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M. Kataram, P. Bhagavatula, P.B. Fisher, R.V. Gopalakrishna, P. Dent, D.T. Curiel, P.J. Mahasreshti; Adenovirus–mediated melanoma differentiation associated gene–7 (mda–7) gene therapy for retinoblastoma . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5193.
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Purpose:To evaluate the therapeutic potential of "melanoma differentiation–associated gene–7" (mda–7), a novel multifunctional anti–cancer agent, by adenovirus–mediated mda–7 (Ad.mda–7) gene therapy for retinoblastoma. Methods:A replication deficient adenovirus Ad.mda–7 encoding mda–7 was constructed and validated. The human retinoblastoma cells Y79 were injected subcutaneously (1x108 cells/nodule) into CB/17 SCID mice and allowed to form tumors. When the tumors have grown to a size of 50–75mm2, they were treated intratumorally with two doses of either Ad.mda–7 or control virus AdLuc 0.5x1010 particles/nodule or PBS on days 36 and 50 post inoculation of cells, and the tumor size was monitored. Determination of apoptosis in tumors was evaluated by TUNEL assay and angiogensis evaluated by immunohistochemistry. Results:The intratumoral treatment of Ad.mda–7 significantly decreased the tumor size in mice. Whereas the tumors treated with either Adluc or PBS continued to grow. Admda–7 induced significant apoptosis in tumors compared to Adluc. Further, inhibition of angiogenesis in tumors treated with Ad.mda–7 was higher compared to controls Conclusions:Our results suggest that adenovirus mediated mda–7 gene therapy can effectively inhibit retinoblastoma tumor growth. We conclude that the adenovirus–mediated mda–7 gene therapy represents a promising strategy to control retinoblastoma tumor growth.
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