Antineoplastic effect of 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in transgenic mice with retinoblastoma

• Published in: Archives of ophthalmology (1960) Vol. 114; no. 11; p. 1396
• Main Authors: Shternfeld, I S, Lasudry, J G, Chappell, R J, Darjatmoko, S R, Albert, D M
• Format: Journal Article
• Language: English
• Published: United States 01.11.1996
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Calcitriol - analogs & derivatives; Calcitriol - pharmacology; Calcitriol - toxicity; Disease Models, Animal; Eye Neoplasms - drug therapy; Eye Neoplasms - genetics; Eye Neoplasms - pathology; Female; Injections, Intraperitoneal; Luteinizing Hormone - genetics; Male; Mice; Mice, Inbred ICR; Mice, Transgenic - genetics; Retinoblastoma - drug therapy; Retinoblastoma - genetics; Retinoblastoma - pathology; Transcriptional Activation
• ISSN: 0003-9950; 1538-3601
• DOI: 10.1001/archopht.1996.01100140596012

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. 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. 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. 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.