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Etude des voies signalétiques impliquées dans la résistance aux agents thérapeuthiques dans le carcinome à cellules rénales humain

Abstract : The renal cell carcinoma is characterized by a high resistance to therapies. Our working hypothesis was that proliferative signaling pathways, anti-apoptotic and / or angiogenic are involved in resistance to therapies. Thus, as part of this thesis, we measured the sensitivity to chemotherapy and targeted therapies in kidney cancer cell lines in vitro as well in vivo.A pilot study was conducted on the basis of the A498 cell line xenografts in nude mice, and then used for analysis on proteome arrays to identify the signaling pathways induced by sunitinib. In vitro, the cell lines of RCC were sensitive to therapy regardless of the VHL status. In vivo, the line A498 appeared resistant to sunitinib. The approach using the proteome array has shown that several angiogenesis proteins are modulated as a result of treatment, including angiogenin. There was no change in the expression of proteins of apoptosis. Phosphorylated forms of Akt were also increased in the treated tumors, as well as Lim1 whereas the phosphorylated form of NFkB was reduced. This work has identified potential targets involved in resistance mechanisms and should define new therapeutic options in renal cancer.
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Submitted on : Tuesday, October 11, 2016 - 11:11:14 AM
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Pascal Mouracade. Etude des voies signalétiques impliquées dans la résistance aux agents thérapeuthiques dans le carcinome à cellules rénales humain. Cancer. Université de Strasbourg, 2015. Français. ⟨NNT : 2015STRAJ055⟩. ⟨tel-01379199⟩

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