. RESULTS. Hypoxia and tumor burden reduction are significantly different between the treatment schedules used (P < 0.001). Eyes treated with 2-FG for 3 weeks showed a significant decrease in hypoxia (P = 0.001) and tumor burden (P = 0.009); whereas those treated with one injection and evaluated at 1 day and 1 week postinjection did not show a decrease in either hypoxia (P = 0.373 and P = 0.782, respectively) or tumor burden (P = 0.203 and P = 0.836, respectively). When evaluating the spatial distribution of hypoxic regions in the different areas of the tumor, 2-FG showed a differential effect on hypoxia depending on the area. Hypoxia was most decreased in the base of the treated eyes with a 95{\%} reduction (P",
author = "Yolanda Pi{\~n}a and Christina Decatur and Murray, {Timothy G.} and Houston, {Samuel K.} and Milena Lopez-Cavalcante and Eleut Hernandez and Magda Celdran and Nikesh Shah and Feuer, {William J} and Theodore Lampidis",
year = "2012",
month = "2",
day = "1",
doi = "10.1167/iovs.11-8265",
language = "English",
volume = "53",
pages = "996--1002",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "2",

}

TY - JOUR

T1 - Retinoblastoma treatment

T2 - Utilization of the glycolytic inhibitor, 2-deoxy-2-fluoro-d-glucose (2-FG), to target the chemoresistant hypoxic regions in LH BETAT AG retinal tumors

AU - Piña, Yolanda

AU - Decatur, Christina

AU - Murray, Timothy G.

AU - Houston, Samuel K.

AU - Lopez-Cavalcante, Milena

AU - Hernandez, Eleut

AU - Celdran, Magda

AU - Shah, Nikesh

AU - Feuer, William J

AU - Lampidis, Theodore

PY - 2012/2/1

Y1 - 2012/2/1

N2 - PURPOSE. To analyze the effect of the glycolytic inhibitor 2-deoxy-2-fluoro-D-glucose (2-FG) on tumor burden, hypoxia, and blood vessels in LH BETAT AG retinal tumors. METHODS. Seventeen-week-old LH BETAT AG retinal tumor eyes (n = 36) were treated with 2-FG and analyzed at 1 day and 1 week post a single treatment, and 1 day post a biweekly treatment for 3 weeks. Tumor sections were analyzed for hypoxia, tumor burden, and vasculature. To assess tumor burden, sections were processed for standard hematoxylin-eosin (H&E) staining. Immunofluorescent techniques were used to stain for new and mature blood vessels. RESULTS. Hypoxia and tumor burden reduction are significantly different between the treatment schedules used (P < 0.001). Eyes treated with 2-FG for 3 weeks showed a significant decrease in hypoxia (P = 0.001) and tumor burden (P = 0.009); whereas those treated with one injection and evaluated at 1 day and 1 week postinjection did not show a decrease in either hypoxia (P = 0.373 and P = 0.782, respectively) or tumor burden (P = 0.203 and P = 0.836, respectively). When evaluating the spatial distribution of hypoxic regions in the different areas of the tumor, 2-FG showed a differential effect on hypoxia depending on the area. Hypoxia was most decreased in the base of the treated eyes with a 95% reduction (P

AB - PURPOSE. To analyze the effect of the glycolytic inhibitor 2-deoxy-2-fluoro-D-glucose (2-FG) on tumor burden, hypoxia, and blood vessels in LH BETAT AG retinal tumors. METHODS. Seventeen-week-old LH BETAT AG retinal tumor eyes (n = 36) were treated with 2-FG and analyzed at 1 day and 1 week post a single treatment, and 1 day post a biweekly treatment for 3 weeks. Tumor sections were analyzed for hypoxia, tumor burden, and vasculature. To assess tumor burden, sections were processed for standard hematoxylin-eosin (H&E) staining. Immunofluorescent techniques were used to stain for new and mature blood vessels. RESULTS. Hypoxia and tumor burden reduction are significantly different between the treatment schedules used (P < 0.001). Eyes treated with 2-FG for 3 weeks showed a significant decrease in hypoxia (P = 0.001) and tumor burden (P = 0.009); whereas those treated with one injection and evaluated at 1 day and 1 week postinjection did not show a decrease in either hypoxia (P = 0.373 and P = 0.782, respectively) or tumor burden (P = 0.203 and P = 0.836, respectively). When evaluating the spatial distribution of hypoxic regions in the different areas of the tumor, 2-FG showed a differential effect on hypoxia depending on the area. Hypoxia was most decreased in the base of the treated eyes with a 95% reduction (P

UR - http://www.scopus.com/inward/record.url?scp=84859941115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859941115&partnerID=8YFLogxK

U2 - 10.1167/iovs.11-8265

DO - 10.1167/iovs.11-8265

M3 - Article

C2 - 22266512

AN - SCOPUS:84859941115

VL - 53

SP - 996

EP - 1002

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 2

ER -