References of "Scholtes, Félix"
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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 detailAurora A plays a dual role in migration and survival of human glioblastoma cells according to the CXCL12 concentration
Willems, Estelle ULiege; Dedobbeleer, Matthias ULiege; Di Gregorio, Marina ULiege et al

in Oncogene (2019)

Primary glioblastoma is the most frequent human brain tumor in adults and is generally fatal due to tumor recurrence. We previously demonstrated that glioblastoma-initiating cells invade the ... [more ▼]

Primary glioblastoma is the most frequent human brain tumor in adults and is generally fatal due to tumor recurrence. We previously demonstrated that glioblastoma-initiating cells invade the subventricular zones and promote their radio-resistance in response to the local release of the CXCL12 chemokine. In this work, we show that the mitotic Aurora A kinase (AurA) is activated through the CXCL12–CXCR4 pathway in an ERK1/2-dependent manner. Moreover, the CXCL12–ERK1/ 2 signaling induces the expression of Ajuba, the main cofactor of AurA, which allows the auto-phosphorylation of AurA. We show that AurA contributes to glioblastoma cell survival, radio-resistance, self-renewal, and proliferation regardless of the exogenous stimulation with CXCL12. On the other hand, AurA triggers the CXCL12-mediated migration of glioblastoma cells in vitro as well as the invasion of the subventricular zone in xenograft experiments. Moreover, AurA regulates cytoskeletal proteins (i.e., Actin and Vimentin) and favors the pro-migratory activity of the Rho-GTPase CDC42 in response to CXCL12. Altogether, these results show that AurA, a well-known kinase of the mitotic machinery, may play alternative roles in human glioblastoma according to the CXCL12 concentration. [less ▲]

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See detailEvidence of an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients: a study comparing 18FDG-PET and visual evoked potentials
Lisicki Martinez, Marco ULiege; D'Ostilio, Kevin; Coppola, Gianluca et al

in Journal of Headache and Pain (2018)

Background: Migraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but ... [more ▼]

Background: Migraine attacks might be triggered by a disruption of cerebral homeostasis. During the interictal period migraine patients are characterized by abnormal sensory information processing, but this functional abnormality may not be sufficient to disrupt the physiological equilibrium of the cortex unless it is accompanied by additional pathological mechanisms, like a reduction in energetic reserves. The aim of this study was to compare resting cerebral glucose uptake (using positron emission tomography (18fluorodeoxyglucose-PET)), and visual cortex activation (using visual evoked potentials (VEP)), between episodic migraine without aura patients in the interictal period and healthy volunteers. Methods: Twenty episodic migraine without aura patients and twenty healthy volunteers were studied. 18FDG-PET and VEP recordings were performed on separate days. The overall glucose uptake in the visual cortex-to-VEP response ratio was calculated and compared between the groups. Additionally, PET scan comparisons adding area under the VEP curve as a covariate were performed. For case-wise analysis, eigenvalues from a specific region exhibiting significantly different FDG-PET signal in the visual cortex were extracted. Standardized glucose uptake values from this region and VEP values from each subject were then coupled and compared between the groups. Results: The mean area under the curve of VEP was greater in migraine patients compared to healthy controls. In the same line, patients had an increased neuronal activation-to-resting glucose uptake ratio in the visual cortex. Statistical parametric mapping analysis revealed that cortical FDG-PET signal in relation to VEP area under the curve was significantly reduced in migraineurs in a cluster extending throughout the left visual cortex, from Brodmann’s areas 19 and 18 to area 7. Within this region, case-wise analyses showed that a visual neuronal activation exceeding glucose uptake was present in 90% of migraine patients, but in only 15% of healthy volunteers. Conclusion: This study identifies an area of increased neuronal activation-to-resting glucose uptake ratio in the visual cortex of migraine patients between attacks. Such observation supports the concept that an activity-induced rupture of cerebral metabolic homeostasis may be a cornerstone of migraine pathophysiology. This article has been selected as the winner of the 2018 Enrico Greppi Award. The Enrico Greppi Award is made to an unpublished paper dealing with clinical, epidemiological, genetic, pathophysiological or therapeutic aspects of headache. Italian Society for the Study of Headaches (SISC) sponsors this award, and the award is supported through an educational grant from Teva Neuroscience. This article did not undergo the standard peer review process for The Journal of Headache and Pain. The members of the 2018 Enrico Greppi Award Selection Committee were: Francesco Pierelli, Paolo Martelletti, Lyn Griffiths, Simona Sacco, Andreas Straube and Cenk Ayata. [less ▲]

