Abstract: Autophagy is typically activated by starvation, allowing cells and organisms to mobilize their energy reserves. It is known that pharmacological modulation of autophagy represents a therapeutic potential. Here the inventors report that a protein that is released from cells in an unconventional, autophagy-dependent manner, namely, diazepam binding inhibitor (DBI), regulates autophagy. In particular, the inventors demonstrate that DBI inhibits autophagy and that the supply of recombinant DBI to mice enhanced glycolysis, enhanced lipogenesis, and inhibited fatty acid oxidation. The inventors show that neutralisation of DBI by a monoclonal antibody and an active immunization by means of an immunogenic DBI derivative eliciting autoantibodies induce autophagy and lead to metabolic changes that increase starvation-induced weight loss, reduce food intake upon refeeding, and reduce weight gain in response to hypercaloric diets.

Abstract: Described are combination therapies for the treatment of solid tumours, said therapies comprising lurbinectedin and an immune checkpoint inhibitor, for example, anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibodies.

Abstract: Autophagy is typically activated by starvation, allowing cells and organisms to mobilize their energy reserves. It is known that pharmacological modulation of autophagy represents a therapeutic potential. Here the inventors report that a protein that is released from cells in an unconventional, autophagy-dependent manner, namely, diazepam binding inhibitor (DBI), regulates autophagy. In particular, the inventors demonstrate that DBI inhibits autophagy and that the supply of recombinant DBI to mice enhanced glycolysis, enhanced lipogenesis, and inhibited fatty acid oxidation. The inventors show that neutralisation of DBI by a monoclonal antibody and an active immunization by means of an immunogenic DBI derivative eliciting autoantibodies induce autophagy and lead to metabolic changes that increase starvation-induced weight loss, reduce food intake upon refeeding, and reduce weight gain in response to hypercaloric diets.

Abstract: The present invention relates to methods and compositions for the care of breast cancer, from diagnosis to treatment management. The inventors show that LINC01087 downregulation contributes to a more aggressive phenotype of BC, and could represents a novel and promising specific biomarker for the diagnosis of triple-negative breast cancer. The inventors show that LINC01087 upregulation contributes to a less aggressive phenotype of BC, and could represents a novel and promising specific biomarker for the diagnosis of luminal BCs. The invention relates to a method comprising the steps of: i) determining the expression level of the long intergenic non-coding RNA 01087 (LINC01087) in a sample obtained from the subject, and ii) comparing the expression level determined at step i) with a predetermined reference value, wherein detecting difference between the expression level determined at step i) and the predetermined reference value is indicative of an aggressive TNBC or less aggressive luminal BCs.

Abstract: The present invention provides novel methods for the modulation of autophagy and the treatment of autophagy-related diseases, including cancer, neurodegenerative diseases, liver diseases, muscle diseases and pancreatitis.

Abstract: The present inventors show that cannibal cells can undergo senescence after entosis in vivo and that the tumor suppressive protein p53 act as a repressor of this phenomenon. They therefore propose new tools to study the molecular pathways involved in the cannibalism process, for example by measuring the expression levels of p53 or splice variants thereof (such as ?133TP53, TP53?, TP53? or ?40TP53), the release of extracellular ATP or purinergic P2Y2 receptor activity. The present inventors also demonstrated that the detection of senescent cannibal cells in breast adenocarcinoma obtained from patients treated with neo-adjuvant therapy positively correlates with good patient's response to treatment. Altogether, these results provide the first evidence that detection of cellular cannibalism and senescence simultaneously in tumors helps for the diagnosis of disease outcomes and for the prediction of treatment efficiency against cancer diseases.

Abstract: In most cases, cancer chemotherapy and immunotherapy fail to yield durable responses, and complete and permanent regression of established tumors are rare. Here the inventors show that so-called caloric restriction mimetics (CRMs), which are natural or synthetic compounds that pharmacologically mimic the effects of fasting or caloric restriction, can be used to enhance the probability of cancer cure. The administration of several chemically distinct CRMs (such as hydroxycitrate, lipoic acid and the natural polyamine spermidine) led to the complete regression and the induction of protective anticancer immune responses in mouse models. This effect was achieved when CRMs were combined with chemotherapy and immunotherapy targeting the immune checkpoint molecules CTLA-4 and/or PD-1. Hence, caloric restriction and CRMs can be used to sensitize cancers to chemo-immunotherapy.

Abstract: Autophagy is a universal anti-aging mechanism the chronic induction of which can extend the health span and lifespan of mammals Here the inventors show that triethylenetetramine (TETA), also called trientine, a drug that is approved for the treatment of Wilson disease, can induce autophagy in mouse tissues in vivo. In particular, chronic autophagy stimulation by TETA can improve the metabolic characteristics of mice kept on a high-fat or high-sugar diet without reducing their food uptake, yet attenuating their weight gain. TETA attenuates adioposity, signs of obesity related type-2 diabetes and hepatosteatosis. TETA also mediates hepatoprotective effects against acute ethanol intoxication. Hence, TETA can be considered as a novel autophagy-inducing agent and thus can be used for the treatment of various diseases and in particular for the treatment of obesity, as well as obesity-related comorbidities.

