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Residual γH2AX foci after ex vivo irradiation of patient samples with known tumour-type specific differences in radio-responsiveness.
Menegakis, Apostolos; De Colle, Chiara; Yaromina, Ala; Hennenlotter, Joerg; Stenzl, Arnulf; Scharpf, Marcus; Fend, Falko; Noell, Susan; Tatagiba, Marcos; Brucker, Sara; Wallwiener, Diethelm; Boeke, Simon; Ricardi, Umberto; Baumann, Michael; Zips, Daniel.
Afiliação
  • Menegakis A; 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.meneg
  • De Colle C; Department of Oncology, Radiation Oncology, University of Turin, Italy.
  • Yaromina A; Department of Radiation Oncology (Maastro), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
  • Hennenlotter J; Department of Urology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
  • Stenzl A; Department of Urology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
  • Scharpf M; Department of Pathology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
  • Fend F; Department of Pathology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
  • Noell S; Department of Neurosurgery, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
  • Tatagiba M; Department of Neurosurgery, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
  • Brucker S; Department of and Research Institute for Women's Health, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
  • Wallwiener D; Department of and Research Institute for Women's Health, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
  • Boeke S; 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.
  • Ricardi U; Department of Oncology, Radiation Oncology, University of Turin, Italy.
  • Baumann M; 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
  • Zips D; 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.
Radiother Oncol ; 116(3): 480-5, 2015 Sep.
Article em En | MEDLINE | ID: mdl-26297183
ABSTRACT

PURPOSE:

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. MATERIALS AND

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.

CONCLUSION:

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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histonas / Neoplasias Tipo de estudo: Evaluation_studies / Observational_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histonas / Neoplasias Tipo de estudo: Evaluation_studies / Observational_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article