Abstract: Methods for Activating endothelial growth factors VEGF-C or VEGF-D with plasmin, and methods of treatment comprising administering a pharmaceutical compositions comprising plasmin. Also disclosed are methods of screening for inhibitors of activation of the growth factors by plasmin, and method of treatment by blocking activation of VEGF-C/D activation by plasmin. Further disclosed are methods for screening for other proteases that activate VEGF-CD, and for inhibitors of such activation. The invention further includes inhibitors of plasmin activity and methods of treating patients in need thereof with said inhibitors.

Abstract: A method for treating and alleviating disease characterized by the expression of VEGF-D involving screening to find an organism with tumor cells expressing VEGF-D and administering an effective amount of a VEGF-D antagonist; a method for screening for neoplastic diseas, where detection of VEGF-D on or in a sample such as tumor cells, blood vessel endothelial cells or lymph vessel endothelial cells indicates neoplastic disease; a method for promoting and maintaining vascularization of normal tissue in an organism involving administering a vascularization promoting amount of VEGF-D or a fragment or analog thereof to the organism; a method for screening tumors for metastatic risk involving detecting expression of VEFG-D by a tumor which indicates metastatic risk; and a method of detecting micro-metastasis of neoplastic disease involving detection of VEGF-D on or in a tissue sample which indicates metastasis of a neoplastic disease.

Abstract: Methods for activating endothelial growth factors VEGF-C or VEGF-D with plasmin, and methods of treatment comprising administering a phamarceutical compositions comprising plasmin. Also disclosed are methods for screening for inhibitors of activation of the growth factors by plasmin, and method of treatment by blocking activation of VEGF-C/D activation by plasmin. Further disclosed are methods for screening for other proteases that activate VEGF-C/D, and for inhibitors of such activation. The invention further includes inhibitors of plasmin activity and methods of treating patients in need thereof with said inhibitors.

Abstract: VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Abstract: VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Abstract: VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Abstract: Proprotein convertase inhibitor has been found to block proteolytic processing and activation of VEGF-C and VEGF-D and inhibit angiogenesis and/or lymphangiogenesis. Method and composition are disclosed for inhibiting angiogenesis and/or lymphangiogenesis, and for treating conditions associated with excessive angiogenesis, such as tumors and/or retinopathies, as well as conditions associated with lymphangiogenesis, such as the metastatic spread of malignancies, macular degeneration, inflammatory mediated diseases, rheumatoid arthritis, diabetic retinopathy and psoriasis in a patient. The inventive method and composition utilize proprotein convertase antagonist selected from the group consisting of an anti-proprotein convertase antibody, an antisense nucleic acid molecule against a polynucleotide coding for a proprotein convertase, and an siRNA for inhibiting proprotein convertase expression, as well as proprotein convertase inhibitors.

Abstract: The present invention provides modified VEGF-D polypeptide variants that are resistant to serine protease processing and methods of making and using the same, as well pharmaceutical compositions comprising the peptide or a polynucleotide encoding the same. The VEGF-D variants comprise a VEGF homology domain, and at least one of (1) a C-terminal propeptide that is not cleavable by a serine protease, and (2) an N-terminal propeptide that is not cleavable by a serine protease. The VEGF-D variants can be made using site-directed mutagenesis. The VEGF-D variants are useful for the treatment of diseases such as cardiovascular disease and primary and secondary lymphedema, and for the prevention of stenosis and restenosis of blood vessels.

Abstract: Isolated nucleic acid molecule comprising an antisense nucleic acid sequence which is antisense to a polynucleotide that encodes a VEGF-D polypeptide, vectors and host cells including the same. Also disclosed are methods of inhibiting VEGF-D function or expression in a mammal, for example, in treating cancer, comprising administering to the mammal in need thereof a vector of the present invention.

Abstract: The present invention relates to materials and methods for modulating angiogenesis and lymphangiogenesis. The compositions of the invention provide chimeric and/or humanized VEGF-D antibody substances, antibodies, polypeptides and fragments thereof useful for modulating angiogenesis and lymphangiogenesis in a subject.

Abstract: The present invention relates to materials and methods for modulating angiogenesis. The compositions of the invention provide antibody substances specific for two or more PDGF/VEGF family members, which are useful for modulating angiogenesis and lymphangiogenesis in a subject.

