Publications of Bernard Rogister
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See detail"Opter pour l'obligation vaccinale est un choix de société"
Muraille, Eric; De Kerchove d'Exaerde, Alban; Drion, Pierre ULiege et al

Article for general public (2021)

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See detailThe Subventricular Zone, a Hideout for Adult and Pediatric High-Grade Glioma Stem Cells
LOMBARD, Arnaud ULiege; Di Gregorio, Marina ULiege; Delcamp, Clément ULiege et al

in Frontiers in Oncology (2021)

Both in adult and children, high-grade gliomas (WHO grades III and IV) account for a high proportion of death due to cancer. This poor prognosis is a direct consequence of tumor recurrences occurring ... [more ▼]

Both in adult and children, high-grade gliomas (WHO grades III and IV) account for a high proportion of death due to cancer. This poor prognosis is a direct consequence of tumor recurrences occurring within few months despite a multimodal therapy consisting of a surgical resection followed by chemotherapy and radiotherapy. There is increasing evidence that glioma stem cells (GSCs) contribute to tumor recurrences. In fact, GSCs can migrate out of the tumor mass and reach the subventricular zone (SVZ), a neurogenic niche persisting after birth. Once nested in the SVZ, GSCs can escape a surgical intervention and resist to treatments. The present review will define GSCs and describe their similarities with neural stem cells, residents of the SVZ. The architectural organization of the SVZ will be described both for humans and rodents. The migratory routes taken by GSCs to reach the SVZ and the signaling pathways involved in their migration will also be described hereafter. In addition, we will debate the advantages of the microenvironment provided by the SVZ for GSCs and how this could contribute to tumor recurrences. Finally, we will discuss the clinical relevance of the SVZ in adult GBM and pediatric HGG and the therapeutic advantages of targeting that neurogenic region in both clinical situations. [less ▲]

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See detailCorrection: In Vivo Tumorigenesis Was Observed after Injection of In Vitro Expanded Neural Crest Stem Cells Isolated from Adult Bone Marrow.
Wislet-Gendebien, Sabine; Poulet, Christophe ULiege; Neirinckx, Virginie ULiege et al

in PLoS ONE (2021), 16(9), 0256477

[This corrects the article DOI: 10.1371/journal.pone.0046425.].

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See detailExploring with [(18)F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy.
Serrano Navacerrada, Maria Elisa ULiege; Bahri, Mohamed Ali ULiege; Becker, Guillaume ULiege et al

in Molecular imaging and biology (2020)

PURPOSE: The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal ... [more ▼]

PURPOSE: The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. PROCEDURES: Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [(18)F]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed. RESULTS: Control rats presented a significant increase in [(18)F]UCB-H binding at the last two scans, compared with the first ones (p < 0.001). This increase existed but was lower in epileptic animals, producing significant group differences in all the phases of the disease (p < 0.028). Furthermore, the quantification of the SV2A expression in vivo with the [(18)F]UCB-H radiotracer or ex vivo with immunofluorescence led to equivalent results, with a positive correlation between both. CONCLUSIONS: Even if further studies in humans are required, the ability to detect a progressive decrease in SV2A expression during the development of temporal lobe epilepsy supports the use of [(18)F]UCB-H as a useful tool to differentiate, in vivo, between healthy and epileptic animals along with the development of the epileptic disease. [less ▲]

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See detailRelevance of Translation Initiation in Diffuse Glioma Biology and its Therapeutic Potential.
Di Gregorio, Marina ULiege; LOMBARD, Arnaud ULiege; Lumapat, Paul Noel ULiege et al

in Cells (2019)

Cancer cells are continually exposed to environmental stressors forcing them to adapt their protein production to survive. The translational machinery can be recruited by malignant cells to synthesize ... [more ▼]

