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    NEW STRATEGY TARGETING STROMA/TUMOR CELL CROSSTALK TO TREAT A CANCER
    1.
    发明申请
    NEW STRATEGY TARGETING STROMA/TUMOR CELL CROSSTALK TO TREAT A CANCER 审中-公开

    公开(公告)号：WO2023089159A1

    公开(公告)日：2023-05-25

    申请号：PCT/EP2022/082555

    申请日：2022-11-21

    Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE ,  UNIVERSITÉ D'AIX MARSEILLE ,  INSTITUT JEAN PAOLI & IRENE CALMETTES

    Inventor： TOMASINI, Richard ,  NIGRI, Jérémy ,  TUBIANA, Sarah

    IPC: G01N33/574 ,  A61P35/00

    Abstract: In this study, the Inventors report that CD9 is a key component of PC-associated CAFs-derived ANXA6+-EVs. They determined that CD9 is expressed by PC-associated CAFs in vitro as well as in vivo. Targeting CD9 impaired CAFs-derived ANXA6+-EVs uptake by pancreatic cancer cells, which consequently decreases their migratory abilities. Signaling pathway arrays highlighted p38/MAPK as activated in pancreatic cancer cells following CAFs-derived ANXA6+/CD9+-EVs uptake. The use of CD9 blocking antibody, p38 siRNA or chemical inhibitors impaired pancreatic cancer cells abilities following incubation with CAFs-derived ANXA6+/CD9+-EVs. Finally, they revealed CD9 expression as an independent poor-prognosis marker in human PC samples. Collectively their data highlight the key role of CD9 in CAFs-derived ANXA6+-EVs internalization by pancreatic cancer cells and the consequent, and mandatory, activation of p38/MAPK pathway to foster their migratory abilities. Measuring the oncogenic CAFs-derived ANXA6+/CD9+-EVs then limiting their action on pancreatic cancer cells abilities might be a promising option for PC stratification and treatment.

    A NUMERICAL METHOD FOR THE SEPARATION OF SHEAR AND COMPRESSION WAVES IN A DISPLACEMENT VECTOR FIELD
    2.
    发明申请
    A NUMERICAL METHOD FOR THE SEPARATION OF SHEAR AND COMPRESSION WAVES IN A DISPLACEMENT VECTOR FIELD 审中-公开

    公开(公告)号：WO2023084129A1

    公开(公告)日：2023-05-19

    申请号：PCT/EP2022/082049

    申请日：2022-11-15

    Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITE DE LYON ,  CENTRE LEON BERARD

    Inventor： SOUCHON, Rémi ,  DERUELLE, Tristan ,  AICHELE, Johannes ,  CATHELINE, Stefan

    IPC: G01R33/563

    Abstract: Nowadays, the interest to use mechanical waves in various field such medical field or geophysical field is well established. Indeed, the study of mechanical waves propagating in a medium allows usually to retrieve the properties of this medium. In solid media, a mechanical wave is composed of two components: a compression wave and a shear wave. Depending on the field of application, it may be preferable to characterize only one of the components. However, the discretization of each component of the mechanical waves may be difficult and conventional methods are not necessarily suitable for some media. The present disclosure overcomes the above drawback by proposing a new method for separating a displacement vector field U resulting from the displacement of a mechanical wave in a medium into its shear component and its compression component. Such method is particularly adapted when the components of the mechanical waves propagate with similar speed in the medium, for instance a shear wave and a slow Biot wave in a poroelastic medium.

    PHOTOACTIVATABLE ION CHANNEL MODULATOR
    3.
    发明申请
    PHOTOACTIVATABLE ION CHANNEL MODULATOR 审中-公开

    公开(公告)号：WO2023067366A1

    公开(公告)日：2023-04-27

    申请号：PCT/IB2021/000737

    申请日：2021-10-18

    Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  NANTES UNIVERSITÉ ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