Abstract: Proprotein convertase inhibitor has been found to block proteolytic processing and activation of VEGF-C and VEGF-D and inhibit angiogenesis and/or lymphangiogenesis. Method and composition are disclosed for inhibiting angiogenesis and/or lymphangiogenesis, and for treating conditions associated with excessive angiogenesis, such as tumors and/or retinopathies, as well as conditions associated with lymphangiogenesis, such as the metastatic spread of malignancies, macular degeneration, inflammatory mediated diseases, rheumatoid arthritis, diabetic retinopathy and psoriasis in a patient. The inventive method and composition utilize proprotein convertase antagonist selected from the group consisting of an anti-proprotein convertase antibody, an antisense nucleic acid molecule against a polynucleotide coding for a proprotein convertase, and an siRNA for inhibiting proprotein convertase expression, as well as proprotein convertase inhibitors.

Abstract: The present invention provides materials and methods for preventing stenosis or restenosis of a blood vessel using Vascular Endothelial Growth Factor C (VEGF-C) and/or Vascular Endothelial Growth Factor D (VEGF-D) genes or proteins.

Abstract: A method for treating and alleviating disease characterized by the expression of VEGF-D involving screening to find an organism with tumor cells expressing VEGF-D and administering an effective amount of a VEGF-D antagonist; a method for screening for neoplastic diseas, where detection of VEGF-D on or in a sample such as tumor cells, blood vessel endothelial cells or lymph vessel endothelial cells indicates neoplastic disease; a method for promoting and maintaining vascularization of normal tissue in an organism involving administering a vascularization promoting amount of VEGF-D or a fragment or analog thereof to the organism; a method for screening tumors for metastatic risk involving detecting expression of VEFG-D by a tumor which indicates metastatic risk; and a method of detecting micro-metastasis of neoplastic disease involving detection of VEGF-D on or in a tissue sample which indicates metastasis of a neoplastic disease.

Abstract: A method for activating only the vascular endothelial growth factor receptor-3 has been created. The method comprises administration of a composition comprising a polypeptide to an animal wherein the composition has the ability to stimulate one or more lymphatic vessel endothelial cells to proliferate, differentiate, migrate, or survive. Methods are also provided to selectively activate a VEGF receptor-3, to screen for neoplastic disease characterized by an increase in lymph vessel endothelial cells, and to identify lymph vessel endothelial cells.

Abstract: A method for activating only the vascular endothelial growth factor receptor-3 has been created. The method comprises administration of a composition comprising a polypeptide to an animal wherein the composition has the ability to stimulate one or more lymphatic vessel endothelial cells to proliferate, differentiate, migrate, or survive. Methods are also provided to selectively activate a VEGF receptor-3, to screen for neoplastic disease characterized by an increase in lymph vessel endothelial cells, and to identify lymph vessel endothelial cells.

Abstract: A method for treating and alleviating disease characterized by the expression of VEGF-D involving screening to find an organism with tumor cells expressing VEGF-D and administering an effective amount of a VEGF-D antagonist; a method for screening for neoplastic diseas, where detection of VEGF-D on or in a sample such as tumor cells, blood vessel endothelial cells or lymph vessel endothelial cells indicates neoplastic disease; a method for promoting and maintaining vascularization of normal tissue in an organism involving administering a vascularization promoting amount of VEGF-D or a fragment or analog thereof to the organism; a method for screening tumors for metastatic risk involving detecting expression of VEFG-D by a tumor which indicates metastatic risk; and a method of detecting micro-metastasis of neoplastic disease involving detection of VEGF-D on or in a tissue sample which indicates metastasis of a neoplastic disease.

Abstract: A method for treating and alleviating melanomas and various cancers characterized by the expression of VEGF-D by the tumor, the method comprising screening to find an organism with tumor cells expressing VEGF-D and administering an effective amount of a VEGF-D antagonist to prevent binding of VEGF-D; methods for screening for neoplastic diseases, where detection of VEGF-D on or in cells such as tumor cells, blood vessel endothelial cells, lymph vessel endothelial cells, and/or cells with potential neoplastic growth indicates neoplastic disease; a method for promoting and maintaining vascularization of normal tissue in an organism by administering VEGF-D or a fragment or analog thereof; methods for screening tumors for metastatic risk where expression of VEFG-D by the tumor indicates metastatic risk; and methods to detect micro-metastasis of neoplastic disease where detection of VEGF-D on or in a tissue sample indicates metastasis of neoplastic disease.