Abstract: The present invention relates to methods and pharmaceutical composition for modulation polarization and activation of macrophages. In particular, the present invention relates to methods for modulating macrophage M1/M2 polarization in a subject in need thereof comprising administering to the subject a therapeutically effective amount of P2Y2 receptor agonists or antagonists.

Abstract: Autophagy is typically activated by starvation, allowing cells and organisms to mobilize their energy reserves. It is known that pharmacological modulation of autophagy represents a therapeutic potential. Here the inventors report that a protein that is released from cells in an unconventional, autophagy-dependent manner, namely, diazepam binding inhibitor (DBI), regulates autophagy. In particular, the inventors demonstrate that DBI inhibits autophagy and that the supply of recombinant DBI to mice enhanced glycolysis, enhanced lipogenesis, and inhibited fatty acid oxidation. The inventors show that neutralisation of DBI by a monoclonal antibody and an active immunization by means of an immunogenic DBI derivative eliciting autoantibodies induce autophagy and lead to metabolic changes that increase starvation-induced weight loss, reduce food intake upon refeeding, and reduce weight gain in response to hypercaloric diets.

Abstract: The present invention provides novel methods for the modulation of autophagy and the treatment of autophagy-re lated diseases, including cancer, neurodegenerative diseases, liver diseases, muscle diseases and pancreatitis.

Abstract: The present invention relates to methods and pharmaceutical composition for modulation polarization and activation of macrophages. In particular, the present invention relates to methods for modulating macrophage M1/M2 polarization in a subject in need thereof comprising administering to the subject a therapeutically effective amount of P2Y2 receptor agonists or antagonists.

Abstract: The present invention provides methods and pharmaceutical compositions for treating human immunodeficiency virus type 1 (HIV-1) infections. In particular, the present invention relates to a method for treating HIV-1 infection in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an inhibitor of SGT1 activity or expression.

Abstract: The present inventors show that cannibal cells can undergo senescence after entosis in vivo and that the tumor suppressive protein p53 act as a repressor of this phenomenon. They therefore propose new tools to study the molecular pathways involved in the cannibalism process, for example by measuring the expression levels of p53 or splice variants thereof (such as ?133TP53, TP53?, TP53? or ?40TP53), the release of extracellular ATP or purinergic P2Y2 receptor activity. The present inventors also demonstrated that the detection of senescent cannibal cells in breast adenocarcinoma obtained from patients treated with neo-adjuvant therapy positively correlates with good patient's response to treatment. Altogether, these results provide the first evidence that detection of cellular cannibalism and senescence simultaneously in tumors helps for the diagnosis of disease outcomes and for the prediction of treatment efficiency against cancer diseases.

Abstract: The present invention provides methods and pharmaceutical compositions for treating human immunodeficiency virus type 1 (HIV-1) infections. In particular, the present invention relates to a method for treating HIV-1 infection in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an inhibitor of SGT1 activity or expression.

Abstract: There is disclosed a combination of inhibitors of Tissue Transglutaminase (TG2), inhibitors of reactive oxygen species (ROS) and CFTR channel activators (potentiators) for separate, sequential or simultaneous administration to CF patients carrying the ?F508-CFTR mutation, and pharmaceutical compositions thereof.

Abstract: The present inventors show that cannibal cells can undergo senescence after entosis in vivo and that the tumor suppressive protein p53 act as a repressor of this phenomenon. They therefore propose new tools to study the molecular pathways involved in the cannibalism process, for example by measuring the expression levels of p53 or splice variants thereof (such as ?133TP53, TP53?, TP53? or ?40TP53), the release of extracellular ATP or purinergic P2Y2 receptor activity. The present inventors also demonstrated that the detection of senescent cannibal cells in breast adenocarcinoma obtained from patients treated with neo-adjuvant therapy positively correlates with good patient's response to treatment. Altogether, these results provide the first evidence that detection of cellular cannibalism and senescence simultaneously in tumors helps for the diagnosis of disease outcomes and for the prediction of treatment efficiency against cancer diseases.

Abstract: The present invention provides novel methods for the modulation of autophagy and the treatment of autophagy-related diseases, including cancer, neurodegenerative diseases, liver diseases, muscle diseases and pancreatitis.

Abstract: The present invention relates to a recombinant inner mitochondrial membrane polypeptide, and its use in methods for treating mitochondrial disorders.

Abstract: There is disclosed a combination of inhibitors of Tissue Transglutaminase (TG2), inhibitors of reactive oxygen species (ROS) and CFTR channel activators (potentiators) for separate, sequential or simultaneous administration to CF patients carrying the ?F508-CFTR mutation, and pharmaceutical compositions thereof.