Effectiveness of 1α-Hydroxyvitamin D2 in InhibitingTumor Growth in a Murine Transgenic Pigmented Ocular Tumor Model | Intraocular Tumors | JAMA Ophthalmology | JAMA Network
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Laboratory Sciences
September 2004

Effectiveness of 1α-Hydroxyvitamin D2 in InhibitingTumor Growth in a Murine Transgenic Pigmented Ocular Tumor Model

Author Affiliations

From the Department of Ophthalmology and Visual Sciences (Drs Albert,Kumar, and Patel, and Mss Darjatmoko, Lokken, and Damico) and the Departmentof Biostatistics and Medical Informatics (Dr Lindstrom), University of WisconsinMedical School, Madison; and Bone Care International, Middleton, Wis (Dr Strugnell).The authors have no relevant financial interest in this article.

Arch Ophthalmol. 2004;122(9):1365-1369. doi:10.1001/archopht.122.9.1365

Objective  To study the effectiveness of the vitamin D analogue 1α-hydroxyvitaminD2 (1α-OH-D2) in inhibiting ocular tumor growthin transgenic "Tyr-Tag" mice that developed pigmented ocular tumors producedwith the simian virus 40 T and t antigens under the control of the mouse tyrosinasegene. These animals develop pigmented intraocular tumors primarily from theretinal pigment epithelium that closely resemble the histologic features andgrowth pattern of human choroidal melanoma.

Methods  A total of 73 Tyr-Tag transgenic mice between 6 and 7 weeks old wererandomly assigned by sex and litter to 3 treatment groups to receive 0.05µg/d, 0.1 µg/d, or 0.2 µg/d of 1α-OH-D2;a control group received vehicle (coconut oil). The drug was administeredby oral gavage 5 times a week for 5 weeks. The animals were then euthanizedand their eyes were enucleated and processed histologically. Three serialsections from each eye were examined microscopically and the mean tumor areameasured using Optimus software version 6.5 (Media Cybernetics LP, SilverSpring, Md). Toxic adverse effects were assessed on the basis of mortality,weight loss, and serum calcium levels.

Results  The mean tumor size in the 0.1-µg/d and 0.2-µg/d dose groupswas smaller than in the controls (P<.001). Nosignificant difference was seen between the 0.05-µg/d dose group andthe control group (P = .64). Survival for the 0.1-µg/dand 0.2-µg/d dose groups was lower than for the controls (95% in thecontrols vs 85.7% and 73.7%, respectively; P<.01).

Conclusion  In the Tyr-Tag transgenic mouse, 1α-OH-D2 inhibitspigmented ocular tumor growth at moderate drug levels with relatively lowmortality.

Clinical Relevance  Vitamin D analogues merit further preclinical study in the treatmentof ocular melanoma.