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Blood, 15 August 2007, Vol. 110, No. 4, pp. 1116-1122. Prepublished online as a Blood First Edition Paper on May 4, 2007; DOI 10.1182/blood-2007-01-067579. This Article Full Text Full Text (PDF) Supplemental Tables Supplemental Tables and Figures All Versions of this Article: blood-2007-01-067579v1 110/4/1116    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Knoops, L. Articles by de Jong, D. Search for Related Content PubMed PubMed Citation Articles by Knoops, L. Articles by de Jong, D. Related Collections Immunobiology Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma Laurent Knoops1,2, Rick Haas3, Sanne de Kemp4, Donné Majoor1, Annegien Broeks4, Eric Eldering5, Jan Paul de Boer6, Marcel Verheij3, Conny van Ostrom6, Annemieke de Vries6, Laura van't Veer1,4, and Daphne de Jong1 1 Department of Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; 2 Experimental Medicine and Hematology Units, Université Catholique de Louvain, Brussels, Belgium; Departments of3 Radiotherapy, 4 Experimental Therapy and Diagnostic Oncology, and 6Hematology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; 5 Department of Experimental Immunology, Academical Medical Centre, Amsterdam, the Netherlands; 6 Laboratory of Toxicology, Pathology and Genetics, National Institute of Public Health and the Environment, Bilthoven, the Netherlands Very low-dose irradiation (2 x 2 Gy) is a new, effective, and safe local treatment for follicular lymphoma. To understand the biologic mechanisms of this extremely effective response, we compared by microarray the gene-expression profile of patients' biopsies taken before and after radiation. In all patients, a major and consistent induction of p53 target genes was seen. p53 targets involved in cell-cycle arrest and apoptosis showed the same mode of regulation, indicating that, in vivo, both are activated simultaneously. p53 up-regulation and p53-mediated proliferation arrest and apoptosis were substantiated using immunohistochemistry, with activation of both the intrinsic and the extrinsic apoptotic pathways. The other induced genes revealed a whole set of biologically meaningful genes related to macrophage activation and TH1 immune response. Immunohistochemical analysis suggested a specific activation or differentiation of resident macrophages by apoptotic cells. These biologic insights are important arguments to advocate the use of low-dose radiotherapy as an effective palliative treatment for follicular lymphoma. Moreover, this study is the first in vivo report of the radiation-induced p53 apoptotic response in patients and suggests that this apoptotic response is not immunologically silent. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. O'Shea, C. O'Riain, C. Taylor, R. Waters, E. Carlotti, F. MacDougall, J. Gribben, A. Rosenwald, G. Ott, L. M. Rimsza, et al. The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival Blood, October 15, 2008; 112(8): 3126 - 3129. [Abstract] [Full Text] [PDF]

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