Abstract: Acute chest syndrome (ACS) is a common and potentially lethal form of acute lung injury in sickle cell disease (SCD). Because pathophysiology remains unclear, therapeutic options are limited to supportive care with empiric antibiotics and red cell transfusion in case of aggravation. A role of inflammation mediated by endothelial and immune cells has been suspected but the levels of pro-inflammatory cytokines and chemokines in the lungs during ACS have not yet been investigated. Here the inventors report dramatically high levels of IL-6, unlike IL-1? and TNF-?, in the sputum from SCD children during ACS (n=12) compared with non-ACS sputum (n=6). By contrast, plasma IL-6 levels were not significantly increased during ACS (n=12), compared with vaso-occlusive crisis (n=12), steady state (n=12) and healthy controls (n=9). IL-6 levels were more than 150-fold higher in sputum than in plasma, suggesting increased local production by inflammatory cells during ACS.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of diseases mediated by the NRP-1/OBR complex signaling pathway. In particular, the present invention relates to a method for treating a disease selected from the group consisting of cancers, obesity and obesity related diseases, anorexia, autoimmune diseases and infectious diseases in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an antagonist of the NRP-1/OBR signaling pathway.

Abstract: A 2-aminoarylthiazole derivative or a pharmaceutically acceptable salt or solvate thereof, in particular masitinib or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of sickle cell disease in a patient in need thereof. Also, a 2-aminoarylthiazole derivative or a pharmaceutically acceptable salt or solvate thereof, in particular masitinib or a pharmaceutically acceptable salt or solvate thereof, for use in the prevention and/or treatment of acute chest syndrome (ACS) in a sickle cell disease patient in need thereof.

Abstract: Adult T-cell leukemia/lymphoma (ATL) is an aggressive proliferation of mature activated CD4+ T cells associated with the human T-cell lymphotropic virus type I (HTLV-I). The inventors performed an integrated genomic analysis of a retrospective cohort of 62 ATL patients mainly originating from Africa and the Caribbean area. In particular, they identified a subset of mutations in the TCR/NF-KB pathway (PLCG1, CARD11, PRKCB, CBLB, IRF4, CSNK1A1, FYN, RHOA, VAV1). Furthermore, the inventors investigated the effects of an anti-CD3 antibody (OKT3) exposure on 4 ATL samples including 2 cases harboring CARD 11 and PRKCB gain of function alterations and 2 cases without any TCR pathway mutation. The data suggest that ATL harboring TCR pathway mutations clearly responded to anti-CD3 (FIG. 1B, red+OKT3) and died by apoptosis possibly by a mechanism resembling AICD. Importantly, these TCR-pathway/NFKB mutated patients also showed poorer outcome as compared to unmutated cases.

Abstract: Neuropilin-1 is henceforth a relevant target in cancer treatment, however way-of-action is remains partly elusive and the development of small inhibitory molecules is therefore required for its study. Here, the inventors report that two neuropilin small-sized antagonists (NRPa-47, NRPa-48), VEGF-A165/NRP-1 binding inhibitors, are able to decrease VEGF-Rs phosphorylation and to modulate their downstream cascades in triple negative breast cancer cell line (MDA-MB-231). In particular, the inventors showed for the first time, how NRPa may altered tumor cell signaling and contributed in the down-modulation of the cancer therapeutic key factor p38?-kinase phosphorylation. More importantly, the association of NRPa with a p38? inhibitor leads to additional and/or synergistic effect of these drugs (depending of the dose used) for significantly reducing breast cancer cell proliferation Thus, the efficient association of NRPa and p38?-kinase inhibitors are thus credible for the treatment of cancer.

Abstract: The inventors demonstrate for the first time the activation of the Hedgehog (HH) signaling pathway in normal and abnormal human mast cells (MCs). These results prompt the inventors to explore the consequence of the inhibition of the HH pathway, especially the canonical pathway, on MC proliferation. They demonstrate that Hedgehog inhibitors inhibit proliferation and induces apoptosis of mast cells. Accordingly the present invention relates to a method of treating a mast cell disease in a patient in need there of comprising administering to the patient a therapeutically effective amount of a Hedgehog inhibitor.

