The Chemokine CXCL12 Is Essential for the Clearance of the Filaria Litomosoides sigmodontis in Resistant Mice

Litomosoides sigmodontis is a cause of filarial infection in rodents. Once infective larvae overcome the skin barrier, they enter the lymphatic system and then settle in the pleural cavity, causing soft tissue infection. The outcome of infection depends on the parasite's modulatory ability and also on the immune response of the infected host, which is influenced by its genetic background. The goal of this study was to determine whether host factors such as the chemokine axis CXCL12/CXCR4, which notably participates in the control of immune surveillance, can influence the outcome of the infection. We therefore set up comparative analyses of subcutaneous infection by L. sigmodontis in two inbred mouse strains with different outcomes: one susceptible strain (BALB/c) and one resistant strain (C57BL/6). We showed that rapid parasite clearance was associated with a L. sigmodontis-specific CXCL12-dependent cell response in C57BL/6 mice. CXCL12 was produced mainly by pleural mesothelial cells during infection. Conversely, the delayed parasite clearance in BALB/c mice was neither associated with an increase in CXCL12 levels nor with cell influx into the pleural cavity. Remarkably, interfering with the CXCL12/CXCR4 axis in both strains of mice delayed filarial development, as evidenced by the postponement of the fourth molting process. Furthermore, the in vitro growth of stage 4 filariae was favored by the addition of low amounts of CXCL12. The CXCL12/CXCR4 axis thus appears to have a dual effect on the L. sigmodontis life cycle: by acting as a host-cell restriction factor for infection, and as a growth factor for worms

Chimiosensibilisation des cancers de l ovaire par inhibition de l expression de Bcl-xL (développement d une stratégie ARN interférence)

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

ImpedanCELL, une plateforme de mesure de l’activité cellulaire en temps réel et à haut débit en Normandie : exemples d’applications en oncologie et en virologie avec la technologie xCELLigence

International audienc

ImpedanCELL, une plateforme de mesure de l’activité cellulaire en temps réel et à haut débit en Normandie : exemples d’applications en oncologie et en virologie avec la technologie xCELLigence.

International audienc

Investigation of chloromethane complexes of cryptophane-A analogue with butoxy groups using C-13 NMR in the solid state and solution along with single crystal X-ray diffraction

International audienc

Bystander effectors of chondrosarcoma cells irradiated at different LET impair proliferation of chondrocytes

International audienceX-rays / Carbon Ion Tumor (Chondrosarcoma) Non irradiated area arrounding tumor Non irradiated area arrounding healthy tissue Direct effect of irradiation Bystander effect Bystander effectors of chondrosarcoma cells irradiated at different LET impair proliferation of chondrocyte

Synthesis of cryptophanes With Two Different Reaction Sites: Chemical Platforms for Xenon Biosensing

International audienceWe report the synthesis of new water-soluble cryptophane host molecules that can be used for the preparation of 129Xe NMR-based biosensors. We show that the cryptophane-223 skeleton can be modified in order to introduce a unique secondary alcohol to the propylenedioxy linker. This chemical functionality can then be exploited to introduce a functional group different from the six chemical groups attached to the aromatic rings. In this approach the generation of a statistical mixture when trying to selectively functionalize a symmetrical host molecule is eliminated, which enables the efficient large-scale production of new cryptophanes that can be used as chemical platforms ready to use for the preparation of xenon biosensors. To illustrate this approach molecular platforms 1 and 2 have been prepared. The ability of these new derivatives to bind xenon has also been investigated

miRNAs as tools for tailoring personalized therapeutic strategies in ovarian carcinoma

International audienceOvarian carcinomas are associated with an extremely poor prognosis, resulting in a 5-year survival of 30% for advanced-stage disease. Unlike other malignancies, no significant improvement in disease management and overall survival has been achieved in the past three decades, underlining the urgent need of new therapeutic opportunities. The cooperation of Bcl-xL and Mcl-1 is required to protect ovarian cancer cells against apoptosis. Given that miRNAs target the expression of several genes, in a coordinated manner, often at the nodes of important regulatory pathways, we hypothesized that among miRNAs able to kill chemoresistant ovarian cancer cell lines some may target both Bcl-xL and Mcl-1. Recently, we demonstrated that miR-491-5p induces apoptosis in several ovarian cancer cells by inhibiting directly Bcl-xL and indirectly Mcl-1 through the targeting of EGFR leading to BIM activation. Interestingly, the apoptotic effect of miR-491-5p could be mimicked by a combining an EGFR inhibitor with a BH3-mimetic molecule (two drugs already used in clinical practice). In addition, the knowledge of the precise molecular effect of miR-491-5p provided ways to identify downstream genetic alterations impeding the pro-apoptotic effect of miR-491-5p in another cellular context. The resistance to this combination treatment was finally counteracted by associating pharmacological molecules affecting the involved pathways at pertinent levels. Altogether, our work highlights the potential of phenotype-based miRNA screening approaches to decipher, in the absence of a preconceived idea, new relevant therapeutic targets harboring synthetic lethal interactions to finally propose new rationale drug combinations. To cite this article: Bernard Lambert, et al. miRNAs as tools for tailoring personalized therapeutic strategies in ovarian carcinoma