Inhibition du canal SK3 et du développement de métastases par un ether-lipide synthétique

Il a été mis en évidence que le canal SK3 est un médiateur de la migration de cellules cancéreuses mammaires, une propriété essentielle à la formation de métastases. Par ailleurs, ce canal est inhibé par l édelfosine, un éther-lipide ayant des propriétés anti-tumorales in vitro mais son usage en clinique a été abandonné en raison d effets secondaires. Une première partie de ce travail a permis de déterminer les parties de l édelfosine nécessaires à l inhibition du canal SK3 et de la migration cellulaire. Ceci nous a permis de sélectionner l Ohmline (1-O-Hexadécyl-2-O-Méthyl-sn-glycéro-lactose), un analogue non toxique de l édelfosine qui conserve son activité inhibitrice de SK3 et de la migration. Dans un deuxième temps, nous avons testé ce lipide dans un modèle murin de développement tumoral et nous avons montré qu il réduisait le développement des métastases sans modifier la tumeur primaire. En conclusion, nous avons décrit l Ohmline qui est le premier inhibiteur lipidique de SK3 et qui pourrait devenir le premier membre d une famille de composés lipidiques inhibiteurs de la formation de métastases.It has been shown that SK3 channel was a mediator of breast cancer cells migration, a fundamental property for metastasis formation. In addition, edelfosine inhibits SK3 channel. This ether-lipid owns a high anti cancerous potential in vitro but its clinical use was hampered by some side effects, Firstly, we showed the structural parts of edelfosine required for SK3 channel inhibition and cell motility inhibition. Moreover, we selected Ohmline (1-O-Hexadécyl-2-O-Méthyl-sn-glycéro-lactose), an edlefosine s analogue that preserves SK3 channel and motility inhibitory properties. Secondly, we evaluated this lipid on tumor development in nude mice model. We showed that this lipid reduces metastasis formation without effect on primary tumor. To conclude, we described Ohmline, the first lipid inhibitor of SK3. This compound should become the first member of a new family of metastasis lipid inhibitors.TOURS-Bibl.électronique (372610011) / SudocSudocFranceF

Role of the ERK pathway in psychostimulant-induced locomotor sensitization

BACKGROUND: Repeated exposure to psychostimulants results in a progressive and long-lasting facilitation of the locomotor response that is thought to have implications for addiction. Psychostimulants and other drugs of abuse activate in specific brain areas extracellular signal-regulated kinase (ERK), an essential component of a signaling pathway involved in synaptic plasticity and long-term effects of drugs of abuse. Here we have investigated the role of ERK activation in the behavioral sensitization induced by repeated administration of psychostimulants in mice, using SL327, a brain-penetrating selective inhibitor of MAP-kinase/ERK kinase (MEK), the enzyme that selectively activates ERK. RESULTS: A dose of SL327 (30 mg/kg) that reduced the number of activated ERK-positive neurons by 62 to 89% in various brain areas, had virtually no effect on the spontaneous locomotor activity or the acute hyperlocomotion induced by cocaine or D-amphetamine. Pre-treatment with SL327 (30 mg/kg) prior to each drug administration prevented the locomotor sensitization induced by repeated injections of D-amphetamine or cocaine. The SL327 pre-treatment abolished also conditioned locomotor response of mice placed in the context previously paired with cocaine or D-amphetamine. In contrast, SL327 did not alter the expression of sensitized response to D-amphetamine or cocaine. CONCLUSION: Altogether these results show that ERK has a minor contribution to the acute locomotor effects of psychostimulants or to the expression of sensitized responses, whereas it is crucial for the acquisition of locomotor sensitization and psychostimulant-conditioned locomotor response. This study supports the important role of the ERK pathway in long-lasting behavioral alterations induced by drugs of abuse

About the Electrospray Ionization Source in Mass Spectrometry: Electrochemistry and On-chip Reactions