Abstract: A number of anti-angiogenic strategies connected with the VEGF signalling pathway are used in current clinical treatment or trial phase, but they either cause adverse effects or are not specific. Various strategies were aimed at identifying peptides inhibiting the VEGF-A165/NRP-1 interaction. A well-known antiangiogenic peptide is the heptapeptide termed “A7R” having the amino acid sequence ATWLPPR, for which various derivatives have been synthesized, which include peptides having the general sequence Lys(hArg)-AA2-AA3-Arg. However, the ability of the known peptides to inhibit the VEGF-A165/NRP-1 interaction was too low for their use as candidate drugs for inhibiting angiogenesis in subjects in need thereof. The present inventors have now conceived a family of novel peptide-like compounds having a nanomolar affinity for NRP-1, which are thus endowed with a powerful capacity to inhibit the VEGF-A165/NRP-1 interaction.

Abstract: Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells QI predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRP1 and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g.

Abstract: The invention relates to the combined use of selective serotonin reuptake inhibitors (SSRIs) and hematopoietic growth factors as a drug and particularly for treating cytopenia related to hematopoietic diseases or chemotherapy, and also to a pharmaceutical kit comprising both SSRIs and hematopoietic growth factors. This combination is more particularly used for treating patients presenting cytopenia, and patients in need of chemotherapy and more particularly to reduce length of chemotherapy-induced aplasia.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations: ROSA ? 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations : ROSA ? 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.

Abstract: The present invention relates to agents capable of inhibiting the binding between Leptin and Neuropilin-1 (NRP1) and uses thereof in the therapeutic field.

Abstract: The present invention relates to the use of hydroxycarbamide (HC) for reducing and/or delaying the extension of capillary nonperfusion, a cause of irreparable visual impairment in patients suffering from central retinal vein occlusion (CRVO). This is the first systemic treatment which makes it possible to reduce retinal ischemic complications in patients in whom (CRVO) has been recently diagnosed and is consequently in a rapidly progressive phase. Given the low toxicity of HC evaluated on a large scale in children and adults in the context of other diseases for decades, the results of the present study open up a new therapeutic approach in the treatment of CRVO.

Abstract: The inventors demonstrate for the first time the activation of the Hedgehog (HH) signaling pathway in normal and abnormal human mast cells (MCs). These results prompt the inventors to explore the consequence of the inhibition of the HH pathway, especially the canonical pathway, on MC proliferation. They demonstrate that Hedgehog inhibitors inhibit proliferation and induces apoptosis of mast cells. Accordingly the present invention relates to a method of treating a mast cell disease in a patient in need there of comprising administering to the patient a therapeutically effective amount of a Hedgehog inhibitor.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations : ROSA ? 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.

Abstract: Provided herein are methods of treating diseases associated with anemia or ineffective erythropoiesis by using the level and/or activity of a ligand of an activin receptor, in particular, Growth differentiation factor 11 (GDF11), as an indicator of responsiveness of a patient to the treatment, efficacy of the treatment, or appropriate dosage for the treatment with an activin type II receptor inhibitor.

Abstract: The present invention relates to methods and pharmaceutical compositions for the treatment of diseases mediated by the NRP-1/OBR complex signaling pathway. In particular, the present invention relates to a method for treating a disease selected from the group consisting of cancers, obesity and obesity related diseases, anorexia, autoimmune diseases and infectious diseases in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an antagonist of the NRP-1/OBR signaling pathway.

Abstract: The present invention relates to a method for determining whether a candidate human transplant donor is at risk of inducing acute graft versus host disease (aGVHD) in a human transplant recipient, which may in turn allow the selection of a donor exhibiting no risk for the recipient. The present invention also relates to a method for adjusting the immunosuppressive treatment administered to a human transplanted recipient following its graft transplantation after having performing the method for determining risk of the invention. The methods comprise expanding the candidate donor's iNKT cells (invariant NKT cells) and determining the presence or absence of expansion of the CD4(?) iNKT cell sub-population. In particular, CD3+CD4? TCRV[alpha]24V[beta]11 cells are determined. Kits are disclosed.

Abstract: The present invention concerns a combination of (i) a DNA methylation inhibitor, and (ii) a Vitamin D receptor agonist, for simultaneous or sequential use in the treatment of a drug resistant cancer and/or in prevention of tumor relapse in a patient suffering from cancer. The present invention also relates to a combination of (i) a DNA methylation inhibitor, and (ii) a Vitamin D receptor agonist, for increasing, restoring or enhancing sensitivity of a patient suffering from cancer to a chemotherapeutic drug in a patient suffering from cancer.

Abstract: The present invention relates to agents capable of inhibiting the binding between Leptin and Neuropilin-1 (NRP1) and uses thereof in the therapeutic field.