PURPOSE: Evaluation of micromilieu-dependent quantified γH2AX 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 γH2AX foci) and 24 h (residual γH2AX foci) after exposure to a single dose of 4 Gy. The initial and residual normalised γH2AX 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 γH2AX foci and TCD50 SDclamp and TCD50 fx for 9 HNSCC tumour xenograft models in vivo was found. Residual normalised γH2AX foci showed higher intertumoural variability and their correlation with TCD50 was more robust. CONCLUSIONS: For the first time a significant negative correlation between γH2AX foci and local tumour control after irradiation has been demonstrated. Our results underline the potential of residual γH2AX foci as a predictive biomarker for local tumour control after radiotherapy.
PURPOSE: Evaluation of micromilieu-dependent quantified γH2AX 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 γH2AX foci) and 24 h (residual γH2AX foci) after exposure to a single dose of 4 Gy. The initial and residual normalised γH2AX 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 γH2AX foci and TCD50 SDclamp and TCD50 fx for 9 HNSCC tumour xenograft models in vivo was found. Residual normalised γH2AX foci showed higher intertumoural variability and their correlation with TCD50 was more robust. CONCLUSIONS: For the first time a significant negative correlation between γH2AX foci and local tumour control after irradiation has been demonstrated. Our results underline the potential of residual γH2AX foci as a predictive biomarker for local tumour control after radiotherapy.
Authors: Michael Baumann; Mechthild Krause; Jens Overgaard; Jürgen Debus; Søren M Bentzen; Juliane Daartz; Christian Richter; Daniel Zips; Thomas Bortfeld Journal: Nat Rev Cancer Date: 2016-03-18 Impact factor: 60.716
Authors: C Norman Coleman; Geoff S Higgins; J Martin Brown; Michael Baumann; David G Kirsch; Henning Willers; Pataje G S Prasanna; Mark W Dewhirst; Eric J Bernhard; Mansoor M Ahmed Journal: Clin Cancer Res Date: 2016-05-06 Impact factor: 12.531
Authors: Hans Liew; Carmen Klein; Frank T Zenke; Amir Abdollahi; Jürgen Debus; Ivana Dokic; Andrea Mairani Journal: Int J Mol Sci Date: 2019-11-30 Impact factor: 5.923
Authors: Ivana Dokic; Andrea Mairani; Martin Niklas; Ferdinand Zimmermann; Naved Chaudhri; Damir Krunic; Thomas Tessonnier; Alfredo Ferrari; Katia Parodi; Oliver Jäkel; Jürgen Debus; Thomas Haberer; Amir Abdollahi Journal: Oncotarget Date: 2016-08-30