Cancer cells are continually exposed to environmental stressors forcing them to adapt their protein production to survive. The translational machinery can be recruited by malignant cells to synthesize proteins required to promote their survival, even in times of high physiological and pathological stress. This phenomenon has been described in several cancers including in gliomas. Abnormal regulation of translation has encouraged the development of new therapeutics targeting the protein synthesis pathway. This approach could be meaningful for glioma given the fact that the median survival following diagnosis of the highest grade of glioma remains short despite current therapy. The identification of new targets for the development of novel therapeutics is therefore needed in order to improve this devastating overall survival rate. This review discusses current literature on translation in gliomas with a focus on the initiation step covering both the cap-dependent and cap-independent modes of initiation. The different translation initiation protagonists will be described in normal conditions and then in gliomas. In addition, their gene expression in gliomas will systematically be examined using two freely available datasets. Finally, we will discuss different pathways regulating translation initiation and current drugs targeting the translational machinery and their potential for the treatment of gliomas. [less ▲]

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See detailThe Distinct Roles of CXCR3 Variants and Their Ligands in the Tumor Microenvironment
Reynders, Nathan; Abboud, Dayana ULiege; Baragli, Alexandra et al

in Cells (2019), 8(6),

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See detailAnxiety-like features and spatial memory problems as a consequence of hippocampal SV2A expression.
Serrano Navacerrada, Maria Elisa ULiege; Bartholomé, Odile ULiege; Van den Ackerveken, Priscillia et al

in PLoS ONE (2019)

The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose presence is reduced both in animal models and in patients with chronic epilepsy. Besides its implication in the epileptic process ... [more ▼]

The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose presence is reduced both in animal models and in patients with chronic epilepsy. Besides its implication in the epileptic process, the behavioural consequences of the changes in its expression remain unclear. The purpose of our research is to better understand the possible role(s) of this protein through the phenotype of cKO (Grik4 Cre+/-, SV2A lox/lox) mice, male and female, which present a specific decrease of SV2A expression levels in the hippocampal glutamatergic neurons but without any epileptic seizures. In this study, we compare the cKO mice with cHZ (Grik4 Cre+/-, SV2A lox/+) and WT (Grik4 Cre+/+, SV2A lox/lox) mice through a battery of tests, used to evaluate different features: the anxiety-related features (Elevated Plus Maze), the locomotor activity (Activity Chambers), the contextual fear-related memory (Contextual Fear Conditioning), and the spatial memory (Barnes Maze). Our results showed statistically significant differences in the habituation to a new environment, an increase in the anxiety levels and spatial memory deficit in the cHZ and cKO groups, compared to the WT group. No statistically significant differences due to the genotype appeared in the spontaneous locomotor activity or the fear-linked memory. However, sexual differences were observed in this last feature. These results highlight not only an important role of the SV2A protein in the cognitive and anxiety problems typically encountered in epileptic patients, but also a possible role in the symptomatology of other neurodegenerative diseases, such as the Alzheimer’s disease. [less ▲]

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See detailEccentric Muscle Contractions: Risks and Benefits.
Hody, Stéphanie ULiege; Croisier, Jean-Louis ULiege; Bury, Thierry ULiege et al

in Frontiers in Physiology (2019)

Eccentric contractions, characterized by the lengthening of the muscle-tendon complex, present several unique features compared with other types of contractions, which may lead to unique adaptations. Due ... [more ▼]

Eccentric contractions, characterized by the lengthening of the muscle-tendon complex, present several unique features compared with other types of contractions, which may lead to unique adaptations. Due to its specific physiological and mechanical properties, there is an increasing interest in employing eccentric muscle work for rehabilitation and clinical purposes. However, unaccustomed eccentric exercise is known to cause muscle damage and delayed pain, commonly defined as "Delayed-Onset Muscular Soreness" (DOMS). To date, the most useful preventive strategy to avoid these adverse effects consists of repeating sessions involving submaximal eccentric contractions whose intensity is progressively increased over the training. Despite an increased number of investigations focusing on the eccentric contraction, a significant gap still remains in our understanding of the cellular and molecular mechanisms underlying the initial damage response and subsequent adaptations to eccentric exercise. Yet, unraveling the molecular basis of exercise-related muscle damage and soreness might help uncover the mechanistic basis of pathological conditions as myalgia or neuromuscular diseases. In addition, a better insight into the mechanisms governing eccentric training adaptations should provide invaluable information for designing therapeutic interventions and identifying potential therapeutic targets. [less ▲]

