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C.M. Damico, L.A. Plum, S. Darjatmoko, J.M. Lokken, H.F. DeLuca, M. Clagett–Dame, D.M. Albert, A. Kumar; Efficacy of a Novel Vitamin D Analog (2–methylene–19–nor–(20S)–1a–hydroxybishomopregnacalciferol, DP006) for Treatment of Human Retinoblastoma in the LH Beta–Tag Mouse Model . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3361.
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Purpose: To evaluate the efficacy and tolerability of a novel vitamin D analog (2–methylene–19–nor–(20S)–1a–hydroxybishomopregnacalciferol, DP006) lacking calcemic activity at effective doses for the treatment of human retinoblastoma in the transgenic LH Beta–Tag mouse model. Methods: Twenty LH Beta–Tag mice were randomly assigned to an experimental or negative control group (n=10/group). The experimental group was treated with 65 mcg per kilogram DP006 in coconut oil five times per week for five weeks via oral gavage and the negative control group received coconut oil vehicle only. All mice were fed a standard rodent chow ad lib. Body weights were performed twice weekly and clinical observations made daily for the duration of the study to monitor for signs of toxicity. After five weeks of treatment, blood was collected from anesthetized mice for serum calcium analysis. Following euthanasia, eyes and kidneys were removed and placed into 10% buffered formalin for histopathologic examination. Eye tumor area was determined in histological sections through the pupil–optic plane stained with hematoxylin/eosin using Optimus software version 6.5 (Media Cybernetics, Silver Spring, MD). Sections of kidneys stained with Von Kossa were examined microscopically to determine the level of calcification, if any. Results: Tumor area (mean +/– standard deviation) was reduced in LH Beta–Tag mice treated with DP006 (5.76 x 104 +/– 8.41 x 104 microns2) compared to negative controls (1.06 x 105 +/– 1.41 x 105 microns2). The serum calcium concentration was significantly decreased in mice treated with DP006 compared to controls receiving vehicle only. There were no significant changes in body weight between the experimental and control groups. Conclusions: The novel vitamin D analog, DP006, is effective at inhibiting retinoblastoma tumor growth in the LH Beta–Tag mouse model without causing hypercalcemia.
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