Abstract | PURPOSE: RESULTS: Levels of hypoxia significantly increase in 16-week-old animals 1 day and 1 week after treatment with anecortave acetate, a known angiostatic agent. Eyes treated with anecortave acetate showed a 28% (P < 0.001) increase in hypoxic regions in comparison with the saline-treated control group 1 day after injection and a 17% (P < 0.001) increase 1 week after injection. In early tumors of 12-week-old animals, levels of hypoxia increased by 2.0% (P = 0.011) 1 day after anecortave acetate injection compared to controls. Levels of hypoxia significantly decrease in 16-week-old animals 1 week and 1 month after treatment with carboplatin, a chemotherapeutic agent. Eyes treated with carboplatin showed a 21.7% (P = 0.017) decrease in hypoxic regions in comparison with the saline-treated control group 1 week after injection and a 4.51% (P < 0.001) decrease 1 month after injection. In early tumors of 12-week-old animals, levels of hypoxia decreased by 0.0429% (P < 0.001) 1 month after carboplatin injection compared with controls. CONCLUSIONS: Treatment with a vessel-targeting agent results in changes in the tumor microenvironment as early as 1 day after treatment. By increasing hypoxia in tumors, vessel-targeting agents can be combined with glycolytic inhibitors which have been shown previously to target hypoxic regions in this transgenic model. This approach may have benefits for children with this disease and should be further investigated.
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Authors | Hinda Boutrid, Yolanda Piña, Colleen M Cebulla, William J Feuer, Theodore J Lampidis, Maria-Elena Jockovich, Timothy G Murray |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 50
Issue 12
Pg. 5537-43
(Dec 2009)
ISSN: 1552-5783 [Electronic] United States |
PMID | 19578014
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Antineoplastic Agents
- Nitroimidazoles
- Pregnadienediols
- pimonidazole
- Carboplatin
- anecortave acetate
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Topics |
- Angiogenesis Inhibitors
(therapeutic use)
- Animals
- Antineoplastic Agents
(therapeutic use)
- Carboplatin
(therapeutic use)
- Disease Models, Animal
- Hypoxia
(diagnosis, etiology)
- Mice
- Mice, Transgenic
- Microscopy, Confocal
- Neovascularization, Pathologic
(drug therapy)
- Nitroimidazoles
(pharmacology)
- Pregnadienediols
(therapeutic use)
- Retinal Neoplasms
(blood supply, pathology)
- Retinoblastoma
(blood supply, pathology)
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