Publications (9) View all
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Article: Letter: thiopurine blood monitoring for patients with inflammatory bowel disease - authors' reply.
Alimentary Pharmacology & Therapeutics 03/2012; 35(6):743-4. · 3.77 Impact Factor -
Article: TPMT status determination: the simplest is the most effective?
Journal of Crohn s and Colitis 04/2012; 6(7):807; author reply 808. · 2.57 Impact Factor -
Article: Microsatellite instability analysis in uterine cavity washings as a screening tool for endometrial cancer in Lynch syndrome.
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ABSTRACT: Although patients with Lynch syndrome (LS) are at high risk of endometrial cancer, gynecologic screening has been poorly investigated and diagnostic value of current screening tests remains unclear. Microsatellite instability (MSI) phenotype is found in more than 90% of endometrial cancers developed in LS patients. Here we report the first two cases of unstable endometrial tumors with detection of MSI in uterine cavity washings cells. This new technique may be a promising screening tool in LS.Familial Cancer 08/2011; 10(4):655-7. · 1.30 Impact Factor -
Article: Genomic consequences of cytochrome P450 2C9 overexpression in human hepatoma cells.
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ABSTRACT: Cytochrome P450 2C9 (P450 2C9) is one of the most important P450 isoforms in the human liver, as it metabolizes numerous exogenous and endogenous substrates. Moreover, it is inducible by several compounds, such as rifampicin, phenobarbital, and NSAIDs (nonsteroidal anti-inflammatories). The aim of this study was to investigate the global cellular consequences of P450 2C9 overexpression at the transcriptional level using an untargeted approach: pangenomic microarrays. Recombinant adenovirus was used to express P450 2C9 instead of an inducer to prevent a per se effect of inducer or its metabolites. P450 2C9 overexpression induced endoplasmic reticulum (ER) stress and regulated genes implicated in the unfolded protein response (UPR) as heat shock protein (HSP) (we studied particurlarly HSPA5 and HSPB1) and in the endoplasmic reticulum associated degradation (ERAD) system as Sec61 and ubiquitin and proteasome pathways. UPR and ERAD are two mechanisms of adaptative response to ER stress. Moreover, activation of Akt was observed in HepG2 cells that overexpress P450 2C9 and might participate in the cellular adaptive response to stress, thus leading to the activation of cell survival pathways. UPR and ERAD should be caused by accumulation of native and misfolded P450 2C9 protein. Our results indicated that P450 2C9 overexpression did not lead to toxicity but induced an ER stress due to protein overexpression rather than mono-oxygenase activity. The ER stress triggered activation of the adaptative response and of pathways leading to cell survival.Chemical Research in Toxicology 06/2009; 22(5):779-87. · 3.78 Impact Factor -
Article: Clinical utility of pharmacogenetics for predicting drug efficacy and toxicity
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ABSTRACT: Reçu le 14 octobre 2011 ; accepté le 24 octobre 2011 © SRLF et Springer-Verlag France 2011 Résumé La réponse aux médicaments est souvent variable d'un individu à l'autre, ce qui rend parfois leur maniement délicat. La prédiction de la réponse devient un problème cru-cial en cas de fenêtre thérapeutique étroite de ces médicaments ou de l'existence d'alternatives thérapeutiques. Des facteurs génétiques affectant le métabolisme et le transport des médi-caments expliquent en partie la variabilité interindividuelle dans la réponse. La pharmacogénétique étudie les mécanismes d'origine génétique intervenant dans la réponse aux médica-ments dans le but d'optimiser les traitements médicamenteux, tant en termes d'efficacité que de sécurité d'emploi. L'exis-tence de polymorphismes génétiques affectant les gènes codant pour les enzymes du métabolisme des médicaments aboutit à distinguer, dans la population générale, différentes classes d'individus en fonction de leur capacité métabolique vis-à-vis d'une enzyme donnée, à savoir des métaboliseurs lents, rapides et même parfois ultrarapides. Des méthodes de phénotypage et de génotypage permettent de déterminer ou de prédire le statut métabolique d'un individu et de savoir ainsi s'il présente un risque particulier d'inefficacité ou de toxicité vis-à-vis de certains médicaments. Plusieurs exemples d'appli-cations cliniques (thiopurines, antivitamine K, codéine et tra-madol) permettent d'illustrer l'intérêt de la pharmacogénétique pour la prise en charge des malades. La validation clinique d'un grand nombre d'analyses pharmacogénétiques et la mise au point de nouvelles technologies très performantes et peu coûteuses de génotypage vont contribuer au développement rapide de cette discipline dans la pratique médicale courante, avec la perspective d'une individualisation des traitements médicamenteux associée à l'amélioration du taux de réponse et la diminution des accidents iatrogènes. Pour citer cette revue : Réanimation 21 (2012). Mots clés Médicament · Variabilité interindividuelle · Pharmacogénétique · Prédiction de la réponse Abstract The narrow therapeutic index of most pharmaceu-tical agents and the severe consequences of undertreatment or overdosing have led to search for molecular predictive factors of toxicity and efficacy. Genetic factors involved in drug metabolism and transport partly explain inter-individual variability in drug response. Pharmacogenetics focuses on the molecular mechanisms involved in drug response. Its ultimate goal is to optimize the treatments, combining the better efficacy with the minimal risk of severe side-effects. Polymorphisms in genes encoding specific drug-metabolising enzymes may be encountered in some indivi-duals and allow characterizing different groups in the general population as low, rapid and even ultra-rapid metabolisers. Phenotyping and genotyping tests are now available to deter-mine or predict the metabolic status of an individual and, thus, enabling to evaluate the risk of drug failure or toxicity. Several clinical applications of pharmacogenetics (thiopurines, antivi-tamine K, codeine, and tramadol) have already been develo-ped in the routine medical practice resulting in significant improvement in patient treatment. The clinical validation of an increasing number of pharmacogenetic tests as well as the development of new highly efficient technologies for genoty-ping should further promote pharmacogenetics in clinical practice and lead to the development of a patient-tailored drug therapy. To cite this journal: Réanimation 21 (2012).Réanimation 01/2011;
