Effectiveness of 1α-hydroxyvitamin D2 in inhibiting tumor growth in a murine transgenic pigmented ocular tumor model

Daniel Albert, Amit Kumar, Stephen A. Strugnell, Soesiawati R. Darjatmoko, Janice M. Lokken, Mary J. Lindstrom, Christine M. Damico, Sarit Patel

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objective: To study the effectiveness of the vitamin D analogue 1α-hydroxyvitamin D2 (1α-OH-D2) in inhibiting ocular tumor growth in transgenic "Tyr-Tag" mice that developed pigmented ocular tumors produced with the simian virus 40 T and t antigens under the control of the mouse tyrosinase gene. These animals develop pigmented intraocular tumors primarily from the retinal pigment epithelium that closely resemble the histologic features and growth pattern of human choroidal melanoma. Methods: A total of 73 Tyr-Tag transgenic mice between 6 and 7 weeks old were randomly assigned by sex and litter to 3 treatment groups to receive 0.05 μg/d, 0.1 μg/d, or 0.2 μg/d of 1α-OH-D2; a control group received vehicle (coconut oil). The drug was administered by oral gavage 5 times a week for 5 weeks. The animals were then euthanized and their eyes were enucleated and processed histologically. Three serial sections from each eye were examined microscopically and the mean tumor area measured using Optimus software version 6.5 (Media Cybernetics LP, Silver Spring, 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 0.2μg/d dose groups was smaller than in the controls (P<.001). No significant difference was seen between the 0.05-μg/d dose group and the control group (P=.64). Survival for the 0.1-μg/d and 0.2-μg/d dose groups was lower than for the controls (95% in the controls vs 85.7% and 73.7%, respectively; P<.01). Conclusion: In the Tyr-Tag transgenic mouse, 1α-OH-D2 inhibits pigmented ocular tumor growth at moderate drug levels with relatively low mortality. Clinical Relevance: Vitamin D analogues merit further preclinical study in the treatment of ocular melanoma.

Original languageEnglish (US)
Pages (from-to)1365-1369
Number of pages5
JournalArchives of ophthalmology
Volume122
Issue number9
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

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Growth
Neoplasms
Vitamin D
Transgenic Mice
Melanoma
Cybernetics
Control Groups
Simian virus 40
Monophenol Monooxygenase
Mortality
Retinal Pigment Epithelium
Poisons
Viral Tumor Antigens
Silver
Pharmaceutical Preparations
Weight Loss
Software
Calcium
Survival
Serum

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Effectiveness of 1α-hydroxyvitamin D2 in inhibiting tumor growth in a murine transgenic pigmented ocular tumor model. / Albert, Daniel; Kumar, Amit; Strugnell, Stephen A.; Darjatmoko, Soesiawati R.; Lokken, Janice M.; Lindstrom, Mary J.; Damico, Christine M.; Patel, Sarit.

In: Archives of ophthalmology, Vol. 122, No. 9, 01.09.2004, p. 1365-1369.

Research output: Contribution to journalArticle

Albert, D, Kumar, A, Strugnell, SA, Darjatmoko, SR, Lokken, JM, Lindstrom, MJ, Damico, CM & Patel, S 2004, 'Effectiveness of 1α-hydroxyvitamin D2 in inhibiting tumor growth in a murine transgenic pigmented ocular tumor model', Archives of ophthalmology, vol. 122, no. 9, pp. 1365-1369. https://doi.org/10.1001/archopht.122.9.1365
Albert, Daniel ; Kumar, Amit ; Strugnell, Stephen A. ; Darjatmoko, Soesiawati R. ; Lokken, Janice M. ; Lindstrom, Mary J. ; Damico, Christine M. ; Patel, Sarit. / Effectiveness of 1α-hydroxyvitamin D2 in inhibiting tumor growth in a murine transgenic pigmented ocular tumor model. In: Archives of ophthalmology. 2004 ; Vol. 122, No. 9. pp. 1365-1369.
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abstract = "Objective: To study the effectiveness of the vitamin D analogue 1α-hydroxyvitamin D2 (1α-OH-D2) in inhibiting ocular tumor growth in transgenic {"}Tyr-Tag{"} mice that developed pigmented ocular tumors produced with the simian virus 40 T and t antigens under the control of the mouse tyrosinase gene. These animals develop pigmented intraocular tumors primarily from the retinal pigment epithelium that closely resemble the histologic features and growth pattern of human choroidal melanoma. Methods: A total of 73 Tyr-Tag transgenic mice between 6 and 7 weeks old were randomly assigned by sex and litter to 3 treatment groups to receive 0.05 μg/d, 0.1 μg/d, or 0.2 μg/d of 1α-OH-D2; a control group received vehicle (coconut oil). The drug was administered by oral gavage 5 times a week for 5 weeks. The animals were then euthanized and their eyes were enucleated and processed histologically. Three serial sections from each eye were examined microscopically and the mean tumor area measured using Optimus software version 6.5 (Media Cybernetics LP, Silver Spring, 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 0.2μg/d dose groups was smaller than in the controls (P<.001). No significant difference was seen between the 0.05-μg/d dose group and the control group (P=.64). Survival for the 0.1-μg/d and 0.2-μg/d dose groups was lower than for the controls (95{\%} in the controls vs 85.7{\%} and 73.7{\%}, respectively; P<.01). Conclusion: In the Tyr-Tag transgenic mouse, 1α-OH-D2 inhibits pigmented ocular tumor growth at moderate drug levels with relatively low mortality. Clinical Relevance: Vitamin D analogues merit further preclinical study in the treatment of ocular melanoma.",
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AU - Kumar, Amit

AU - Strugnell, Stephen A.

AU - Darjatmoko, Soesiawati R.

AU - Lokken, Janice M.

AU - Lindstrom, Mary J.

AU - Damico, Christine M.

AU - Patel, Sarit

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