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November 1996

Antineoplastic Effect of 1,25-Dihydroxy-16-ene-23-yne-Vitamin D3 Analogue in Transgenic Mice With Retinoblastoma

Author Affiliations

From the Departments of Ophthalmology and Visual Sciences (Drs Shternfeld, Lasudry, and Albert and Ms Darjatmoko) and Biostatistics and Statistics (Dr Chappell), University of Wisconsin Medical School, Madison. The authors do not have any commercial or proprietary interest in 1,25(OH)2-16-ene-23-yne-D3 and have not received payment and acted as consultants or evaluators for Hoffmann-LaRoche for 1,25(OH)2-16-ene-23-yne-D3.

Arch Ophthalmol. 1996;114(11):1396-1401. doi:10.1001/archopht.1996.01100140596012

Objective:  To evaluate the in vivo efficacy and clinical toxic effects of the 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in β-luteinizing hormone-Tag (LHβ-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 μg 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.

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