Abstract: The present findings point to mutant HSCs as the cause of BM neuroglial damage that compromises MSC survival and function, critically contributing to MPN pathogenesis. In this sense, the present invention shows that the niche damage triggered by the mutant HSC is essential for the development of a haematopoietic malignancy previously considered to be caused by the HSC alone. Targeting HSC niche-forming MSCs and their neural regulation paves the way to more efficient therapeutic strategies in MPN. For this purpose, the present invention shows that an efficient therapeutic strategy for the treatment of MPN lies on the administration of neuroprotective compounds, such as 4-methylcatechol, capable of protecting BM sympathetic nerve fibres. Additionally, another efficient therapeutic strategy is shown herein as the administration of selective ?3-adrenergic agonists such as BRL37344 or Mirabegron, since this strategy will compensate for deficient sympathetic stimulation of nestin+ MSCs.

Abstract: The present invention relates to a pharmaceutical composition which includes a HMG-CoA reductase inhibitor, in particular, a statin and acetylsalicylic acid in a manner to minimize interaction of acetylsalicylic acid with the statin, for use in the prevention or treatment of cardiovascular diseases.

Abstract: There is provided compounds of formula I, wherein R1, R2a, R2b, R2c, X, Y, Z, R3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds.

Abstract: There is provided compounds of formula (I), wherein A1, A4, A4a, A5, B1, B1a, B2, B2a, B3, B3a, B4, B4a and R3 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

Abstract: The present invention relates to a novel antibody against ephrin B2 and its use to detect the protein and as a medicament for inhibiting angiogenesis and lymphangiogenesis in the treatment of diseases in which these processes are implicated, for example, cancer.

Abstract: The invention relates inhibiting nucleic acids directed at mammalian homologues of the Drosophila fwe gene (Flower) and to antibodies against the respective proteins, and their use in diagnosing, preventing and treating cancer.

Abstract: There is provided compounds of formula I, wherein R1, R2a, R2b, R2c, X, Y, Z, R3 and ring A/B have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K, PIM family kinase and/or mTOR) is desired and/or required, and particularly in the treatment of cancer. The invention also relates to combinations containing such compounds.

Abstract: There is provided compounds of formula (I): wherein R1, R2 and R3 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K) is desired and/or required, and particularly in the treatment of cancer.

Abstract: There is provided compounds of formula (I), wherein R1, R2, R3, R4 and R5 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

Abstract: Process for the identification of compounds for treating cancer. The invention relates to a method for identifying candidate compounds for use as therapeutic agents for the treatment of cancer, among those who are able to activate the MDA-5 protein or increase NOXA protein levels and to trigger autophagy. It is based on the fact that activation of dsRNA sensor MDA-5 is able to trigger the destruction of cancer cells by activation both autophagy and apoptosis, autonomously and selectively in tumor cells, without provoking the stabilization of the natural antagonist NOXA, MCL-1. The invention also relates to the use of double-stranded RNAs of the same or similar nature such as polyinosinic-polycytidylic acid (pIC), complexed with carriers such as polyethylenimine polycation (PEI), for the manufacture of medicines for the treatment of cancer.

Abstract: The first aspect of the invention relates to a phosphoinositide 3-kinase inhibitor for use in the treatment or prevention of a disease or condition associated with the expression of peroxisome proliferator-activated receptor gamma coactivator 1-? (Pgd1?) and/or uncoupling protein 1 (Thermogenin/Ucp1) in brown adipocytes. The disease or condition may be positive energy imbalance-associated, for example, obesity, an obesity-associated disease or condition, steatosis and biological aging (performance aging). Another aspect of the invention provides the use of a phosphoinositide 3-kinase inhibitor for promoting weight loss in an individual.

Abstract: The present invention relates to a novel antibody against ephrin B2 and its use to detect the protein and as a medicament for inhibiting angiogenesis and lymphangiogenesis in the treatment of diseases in which these processes are implicated, for example, cancer.

Abstract: There is provided compounds of formula (I), wherein A1, A4, A4a, A5, B1, B1a, B2, B2a, B3, B3a, B4, B4a and R3 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

Abstract: There is provided compounds of formula (I), wherein R1, R2, R3 and R4 have meanings given in the description (and which compounds are optionally substituted as indicated in the description), and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PIM family kinase, such as PIM-1, PIM-2 and/or PIM-3) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease. There is also provided combinations comprising the compounds of formula (I).

Abstract: There is provided compounds of formula (I), wherein A1, A4, A4a, A5, B1, B1a, B2, B2a, B3, B3a, B4, B4a and R3 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

Abstract: There is provided compounds of formula (I), wherein A1, A2, A3, A4, n, the dotted lines, B1, B1a, B2, B2a, B3, B3a, B4, B4a, R2 and R3 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.

Abstract: The present invention relates to the use of at least one isolated multipotent stem cell for maintaining haematopoiesis in vitro, in which said multipotent stem cell is preferably a mesenchymal stem cell or, more preferably, said mesenchymal stem cell is a mesenchymal stem cell capable of expressing the nestin protein. The present invention also relates to an isolated cell population of adult nestin-positive mesenchymal cells from a mammal, including humans, to the use thereof for producing a drug for maintaining haematopoiesis in a mammal, for the prevention and/or treatment of at least one disease associated with a malfunction in maintaining haematopoiesis in a mammal, and for maintaining and expanding adult haematopoietic stem cells of said mammal, including a human. Furthermore, the present invention also relates to a method for maintaining haematopoiesis in vitro or to a method for evaluating the haematopoietic capacity of a mammal.

Abstract: Process for the identification of compounds for treating cancer. The invention relates to a method for identifying candidate compounds for use as therapeutic agents for the treatment of cancer, among those who are able to activate the MDA-5 protein or increase NOXA protein levels and to trigger autophagy. It is based on the fact that activation of dsRNA sensor MDA-5 is able to trigger the destruction of cancer cells by activation both autophagy and apoptosis, autonomously and selectively in tumor cells, without provoking the stabilization of the natural antagonist NOXA, MCL-1. The invention also relates to the use of double-stranded RNAs of the same or similar nature such as polyinosinic-polycytidylic acid (pIC), complexed with carriers such as polyethylenimine polycation (PEI), for the manufacture of medicines for the treatment of cancer.

Abstract: There is provided compounds of formula (I): wherein R1, R2 and R3 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. PI3-K, particularly class I PI3K) is desired and/or required, and particularly in the treatment of cancer.

Abstract: There is provided compounds of formula (I), wherein R1, R2, R3, R4 and R5 have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. a PI3-K and/or mTOR) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.