References of "LOMBARD, Arnaud"
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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 detailDeciphering the response of subventricular zone-nested glioblastoma cells after surgery
LOMBARD, Arnaud ULiege; Dedobbeleer, Matthias ULiege; DEWANDRE, Quentin ULiege et al

Poster (2018, November)

INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant brain tumor in adults, with really poor prognosis, subsequent to systematic recurrences, which occur in 80% of cases in the ... [more ▼]

INTRODUCTION: Glioblastoma (GBM) is the most frequent primary malignant brain tumor in adults, with really poor prognosis, subsequent to systematic recurrences, which occur in 80% of cases in the resection margin of initial tumor. We previously demonstrated that, after experimental striatal xenotransplantation, GBM cells, and particularly GBM-initiating cells (GIC), are able to escape the tumor mass and specifically colonize the sub-ventricular zone (SVZ), a well-known neurogenic zone in adult brains. We also demonstrated that this specific oriented migration is driven by a CXCL12-CXCR4 signalization. In this study, we address the potential implication of SVZ-nested tumor cells in local GBM relapses. MATERIALS AND METHODS: We engrafted in the right striatum of nude mice GBM cells (GB138) from a human primary culture, which are previously transfected with a lentiviral construction in order to express the RFP spontaneously, while they conditionally express eGFP, only in presence of Cre-recombinase. As the GB138 cells reach the SVZ, we injected in the lateral ventricle an Adeno-Associated Viral vector expressing Cre-recombinase, which is able to infect nearby GB138 cells. We finally compared 3 mice that were not operated (control group) with 3 mice that underwent tumor resection (surgery group) and quantify green spots in the tumor mass (TM) and/or resection cavity (RC) every 20 microns thanks to Clarity Lightsheet microscope. RESULTS: We found that the median of green spots for the 3 mice of the control group was respectively 1, 0 and 0 in TM, while the median for the surgery group was 7, 8 and 47 in RC. The Standard Deviation (SD) for the control group was respectively 1.1, 0.4 and 0.6, while SD for the surgery group was respectively 1.5, 1.7 and 16. CONCLUSION: SVZ-nested GBM cells seem to be recruited for tumor relapse after surgery. [less ▲]

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See detailThe functional diversity of Aurora kinases: a comprehensive review
Willems, Estelle ULiege; Dedobbeleer, Matthias ULiege; Di Gregorio, Marina ULiege et al

in Cell Division (2018)

Aurora kinases are serine/threonine kinases essential for the onset and progression of mitosis. Aurora members share a similar protein structure and kinase activity, but exhibit distinct cellular and ... [more ▼]

Aurora kinases are serine/threonine kinases essential for the onset and progression of mitosis. Aurora members share a similar protein structure and kinase activity, but exhibit distinct cellular and subcellular localization. AurA favors the G2/M transition by promoting centrosome maturation and mitotic spindle assembly. AurB and AurC are chromosome-passenger complex proteins, crucial for chromosome binding to kinetochores and segregation of chromosomes. Cellular distribution of AurB is ubiquitous, while AurC expression is mainly restricted to meiotically-active germ cells. In human tumors, all Aurora kinase members play oncogenic roles related to their mitotic activity and promote cancer cell survival and proliferation. Furthermore, AurA plays tumor-promoting roles unrelated to mitosis, including tumor stemness, epithelial-to-mesenchymal transition and invasion. In this review, we aim to understand the functional interplay of Aurora kinases in various types of human cells, including tumor cells. The understanding of the functional diversity of Aurora kinases could help to evaluate their relevance as potential therapeutic targets in cancer. [less ▲]

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See detailPhosphatases and solid tumors: focus on glioblastoma initiation, progression and recurrences
Dedobbeleer, Matthias ULiege; Willems, Estelle ULiege; Freeman, Stephen ULiege et al

in Biochemical Journal (2017), 474(17), 2903-2924

Phosphatases and cancer have been related for many years now, as these enzymes regulate key cellular functions, including cell survival, migration, differentiation and proliferation. Dysfunctions or ... [more ▼]

Phosphatases and cancer have been related for many years now, as these enzymes regulate key cellular functions, including cell survival, migration, differentiation and proliferation. Dysfunctions or mutations affecting these enzymes have been demonstrated to be key factors for oncogenesis. The aim of this review is to shed light on the role of four different phosphatases (PTEN, PP2A, CDC25 and DUSP1) in five different solid tumors (breast cancer, lung cancer, pancreatic cancer, prostate cancer and ovarian cancer), in order to better understand the most frequent and aggressive primary cancer of the central nervous system, glioblastoma. [less ▲]

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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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See detailThe unexpected role of Aurora A kinase in glioblastoma recurrences
Willems, Estelle ULiege; LOMBARD, Arnaud ULiege; Dedobbeleer, Matthias ULiege et al

in Targeted Oncology (2017)

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See detailImplication of AurA kinase in GBM cells chemotaxis in response to the production of CXCL12 in the subventricular zones
Willems, Estelle ULiege; Dedobbeleer, Matthias ULiege; LOMBARD, Arnaud ULiege et al

Poster (2016, October 13)

Despite great improvement in standard therapies (i.e. surgery, radiotherapy and chemotherapy) of glioblastoma (GBM), the median survival rate is 15 months due to patient relapses. A major advance in the ... [more ▼]

