title: Residual γH2AX foci after ex vivo irradiation of patient samples with known tumour-type specific differences in radio-responsiveness.
abstract: OBJECTIVE
  To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method.
  
  
  METHODS
  Evaluation of residual γH2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included.
  
  
  RESULTS
  Linear dose response of residual γH2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14-0.24) to 3.26 (95% CI: 4.13-2.62) for chondrosarcomas (radioresistant) and classical seminomas (radiosensitive) respectively. Simulations suggest that omitting dose levels might simplify the assay without compromising robustness.
  
  
  CONCLUSIONS
  Here we confirm clinical feasibility of the assay. The slopes of the residual foci number are well in line with the expected differences in radio-responsiveness of different tumour types implying that intrinsic radiation sensitivity contributes to tumour radiation response. Thus, this assay has a promising potential for individualized radiation therapy and prospective validation is warranted.
authors: Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany; German Cancer Research Center (DKFZ), Heidelberg and German Consortium for Translational Cancer Research (DKTK) Partner Sites Tübingen, Germany. Electronic address: apostolos.menegakis@uni-tuebingen.de.
authors: Apostolos
authors: A
authors: Menegakis
authors: Department of Oncology, Radiation Oncology, University of Turin, Italy.
authors: Chiara
authors: C
authors: De Colle
authors: Department of Radiation Oncology (Maastro), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors: Ala
authors: A
authors: Yaromina
authors: Department of Urology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
authors: Joerg
authors: J
authors: Hennenlotter
authors: Department of Urology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
authors: Arnulf
authors: A
authors: Stenzl
authors: Department of Pathology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
authors: Marcus
authors: M
authors: Scharpf
authors: Department of Pathology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
authors: Falko
authors: F
authors: Fend
authors: Department of Neurosurgery, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
authors: Susan
authors: S
authors: Noell
authors: Department of Neurosurgery, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
authors: Marcos
authors: M
authors: Tatagiba
authors: Department of and Research Institute for Women's Health, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
authors: Sara
authors: S
authors: Brucker
authors: Department of and Research Institute for Women's Health, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
authors: Diethelm
authors: D
authors: Wallwiener
authors: Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany; German Cancer Research Center (DKFZ), Heidelberg and German Consortium for Translational Cancer Research (DKTK) Partner Sites Tübingen, Germany.
authors: Simon
authors: S
authors: Boeke
authors: Department of Oncology, Radiation Oncology, University of Turin, Italy.
authors: Umberto
authors: U
authors: Ricardi
authors: German Cancer Research Center (DKFZ), Heidelberg and German Consortium for Translational Cancer Research (DKTK) Partner Sites Dresden, Germany; Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität, Germany; OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Germany.
authors: Michael
authors: M
authors: Baumann
authors: Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany; German Cancer Research Center (DKFZ), Heidelberg and German Consortium for Translational Cancer Research (DKTK) Partner Sites Tübingen, Germany.
authors: Daniel
authors: D
authors: Zips
mesh_terms: D000704:Analysis of Variance; D004260:DNA Repair / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000532:radiotherapy*; D011446:Prospective Studies; D011836:Radiation Tolerance
chemical_list: C468783:H2AX protein, human; D006657:Histones
keywords: DNA repair; Intrinsic radiation sensitivity; Personalized radiation oncology; Radiotherapy; Tumour specimens; γH2AX foci