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See detailSemantic processing in relation to anatomical integrity of the ventral language stream in schizophrenia
Surbeck, Werner; Hänggi, Jürgen; Scholtes, Félix ULiege et al

Poster (2018)

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See detailPersonality traits in neurologists, neurosurgeons and psychiatrists
Scholtes, Félix ULiege; Stienen, Martin; Samuel, Robin et al

Poster (2018)

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See detailDifferent but similar: personality traits of surgeons and internists-results of a cross-sectional observational study.
Stienen, Martin N.; Scholtes, Félix ULiege; Samuel, Robin et al

in BMJ Open (2018), 8(7), 021310

OBJECTIVES: Medical practice may attract and possibly enhance distinct personality profiles. We set out to describe the personality profiles of surgical and medical specialties focusing on board-certified ... [more ▼]

OBJECTIVES: Medical practice may attract and possibly enhance distinct personality profiles. We set out to describe the personality profiles of surgical and medical specialties focusing on board-certified physicians. DESIGN: Prospective, observational. SETTING: Online survey containing the Ten-Item Personality Inventory (TIPI), an internationally validated measure of the Five Factor Model of personality dimensions, distributed to board-certified physicians, residents and medical students in several European countries and Canada. Differences in personality profiles were analysed using multivariate analysis of variance and Canonical Linear Discriminant Analysis on age-standardised and sex-standardised z-scores of the personality traits. Single personality traits were analysed using robust t-tests. PARTICIPANTS: The TIPI was completed by 2345 board-certified physicians, 1453 residents and 1350 medical students, who also provided demographic information. RESULTS: Normal population and board-certified physicians' personality profiles differed (p<0.001). The latter scored higher on conscientiousness, extraversion and agreeableness, but lower on neuroticism (all p<0.001). There was no difference in openness to experience. Board-certified surgical and medical doctors' personality profiles were also different (p<0.001). Surgeons scored higher on extraversion (p=0.003) and openness to experience (p=0.002), but lower on neuroticism (p<0.001). There was no difference in agreeableness and conscientiousness. These differences in personality profiles were reproduced at other levels of training, that is, in students and training physicians engaging in surgical versus medical practice. CONCLUSION: These results indicate the existence of a distinct and consistent average 'physician personality'. Despite high variability within disciplines, there are moderate but solid and reproducible differences between surgical and medical specialties. [less ▲]

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See detailLa prise en charge des anévrismes intracrâniens non rompus
Martin, Didier ULiege; OTTO, Bernard ULiege; DARSAUT, Tim et al

in Revue Médicale de Liège (2018), 73

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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 detailGBM cells from the tumour mass versus the subventricular zone: molecular and functional characterisation
Di Gregorio, Marina ULiege; Willems, Estelle ULiege; Dedobbeleer, Matthias ULiege et al

Poster (2017, May)

Life expectancy after diagnosis of glioblastoma (GBM) remains poor even with the best available treatment. This catastrophic survival is the direct consequence of systematic tumour recurrence. It has ... [more ▼]

Life expectancy after diagnosis of glioblastoma (GBM) remains poor even with the best available treatment. This catastrophic survival is the direct consequence of systematic tumour recurrence. It has previously been demonstrated that the subventricular zone (SVZ, a neurogenic niche of the adult central nervous system) attracts and harbours GBM cells, expressing stem cell biomarkers that act like glioblastoma-initiating cells. These cells hosted in the SVZ may be responsible for tumour recurrence. To better understand the difference between cells from the tumour mass (TM) and those migrating to the SVZ, this project will focus on two axes. First, a proteomic and transcriptomic approach will be used to identify one or more biomarkers that might help to establish if recurrences originate from the TM or the SVZ. The second aim of the project is to compare these two populations of cells from a functional point of view. Some functional differences have already been observed: cells derived from SVZ form more spheroids than those derived from TM (1). U87MG cells from SVZ also form tumours more easily in mice compared to cells derived from the TM (2). However, preliminary results in chemo- and radioresistance assays on the cultured cells (U87MG) do not show significant differences between the two populations. Therefore, it might be the SVZ environment that plays a key role in therapeutic resistance, rather than intrinsic biological differences of cells from the TM versus the SVZ. [less ▲]

