UvA-DARE (Digital Academic Repository) Tumor control and normal tissue toxicity: The two faces of radiotherapy van Oorschot, B. Link to publication Citation for published version (APA): van Oorschot, B. (2016). Tumor control and normal tissue toxicity: The two faces of radiotherapy General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (http://dare.uva.nl) Download date: 24 Dec 2018
TUMOR CONTROL AND NORMAL TISSUE TOXICITY: The Two Faces of Radiotherapy Bregje van Oorschot
ISBN: 978-94-6182-710-4 The research described in this thesis was performed at the Center for Experimental and Molecular Medicine (CEMM), Laboratory for Experimental Oncology and Radiobiology (LEXOR) and the department of Radiotherapy at the Academic Medical Center, University of Amsterdam, the Netherlands. Copyright 2016 by B. van Oorschot. All right reserved. No part of this book may be reproduced in any form or by any means, without prior permission of the author. About the cover: Representation of the main cellular effect of ionizing radiation: the induction of DNA damage. As elaborated in this thesis, repair processes (wheels) are key elements in determining tumor radiosensitivity ánd preventing collateral damage. Cover design: Pascal Franken. Printing: Off Page, www.offpage.nl The research was supported by a generous grant of the Dutch Society of Cancer (KWF-Kankerbestrijding), KWF project UVA 2008-4019, and Stichting Vanderes. This support is gratefully acknowledged. Printing of this thesis was financially supported by the Academic Medical Center, Amsterdam, the Netherlands.
TUMOR CONTROL AND NORMAL TISSUE TOXICITY: The Two Faces of Radiotherapy ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. ir. K.I.J. Maex ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Aula der Universiteit op woensdag 21 september 2016, te 13:00 uur door Bregje van Oorschot geboren te Bergen op Zoom
PROMOTIECOMMISSIE: Promotores: prof. dr. J.P. Medema Universiteit van Amsterdam prof. dr. L.J.A. Stalpers Universiteit van Amsterdam Copromotores: dr. N.A.P. Franken Universiteit van Amsterdam dr. H. Vrieling Leids Universitair Medisch Centrum Overige leden: prof. dr. C.R.N. Rasch Universiteit van Amsterdam prof. dr. C.J.F. van Noorden Universiteit van Amsterdam prof. dr. J. Borst Universiteit van Amsterdam dr. A.D. Bins Universiteit van Amsterdam prof. dr. R.P. Coppes Rijksuniversiteit Groningen prof. dr. R. Kanaar Erasmus Universiteit Rotterdam Faculteit der Geneeskunde
I am among those who think that science has a great beauty. ( ) - Marie Curie as quoted in Madame Curie: A Biography (1937) by Eve Curie Labouisse
TABLE OF CONTENTS Chapter 1: General Introduction 9 PART I. RADIATION RESPONSE IN CANCER CELLS Chapter 2: Decay of γ-h2ax foci correlates with potentially lethal damage repair 31 and P53 status Chapter 3: Targeting DNA Double Strand Break Repair to enhance the effect of 47 radiation treatment Chapter 4: Predicting Radiosensitivity with Gamma-H2AX Foci Assay after Single 69 High-Dose-Rate and Pulsed Dose-Rate Ionizing Irradiation PART II. RADIATION RESPONSE IN NORMAL TISSUES Chapter 5: Reduced Activity of Double-Strand Break Repair Genes in Prostate 91 Cancer Patients with Late Normal Tissue Radiation Toxicity Chapter 6: Inefficient DNA-DSB Repair via the Homologous Recombination 111 Pathway in Prostate Cancer Patients with Late Radiation Toxicity Chapter 7: Summary and General Discussion 135 Addendum: Nederlandse samenvatting 153 PhD Portfolio 159 List of Publications 160 Dankwoord 161 Curriculum Vitae 165