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Prognostic value of HIF-1α expression during fractionated irradiation
L Helbig1, A Yaromina, S N Sriramareddy
1Dept. of Radiation Oncology/ OncoRay National Center for Radiation Research, Medical Faculty and University Hospital Carl Gustav Carus Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
Background And Purpose:
Hypoxia and reoxygenation are important determinants of outcome after radiotherapy. HIF-1α is a key molecule involved in cellular response to hypoxia. HIF-1α expression levels have been shown to change after irradiation. The objective of the present study was to explore the prognostic value of HIF-1α expression during fractionated irradiation.
Materials And Methods:
Six human squamous cell carcinoma models xenografted in nude mice were analysed. Tumours were excised after 3, 5 and 10 fractions. HIF-1α expression was quantified by western blot. For comparative analysis, previously published data on local tumour control data and pimonidazole hypoxic fraction was used.
Results:
HIF-1α expression in untreated tumours exhibited intertumoural heterogeneity and did not correlate with pimonidazole hypoxic fraction. During fractionated irradiation the majority of tumour models exhibited a decrease in HIF-1α expression, whereas in UT-SCC-5 no change was observed. Neither kinetics nor expression levels during fractionated irradiation correlated with local tumour control.
Conclusion:
Our data do not support the use of HIF-1α determined during treatment as a biomarker to predict outcome after fractionated irradiation.