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See detailAphasie transitoire survenue dans les suites d’un abord sous-temporal – Illustration de l’évolution des concepts neuroanatomiques fonctionnels du langage humain
Surbeck, Werner Theodor ULiege; BARJONA MORGADO DE MOURA, Aude ULiege; MARTIN, Didier ULiege et al

Poster (2017)

Under the influence of recent advances in brain imaging, as well as perioperative functional assessment during awake brain surgery, the understanding of representation of language within the human brain ... [more ▼]

Under the influence of recent advances in brain imaging, as well as perioperative functional assessment during awake brain surgery, the understanding of representation of language within the human brain is evolving. The classical associationist models are increasingly giving way to network concepts where specialised cortical subregions subserve different but related functions and interact via parallel, bidirectional white matter pathways. This may account for the anatomical infrastructure of higher cognitive functions, including verbal communication, more satisfactorily. The adequacy of models of brain function is, by tradition and common sense, judged by clinical observation. In the following report, the usefulness of contemporary concepts of the functional anatomy of language are illustrated by the occurrence of severe speech dysfunction in the presence of a temporary basal temporal lesion, anatomically distant from the classical “language areas” of the brain. [less ▲]

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See detailSurgical clipping or endovascular coiling for unruptured intracranial aneurysms: a pragmatic randomised trial.
Darsaut, Tim E.; Findlay, J. Max; Magro, Elsa et al

in Journal of Neurology, Neurosurgery and Psychiatry (2017), 88(8), 663-668

BACKGROUND: Unruptured intracranial aneurysms (UIAs) are increasingly diagnosed and are commonly treated using endovascular treatment or microsurgical clipping. The safety and efficacy of treatments have ... [more ▼]

BACKGROUND: Unruptured intracranial aneurysms (UIAs) are increasingly diagnosed and are commonly treated using endovascular treatment or microsurgical clipping. The safety and efficacy of treatments have not been compared in a randomised trial. How to treat patients with UIAs suitable for both options remains unknown. METHODS: We randomly allocated clipping or coiling to patients with one or more 3-25 mm UIAs judged treatable both ways. The primary outcome was treatment failure, defined as: initial failure of aneurysm treatment, intracranial haemorrhage or residual aneurysm on 1-year imaging. Secondary outcomes included neurological deficits following treatment, hospitalisation >5 days, overall morbidity and mortality and angiographic results at 1 year. RESULTS: The trial was designed to include 260 patients. An analysis was performed for slow accrual: 136 patients were enrolled from 2010 through 2016 and 134 patients were treated. The 1-year primary outcome, available for 104 patients, was reached in 5/48 (10.4% (4.5%-22.2%)) patients allocated surgical clipping, and 10/56 (17.9% (10.0%-29.8%)) patients allocated endovascular coiling (OR: 0.54 (0.13-1.90), p=0.40). Morbidity and mortality (modified Rankin Scale>2) at 1 year occurred in 2/48 (4.2% (1.2%-14.0%)) and 2/56 (3.6% (1.0%-12.1%)) patients allocated clipping and coiling, respectively. New neurological deficits (15/65 vs 6/69; OR: 3.12 (1.05-10.57), p=0.031), and hospitalisations beyond 5 days (30/65 vs 6/69; OR: 8.85 (3.22-28.59), p=0.0001) were more frequent after clipping. CONCLUSION: Surgical clipping or endovascular coiling of UIAs did not show differences in morbidity at 1 year. Trial continuation and additional randomised evidence will be necessary to establish the supposed superior efficacy of clipping. [less ▲]

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See detailNew role of osteopontin in DNA repair and impact on human glioblastoma radiosensitivity
Henry, Aurélie ULiege; Nokin, Marie-Julie ULiege; Leroi, Natacha ULiege et al

in Oncotarget (2016)

Glioblastoma (GBM) represents the most aggressive and common solid human brain tumor. We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness ... [more ▼]

