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SUMMARY:Thesis – Kasandra AGUILAR CÁZAREZ
DESCRIPTION:Patient-derived models of IDH1-mutant diffuse gliomas: from long-term culture to neuron-tumor interactions\nJury\n\nThierry VIROLLE, Research Director, Institut de Biologie Valrose, Nice – Reviewer\nEmmanuelle HUILLARD, Research Scientist, Institut du Cerveau, Paris – Reviewer\nDavid CASTEL, Research Scientist, Institut Gustave Roussy, Paris – Examinator\nErika COSSET, Research Scientist, Centre de Recherche en Cancérologie, Lyon – Examinator\nTristan BOUSCHET, Research Scientist, IGF, University of Montpellier – Guest\nJean-Philippe HUGNOT, Professor, IGF, University of Montpellier – Thesis supervisor\nHugues DUFFAU, Professor-Hospital Physician, IGF, University of Montpellier – Thesis co-supervisor\n\n \nSummary\nAdult IDH-mutant diffuse gliomas are infiltrative brain tumors whose interactions with the neuronal microenvironment remain poorly understood. Their study is further limited by the lack of patient-derived models suitable for long-term in vitro models. This thesis aimed to develop complementary human models of IDH-mutant gliomas and investigate their interactions with neurons. First, a non-enzymatic explant culture method was established to generate primary glioma cultures while preserving key tumor characteristics; to overcome their limited proliferative capacity, an immortalization strategy combining hTERT expression and CDKN2A/B disruption was developed. Neuron–glioma interactions were then studied using human induced neurons in two-dimensional co-cultures, revealing increased glioma cell proliferation and phenotypic remodeling, accompanied by transcriptional and proteomic changes. Together, this work provides complementary patient-derived models and highlights the influence of the neuronal microenvironment on IDH-mutant glioma proliferation, plasticity and progression.\n
URL:https://www.igf.cnrs.fr/en/events/thesis-kasandra-aguilar-cazarez/
CATEGORIES:Thesis
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