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See detailConstruction of an oncolytic herpes virus (oHSV) for inducing apoptosis in glioblastoma: proof of concept
Sanchez Gil, Judith ULiege; Collignon, Alice; Lebrun, Marielle et al

Poster (2019, January 15)

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See detailDecrease in SV2A expression in the hippocampus involves changes in cognition and anxiety-like features.
Serrano Navacerrada, Maria Elisa ULiege; Bartholomé, Odile ULiege; Van Den Ackerveken, Priscilla ULiege et al

Poster (2018, July)

The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose link with the epilepsy has been reported in multiples articles. However, the behavioral consequences of the decrease in its ... [more ▼]

The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose link with the epilepsy has been reported in multiples articles. However, the behavioral consequences of the decrease in its expression remain still unclear. The purpose of our research is to better understand the role of this protein through the evaluation of cKO (Grik4 +/-, SV2A lox/lox) mice of both sexes, which present a specific decrease in the hippocampus. After a first evaluation of the SV2A levels in the hippocampus with the in vitro [18F]UCB-H autoradiography, differences in brain metabolism were assessed with [18F]FDG in mPET and ex vivo autoradiography. Finally, the phenotype of cKO mice was analyzed with a behavioral test battery. Our results showed a strong reduction of SV2A expression in the whole hippocampus of cKO mice, with regard to the WT mice, not accompanied by statistically significant differences in brain metabolism between groups, either in vivo or ex vivo. No statistically significant differences were found in spontaneous locomotor activity or fear-linked memory. However, cKO males showed significant more anxiety than WT (less percent of entries in open arms) and females presented spatial memory deficits measured in the Barnes Maze (less time spend in quadrant during the test). These results could explain the comorbidity between anxiety, memory impairment and epilepsy present both in animal models and in humans, suggesting an important role of SV2A in the symptomatology of other neurodegenerative diseases, such as the Alzheimer disease, or in anxiety-related pathologies. [less ▲]

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See detailFrom Neural Crest Development to Cancer and Vice Versa: How p75NTR and (Pro)neurotrophins Could Act on Cell Migration and Invasion?
Wislet, Sabine ULiege; Vandervelden, Geoffrey ULiege; Rogister, Bernard ULiege

in Frontiers in Molecular Neuroscience (2018), 11

The p75 neurotrophin receptor (p75NTR), also known as low-affinity nerve growth factor, belongs to the tumor necrosis factor family of receptors. p75NTR is widely expressed in the nervous system during ... [more ▼]

The p75 neurotrophin receptor (p75NTR), also known as low-affinity nerve growth factor, belongs to the tumor necrosis factor family of receptors. p75NTR is widely expressed in the nervous system during the development, as well as, in the neural crest population, since p75NTR has been described as ubiquitously expressed and considered as a neural crest marker. Neural crest cells (NCCs) constitute an transient population accurately migrating and invading, with precision, defined sites of the embryo. During migration, NCCs are guided along distinct migratory pathways by specialized molecules present in the extracellular matrix or on the surfaces of those cells. Two main processes direct NCC migration during the development: (1) an epithelial-to-mesenchymal transition and (2) a process known as contact inhibition of locomotion. In adults, p75NTR remains expressed by NCCs and has been identified in an increasing number of cancer cells. Nonetheless, the regulation of the expression of p75NTR and the underlying mechanisms in stem cell biology or cancer cells have not yet been sufficiently addressed. The main objective of this review is therefore to analyze elements of our actual knowledge regarding p75NTR roles during the development (mainly focusing on neural crest development) and see how we can transpose that information from development to cancer (and vice versa) to better understand the link between p75NTR and cell migration and invasion. In this review, we successively analyzed the molecular mechanisms of p75NTR when it interacts with several coreceptors and/or effectors. We then analyzed which signaling pathways are the most activated or linked to NCC migration during the development. Regarding cancer, we analyzed the described molecular pathways underlying cancer cell migration when p75NTR was correlated to cancer cell migration and invasion. From those diverse sources of information, we finally summarized potential molecular mechanisms underlying p75NTR activation in cell migration and invasion that could lead to new research areas to develop new therapeutic protocols. © 2018 Wislet, Vandervelden and Rogister. [less ▲]

