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- W2025312144 abstract "L'arsenal thérapeutique dans la polyarthrite rhumatoïde s'est récemment considérablement élargi avec en particulier l'avènement des biothérapies. Cependant, les échecs et l'apparition d'échappement à ces nouveaux traitements incitent à envisager de nouvelles perspectives thérapeutiques. Les voies de signalisation intracellulaire en particulier les protéines kinases MAPK, PI3 Kinase, et les facteurs de transcription NF-κB, AP-1, C/EBP et Stat représentent des cibles potentielles. Pour inhiber ces voies de signalisation, trois stratégies principales sont envisageables : des inhibiteurs pharmacologiques, des inhibiteurs plus spécifiques comme les oligonucléotides antisens, et la surexpression d'inhibiteurs physiologiques. Des essais cliniques sont en cours avec les inhibiteurs pharmacologiques, en particulier de la p38 MAPK. Même si les résultats préliminaires sont encourageants, leur efficacité et leur bonne tolérance restent à démontrer. Enfin, ces voies de signalisation participent aussi à des processus physiologiques et les conséquences de leur inhibition ne sont pas encore bien connues. Biotherapies and other new treatments introduced over the last few years have considerably enriched the therapeutic armamentarium for rheumatoid arthritis. Nevertheless, primary refractoriness or secondary escape phenomenon may occur, indicating a need for identifying new treatment targets. Promising candidates can be found among compounds involved in signal transduction pathways, most notably protein kinases (mitogen-activated protein kinase [MAPK] and phosphatidylinositol-3 protein kinase[PI3]) and transcription factors (nuclear factor kappa B [NF-κB], activating protein 1 [AP-1], CCAAT/enhancer-binding protein [C/EBP], and signal transducer and activator of transcription [Stat]). Inhibition of signal transduction pathways may be achievable via three main strategies: pharmacological inhibitors, anti-sense oligonucleotides or other relatively specific inhibitors, and induced overexpression of naturally occurring inhibitors. Clinical trials are under way to evaluate pharmacological inhibitors such as p38 mitogen-activated protein kinase. Although the preliminary results are promising, proof of safety has not yet been obtained. Signal transduction pathways are involved in normal processes, whose inhibition might produce untoward effects." @default.
- W2025312144 created "2016-06-24" @default.
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- W2025312144 date "2004-05-01" @default.
- W2025312144 modified "2023-09-25" @default.
- W2025312144 title "Les voies de signalisation intracellulaireB: de nouvelles cibles th�rapeutiques dans la polyarthrite rhumato�de" @default.
- W2025312144 doi "https://doi.org/10.1016/s1169-8330(04)00151-6" @default.
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