Abstract: The present application relates to the field of leukemias, and more in particular to how P1 GF inhibition can help to treat Philadelphia chromosome positive (Ph+) leukemias. Methods are provided for treating Ph+ leukemias by administering P1 GF inhibitors. Also disclosed are uses of P1 GF inhibitors in the treatment of Ph+ leukemias, or for the preparation of a medicament against Ph+ leukemias.

Abstract: The invention is concerned with a method of determining whether a patient is more suitably treated by a therapy with an angiogenesis inhibitor, such as bevacizumab, by determining the genotype of VEGFR-1 gene. The invention further relates to a pharmaceutical composition comprising an angiogenesis inhibitor, such as bevacizumab, for the treatment of a patient suffering from cancer based on the genotype of VEGFR-1 gene. The invention further relates to a method for improving the treatment effect of chemotherapy of a patient suffering from cancer by adding an angiogenesis inhibitor, such as bevacizumab, based on the genotype of VEGFR-1 gene.

Abstract: The present invention relates to an extracellular binding domain for an allosteric inhibitor, whereby said binding domain is derived from a single membrane span tyrosine kinase receptor. More specifically, the invention relates to an extracellular domain derived from a Fibroblast Growth Factor Receptor (FGFR). It further relates to the use of this domain for the identification of similar domains in the extracellular part of other tyrosine kinase receptors, and to a screening method for identification of a small compound allosteric inhibitor.

Abstract: This disclosure relates to the field of angiogenesis, more particularly to the field of pathological angiogenesis. In particular, the disclosure has found that inhibitors reducing the activity of the enzyme carnitine palmitoyltransferase 1A can be used for treatment of diseases in which pathological angiogenesis is involved. In particular, the disclosure provides siRNAs directed against carnitine palmitoyltransferase 1A for the treatment of pathological angiogenesis. The disclosure also provides the use of a therapeutically effective amount of inhibitors of carnitine palmitoyltransferase 1A, or a pharmaceutically acceptable salt thereof, for the treatment of pathological angiogenesis.

Abstract: The present invention relates to an extracellular binding domain for an allosteric inhibitor, whereby said binding domain is derived from a single membrane span tyrosine kinase receptor. More specifically, the invention relates to an extracellular domain derived from a Fibroblast Growth Factor Receptor (FGFR). It further relates to the use of this domain for the identification of similar domains in the extracellular part of other tyrosine kinase receptors, and to a screening method for identification of a small compound allosteric inhibitor.

Abstract: The present invention provides novel monoclonal antibodies directed to PlGF and fragments and derivatives thereof, more particularly to humanized antibodies and fragments thereof for use in the treatment and/or prevention of pathological angiogenesis.

Abstract: The invention is concerned with a method of determining whether a patient is more suitably treated by a therapy with an angiogenesis inhibitor, such as bevacizumab, by determining the genotype of VEGFR-1 gene. The invention further relates to a pharmaceutical composition comprising an angiogenesis inhibitor, such as bevacizumab, for the treatment of a patient suffering from cancer based on the genotype of VEGFR-1 gene. The invention further relates to a method for improving the treatment effect of chemotherapy of a patient suffering from cancer by adding an angiogenesis inhibitor, such as bevacizumab, based on the genotype of VEGFR-1 gene.

Abstract: The present invention provides novel monoclonal antibodies directed to P1GF and fragments and derivatives thereof, more particularly to humanized antibodies and fragments thereof for use in the treatment and/or prevention of pathological angiogenesis.

Abstract: The present invention provides novel monoclonal antibodies directed to PlGF and fragments and derivatives thereof, more particularly to humanized antibodies and fragments thereof for use in the treatment and/or prevention of pathological angiogenesis.

Abstract: A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. Therefore the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2+/? mice was studied. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation, and inhibited tumor cell invasion, intravasation and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent phenotype of a filopodia-lacking “phalanx” cell type. Without being bound to a particular mechanism, this transition could at least in part be explained by upregulation of (soluble) VEGFR-1 and VE-cadherin.

Abstract: The present invention relates to the field of pathological angiogenesis and arteriogenesis and, in particular, to a stress-induced phenotype in a transgenic mouse (PIGF?/?) that does not produce Placental Growth Factor (PIGF) and that demonstrates an impaired vascular endothelial growth factor (VEGF)-dependent response. PIGF deficiency has a negative influence on diverse pathological processes of angiogenesis, arteriogenesis and vascular leakage comprising ischemic retinopathy, tumor formation, pulmonary hypertension, vascular leakage (edema formation) and inflammatory disorders. The invention thus relates to molecules that can inhibit the binding of PIGF to its receptor (VEGFR-1), such as monocloncal antibodies and tetrameric peptides, and to the use of these molecules to treat the above-mentioned pathological processes.

Abstract: The present invention relates to the field of pathological angiogenesis and arteriogenesis and, in particular, to a stress-induced phenotype in a transgenic mouse (PIGF?/?) that does not produce Placental Growth Factor (PIGF) and that demonstrates an impaired vascular endothelial growth factor (VEGF)-dependent response. PIGF deficiency has a negative influence on diverse pathological processes of angiogenesis, arteriogenesis and vascular leakage comprising ischemic retinopathy, tumor formation, pulmonary hypertension, vascular leakage (edema formation) and inflammatory disorders. The invention thus relates to molecules that can inhibit the binding of PIGF to its receptor (VEGFR-1), such as monocloncal antibodies and tetrameric peptides, and to the use of these molecules to treat the above-mentioned pathological processes.

