title: Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy creator: Blattmann, Claudia creator: Oertel, Susanne creator: Thiemann, Markus creator: Dittmar, Anne creator: Roth, Eva creator: Kulozik, Andreas E. creator: Ehemann, Volker creator: Weichert, Wilko creator: Huber, Peter E. creator: Stenzinger, Albrecht creator: Debus, Jürgen subject: 610 subject: 610 Medical sciences Medicine description: Background: Minimal improvements in treatment or survival of patients with osteosarcoma have been achieved during the last three decades. Especially in the case of incomplete tumor resection, prognosis remains poor. Heavy ion radiotherapy (HIT) and modern anticancer drugs like histone deacetylase inhibitors (HDACi) have shown promising effects in osteosarcoma in vitro. In this study, we tested the effect of HIT and the combination of HIT and the HDACi suberoylanilide hydroxamic acid (SAHA) in a xenograft mouse model. Methods: Osteosarcoma xenografts were established by subcutaneous injection of KHOS-24OS cells and treated with either vehicle (DMSO), SAHA, HIT or HIT and SAHA. Tumor growth was determined and tumor necrosis, proliferation rate, apoptotic rate as well as vessel density were evaluated. Results: Here, we show that the combination of HIT and SAHA induced a significant delay of tumor growth through increased rate of apoptosis, increased expression of p53 and p21Waf1/Cip1, inhibition of proliferation and angiogenesis compared to tumors treated with HIT only. Conclusion: HIT and in particular the combination of HIT and histone deacetylase inhibition is a promising treatment strategy in OS and may be tested in clinical trials. publisher: BioMed Central date: 2015 type: Article type: info:eu-repo/semantics/article type: NonPeerReviewed format: application/pdf identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/19431/1/13014_2015_Article_455.pdf identifier: DOI: identifier: urn:nbn:de:bsz:16-heidok-194313 identifier: Blattmann, Claudia ; Oertel, Susanne ; Thiemann, Markus ; Dittmar, Anne ; Roth, Eva ; Kulozik, Andreas E. ; Ehemann, Volker ; Weichert, Wilko ; Huber, Peter E. ; Stenzinger, Albrecht ; Debus, Jürgen (2015) Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy. Radiation Oncology, 10 (146). pp. 1-11. ISSN 1748-717X relation: https://archiv.ub.uni-heidelberg.de/volltextserver/19431/ rights: info:eu-repo/semantics/openAccess rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id) language: eng