Antineoplastic effect of 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in transgenic mice with retinoblastoma
I. S. Shternfeld, J. G. Lasudry, R. J. Chappell, S. R. Darjatmoko and D. M. Albert
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, USA.
OBJECTIVE: To evaluate the in vivo efficacy and clinical toxic effects of
the 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in beta-luteinizing
hormone-Tag (LH beta-Tag) transgenic mice with heritable retinoblastoma.
METHODS: Forty-two mice (8-10 weeks old), randomly assigned to experimental
(n = 21) or control (n = 21) groups, received intraperitoneal injections of
0.05 microgram of 1,25-dihydroxy-16-ene-23-yne-D3 in 0.5-mL mineral oil
vehicle (experimental group) or 0.5 mL of mineral oil vehicle (control
group) for 5 weeks. One experimental and 3 control animals died of
injection-related trauma. Eyes were enucleated 1 week after treatment and
were examined histologically in a masked fashion. RESULTS: All experimental
and control animals showed evidence of tumor. The tumors in the
experimental mice showed a significantly smaller cross-sectional area (0.88
+/- 0.08 mm2) compared with that in the control mice (1.12 +/- 0.12 mm2) (P
= .02). All mice completed the treatment and showed no clinical evidence of
toxic effects. CONCLUSIONS: Tumors in transgenic mice with retinoblastoma
treated with 1,25(OH)2-16-ene-23-yne-D3 showed a 21% smaller
cross-sectional area compared with that in the control mice, without
producing clinically apparent toxic effects. This compound may be useful as
adjunctive therapy in the treatment of retinoblastoma.