    Inventor： DE WAARD, Michel ,  MONTNACH, Jérôme

    IPC: A61K38/17 ,  A61P9/00

    Abstract: Despite the presence of multiple disulphide bridges and the complicated tertiary structure of the venom peptide, the inventors in the present application showed that caging strategy involving covalent attachment of a photolabile protecting group on the lateral chain of a key residue for venom peptide activity causes steric clashes which are important enough to reduce the ion channel modulation efficacy. The inventors showed that the photoactivatable venom peptide which presents a shift of at least 100-fold of the dose-response value of normalized ion channel current in comparison to wild-type venom peptide is required to be effective under physiological conditions. The inventors showed for the first time that the chemical and photosensitive properties conferred to toxins allowed to probe the role of ion channel function in vivo with high spatial resolution making its therapeutic use possible. As further shown by the inventors, the technique can be generalized to toxins possessing more or less ion channel selectivity and is applicable to both inhibitors and activators. The present disclosure relates to a photoactivatable ion channel modulator, in particular for use in the treatment of an ion channel-related disease wherein said photoactivatable ion channel modulator is a disulphide-rich venom peptide comprising a photolabile protecting group.

    METHODS FOR TREATING AUTISM SPECTRUM DISORDERS
    7.
    发明申请
    METHODS FOR TREATING AUTISM SPECTRUM DISORDERS 审中-公开

    公开(公告)号：WO2023031379A1

    公开(公告)日：2023-03-09

    申请号：PCT/EP2022/074419

    申请日：2022-09-02

    Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  UNIVERSITÉ DE TOURS

    Inventor： BECKER, Jérôme ,  LE MERRER, Julie

    IPC: A61K31/167 ,  A61K33/14 ,  A61P25/00

    Abstract: Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behavior. To date, no pharmacological treatment has been approved that ameliorates social behavior in patients with ASD. Based on the excitation/inhibition imbalance theory of autism, the Inventors hypothesized that bromide ions, long used as an antiepileptic medication, could relieve core symptoms of ASD. They evaluated the effects of chronic sodium bromide (NaBr) administration on autistic-like symptoms in three genetic mouse models of autism: Oprm1-/-, Fmr1-/- and Shank3Δex13-16-/- mice. They showed that chronic NaBr treatment relieved autistic-like behaviors in these three models. In Oprm1-/- mice, these beneficial effects were superior to those of chronic bumetanide administration. At transcriptional level, chronic NaBr in Oprm1 null mice was associated with increased expression of genes coding for chloride ions transporters, GABAA receptor subunits, oxytocin and mGlu4 receptor. Lastly, they uncovered synergistic alleviating effects of chronic NaBr and a positive allosteric modulator (PAM) of mGlu4 receptor on autistic-like behavior in Oprm1-/- mice. They evidenced in heterologous cells that bromide ions behave as PAMs of mGlu4, providing a molecular mechanism for such synergy. Their data reveal the therapeutic potential of bromide ions, alone or in combination 0 with a PAM of mGlu4 receptor, for the treatment of ASDs.

    USE OF BRANCHED CHAIN FATTY ACIDS (BCFAS) FOR THE TREATMENT OF INTESTINAL INFLAMMATION
    8.
    发明申请
    USE OF BRANCHED CHAIN FATTY ACIDS (BCFAS) FOR THE TREATMENT OF INTESTINAL INFLAMMATION 审中-公开

    公开(公告)号：WO2023031226A1

    公开(公告)日：2023-03-09

    申请号：PCT/EP2022/074122

    申请日：2022-08-30

    Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  CENTRE HOSPITALIER UNIVERSITAIRE DE ROUEN ,  UNIVERSITÉ DE ROUEN NORMANDIE

    Inventor： RIBET, David ,  DECHELOTTE, Pierre ,  EZZINE, Chaima

    IPC: A61K31/19 ,  A61P1/00

    Abstract: The gut microbiota produces a wide variety of metabolites, which interact with intestinal cells by modulating either gene transcription or post-translational modifications of gut proteins. The effect of gut commensal bacteria on SUMOylation, an essential ubiquitin-like modification in intestinal physiology, remains however unknown. Here, the inventors show that branched chain fatty acids (BCFAs) increase protein SUMOylation in different intestinal cell lines. They demonstrated that the hyperSUMOylation induced by BCFAs inhibits the activation of the NF-κB pathway by blocking the degradation of the inhibitory factor ΙκBα in response to TNFα. This results in a decrease in pro-inflammatory cytokines expression as well as a decrease in intestinal epithelial permeability in response to TNFα. Accordingly, the present invention relates to the use of Branched Chain Fatty Acids (BCFAs) for the treatment of diseases associated with intestinal inflammation such as Inflammatory Bowel Diseases and Irritable Bowel Syndrome.

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