K Goetze1, S S Meyer, A Yaromina, D Zips, M Baumann, W Mueller-Klieser. 1. Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128, Mainz, Germany. goetze@uni-mainz.de
Abstract
BACKGROUND AND PURPOSE: Lactate was previously shown to be a prognostic but not a predictive pre-therapeutic marker for radiation response of tumor xenografts. We hypothesize that metabolic changes during fractionated irradiation may restrict the predictiveness of lactate regarding tumor radiosensitivity. MATERIALS AND METHODS: Tumor xenografts were generated in nude mice by implanting 4 head and neck squamous cell carcinoma lines with different sensitivities to fractionated irradiation. Tumors were irradiated with up to 15 fractions of 2 Gy over a period of 3 weeks, and ATP and lactate levels were measured in vital tumor areas with induced metabolic bioluminescence imaging. Corresponding changes in mRNA expression of glycolysis-related genes were determined by quantitative RT-PCR. RESULTS: Lactate content decreased significantly in 3 out of 4 cell lines in the course of irradiation showing no correlation with cell line-specific radiosensitivity. Radiation-induced changes in ATP levels and glycolysis-related mRNA expression, however, only occurred in radiosensitive or intermediately radioresistant xenografts, whereas these parameters remained unchanged in radioresistant tumors. CONCLUSION: Sensitivity-related differences in the transcriptional response of tumors to radiotherapy may be exploited in the clinic for better individualization of tumor treatment.
BACKGROUND AND PURPOSE:Lactate was previously shown to be a prognostic but not a predictive pre-therapeutic marker for radiation response of tumor xenografts. We hypothesize that metabolic changes during fractionated irradiation may restrict the predictiveness of lactate regarding tumor radiosensitivity. MATERIALS AND METHODS:Tumor xenografts were generated in nude mice by implanting 4 head and neck squamous cell carcinoma lines with different sensitivities to fractionated irradiation. Tumors were irradiated with up to 15 fractions of 2 Gy over a period of 3 weeks, and ATP and lactate levels were measured in vital tumor areas with induced metabolic bioluminescence imaging. Corresponding changes in mRNA expression of glycolysis-related genes were determined by quantitative RT-PCR. RESULTS:Lactate content decreased significantly in 3 out of 4 cell lines in the course of irradiation showing no correlation with cell line-specific radiosensitivity. Radiation-induced changes in ATP levels and glycolysis-related mRNA expression, however, only occurred in radiosensitive or intermediately radioresistant xenografts, whereas these parameters remained unchanged in radioresistant tumors. CONCLUSION: Sensitivity-related differences in the transcriptional response of tumors to radiotherapy may be exploited in the clinic for better individualization of tumor treatment.
Authors: Ala Yaromina; Theresa Kroeber; Andreas Meinzer; Simon Boeke; Howard Thames; Michael Baumann; Daniel Zips Journal: Int J Radiat Oncol Biol Phys Date: 2011-04-12 Impact factor: 7.038
Authors: Daniel Zips; Simon Böke; Theresa Kroeber; Andreas Meinzer; Kerstin Brüchner; Howard D Thames; Michael Baumann; Ala Yaromina Journal: Strahlenther Onkol Date: 2011-04-26 Impact factor: 3.621
Authors: Ala Yaromina; Daniel Zips; Howard D Thames; Wolfgang Eicheler; Mechthild Krause; Andrea Rosner; Michael Haase; Cordula Petersen; James A Raleigh; Verena Quennet; Stefan Walenta; Wolfgang Mueller-Klieser; Michael Baumann Journal: Radiother Oncol Date: 2006-09-07 Impact factor: 6.280
Authors: Ulrike G A Sattler; Sandra S Meyer; Verena Quennet; Christian Hoerner; Hannah Knoerzer; Christian Fabian; Ala Yaromina; Daniel Zips; Stefan Walenta; Michael Baumann; Wolfgang Mueller-Klieser Journal: Radiother Oncol Date: 2009-12-28 Impact factor: 6.280
Authors: N Meggyeshazi; G Andocs; L Balogh; P Balla; G Kiszner; I Teleki; A Jeney; T Krenacs Journal: Strahlenther Onkol Date: 2014-02-22 Impact factor: 3.621
Authors: Nils H Nicolay; Eva Sommer; Ramon Lopez Perez; Ute Wirkner; Tilman Bostel; Anthony D Ho; Michael Lahn; Jürgen Debus; Rainer Saffrich; Peter E Huber Journal: Strahlenther Onkol Date: 2014-05-27 Impact factor: 3.621
Authors: Sebastian Blatt; Nadine Voelxen; Keyvan Sagheb; Andreas Max Pabst; Stefan Walenta; Thies Schroeder; Wolfgang Mueller-Klieser; Thomas Ziebart Journal: Clin Oral Investig Date: 2016-01-04 Impact factor: 3.573
Authors: Niamh Lynam-Lennon; Stephen G Maher; Aoife Maguire; James Phelan; Cian Muldoon; John V Reynolds; Jacintha O'Sullivan Journal: PLoS One Date: 2014-06-26 Impact factor: 3.240