Glioblastoma (GBM) represents the most aggressive and common solid human brain tumor. We have recently demonstrated the importance of osteopontin (OPN) in the acquisition/maintenance of stemness characters and tumorigenicity of glioma initiating cells. Consultation of publicly available TCGA database indicated that high OPN expression correlated with poor survival in GBM patients. In this study, we explored the role of OPN in GBM radioresistance using an OPN-depletion strategy in U87-MG, U87-MG vIII and U251-MG human GBM cell lines. Clonogenic experiments showed that OPN-depleted GBM cells were sensitized to irradiation. In comet assays, these cells displayed higher amounts of unrepaired DNA fragments post-irradiation when compared to control. We next evaluated the phosphorylation of key markers of DNA double-strand break repair pathway. Activating phosphorylation of H2AX, ATM and 53BP1 was signi cantly decreased in OPN-de cient cells. The addition of recombinant OPN prior to irradiation rescued phospho-H2AX foci formation thus establishing a new link between DNA repair and OPN expression in GBM cells. Finally, OPN knockdown improved mice survival and induced a signi cant reduction of heterotopic human GBM xenograft when combined with radiotherapy. This study reveals a new function of OPN in DNA damage repair process post-irradiation thus further con rming its major role in GBM aggressive disease. [less ▲]

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See detailOsteopontin predicts radiotherapy response of glioblastoma patients : new role in DNA damage repair
Henry, Aurélie ULiege; Nokin, Marie-Julie ULiege; Leroi, Natacha ULiege et al

Conference (2016, March 22)

- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These ... [more ▼]

- Introduction: Glioblastoma (GBM) is the most aggressive and common solid human brain tumor. Because of GBM heterogeneity, location and aggressiveness, none of the available treatment is curative. These treatments include maximal surgical resection, radiotherapy and concomitant or adjuvant chemotherapy with Temozolomide. However, the prognosis of adult patients with GBM remains poor and the survival outcome after treatment does not exceed 15 months. GBM-composing cells have developed many strategies to counteract these current therapies. Among the wide hallmarks acquired to survive, high osteopontin (OPN) expression correlates with lower overall and disease-free/relapse-free survival in all tumors combined, as well in brain cancer. Our recent study (Lamour V and Henry A, IJC 2015) has demonstrated the role of OPN in the tumorigenicity of glioblastoma cells and its importance in the maintenance of the stem characters. In the continuation of this work, our recent studies focused on the potential role of OPN in the resistance of GBM cells to radiotherapy and its potential implication in the initiation of Double Strand Breaks (DSBs) repair mechanisms. - Aims: In the context of this study, different GBM cell lines (U251-MG, U87-MG and U87 Viii) were used to assess the role of OPN in the initiation of the DSBs repair mechanism after an exposure to gamma-irradiation. - Methods and results: We performed the transient transfection of different GBM cell lines (U251-MG, U87-MG and U87-MG overexpressing EGFR VIII) with siRNAs specifically directed against OPN. After irradiation, all these OPN-depleted cells consistently showed a lower induction of γ–H2AX compared to control (irrelevant siRNA) as evidenced by western blot and immunofluorescence techniques. Thereafter, clonogenic assays allowed to prove that the survival of OPN-depleted cells was affected after an exposure to irradiation. To assess the importance of OPN expression in the response to radiotherapy, an heterotopic xenograft model was used. In brief, IPTG-inducible U87 shOPN clones were injected subcutaneously in NOD-SCID mice and were allowed to form a tumor. When average tumor volume reached a predetermined size range, mice were treated (or not) with IPTG by intraperitoneal injection during five days. At the end of the treatment, tumors were selectively exposed to gamma-irradiation by using a small animal irradiator X-RAD 225Cx (Precision X-Ray Inc., North Branford, CT). One week later, mice were sacrificed and tumors were measured. In this pilot study, we observed that mice in which the tumor was depleted in OPN displayed a slight regression in the tumor growth compared to mice that received radiotherapy alone (no IPTG), where the tumor volume remained constant. - Conclusions: Taken together, these preliminary data meet the fact that OPN is important in the response of GBM to radiotherapy. The in vitro results converge to the fact that OPN might be implicated in the initiation of the DSBs repair following irradiation. Currently, we would like to investigate this hypothesis in vivo but also to check the effect of OPN depletion combined to radiotherapy on the survival of mice in an orthotopic xenograft model. [less ▲]

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See detailClinical and molecular classification of glioblastoma patients
Lambert, Jérémy ULiege; Kaoma, Tony; Van Dyck, Eric et al

Poster (2016, March 19)

