Publications of Arnaud Lombard
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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 detailMultiparameter quantitative histological MRI values in high-grade gliomas: a potential biomarker of tumor progression
REUTER, Gilles ULiege; Lommers, Emilie ULiege; Balteau, Evelyne ULiege et al

in Neuro-Oncology Practice (2020)

Background. Conventional MRI poorly distinguishes brain parenchyma microscopically invaded by high-grade gliomas (HGGs) from the normal brain. By contrast, quantitative histological MRI (hMRI) measures ... [more ▼]

Background. Conventional MRI poorly distinguishes brain parenchyma microscopically invaded by high-grade gliomas (HGGs) from the normal brain. By contrast, quantitative histological MRI (hMRI) measures brain microstructure in terms of physical MR parameters influenced by histochemical tissue composition. We aimed to determine the relationship between hMRI parameters in the area surrounding the surgical cavity and the presence of HGG recurrence. Methods. Patients were scanned after surgery with an hMRI multiparameter protocol that allowed for estimations of longitudinal relaxation rate (R1) = 1/T1, effective transverse relaxation rate (R2)*=1/T2*, magnetization transfer saturation (MTsat), and proton density. The initial perioperative zone (IPZ) was segmented on the postoperative MRI. Once recurrence appeared on conventional MRI, the area of relapsing disease was delineated (extension zone, EZ). Conventional MRI showing recurrence and hMRI were coregistered, allowing for the extraction of parameters R1, R2*, MTsat, and PD in 3 areas: the overlap area between the IPZ and EZ (OZ), the peritumoral brain zone, PBZ (PBZ = IPZ – OZ), and the area of recurrence (RZ = EZ – OZ). Results. Thirty-one patients with HGG who underwent gross-total resection were enrolled. MTsat and R1 were the most strongly associated with tumor progression. MTsat was significantly lower in the OZ and RZ, compared to PBZ. R1 was significantly lower in RZ compared to PBZ. PD was significantly higher in OZ compared to PBZ, and R2* was higher in OZ compared to PBZ or RZ. These changes were detected 4 to 120 weeks before recurrence recognition on conventional MRI. Conclusions. HGG recurrence was associated with hMRI parameters’ variation after initial surgery, weeks to months before overt recurrence. [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 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 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)

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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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