Abstract: The present invention relates to the field of pathological angiogenesis and arteriogenesis and, in particular, to a stress-induced phenotype in a transgenic mouse (PIGF?/?) that does not produce Placental Growth Factor (PIGF) and that demonstrates an impaired vascular endothelial growth factor (VEGF)-dependent response. PIGF deficiency has a negative influence on diverse pathological processes of angiogenesis, arteriogenesis and vascular leakage comprising ischemic retinopathy, tumor formation, pulmonary hypertension, vascular leakage (edema formation) and inflammatory disorders. The invention thus relates to molecules that can inhibit the binding of PIGF to its receptor (VEGFR-1), such as monocloncal antibodies and tetrameric peptides, and to the use of these molecules to treat the above-mentioned pathological processes.

Abstract: The disclosure relates to the field of ischemia and how to increase tissue perfusion in ischemic tissue by cellular therapy. Specifically, the beneficial effects of myeloid (bone marrow-derived) cells with a particular arteriogenic gene expression profile are shown, and it is shown that increased arteriogenesis and perfusion is specifically due to the effects of combined PDGFB and SDF-1. The arteriogenic gene profile of the myeloid cells used for therapy can, for instance, be obtained by inhibition of PHD2.

Abstract: The present invention relates to the field of pathological angiogenesis and arteriogenesis and, in particular, to a stress-induced phenotype in a transgenic mouse (PIGF?/?) that does not produce Placental Growth Factor (PIGF) and that demonstrates an impaired vascular endothelial growth factor (VEGF)-dependent response. PIGF deficiency has a negative influence on diverse pathological processes of angiogenesis, arteriogenesis and vascular leakage comprising ischemic retinopathy, tumor formation, pulmonary hypertension, vascular leakage (edema formation) and inflammatory disorders. The invention thus relates to molecules that can inhibit the binding of PIGF to its receptor (VEGFR-1), such as monocloncal antibodies and tetrameric peptides, and to the use of these molecules to treat the above-mentioned pathological processes.

Abstract: The present invention relates to methods for improving the overall survival of a patient suffering from a malignant disease or a disease involving physiological and pathological angiogenesis by treatment with an angiogenesis inhibitor, such as bevacizumab, by determining the presence of one or more variant alleles of the vascular endothelial growth factor receptor 1 (VEGFR-1) gene. The present invention further provides methods for improving the progression-free survival of a patient suffering from a malignant disease or a disease involving physiological and pathological angiogenesis by treatment with an angiogenesis inhibitor, such as bevacizumab, by determining the presence of one or more variant alleles of the VEGFR-1 gene. The present invention also provides for methods for assessing the responsiveness of a patient to an angiogenesis inhibitor by determining the presence of one or more variant alleles of the VEGFR-1 gene.

Abstract: The present invention relates to an extracellular binding domain for an allosteric inhibitor, whereby said binding domain is derived from a single membrane span tyrosine kinase receptor. More specifically, the invention relates to an extracellular domain derived from a Fibroblast Growth Factor Receptor (FGFR). It further relates to the use of this domain for the identification of similar domains in the extracellular part of other tyrosine kinase receptors, and to a screening method for identification of a small compound allosteric inhibitor.

Abstract: A key function of blood vessels, to supply oxygen, is impaired in tumors because of abnormalities in their endothelial lining. PHD proteins serve as oxygen sensors and may regulate oxygen delivery. Therefore the role of endothelial PHD2 in vessel shaping by implanting tumors in PHD2+/? mice was studied. Haplodeficiency of PHD2 did not affect tumor vessel density or lumen size, but normalized the endothelial lining and vessel maturation. This resulted in improved tumor perfusion and oxygenation, and inhibited tumor cell invasion, intravasation and metastasis. Haplodeficiency of PHD2 redirected the specification of endothelial tip cells to a more quiescent phenotype of a filopodia-lacking “phalanx” cell type. Without being bound to a particular mechanism, this transition could at least in part be explained by upregulation of (soluble) VEGFR-1 and VE-cadherin.

Abstract: The present invention relates to neurological and physiological dysfunction associated with neuron disorders. In particular, the invention relates to the involvement of vascular endothelial growth factor (VEGF) and homologues in the aetiology of motor neuron disorders. The invention further concerns a novel, mutant transgenic mouse (VEGFm/m) with a homozygous deletion in the hypoxia responsive element (HRE) of the VEGF promoter which alters the hypoxic upregulation of VEGF. These mice suffer severe adult onset muscle weakness due to progressive spinal motor neuron degeneration which is reminiscent of amyotrophic lateral sclerosis (ALS)—a fatal disorder with unknown aetiology. Furthermore, the neuropathy of these mice is not caused by vascular defects, but is due to defective VEGF-mediated survival signals to motor neurons.

Abstract: The present application relates to the field of leukemias, and more in particular to how P1 GF inhibition can help to treat Philadelphia chromosome positive (Ph+) leukemias. Methods are provided for treating Ph+ leukemias by administering P1 GF inhibitors. Also disclosed are uses of P1 GF inhibitors in the treatment of Ph+ leukemias, or for the preparation of a medicament against Ph+ leukemias.