Despite great improvement in standard therapies (i.e. surgery, radiotherapy and chemotherapy) of glioblastoma (GBM), the median survival rate is 15 months due to patient relapses. A major advance in the understanding of GBM recurrences has been the identification of GBM-initiating cells (GIC). GIC are thought to be deeply involved in GBM recurrences. Our lab designed a mouse model by grafting human GBM cells in the striatum. After the graft, we observed that tumors develop in the mouse striatum and that GIC specifically invade the subventricular zones (SVZ). SVZ are stem cells niches crucial for adult neurogenesis which seems particularly propitious for gliomagenesis since they are abundant in growth factors and permissive to proliferation. We therefore looked for soluble factors secreted by the SVZ environment and demonstrated that the local production of the CXCL12 chemokine in the SVZ is responsible for the GIC-directed migration. In this work, we aim to study the role GBM therapeutic resistance associated with the invasion of the SVZ. In this work, we identified a new actor of the CXCL12 pathway by the phosphoproteome analysis of U87MG cells stimulated with CXCL12: the mitotic kinase Aurora A (AurA) whose activity seems crucial for the CXCL12-dependent chemotaxis of GBM cells [less ▲]

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See detailThe Unexpected Roles of Aurora A Kinase in Gliobastoma Recurrences
Willems, Estelle ULiege; LOMBARD, Arnaud ULiege; Dedobbeleer, Matthias ULiege et al

in Targeted Oncology (2016), 12

The main obstacle for the cure of glioblastoma (GBM) is systematic tumor recurrence after treatment. More than 90 % of GBM tumors are indeed recurrent within 5 years after diagnosis and treatment. We ... [more ▼]

The main obstacle for the cure of glioblastoma (GBM) is systematic tumor recurrence after treatment. More than 90 % of GBM tumors are indeed recurrent within 5 years after diagnosis and treatment. We urgently need new therapies to specifically address these deadly relapses. A major advance in the understanding of GBM recurrence is the identification of GBMInitiating Cells (GIC), characterized by their abilities for self-renewal, multilineage differentiation, and proliferation. It appears that these features of GIC could be modulated by the mitotic kinase Aurora A (AurA). Indeed, besides its role in mitosis, AurA has recently been identified to regulate alternative functions like cell polarity, asymmetric cell division, and epithelial to mesenchymal transition. All these properties may help explain GBM therapeutic resistance and recurrence. In this review, we make the hypothesis that AurA could significantly contribute to GBM recurrences and we focus on the possible roles of AurA in GIC. [less ▲]

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See detailCXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone
Goffart, Nicolas; LOMBARD, Arnaud ULiege; Dedobbeleer, Matthias ULiege et al

in Neuro-Oncology (2016)

Patients with glioblastoma multiforme (GBM) have an overall median survival of 15 months despite multimodal therapy, due to systematic relapses. We previously demonstrated that GBM-initiating cells (GIC ... [more ▼]

Patients with glioblastoma multiforme (GBM) have an overall median survival of 15 months despite multimodal therapy, due to systematic relapses. We previously demonstrated that GBM-initiating cells (GIC) are able to escape the tumor mass and specifically colonize the sub-ventricular zone (SVZ) after experimental striatal xenotransplantation. Using the same approach, we demonstrated in vivo a higher survival rate of SVZ-nested GIC after irradiation and investigated the pathway implied. [less ▲]

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See detailRole of AurA in glioblastoma
Willems, Estelle ULiege; Dedobbeleer, Matthias ULiege; LOMBARD, Arnaud ULiege et al

Poster (2015, December 03)

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See detailGlioblastoma Circulating Cells: Reality, Trap or Illusion?
LOMBARD, Arnaud ULiege; Goffart, Nicolas ULiege; Rogister, Bernard ULiege

in Stem Cells International (2015)

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See detailCortical spreading depression decreases Fos expression in rat periaqueductal gray matter
Borysovych Bogdanov, V.; Bogdanova, O. V.; LOMBARD, Arnaud ULiege et al

in Neuroscience Letters (2015), 585

The migraine headache involves activation and central sensitization of the trigeminovascular pain pathway. The migraine aura is likely due to cortical spreading depression (CSD), a propagating wave of ... [more ▼]

The migraine headache involves activation and central sensitization of the trigeminovascular pain pathway. The migraine aura is likely due to cortical spreading depression (CSD), a propagating wave of brief neuronal depolarization followed by prolonged inhibition. The precise link between CSD and headache remains controversial. Our objectives were to study the effect of CSD on neuronal activation in the periaqueductal grey matter (PAG), an area known to control pain and autonomic functions, and to be involved in migraine pathogenesis. Fos-immunoreactive nuclei were counted in rostral PAG and Edinger-Westphal nuclei (PAG-EWn bregma -6.5. mm), and caudal PAG (bregma -8. mm) of 17 adult male Sprague-Dawley rats after KCl-induced CSD under chloral hydrate anesthesia. Being part of a pharmacological study, six animals had received, for the preceding 4 weeks daily, intraperitoneal injections of lamotrigine (15. mg/kg), six others had been treated with saline, while five sham-operated animals served as controls. We found that the number of Fos-immunoreactive nuclei in the PAG decreased after CSD provocation. There was no difference between lamotrigine- and saline-treated animals. The number of CSDs correlated negatively with Fos-immunoreactive counts. CSD-linked inhibition of neuronal activity in the PAG might play a role in central sensitization during migraine attacks and contribute to a better understanding of the link between the aura and the headache. © 2014 Published by Elsevier Ireland Ltd. [less ▲]

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See detailCortical spreading depression decreases Fos expression in rat periaqueductal gray matter.
Borysovich Bogdanov, Volodymir; LOMBARD, Arnaud ULiege; Multon, Sylvie ULiege et al

in Neuroscience Letters (2015)

Detailed reference viewed: 53 (21 ULiège)