Jackie Vergote

Quercetin, Siamois 1 and siamois 2 induce apoptosis in human breast cancer MDA-MB-435 cells xenograft in vivo

We sought to investigate the apoptosis-inducing activities of quercetin, Siamois 1, and Siamois 2 against invasive estrogen-receptor negative MDA-MB 435 cells xenografted in athymic nude mice. This study clearly demonstrated that these compounds exhibited apoptosis-inducing activities in cell culture system. Quercetin (20 μg/mL), Siamois 1 (100 μg/mL), and Siamois 2 (200 μg/mL) can induce apoptotic cell death by 40± 5%, 44 ± 14 %, and 31 ± 13 %, respectively. Two-fold of IC50 of these compounds were clearly found to induce apoptosis in breast tumor tissue which can be determined by 99mTc-annexin V scintigraphy and histological staining. This is the first report that the apoptosis-inducing effects of quercetin, Siamois 1, and Siamois 2 on the MDA-MB 435 cell in vitro were effectively extrapolated to the in vivo situation. These compounds might be considered as a simple dietary supplement and with further clinical investigation for their use as a nutrition-based intervention in breast cancer treatment.

Longitudinal and parallel monitoring of neuroinflammation and neurodegeneration in a 6-hydroxydopamine rat model of Parkinson's disease

As neuroinflammatory processes are involved in the pathogenesis of Parkinsons disease (PD), we achieved the longitudinal evaluation of them in parallel with the modifications of dopaminergic function at several time‐points after 6‐hydroxydopamine (6‐OHDA) lesion in the rat mimicking an early stage of PD. After unilateral intrastriatal 6‐OHDA administration, we quantified the temporal evolution of the 18 kDa translocator protein (TSPO), TH‐immunoreactivity and dopamine transporters in the striatum and substantia nigra pars compacta (SNc) from 3‐ to 56‐days postlesion (dpl). Increased binding of TSPO ligands used, i.e., [3H]PK11195 and [125I]CLINDE, was observed in the lesioned striatum at 3, 7, and 14 dpl, followed by a progressive return to the basal level at 56 dpl. The binding profile in the SNc showed progressive binding beginning at 3 dpl, peaking at 14 dpl, and progressively decreasing until 56 dpl. In this model, the neuroinflammatory and neurodegenerative processes occurred concomitantly. The transitory occurrence of microglial activation could be involved in the lasting installation of dopaminergic neuron loss. Synapse, 2012.

Delivery of dopamine transporter tracer (PE2I) through blood brain barrier with ultrasound and microbubbles

The blood-brain barrier plays a major role in controlling the delivery of therapeutic and imaging agents to the brain. The aim of this study was to investigate the use of ultrasound and microbubbles to increase its delivery through the BBB and by determining the optimal experimental conditions that achieve a transient and safe BBB disruption. First, we established the ultrasound conditions that achieved a transient BBB disruption in rats using a non-permeant marker, Evans blue. Hence SonoVue® (450 μL/kg) and Evans blue (100 mg/kg) were intravenously administered. BBB leakage was obtained using ultrasound insonation through the rat skull at 1.6 MPa, PRF 1 Hz, duty cycle 12%, burst 10 ms during 120 sec. BBB disruption was observed in all treated animals (N=4) by histological analysis. The same experimental conditions were applied to enhance brain uptake of PE2I. Biological samples were analyzed using a scintillation counter apparatus. The results showed 50% and 20% increase of 125I-PE2I uptake in the striatum and cerebral cortex, respectively, in the treated rats (N=5) versus control (N=4). Similar enhancements were observed using SonoVue® at half concentration. This innovative method provides a great potential for intracerebral delivery of molecular ligands that could be used for the therapy of brain diseases.The blood-brain barrier plays a major role in controlling the delivery of therapeutic and imaging agents to the brain. The aim of this study was to investigate the use of ultrasound and microbubbles to increase its delivery through the BBB and by determining the optimal experimental conditions that achieve a transient and safe BBB disruption. First, we established the ultrasound conditions that achieved a transient BBB disruption in rats using a non-permeant marker, Evans blue. Hence SonoVue® (450 μL/kg) and Evans blue (100 mg/kg) were intravenously administered. BBB leakage was obtained using ultrasound insonation through the rat skull at 1.6 MPa, PRF 1 Hz, duty cycle 12%, burst 10 ms during 120 sec. BBB disruption was observed in all treated animals (N=4) by histological analysis. The same experimental conditions were applied to enhance brain uptake of PE2I. Biological samples were analyzed using a scintillation counter apparatus. The results showed 50% and 20% increase of 125I-PE2I uptake in the striat...