期刊
RADIOTHERAPY AND ONCOLOGY
卷 108, 期 3, 页码 434-439出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2013.06.022
关键词
gamma H2AX; Radiotherapy; DNA repair; Local tumour control; Tumour micromilieu; Biomarker
资金
- Deutsche Krebshilfe e.V. (DKH) [108983]
- Deutsche Forschungsgemeinschaft (DFG) [Ba 1433/4, Ba 1433/5]
- German Federal Ministry of Education and Research (BMBF) [03ZIK/OncoRay]
Purpose: Evaluation of micromilieu-dependent quantified gamma H2AX foci as a potential predictive biomarker in well-oxygenated tumour areas in 9 HNSCC xenograft models in vivo. Materials & methods: GammaH2AX foci were quantified in perfused tumour areas 30 min (initial gamma H2AX foci) and 24 h (residual gamma H2AX foci) after exposure to a single dose of 4 Gy. The initial and residual normalised gamma H2AX foci were correlated with TCD50 after single dose irradiation under clamped blood flow (SDclamp) or a fractionated irradiation setting under ambient blood flow (fx). Results: A significant negative correlation between initial and residual normalised gamma H2AX foci and TCD50 SDclamp and TCD50 fx for 9 HNSCC tumour xenograft models in vivo was found. Residual normalised gamma H2AX foci showed higher intertumoural variability and their correlation with TCD50 was more robust. Conclusions: For the first time a significant negative correlation between gamma H2AX foci and local tumour control after irradiation has been demonstrated. Our results underline the potential of residual gamma H2AX foci as a predictive biomarker for local tumour control after radiotherapy. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 108 (2013) 434-439
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