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Neuronal and Electrophysiological Markers of GliomaGhinda, Cristina Diana 27 February 2020 (has links)
The research performed in this thesis aims to improve our understanding about one of the most malignant tumors of the human brain – glioma. From the early stages of my career I was confronted with the cruel reality of losing patients due to this devastating disease. The studies performed over the last four years involve extensive data analysis in different clinical and laboratory settings. The direct application of different analysis methods and tools in order to investigate the glioma infiltration delineation has potentially lead to direct applications of our results in the clinical setting. The overall approach of the study is based on three primary outcome measures, i.e., neuronal, electrophysiological and genetic/molecular features for distinguishing infiltrated and non-infiltrated zones within specifically peritumoral tissue (PT) and, more extensively, across the radiologically-defined boundaries of healthy, peritumoral and tumoral tissues. As such, we propose for the first time an objective demarcation and characterization of the PT and we detail how the genetic and epigenetic alterations within the tumoral and peritumoral area are linked with macroscopic functional MRI results. We also describe scale-free features (power law exponent) as well as distinct spectral features and reactivity to external stimulus in the tumoral and adjacent tissue of patients and provide novel insights in terms of glioma’s electrophysiology. The insights gained from these empirical studies further improve our understanding about the pathophysiology of this disease at micro- and macroscopic scales allowing us to envisage novel management methods for patients affected by glioma.
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Au delà des frontières du glioblastome : caractérisation de la zone péritumorale des glioblastomes / Beyond the frontiers of glioblastoma : multidisciplinary characterisation of glioblastoma's peritumoral brain zoneLemée, Jean-Michel 26 February 2015 (has links)
Le glioblastome (GB) est une tumeur hétérogène, agressive devant laquelle les possibilités thérapeutiques disponibles restent limitées. L’étude de la zone péritumorale macroscopiquement normale (ZMN) des GB est essentielle à la compréhension de ses mécanismes de progression et de récidive. Le premier objectif de ce travail de Thèse a été de comparer les données de transcriptomique et de protéomique issues de l’analyse de la zone tumorale des GB dans le cadre du Projet Gliome Grand Ouest. Le taux de concordance entre les 2 modalités est faible, retrouvant toutefois comme point commun une dysrégulation de la protéine légère des neurofilaments qui pourrait servir de biomarqueur potentiel des GB. Le deuxième objectif de ce travail de Thèse a été la caractérisation de la ZMN des GB. Nous avons mis en évidence que cette zone, dont l’aspect est similaire à première vue à celui du tissu cérébral sain, n’est pas une simple zone de transition entre le GB et le tissu cérébral sain. En effet, la ZMN est une entité spécifique possédant des caractéristiques qui lui sont propres, comme la présence d’un phénotype particulier de cellules tumorales infiltrantes et de cellules stromales et une sur’expression des protéines CRYAB et H3F3A. Ce travail de Thèse a aussi été l’occasion de développer de nouvelles techniques d’imagerie per-opératoire de la ZMN, afin d’évaluer la présence d’un contingent tumoral et ainsi optimiser la qualité de la résection chirurgicale. La caractérisation de cette ZMN nous permet de mieux appréhender son implication dans la tumorogenèse et la présence de caractéristiques spécifiques de cette zone ouvre la porte à la détection de biomarqueurs spécifiques, ainsi qu’au développement de thérapies ciblées. Ce travail de Thèse a été valorisé par 2 publications, 2 articles soumis et un brevet est en cours de dépôt et d’évaluation par un cabinet de brevet. / Glioblastoma (GB) is a heterogeneous andaggressive tumor, before which therapeutic options arelimited. The study of the macroscopically normalperitumoral brain zone (PBZ) of GB is essential tounderstand its mechanisms of progression andrecurrence.The first objective of this thesis work was tocompare the transcriptomic and proteomic data from theGB tumor area obtained through the “Grand Ouest”glioma Project. The concordance rate between the 2modalities is low. However, one of the common featureis the dysregulation of neurofilament light polypeptide,which could serve as a biomarker potential of GB.The second objective of this thesis was thecharacterization of the PBZ. We have shown that thisarea, similar at first glance to that of healthy braintissue, is not a simple transition area between the GBand healthy brain tissue but a specific entity withcharacteristics of its own. For example, the ZMNpresents a particular phenotype of infiltrating GB cellsand stromal cells and a surexpression of CRYAB andH3F3A proteins.This thesis work was also an opportunity todevelop new intraoperative imaging techniques of thePBZ, with the aim to assess the presence of a tumoralinfiltration and optimize the quality of the surgicalresection.The characterization of this PBZ allows us tobetter understand its involvement in tumorigenesis andthe presence of specific characteristics of this areaopens the door for the detection of specific biomarkersand the development of targeted therapies.This thesis work was led to 2 publications, 2articles submitted and a patent being evaluated andredacted by a patent office.
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