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See detailLa souris, le patient, et le faux expert. Décryptage d'une mystification.
Bakker, Julie ULiege; Balthazart, Jacques ULiege; Baron, Frédéric ULiege et al

Article for general public (2018)

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les ... [more ▼]

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les contrôles qui y sont associés induisent de nombreuses contraintes pratiques, des charges administratives et des coûts financiers importants que les chercheurs seraient certainement heureux d'éviter s'il existait une alternative à l'expérimentation animale. [less ▲]

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See detailL’expérimentation animale reste indispensable (OPINION)
Amorim, Christiani; Andris, Fabienne; Arckens, Lut et al

Article for general public (2017)

Trop fréquemment, l’expérimentation animale est présentée comme une pratique archaïque. Elle a bien changé. Et 100 % des patients traités le sont grâce aux concepts et techniques développés grâce à elle.

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See detailDiscovery and Characterization of R/S-N-3-Cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea, a New Histone Deacetylase Class III Inhibitor Exerting Antiproliferative Activity against Cancer Cell Lines
Schnekenburger, M; Goffin, Eric ULiege; Lee, J-Y et al

in Journal of Medicinal Chemistry (2017), 60(11), 4714-4733

A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting ... [more ▼]

A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, we selected compound 18 [R/S-N-3-cyanophenyl-N'-(6-tert-butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea] which displays a potent antiproliferative activity on various glioma cell types, assessed by quantitative videomicroscopy, eventually triggering senescence. The impact on normal glial cells was lower with a selectivity index of >10. Furthermore, human U373 and Hs683 glioblastoma cell lines served to demonstrate the inhibitory activity of 18 against histone deacetylase (HDAC) class III sirtuins 1 and 2 (SIRT1/2) by quantifying acetylation levels of histone and non-histone proteins. The translational potential of 18 was validated by an NCI-60 cell line screen and validation of growth inhibition of drug resistant cancer cell models. Eventually, the anticancer potential of 18 was validated in 3D glioblastoma spheroids and in vivo by zebrafish xenografts. In summary, compound 18 is the first representative of a new class of SIRT inhibitors opening new perspectives in the medicinal chemistry of HDAC inhibitors. [less ▲]

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See detailPuzzling Out Synaptic Vesicle 2 Family Members Functions
Bartholomé, Odile ULiege; Van Den Ackerveken, Priscilla ULiege; Sanchez Gil, Judit ULiege et al

in Frontiers in Molecular Neuroscience (2017)

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See detailThe Radioprotective role of MKP1 in GBM cells
Dedobbeleer, Matthias ULiege; Willems, Estelle ULiege; Di Gregorio, Marina ULiege et al

Poster (2017, May 19)

In patients with glioblastoma multiform (GBM), recurrenceis the rule despite continuous advances in surgery, radio-and chemotherapy. Within these most frequent primary brain tumors, glioblastoma stem ... [more ▼]

In patients with glioblastoma multiform (GBM), recurrenceis the rule despite continuous advances in surgery, radio-and chemotherapy. Within these most frequent primary brain tumors, glioblastoma stem cells or initiating cells (GIC) have recently been described and were shown to be involved in these recurrences. Our lab recently demonstrated that GIC, once injected into the striatum of immunodeficient nude mice, exhibit a tropism for the subventricular zones (SVZ), one of the adult neurogenic niches bringing them an appropriate molecular and cellular environment to growth. After irradiation of these mice, we still discovered cells inside the SVZ. We then questionned the role of the CXCL12/CXCR4 pathway in radioprotection phenotype. After demonstrating that CXCL12 could play a radioprotectiverole, we wanted to know by which mechanism it happens. Knowing that MKP1, the major regulator of the MAP kinase pathway, shown a higher phosphorylation profile after CXXL12 stimulation, and that this protein is involve in many cancers and that its role in glioblamstoma remain unclear, we wanted to know could have a radioprotectiverole link or not to the CXCL12/CXCR4 signalling pathway [less ▲]

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