TY  - JOUR
SP  - 1
CY  - London
SN  - 1748-717X
ID  - heidok19431
AV  - public
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/19431/
PB  - BioMed Central
EP  - 11
VL  - 10
JF  - Radiation Oncology
TI  - Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy
Y1  - 2015///
IS  - 146
A1  - Blattmann, Claudia
A1  - Oertel, Susanne
A1  - Thiemann, Markus
A1  - Dittmar, Anne
A1  - Roth, Eva
A1  - Kulozik, Andreas E.
A1  - Ehemann, Volker
A1  - Weichert, Wilko
A1  - Huber, Peter E.
A1  - Stenzinger, Albrecht
A1  - Debus, Jürgen
N2  - 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.  
ER  -