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Alexander Viktor Tschulakow, H. Peter Rodemann, Stephan M. Huber, Monika Rittgarn, Dominik Klumpp, Benjamin Steegen, Ulrich Schraermeyer, Sylvie Julien-Schraermeyer; Effect of the pre-treatment with the radioprotector ortho-phospho-L-tyrosine (pTyr) in a xenograft retinoblastoma mouse model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1775.
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© ARVO (1962-2015); The Authors (2016-present)
Retinoblastoma (Rb) is the most frequent intraocular tumor in children and if left untreated, can cause death. Like most head and neck tumors, Rb is sensitive to radiotherapy (RT). However, the residual risk of a recurrence and development of treatment-induced secondary tumors still remains. In a previous study (Tschulakow et al., IOVS 2015; 56(7):72), we analyzed the ability of the radioprotector ortho-phospho-L-tyrosine (pTyr) to prevent radiation therapy-induced secondary tumors in Rb+/- mice, a model for Rb patients with hereditary Rb who are predisposed to secondary malignancies after RT. We showed that the pre-treatment with pTyr significantly reduces the negative effects of radiation on the hair coat as well as in the retina (retinal thickness reduction and photoreceptor loss) of Rb+/- mice. However, independent of the pre-treatment with pTyr, no secondary tumors were detectable.In this study, we used a new xenograft Rb mouse model, which was developed by our group (Tschulakow et al., 2016), to investigate the tumor’s recurrence and the occurrence of secondary tumors after radiotherapy and possible ways of preventing them by the application of pTyr.
Immune-deficient nude mice carrying orthotopic human Y79 xenograft tumors were treated by RT (15 fractions of 5 Gy 6 MV photons during 3 weeks) with and without pre-treatment with pTyr. The animals were investigated in vivo using SLO/OCT and histologically 1, 3, 6 and 9 months after RT. Success of the RT as well as radiation-induced tumor development and normal tissue radiation toxicity were evaluated as a function of pTyr treatment.
In the xenografted Rb model, tumor control was reached in 16 out of 22 control eyes after RT whereas it was not observed in all of the 24 pTyr-treated eyes. No secondary tumors were detected.
Although pTyr has a protective effect on normal tissues, unfortunately it dramatically lowers the efficacy of RT and is therefore not suitable for RT in Rb patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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