TWIST1 a New Determinant of Epithelial to Mesenchymal Transition in EGFR Mutated Lung Adenocarcinoma

Metastasis is a multistep process and the main cause of mortality in lung cancer patients. We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenesis that may be reactivated in cancers promoting both malignant conversion and cancer progression through an epithelial to mesenchymal transition (EMT). The aim of this study was to investigate the possible implication of TWIST1 reactivation on the acquisition of a mesenchymal phenotype in EGFR mutated lung cancer. We studied a series of consecutive lung adenocarcinoma from Caucasian non-smokers for which surgical frozen samples were available (n = 33) and showed that TWIST1 expression was linked to EGFR mutations (P<0.001), to low CDH1 expression (P<0.05) and low disease free survival (P = 0.044). To validate that TWIST1 is a driver of EMT in EGFR mutated lung cancer, we used five human lung cancer cell lines and demonstrated that EMT and the associated cell mobility were dependent upon TWIST1 expression in cells with EGFR mutation. Moreover a decrease of EGFR pathway stimulation through EGF retrieval or an inhibition of TWIST1 expression by small RNA technology reversed the phenomenon. Collectively, our in vivo and in vitro findings support that TWIST1 collaborates with the EGF pathway in promoting EMT in EGFR mutated lung adenocarcinoma and that large series of EGFR mutated lung cancer patients are needed to further define the prognostic role of TWIST1 reactivation in this subgroup

Gastric submucosal dissection with water-jet knife (« Flush knife ») on a porcine experimental model under spontaneous ventilation

Du 18 au 26 mai 2007, a été effectuée, chez dix porcs anesthésiés en ventilation spontanée, une dissection sous-muqueuse gastrique étendue de 6 cm2 avec un dissecteur à jet d’eau de type «Flush knife» afin d’apprécier l’efficacité et l’innocuité de cette nouvelle méthode de dissection au regard des complications possibles (perforation, hémorragie, immédiate ou tardive). Le modèle expérimental porcin anesthésié en ventilation spontanée a été jugé intéressant pour l’apprentissage de la dissection sousmuqueuse car simple à manipuler du point de vue anesthésique, avec des doses totales de 2 à 3 mL de Zoletil 100® en injections à la demande par paliers de 0,2 à 0,3 mL. La dissection sous-muqueuse au « Flush knife» est de réalisation simple et a été effectuée dans cette étude par des endoscopistes pratiquant moins de 10 dissections par an avec un temps moyen de 10 mn par cm2, cela sans complication immédiate ou tardive

Development of colonic stenosis following severe acute pancreatitis

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