The antineoplastic effect of 1,25-dihydroxy-16-ene-23-yne-cholecalciferol in transgenic mice with retinoblastoma

I. S. Shternfeld, J. G.H. Lasudry, R. J. Chappell, S. K. Chan, C. D. Pelzek, N. A. Syed, D. M. Albert

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Abstract

Purpose. Vitamin D has been shown to inhibit tumor growth and reduce tumor vascularity in the LHβ murine mode of retinoblastoma. However, concentrations required for tumor control caused morbidity and mortality from hypercalcemia. Several synthetic vitamin D analogs with reduced calcium mobilizing activity have been recently developed. The in vivo efficacy and effect on angiogenesis of one of these compounds, 1,25-dihydroxy-16-ene-23-yne-cholecalciferol (1,25(OH)2-16-ene-23-yne-D3), was examined in this model. Methods. Mice, age 8-10 weeks, were injected transperitoneally for five weeks (n=38). Experimental animals received .05 μg of 1,25(OH)2-16-ene-23-yne-D3 (n=20). Control animals received a mineral oil vehicle (n=18). Eyes were enucleated one week following treatment and were examined histologically in a masked fashion. Eyes from additional treated (n=16) and matched controls (n=16) were stained with GS-1, a lectin specific for vascular endothelium. Results. All experimental and control animals showed evidence of tumor. The size of intraocular tumors was significantly smaller in the treated group, compared with controls (p<.05). The treated group had a mean vessel count of 12.3 vessels per high power field versus 25.7 in the control group (p=0.0019). All mice completed the treatment and showed no evidence of overt toxicity. Conclusions. 1,25(OH)2-16-ene-23-yne-D3, a synthetic analog of vitamin 1,25(OH)2D3, inhibited the growth of retinoblastoma without producing toxicity. Smaller vessel count in treated animals supports the hypothesis that inhibition of angiogenesis plays a role in the antineoplastic activity of vitamin D and its analogs.

Original languageEnglish (US)
Pages (from-to)S1131
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

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ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Shternfeld, I. S., Lasudry, J. G. H., Chappell, R. J., Chan, S. K., Pelzek, C. D., Syed, N. A., & Albert, D. M. (1996). The antineoplastic effect of 1,25-dihydroxy-16-ene-23-yne-cholecalciferol in transgenic mice with retinoblastoma. Investigative Ophthalmology and Visual Science, 37(3), S1131.