Abstract: The present invention is directed to methods and compositions for suppressing lymphangiogenesis, angiogenesis and/or tumor growth. The methods comprise contacting the tumor with a compound that (i) stabilizes a protein kinase in the inactive state and (ii) is not an ATP competitive inhibitor of the protein kinase in the active state.

Abstract: In alternative embodiments, the invention provides compositions and methods for identifying individuals that would be responsive to a treatment comprising (including) blocking activation of integrin polypeptide alphav-beta3 (or ?v-?3), or blocking the interaction of a ligand with integrin polypeptide alphav-beta3 (or ?v-?3). The invention provides compositions and methods for determining the effectiveness of such a treatment and can contribute to a prognosis for the patient.

Abstract: In alternative embodiments, the invention provides compositions and methods comprising use of microRNAs and microRNA inhibitors to modulate blood vessel growth (angiogenesis), e.g., act as anti-angiogenic agents, and modulate cell and tumor microenvironment patterning, cancer cell and tumor growth and malignant disease (metastasis). In alternative embodiments, the invention provides compositions and methods that can sensitize blood vessels, e.g., tumor blood vessels, to radiation and agents and chemotherapies that cause DNA damage.

Abstract: In alternative embodiments, the invention provides methods for regulating or modulating RAF kinases. In alternative embodiments, the invention provides methods for ameliorating, preventing and/or treating diseases, infections and/or conditions having unwanted, pathological or aberrant cell proliferation, or that are responsive to inhibition or arrest of cell growth, by administration of an allosteric RAF inhibitor and/or any agent which prevents localization of RAF to mitotic spindles or mid-bodies.

Abstract: The invention provides nanostructures or products of manufacture for use as ex vivo or in vivo composition (e.g., a drug, or a therapeutic, diagnostic or imaging reagent) delivery vehicles. In one aspect, the invention provides nanoparticles comprising several compartments which in unison function as a composite nanostructure. In one embodiment, the nanoparticles of the invention comprise a combination of polymer core/lipid bilayer interface which incorporate covalently attached lipid-vascular targeting ligands. These composite nanoparticles can deliver highly effective and selective payloads for diagnostic, prophylactic or therapeutic applications.

Abstract: The invention provides methods for treating tumors and tumor metastases in a mammal comprising administering, to a mammal in need of treatment, a therapeutic amount of an antagonist sufficient to inhibit angiogenesis in combination with a therapeutic amount of anti-tumor immunotherapeutic agent, such as a anti-tumor antigen antibody/cytokine fusion protein having a cytokine and a recombinant immunoglobulin polypeptide chain sufficient to elicit a cytokine-specific biological response.

Abstract: This invention relates to the discovery of the convergence of diverse receptors and signaling pathways on the PI3gamma dependent activation of VLA4 (integrin a4b1). In particular, the invention relates to the role of myeloid cells in tumor inflammation and metastasis. The invention provides methods for inhibiting cancer in a subject comprising administering to a subject having cancer that comprises endothelial cells a therapeutically effective amount of a PI-3-kinase gamma inhibitor that reduces at least one of (a) adhesion of myeloid cells to the endothelial cells, (b) migration of myeloid cells into the cancer, (c) growth of the cancer, (d) activation of integrin a4b1 that is comprised on the myeloid cells, and (e) clustering of integrin a4b1 that is comprised on the myeloid cells.

Abstract: ?v?3 Integrin receptor targeting liposomes comprise a cationic amphiphile such as a cationic lipid, a neutral lipid, and a targeting lipid. The targeting lipid includes a non-peptidic ?v?3 integrin antagonist.

Abstract: The invention provides compositions, e.g., small molecules, that disrupt the activity of protein kinases, including constitutively activated protein kinases, such as kinases constitutively activated through mutations, and kinases in their native inactivated state, and methods for making and using them. In one aspect, compositions of the invention bind a protein kinase in its inactive conformation involving the conserved asparagine-phenylalanine-glycine residue motif, or “Asp-Phe-Gly” or “DFG” motif, of the activation loop in the allosteric binding site. The small molecule protein kinase inhibitors of the invention comprise or are derivatives or analogs of oxadiazoles, thiadiazoles, oxazoles, thiazoles, arylamides, quinolones, pyrazoles, pyrazolones, imides, pyrolles, imidazoles and/or triazoles.

