Integrated analysis of randomized controlled trials evaluating bortezomib + lenalidomide + dexamethasone or bortezomib + thalidomide + dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma

ObjectiveProviding the most efficacious frontline treatment for newly diagnosed multiple myeloma (NDMM) is critical for patient outcomes. No direct comparisons have been made between bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) induction regimens in transplant-eligible NDMM.MethodsAn integrated analysis was performed using patient data from four trials meeting prespecified eligibility criteria: two using VRD (PETHEMA GEM2012 and IFM 2009) and two using VTD (PETHEMA GEM2005 and IFM 2013-04).ResultsThe primary endpoint was met, with VRD demonstrating a noninferior rate of at least very good partial response (>= VGPR) after induction vs VTD. GEM comparison demonstrated improvement in the >= VGPR rate after induction for VRD vs VTD (66.3% vs 51.2%; P = .00281) that increased after transplant (74.4% vs 53.5%). Undetectable minimal residual disease rates post induction (46.7% vs 34.9%) and post transplant (62.4% vs 47.3%) support the benefit of VRD vs VTD. Treatment-emergent adverse events leading to study and/or treatment discontinuation were less frequent with VRD (3%, GEM2012; 6%, IFM 2009) vs VTD (11%, IFM 2013-04).ConclusionThese results supported the benefit of VRD over VTD for induction in transplant-eligible patients with NDMM. The trials included are registered with ClinicalTrials.gov (NCT01916252, NCT01191060, NCT00461747, and NCT01971658)

Déterminants protéiques de la voie de sécrétion Sec impliqués dans la formation de biofilm chez Listeria monocytogenes

Listeria monocytogenes est une bactérie pathogène impliquée dans la toxi-infection alimentaire à l origine de la listeriose, une maladie peu fréquente mais avec un taux de mortalité de 25 % chez l homme. Cette bactérie est capable de former un biofilm lui permettant de mieux résister aux stress environnementaux ainsi qu aux traitements de décontamination. Une nouvelle stratégie d analyse génomique a été développée et a permis de cibler des systèmes de sécrétion et des protéines potentiellement impliqués dans la formation de biofilm. L inactivation de la voie SecA2 entraîne la formation d un biofilm aérien et par conséquent fragile. Ce morphotype est capable de croître de façon sessile à 20C sur du polystyrène alors que ce n est pas le cas pour la souche sauvage. De nouvelles protéines sécrétées de façon SecA2 dépendante ont été identifiées par l étude de l exoprotéome du mutant secA2 en comparaison avec celui de la souche sauvage. Le rôle des lipoprotéines dans la formation de biofilm ainsi que leur maturation par les peptidases signal de type II, LspA et LspB, a également été abordé. La combinaison d'une analyse de l expression des gènes codant les lipoprotéines au cours de la formation de biofilm avec l analyse génomique basé sur le sécrétome a permis de cibler trois lipoprotéines, dont LpeA qui serait impliquée dans les phases tardives de formation de biofilm. Enfin, l importance majeure de LspA dans la maturation des lipoprotéines, a été mise en évidence par l étude de l exoprotéome des doubles mutant lgt lspA et lgt lspB en comparaison avec celui de lgt.Listeria monocytogenes is a foodborne pathogenic bacteria responsible for listeriosis, a rare but high mortality rate disease in humans (25 %). This bacterium can form biofilm allowing a better resistance to environmental stresses as well as decontamination treatments. A new strategy for genomic analysis was developed and allowed to target secretion systems and proteins potentially involved in biofilm formation. Inactivation of the SecA2 pathway leads to the formation of an aerial and fragile biofilm. This morphotype is able to grow in a sessile mode at 20 C on polystyrene whereas this is not the case for the wild type strain. New proteins secreted in a SecA2 manner were identified by comparing the secA2 exoproteome to the one of the wild type. The role of lipoproteins in biofilm formation and their maturation by the signal peptidase II, LpsA and LspB, was also tackled. Combining expression analysis of genes encoding lipoproteins during biofilm formation with genomic analysis based on the secretome allowed targeting three lipoproteins, including LpeA, which appeared to be involved in the later stages of biofilm formation. Finally, the importance of LspA in the maturation of lipoproteins,was highlighted by comparing of the double mutant lgt lspA and lgt lspB exoproteomes to the one of lgt.CLERMONT FD-Bib.électronique (631139902) / SudocSudocFranceF

Design of Colored Multilayered Electrophoretic Particles for Electronic Inks

The preparation of multilayered latex particles with surface functional groups suitable for use as electrophoretic particles in electronic inks has been studied. The particles are formed by dispersion polymerization and have a polystyrene core, slightly cross-linked with divinylbenzene (DVB), and a poly(methyl methacrylate) (PMMA) or a poly(acrylic acid) (PAA) shell. After grafting alkyl chains on their surface, the particles are negatively or positively charged and sterically stabilized against aggregation in nonpolar solvent. The particles were dyed by incorporation of Nigrosin during polymerization or by swelling in supercritical CO(2) in the presence of a dye. Particle size, morphology, incorporated dye content and zeta potential were determined. A dual-particle electronic ink based on a mixture of the colored multilayered particles and white hybrid TiO(2)-polymer particles was prepared and electro-optically tested

Electrospinning in water and in situ crosslinking of hyaluronic acid / cyclodextrin nanofibers: Towards wound dressing with controlled drug release

International audienceHyaluronic acid (HA) is widely investigated due to its high potential for wound dressing applications. The fabrication of biomimetic HA-based scaffolds by electrospinning is thus extensively studied. However, HA is often dissolved in toxic organic solvents to allow the efficient production of electrospun nanofibers. Indeed, although HA is soluble in water, its ionic nature leading to long-range electrostatic interactions and the presence of counter ions induce a dramatic increase of the viscosity of aqueous HA solutions without insuring enough chain entanglements necessary for a stable and efficient electrospinning. In this study, biocompatible insoluble HA-based nanofibers were fabricated by electrospinning in pure water. To this end, poly(vinyl alcohol) (PVA) was added as a carrier polymer and it was found that the addition of hydroxypropyl-beta cyclodextrin (HP beta CD) stabilized the process of electrospinning and led to the efficient formation of uniform nanofibrous scaffolds. An in situ crosslinking process of the scaffolds is also proposed, insuring a whole fabrication process without any toxicity. Furthermore, the beneficial presence of HP beta CD in the HA-based scaffolds paves the way for wound dressing applications with controlled drug encapsulation-release properties. As a proof of concept, naproxen (NAP), a non-steroidal anti-inflammatory drug was chosen as a model drug. NAP was impregnated into the scaffolds either in aqueous solution or under supercritical CO2. The resulting functional scaffolds showed a regular drug release profile along several days without losing the fibrous structure. This study proposes a simple approach to form stable HA-based nanofibrous scaffolds embedding HP beta CD using water as the only solvent, enabling the development of safe functional wound dressings

Isolement et caractérisation des champignons anaérobies stricts du rumen de moutons. Premiers résultats

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A multi-layered nerve guidance conduit design adapted to facilitate surgical implantation

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Nanocomposite Polymer Scaffolds Responding under External Stimuli for Drug Delivery and Tissue Engineering Applications

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