Reference : Mechanism of reoxygenation after antiangiogenic therapy using SU5416 and its importance ...
Scientific journals : Article
Human health sciences : Radiology, nuclear medicine & imaging
Human health sciences : Oncology
http://hdl.handle.net/2268/73973
Mechanism of reoxygenation after antiangiogenic therapy using SU5416 and its importance for guiding combined antitumor therapy
English
[fr] Mécanisme de réoxygénation après la thérapie anti-angiogénique SU5416 à l'aide et son importance pour guider la thérapie antitumorale combinés.
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 mailto [Université Catholique de Louvain - UCL > > > >]
GREGOIRE [> >]
FERON [> >]
GALLEZ [> >]
1-Oct-2006
Cancer Research
American Association for Cancer Research, Inc. (AACR)
66
19
9698/704
Yes (verified by ORBi)
International
0008-5472
1538-7445
Baltimore
MD
[en] Antineoplastic agent ; Mechanism of action ; Antiangiogenic agent ; Combined treatment
[fr] Anticancéreux ; Mécanisme action ; Antiangiogénique ; Traitement associé
[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.
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/73973
also: http://hdl.handle.net/2268/17884

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