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A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. We therefore studied the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2(+/-) mice. Haplodeficiency of PHD2 did not affect tumor vessel(More)
PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage. However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of(More)
Switching to a glycolytic metabolism is a rapid adaptation of tumor cells to hypoxia. Although this metabolic conversion may primarily represent a rescue pathway to meet the bioenergetic and biosynthetic demands of proliferating tumor cells, it also creates a gradient of lactate that mirrors the gradient of oxygen in tumors. More than a metabolic waste, the(More)
The aim of this study was to develop an MRI fluorocarbon oximetry technique using snapshot inversion recovery and compare it with fluorescence quenching fiber-optic probe oximetry (OxyLite) performed simultaneously in experimental mouse tumors. The oxygen reporter probe hexafluorobenzene (HFB) was injected directly into the tumors, along with the insertion(More)
PURPOSE Quantitative dynamic contrast-enhanced MRI requires an accurate arterial input function (AIF). At high field, increased susceptibility effects and decreased longitudinal relaxivity of contrast agents lead to predominant T2* effects in blood vessels, producing a dip in signal during passage of the contrast agent bolus. This study determined(More)
Vascular endothelial growth factor (VEGF) regulates angiogenesis, but also has important, yet poorly characterized roles in neuronal wiring. Using several genetic and in vitro approaches, we discovered a novel role for VEGF in the control of cerebellar granule cell (GC) migration from the external granule cell layer (EGL) toward the Purkinje cell layer(More)
Blood oxygen level-dependent (BOLD) contrast-based functional MRI (fMRI) has been reported as a method to assess the evolution of tumor oxygenation after hyperoxic treatments, because of its sensitivity to changes in blood flow and deoxyhemoglobin content. However a number of questions remain: 1) In view of tumor heterogeneity, how good is the correlation(More)
Relative perfusion, pO2, and bioreduction were measured simultaneously in vivo in tissues in mice by following changes in the intensity and shape of the EPR spectra of nitroxides injected directly into the tissues, using low frequency (1.1 GHz) localized EPR spectroscopy. Using normal and blood flow restricted gastrocnemius muscles it was shown that the(More)
EPR oximetry using an implantable paramagnetic probe was used to quantify the partial pressure of oxygen (pO(2)) in tissues in a transplantable mouse tumor model (TLT) after administration of 34 different vasodilators belonging to one of the following classes: angiotensin-converting enzyme inhibitors, calcium antagonists, alpha antagonists, potassium(More)
T2*-weighted gradient-echo magnetic resonance imaging (T2*-weighted GRE MRI) was used to investigate spontaneous fluctuations in tumour vasculature non-invasively. FSa fibrosarcomas, implanted intramuscularly (i.m.) in the legs of mice, were imaged at 4.7 T, over a 30 min or 1 h sampling period. On a voxel-by-voxel basis, time courses of signal intensity(More)