HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Increased hypoxia following vessel targeting in a murine model of retinoblastoma.

AbstractPURPOSE:
The purpose of this study was to evaluate the effects of vessel targeting and chemotherapy agents on inducing hypoxic regions in LH(BETA)T(AG) murine retinal tumors. METHODS. Twelve- and 16-week-old LH(BETA)T(AG) transgenic retinoblastoma mice were treated with periocular injections to the right eye only of saline (n = 42), anecortave acetate (a single injection; 300 microg/20 microL; n = 42), or carboplatin (two injections per week for 3 weeks; 62.5 microg/20 microL; n = 42). Eyes were enucleated 1 day, 1 week, and 1 month after injection. To assess hypoxia, mice received 60 mg/kg pimonidazole via intraperitoneal injection. Eyes were enucleated, and tumor sections were analyzed.
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.
AuthorsHinda Boutrid, Yolanda Piña, Colleen M Cebulla, William J Feuer, Theodore J Lampidis, Maria-Elena Jockovich, Timothy G Murray
JournalInvestigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 50 Issue 12 Pg. 5537-43 (Dec 2009) ISSN: 1552-5783 [Electronic] United States
PMID19578014 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Nitroimidazoles
  • Pregnadienediols
  • pimonidazole
  • Carboplatin
  • anecortave acetate
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: