Browsing by Subject "Pediatric"

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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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    Impairment of vestibulo-collic reflex and linear vestibulo-ocular reflex in pediatric-onset multiple sclerosis patients
    (Elsevier Ireland Ltd., 2021-08) Ertuğrul, G.; Aksoy, S.; Konuşkan, B.; Eskandarian, L.; Oğuz, Kader Karlı; Anlar, B.
    Objectives, This study aimed to examine the vestibulo-collic reflex (VCR) and linear vestibulo-ocular reflex (lVOR) and their correlation with brain lesions in pediatric-onset multiple sclerosis (POMS). Methods, The study group consisted of 17 patients (34 ears) with POMS (mean age 18.73 ± 2.02, mean age at disease onset 14.64 ± 1.36 years), and the control group included 11 age-matched healthy subjects (22 ears). Ocular and cervical Vestibular Evoked Myogenic Potentials (oVEMP and cVEMP) were performed to assess IVOR and VCR pathways. Magnetic Resonance Imaging was evaluated in the study group. Results, In the POMS group, 47.05 % of oVEMPs and 17.64 % of the cVEMPs were abnormal, while all VEMPs were normal in the control group. The oVEMP amplitude was associated with infratentorial lesion volume (r = −0.459, p = 0.01) and total lesion volume of the brainstem and cerebellum (r = −0.450, p = 0.01). The cVEMP asymmetry ratio was correlated with the deep white matter lesion volume (r = 0.683, p < 0.001). The MVEMP scores were found to correlate only with lesion volumes in the cerebellum (r = 0.488, p = 0.04) and infratentorial region (r = 0.573, p = 0.01). Conclusions, Ocular and cervical VEMP abnormalities confirm that lVOR and VCR pathways may be affected in early POMS. Significance, Routine use of the VEMP test, especially the oVEMP test is recommended as a useful tool in the follow-up of POMS patients.