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Cisplatin radiosensitizes radioresistant human mesenchymal stem cells

Abstract: Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem ce...

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Main Authors: Rühle, Alexander (Author) , Lopez Perez, Ramon (Author) , Glowa, Christin (Author) , Weber, Klaus-Josef (Author) , Ho, Anthony Dick (Author) , Debus, Jürgen (Author) , Saffrich, Rainer (Author) , Huber, Peter E. (Author) , Nicolay, Nils (Author)
Format: Article (Journal)
Language:English
Published: September 23, 2017
In: OncoTarget
Year: 2017, Volume: 8, Issue: 50, Pages: 87809-87820
ISSN:1949-2553
DOI:10.18632/oncotarget.21214
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.18632/oncotarget.21214
Verlag, kostenfrei, Volltext: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=21214&pubmed-linkout=1
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Author Notes:Alexander Rühle, Ramon Lopez Perez, Christin Glowa, Klaus-Josef Weber, Anthony D. Ho, Jürgen Debus, Rainer Saffrich, Peter E. Huber and Nils H. Nicolay
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Summary:Abstract: Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem cells remains unknown. Here we demonstrate that cisplatin treatment radiosensitized human bone marrow-derived MSCs in a dose-dependent manner and increased levels of radiation-induced apoptosis. However, the defining stem cell properties of MSCs remained largely intact after cisplatin-based chemo-radiation, and stem cell motility, adhesion, surface marker expression and the characteristic differentiation potential were not significantly influenced. The increased cisplatin-mediated radiosensitivity was associated with a cell cycle shift of MSCs towards the radiosensitive G2/M phase and increased residual DNA double-strand breaks. These data demonstrate for the first time a dose-dependent radiosensitization effect of MSCs by cisplatin. Clinically, the observed increase in radiation sensitivity and subsequent loss of regenerative MSCs may contribute to the often severe late toxicities observed after cisplatin-based chemo-radiotherapy in cancer patients.
Item Description:Gesehen am 08.05.2018
Physical Description:Online Resource
ISSN:1949-2553
DOI:10.18632/oncotarget.21214

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