March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Effect of anti-VEGF Therapy on Cellular Markers during the Proliferative Phase of Capillary Hemangioma Growth
Author Affiliations & Notes
  • Brett W. Davies
    Ophthalmology, Wilford Hall Medical Center, San Antonio, Texas
  • Footnotes
    Commercial Relationships  Brett W. Davies, None
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    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2968. doi:
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      Brett W. Davies; Effect of anti-VEGF Therapy on Cellular Markers during the Proliferative Phase of Capillary Hemangioma Growth. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2968.

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Abstract

Purpose: : The proliferative phase of capillary hemangioma growth is characterized by high expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), CD 31, and von Willebrand factor (vWF). The purpose of this study is to determine the effect of anti-VEGF therapy on capillary hemangioma growth, and to specifically look at the effect on these signaling markers.

Methods: : A baseline litter of Wistar R rat pups (n=10) were injected with 109.7 plaque forming units of murine polyomavirus biweekly. Capillary hemangioma growth was confirmed in 100% of the pups after 3 weeks of life. Rat pups were then separated into a control group (n=12) or a treatment group (n=15). The control group received biweekly doses of the polyomavirus until week 3.5, and then four pups were sacrificed each week thereafter. The treatment group also received biweekly doses of the polyomavirus until week 3, and then received biweekly doses of bevacizumab (Avastin, Genentech) 5mg/kg. A percentage of the pups in the treatment group were also sacrificed each week. At the time of sacrifice, each rat underwent gross and microscopic evaluation to determine the presence of hemangiomas. When found, the hemangiomas were tested for the presence of VEGF, PCNA, CD31, and vWF.

Results: : Hemangiomas were found in 12/12 (100%) pups in the control group, and in 10/15 (66%) pups in the treatment group. This was a statistically significant reduction in incidence (p<0.05). Only 44% of the hemangiomas from the control group tested positive for VEGF, while 80% were positive from the treatment group. Hemangiomas from the control group were more likely to stain positive in the 1st week compared to the treatment group (75% vs 37%). There was no significant difference between the groups with respect to the PCNA, CD 31, and vWF.

Conclusions: : While anti-VEGF therapy reduced the incidence of capillary hemangiomas in the treatment group, it did not reduce VEGF production in the lesions when compared to the control group. It is hypothesized up regulation of VEGF may have occurred at the treatment dose and route given. VEGF remains a potential target to disrupt capillary hemangioma growth.

Keywords: tumors • growth factors/growth factor receptors • immunohistochemistry 
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