Browsing by Author "Moussallieh, F. M."

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    Characterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1a...
    (Impact Journals LLC, 2017-03-23) Nguyen, A.; Moussallieh, F. M.; Mackay, A.; Cicek, A. E.; Coca, A.; Chenard, M. P.; Weingertner, N.; Lhermitte, B.; Letouzé, E.; Guérin, E.; Pencreach, E.; Jannier, S.; Guenot, D.; Namer, I. J.; Jones, C.; Entz-Werlé, N.
    Pediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment. To establish, the crucial role of the hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic deregulations in a pediatric cohort of pHGGs and in pHGG’s cell lines, cultured in both normoxic and hypoxic conditions. Secondly, based on the concept of a bi-therapy targeting in pHGGs mTORC1 (rapamycin) and HIF-1α (irinotecan), we hypothesized that the balanced expressions between RAS/ERK, PI3K/AKT and HIF-1α/HIF-2α/MYC proteins or genes may provide a modulation of the cell response to this double targeting. Finally, we could evidence three protein, genomic and metabolomic profiles of response to rapamycin combined with irinotecan. The pattern of highly sensitive cells to mTOR/HIF-1α targeting was linked to a MYC/ERK/HIF-1α over-expression and the cell resistance to a major hyper-expression of HIF-2α.
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    Metabolomics approaches in experimental allergic encephalomyelitis
    (Elsevier, 2018) Battini, B.; Bund, C.; Moussallieh, F. M.; Çiçek, A. Ercüment; De Sèze, J.; Namer, I. J.
    A myelin basic protein (MBP)-induced experimental allergic encephalomyelitis (EAE) involves paraplegia due to a reversible thoracolumbar spinal cord impairment. The aims of this study were thus to find significant metabolic biomarkers of inflammation and identify the site of inflammation in the central nervous system (CNS) during the acute signs in of the disease using metabolomics. All the EAE samples were associated with higher levels of lactate, ascorbate, glucose and amino acids, and decreased level of N-acetyl-aspartate (NAA) compared to the control group. A decreased NAA level has been particularly shown in lumbar spinal cord in relationship with the clinical signs.