Article (Scientific journals)
Mechanism of reoxygenation after antiangiogenic therapy using SU5416 and its importance for guiding combined antitumor therapy
ANSIAUX, Réginald; BAUDELET, Christine; JORDAN, Bénédicte et al.
2006In Cancer Research, 66 (19), p. 9698/704
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Keywords :
Antineoplastic agent; Mechanism of action; Antiangiogenic agent; Combined treatment; Anticancéreux; Mécanisme action; Antiangiogénique; Traitement associé
Abstract :
[en] Emerging preclinical studies support the concept of a transient "normalization" of tumor vasculature during the early stage of antiangiogenic treatment, with possible beneficial effects on associated radiotherapy or chemotherapy. One key issue in this area of research is to determine whether this feature is common to all antiangiogenic drugs and whether the phenomenon occurs in all types of tumors. In the present study, we characterized the evolution of the tumor oxygenation (in transplantable liver tumor and FSAII tumor models) after administration of SU5416, an antagonist of the vascular endothelial growth factor receptor. SU5416 induced an early increase in tumor oxygenation [measured by electronic paramagnetic resonance (EPR)], which did not correlate with remodeling of the tumor vasculature (assessed by CD31 labeling using immunohistochemistry) or with tumor perfusion (measured by dynamic contrast enhanced-magnetic resonance imaging). Inhibition of mitochondrial respiration (measured by EPR) was responsible for this early reoxygenation. Consistent with these unique findings in the tumor microenvironment, we found that SU5416 potentiated tumor response to radiotherapy but not to chemotherapy. In addition to the fact that the characterization of the tumor oxygenation is essential to enable correct application of combined therapies, our results show that the long-term inhibition of oxygen consumption is a potential novel target in this class of compounds.
[en] Emerging preclinical studies support the concept of a transient "normalization" of tumor vasculature during the early stage of antiangiogenic treatment, with possible beneficial effects on associated radiotherapy or chemotherapy. One key issue in this area of research is to determine whether this feature is common to all antiangiogenic drugs and whether the phenomenon occurs in all types of tumors. In the present study, we characterized the evolution of the tumor oxygenation (in transplantable liver tumor and FSAII tumor models) after administration of SU5416, an antagonist of the vascular endothelial growth factor receptor. SU5416 induced an early increase in tumor oxygenation [measured by electronic paramagnetic resonance (EPR)], which did not correlate with remodeling of the tumor vasculature (assessed by CD31 labeling using immunohistochemistry) or with tumor perfusion (measured by dynamic contrast enhanced-magnetic resonance imaging). Inhibition of mitochondrial respiration (measured by EPR) was responsible for this early reoxygenation. Consistent with these unique findings in the tumor microenvironment, we found that SU5416 potentiated tumor response to radiotherapy but not to chemotherapy. In addition to the fact that the characterization of the tumor oxygenation is essential to enable correct application of combined therapies, our results show that the long-term inhibition of oxygen consumption is a potential novel target in this class of compounds.
Disciplines :
Oncology
Radiology, nuclear medicine & imaging
Author, co-author :
ANSIAUX, Réginald;  Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance
BAUDELET, Christine;  Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance ; Laboratory of Medicinal Chemistry and Radiopharmacy
JORDAN, Bénédicte;  Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance ; Laboratory of Medicinal Chemistry and Radiopharmacy
CROKART, Nathalie;  Université Catholique de Louvain - UCL > Laboratory of Biomedical Magnetic Resonance
DEWEVER, Julie;  Université Catholique de Louvain - UCL > Laboratory of Pharmacology and Therapeutics
MARTINIVE, Philippe ;  Université Catholique de Louvain - UCL
GREGOIRE, Vincent
FERON, Olivier
GALLEZ
Language :
English
Title :
Mechanism of reoxygenation after antiangiogenic therapy using SU5416 and its importance for guiding combined antitumor therapy
Alternative titles :
[fr] Mécanisme de réoxygénation après la thérapie anti-angiogénique SU5416 à l'aide et son importance pour guider la thérapie antitumorale combinés.
Publication date :
01 October 2006
Journal title :
Cancer Research
ISSN :
0008-5472
eISSN :
1538-7445
Publisher :
American Association for Cancer Research, Inc. (AACR), Baltimore, United States - Maryland
Volume :
66
Issue :
19
Pages :
9698/704
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 05 August 2009

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