The present work shows that the electrochemical properties of electrospray ionization (ESI) can be used to add functions to the process. As example, we show how the choice of the electrode material can be used to study interactions between metal ions and biomolecules in mass spectrometry (MS). In positive ionization MS, an electrospray device acts as anode, which implies oxidation reactions. Sacrificial electrodes (made of copper or zinc) are used to supply the electrospray current and to produce cations that are able to react on-line with compounds of interest. Thus, the interactions between copper ions and ligands or peptides were investigated by using a copper electrode. Another example is the in situ electrogeneration of a dinuclear zinc(II) complex for the mass tagging of phosphopeptides when working with a zinc electrode. In order to perform these reactions on the same microchip, a dual-channel microsprayer was used, where one channel was dedicated to the tag electrogeneration and the other to the infusion of a phosphopeptides solution. Finally, this dual-channel microsprayer was used to study complexation at liquid-liquid interfaces in biphasic ESI-MS, such as thioether crowns and lead ions or peptides and phospholipids complexes. These examples illustrate the use of electrochemistry and on-chip reactions in ESI-MS analysis

Laser Fabry-Perot verrouillé en longueur d'onde par injection optique pour le réseau d'accès

session orale Lu2 « Amplificateurs et Lasers à semi-conducteurs » [Lu2.2]National audiencePour les futurs réseaux d'accès optique multiplexés en longueur d'onde (de type WDM-PON), des émetteurs optiques bas-coûts et identiques pour chaque abonné sont souhaitables. Ces composants doivent pouvoir être modulés à 10 Gbps, tout en ayant une accordabilité en longueur d'onde. Cette dernière propriété peut-être assurée en verrouillant un laser Fabry-Perot multimode par injection optique. Nous présentons les propriétés d'un tel laser injecté : son efficacité en verrouillage, la réduction du bruit d'intensité et l'amélioration très importante de la fréquence de relaxation

Standard addition strip for quantitative electrostatic spray ionization mass spectrometry analysis: Determination of caffeine in drinks

Standard addition strips were prepared for the quantitative determination of caffeine in different beverages by electrostatic spray ionisation mass spectrometry (ESTASI-MS). The gist of this approach is to dry spots of caffeine solutions with different concentrations on a polymer strip, then to deposit a drop of sample mixed with an internal standard, here theobromine on each spot and to measure the mass spectrometry signals of caffeine and theobromine by ESTASI-MS. This strip approach is very convenient and provides quantitative analyses as accurate as the classical standard addition method by MS or liquid chromatography

Noninvasive mechanical ventilation in high-risk pulmonary infections: a clinical review

The aim of this article was to review the role of noninvasive ventilation (NIV) in acute pulmonary infectious diseases, such as severe acute respiratory syndrome (SARS), H1N1 and tuberculosis, and to assess the risk of disease transmission with the use of NIV from patients to healthcare workers. We performed a clinical review by searching Medline and EMBASE. These databases were searched for articles on "clinical trials" and "randomised controlled trials". The keywords selected were non-invasive ventilation pulmonary infections, influenza-A (H1N1), SARS and tuberculosis. These terms were cross-referenced with the following keywords: health care workers, airborne infections, complications, intensive care unit and pandemic. The members of the International NIV Network examined the major results regarding NIV applications and SARS, H1N1 and tuberculosis. Cross-referencing mechanical ventilation with SARS yielded 76 studies, of which 10 studies involved the use of NIV and five were ultimately selected for inclusion in this review. Cross-referencing with H1N1 yielded 275 studies, of which 27 involved NIV. Of these, 22 were selected for review. Cross-referencing with tuberculosis yielded 285 studies, of which 15 involved NIV and from these seven were selected. In total 34 studies were selected for this review. NIV, when applied early in selected patients with SARS, H1N1 and acute pulmonary tuberculosis infections, can reverse respiratory failure. There are only a few reports of infectious disease transmission among healthcare workers

Quantifying the Flexibility of Real-Time Systems

International audienceIn this paper we define the flexibility of a system as its capability to schedule a new task. We present an approach to quantify the flexibility of a system. More importantly, we show that it is possible under certain conditions to identify the task that will directly induce the limitations on a possible software update. If performed at design time, such a result can be used to adjust the system design by giving more slack to the limiting task. We illustrate how these results apply to a simple system

16x2.5 Gbit/s Downstream Transmission in Colorless WDM-PON based on Injection-Locked Fabry-Perot Laser Diode using a single Quantum Dash mode-locked Fabry-Perot laser as multi-wavelength seeding source

technical session OThA " WDM-Access II "International audienceError-free colorless WDM-PON downstream over 25 km for 16 channels with 85 GHz channel spacing is experimentally demonstrated at 2.5 Gbit/s, using an injection-locked Fabry-Perot laser and a quantum dash mode-locked laser as a coherent seeding source