Antineoplastic effect of 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in transgenic mice with retinoblastoma.
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.
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, USA.
I S
IS
Shternfeld
J G
JG
Lasudry
R J
RJ
Chappell
S R
SR
Darjatmoko
D M
DM
Albert
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D004195:Disease Models, Animal; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D007274:Injections, Intraperitoneal; D007986:Luteinizing Hormone / Q000235:genetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic / Q000235:genetics; D012175:Retinoblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015533:Transcriptional Activation
D000970:Antineoplastic Agents; D007986:Luteinizing Hormone; D002117:Calcitriol; C064183:Ro 23-7553