Multicellular tumor spheroid model to evaluate spatio-temporal dynamics effect of chemotherapeutics: application to the gemcitabine/CHK1 inhibitor combination in pancreatic cancer

International audienceUNLABELLED: ABSTRACT: BACKGROUND: The multicellular tumor spheroid (MCTS) is an in vitro model associating malignant-cell microenvironment and 3D organization as currently observed in avascular tumors. METHODS: In order to evaluate the relevance of this model for pre-clinical studies of drug combinations, we analyzed the effect of gemcitabine alone and in combination with the CHIR-124 CHK1 inhibitor in a Capan-2 pancreatic cell MCTS model. RESULTS: Compared to monolayer cultures, Capan-2 MCTS exhibited resistance to gemcitabine cytotoxic effect. This resistance was amplified in EGF-deprived quiescent spheroid suggesting that quiescent cells are playing a role in gemcitabine multicellular resistance. After a prolonged incubation with gemcitabine, DNA damages and massive apoptosis were observed throughout the spheroid while cell cycle arrest was restricted to the outer cell layer, indicating that gemcitabine-induced apoptosis is directly correlated to DNA damages. The combination of gemcitabine and CHIR-124 in this MCTS model, enhanced the sensitivity to the gemcitabine antiproliferative effect in correlation with an increase in DNA damage and apoptosis. CONCLUSIONS: These results demonstrate that our pancreatic MCTS model, suitable for both screening and imaging analysis, is a valuable advanced tool for evaluating the spatio-temporal effect of drugs and drug combinations in a chemoresistant and microenvironment-depending tumor model

Les sciences du pharmacien appliquées au métier de l'oenologue

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Note technique. Définition des modalités de l’évaluation qualitative appliquée à certains habitats benthiques dans le cadre de l’évaluation DCSMM cycle 3. Thématique D1 - habitats benthiques

L’objectif du présent document est de fournir un cadrage méthodologique pour la mise en oeuvre d’une évaluation qualitative, c’est-à-dire fondée sur du dire d’expert, de certains habitats benthiques lors de l'évaluation DCSMM - cycle 3 du Bon État Écologique du Descripteur 1-Habitats benthiques. Sont concernés par ces évaluations : - deux habitats équivalant à la catégorie Grands Types d’Habitats : - les roches intertidales ; - les roches infralittorales ; - trois habitats équivalant à la catégorie Autres Types d’habitats : - les récifs intertidaux à Sabellaria alveolata ; - les bancs de maërl ; - les herbiers de Zostera marina et Z. noltei. Les éléments de cadrage explicités dans la suite du document doivent garantir une certaine homogénéité/cohérence dans le rendu des résultats finaux et la traçabilité du dire d’expert. Ils doivent également permettre à un large public (gestionnaires, citoyens, politiques publiques, etc) de mieux appréhender la méthode d’évaluation utilisée pour les habitats mentionnés ci-dessus. Ce document de cadrage s’inspire largement du guide de lecture rédigé par le groupe de travail ICG-POSH (Intersessional Correspondence Group on the implementation and follow up of measures for the protection and conservation of species and habitats) d’OSPAR [documents (ospar.org)]

Le chainon manquant du rempart de Saint-Lizier (Ariège) : étude stratigraphique et architecturale de la courtine effondrée au chemin de Nargach

International audienc

PPR2263, a DYW-Subgroup Pentatricopeptide Repeat Protein, Is Required for Mitochondrial nad5 and cob Transcript Editing, Mitochondrion Biogenesis, and Maize Growth

International audienceRNA editing plays an important role in organelle gene expression in various organisms, including flowering plants, changing the nucleotide information at precise sites. Here, we present evidence that the maize (Zea mays) nuclear gene Pentatricopeptide repeat 2263 (PPR2263) encoding a DYW domain-containing PPR protein is required for RNA editing in the mitochondrial NADH dehydrogenase5 (nad5) and cytochrome b (cob) transcripts at the nad5-1550 and cob-908 sites, respectively. Its putative ortholog, MITOCHONDRIAL EDITING FACTOR29, fulfills the same role in Arabidopsis thaliana. Both the maize and the Arabidopsis proteins show preferential localization to mitochondria but are also detected in chloroplasts. In maize, the corresponding ppr2263 mutation causes growth defects in kernels and seedlings. Embryo and endosperm growth are reduced, leading to the production of small but viable kernels. Mutant plants have narrower and shorter leaves, exhibit a strong delay in flowering time, and generally do not reach sexual maturity. Whereas mutant chloroplasts do not have major defects, mutant mitochondria lack complex III and are characterized by a compromised ultrastructure, increased transcript levels, and the induction of alternative oxidase. The results suggest that mitochondrial RNA editing at the cob-908 site is necessary for mitochondrion biogenesis, cell division, and plant growth in maize