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See detailClinical and molecular classification of glioblastoma patients
Lambert, Jérémy ULiege; Gorlia, Thierry; Van Dyck, Eric et al

Scientific conference (2015, December 03)

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See detailLe syndrome "pseudotumor cerebri" primaire ou hypertension intracrânienne idiopathique : aspects cliniques et thérapeutiques
Timmermans, Grégory ULiege; Scholtes, Félix ULiege; ANDRIS, Cécile ULiege et al

in Revue Médicale de Liège (2015), 70(10), 488-494

«Pseudotumor cerebri» generally refers to a syndrome associating signs and symptoms of intracranial hypertension, increased cerebrospinal fluid (CSF) pressure and normal CSF composition, without any ... [more ▼]

«Pseudotumor cerebri» generally refers to a syndrome associating signs and symptoms of intracranial hypertension, increased cerebrospinal fluid (CSF) pressure and normal CSF composition, without any identifiable intracranial abnormality, particularly by neuroimaging studies. Although the «idiopathic» variant of the syndrome is most common, there are secondary forms where a cause can be found. The term «benign intracranial hypertension» should be abandoned, since permanent visual impairment can complicate the condition. This disaster can be avoided by early recognition and medical or surgical treatment of the disease. This article discusses the terminology, as well as diagnostic and therapeutic aspects of the syndrome. [less ▲]

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See detailAge and WHO Performance Score are major clinical prognostic factors in glioblastoma
Lambert, Jérémy ULiege; Scholtes, Félix ULiege; MARTIN, Didier ULiege

Conference (2015, March 21)

In glioblastoma patients with similar prognostic factors—like age, performance status and extent of surgical resection—clinical evolution is still variable. In addition, the benefit of resection of ... [more ▼]

In glioblastoma patients with similar prognostic factors—like age, performance status and extent of surgical resection—clinical evolution is still variable. In addition, the benefit of resection of recurrent tumours is uncertain. In this study, prognostic subgroups are established on a clinical basis and the benefit of surgery for recurrence is compared between them. Recursive partitioning analysis on EORTC sample 26981 (n=239) identified clinical factors influencing Progression-Free Survival (PFS), in order to create prognostic subgroups, whose PFS and survival after recurrence were compared using Kaplan-Meier curves and log-rank tests. Results were validated on a sample from Liège University Hospital (n=92). WHO Performance Status (WHO-PS) and age at first intervention (“age”) defined 4 subgroups. PFS was shorter in WHO-PS 2–3 than WHO PS 0–1 patients. In both groups, age was the second classifying factor (cut-off: 47.5y for WHO-PS 0–1, 60.5y for WHO-PS 2–3). The 4 subgroups had significantly different median PFS (77.5, 144, 234.5 and 346.5 days) and median overall survival (126, 330, 476 and 675 days). Survival after recurrence was correlated with PFS, and recurrence resection was associated with longer survival, regardless of the prognostic subgroup. Clinical prognostic glioblastoma subgroups with distinct PFS exist and can be defined by WHO-PS and age. This classification can be used as a clinical basis to identify molecular patterns associated with prognosis. In addition, in all subgroups, this retrospective analysis suggests a benefit of surgical resection when feasible. [less ▲]

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See detailHead Trauma and Distal Anterior Cerebral Artery Aneurysm: Potential Role of an Adhesion to the Falx
Scholtes, Félix ULiege; HENROTEAUX, Adrienne ULiege; OTTO, Bernard ULiege et al

in Journal of Neurological Surgery. Part A, Central European Neurosurgery (2015), 76(1), 72-75

Proximity of the distal anterior cerebral artery (dACA) and the edge of the falx has been hypothetically implicated in the pathogenesis of traumatic dACA aneurysms. A 57-year-old patient presented with ... [more ▼]

Proximity of the distal anterior cerebral artery (dACA) and the edge of the falx has been hypothetically implicated in the pathogenesis of traumatic dACA aneurysms. A 57-year-old patient presented with posttraumatic intracranial hemorrhage and an A3-bifurcation aneurysm that increased in size over the following 2 weeks. Because of higher endovascular risk, surgical clipping was preferred. Surgery revealed a fibrous adhesion between the falx and the dACA at the aneurysm site. This adhesion could provide an anatomical reason for the formation of a traumatic dACA aneurysm at the edge of the falx or rupture of a preexisting aneurysm [less ▲]

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