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Recherche de biomarqueurs de la neurotoxicité des traitements anticancéreux à base d'oxaliplatine: approche protéomique quantitative

Abstract : Oxaliplatin is a reference drug in the treament of metastatic colorectal cancer. However Oxaliplatin causes a neurological toxicity which alters the quality of life of some predisposed patients. We analysed for the first ti me oxaliplatin neurotoxicity by a proteomic approach. An experimental protocol associating iTRAQ labelling and OFFGEL-IEF fractionation was developed in order to improve the proteome coverage of complex samples. Then, the differential protein expression following a clinically relevant oxaliplatin treatment was globally analysed both in the intracellular proteome and in the secretome using a human cellular mode1 for neurotoxicity. The intracellular proteome analysis allowed the identification of more than 2700 proteins and offers new perspectives into the molecular mechanisms of oxaliplatin neurotoxicity. Oxaliplatin alters the expression of proteins involved in DNA damage response, cell cycle control, oxidative stress, energy metabolism, proteotoxic stress, multidrug resistance, neuronal plasticity and calcium homeostasis. The secretome analysis exhibited 23 over-expressed secreted proteins following oxaliplatin treatment. We suggest for the first time that Calmodulin,Thymosin beta-10 and the neurotrophic factor Neudesin could be potentiaI biomarkers for oxaliplatin neuronal injuy.
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https://tel.archives-ouvertes.fr/tel-00668340
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Submitted on : Thursday, February 9, 2012 - 4:13:06 PM
Last modification on : Wednesday, November 10, 2021 - 3:32:02 PM
Long-term archiving on: : Thursday, May 10, 2012 - 2:50:31 AM

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  • HAL Id : tel-00668340, version 1

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Emilie Ernoult. Recherche de biomarqueurs de la neurotoxicité des traitements anticancéreux à base d'oxaliplatine: approche protéomique quantitative. Biologie cellulaire. Université d'Angers, 2011. Français. ⟨tel-00668340⟩

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