Abstract: The present invention describes methods for inhibition angiogenesis in tissues using vitronectin ?v?3 antagonists, and particularly for inhibiting angiogenesis in inflamed tissues and in tumor tissues and metastases using therapeutic compositions containing ?v?3 antagonists.

Abstract: The present invention describes methods for modulating angiogenesis in tissues using Src protein, modified Src protein, and nucleic acids encoding for such. Particularly the invention describes methods for inhibiting angiogenesis using an inactive Src protein, or nucleic acids encoding therefor, or for potentiating angiogenesis using an active Src protein, or nucleic acids encoding therefor. The invention also describes the use of gene delivery systems for providing nucleic acids encoding for the Src protein, or modified forms thereof.

Abstract: The invention provides methods for treating tumors and tumor metastases in a mammal comprising administering, to a mammal in need of treatment, a therapeutic amount of an antagonist sufficient to inhibit angiogenesis in combination with a therapeutic amount of anti-tumor immunotherapeutic agent, such as a anti-tumor antigen antibody/cytokine fusion protein having a cytokine and a recombinant immunoglobulin polypeptide chain sufficient to elicit a cytokine-specific biological response.

Abstract: The present invention describes methods for inhibition angiogenesis in tissues using vitronectin ?v?3 antagonists, and particularly for inhibiting angiogenesis in inflamed tissues and in tumor tissues and metastases using therapeutic compositions containing ?v?3 antagonists.

Abstract: Myocardial infarction in a mammal is treated by administering to the mammal a therapeutically effective amount of a chemical Src family tyrosine kinase protein inhibitor and the use of such inhibitor compounds for the preparation of a medicament for treating myocardial infarction. Myocardial infarction can be prevented by administering to the mammal a prophylactic amount of the inhibitor. The inhibitor preferably is an inhibitor of Src protein selected from the group consisting of a pyrazolopyrimidine class Src family tyrosine kinase inhibitor, a macrocyclic dienone class Src family tyrosine kinase inhibitor, a pyrido[2,3-d]pyrimidine class Src family tyrosine kinase inhibitor, a 4-anilino-3-quinolinecarbonitrile class Src family tyrosine kinase inhibitor, and a mixture thereof. The Src family tyrosine kinase inhibitors can be used to prepare medicaments for the treatment of myocardial infarction. Also disclosed are articles of manufacture containing a chemical Src family tyrosine kinase inhibitor.

Abstract: The present invention describes methods for inhibition angiogenesis in tissues using vitronectin ?v?3 antagonists, and particularly for inhibiting angiogenesis in inflamed tissues and in tumor tissues and metastases using therapeutic compositions containing ?v?3 antagonists.

Abstract: Angiogenesis, tumor growth, and metalloproteinase 2 (MMP2) interaction with integrin-?v?3 are inhibited by an inhibitor compound of formula: wherein G1 and G2 are each independently —NH—C(O)—O—(CH2)v—(C6H4)—X3 ; Y1 and Y2 are each independently —OH or C1-C4 alkoxy; X1 and X2 are each independently halo or C1-C4 alkoxy; X3 is fluoro, nitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is —C?C—, —C6H4—, cis-CH?CH—, trans-CH?CH—, cis-CH2—CH?CH—CH2—, trans-CH2—CH?CH—CH2—, 1,4-naphthyl, cis-1,3-cyclohexyl, trans-1,3-cyclohexyl, cis-1,4-cyclohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each 1; t is an integer having a value of 0 or 1; p and r are each 2, and v is 1; with the proviso that when A is H, t is 0, and when A is a covalent bond, t is 1.

Abstract: The invention provides methods for treating tumors and tumor metastases in a mammal comprising administering, to a mammal in need of treatment, a therapeutic amount of an antagonist sufficient to inhibit angiogenesis in combination with a therapeutic amount of anti-tumor immunotherapeutic agent, such as a anti-tumor antigen antibody/cytokine fusion protein having a cytokine and a recombinant immunoglobulin polypeptide chain sufficient to elicit a cytokine-specific biological response.

Abstract: The present invention describes methods for inhibition angiogenesis in tissues using vitronectin ?v?3 antagonists, and particularly for inhibiting angiogenesis in inflamed tissues and in tumor tissues and metastases using therapeutic compositions containing ?v?3 antagonists.

Abstract: The present invention describes methods for inhibition angiogenesis in tissues using vitronectin ?v?3 antagonists, and particularly for inhibiting angiogenesis in inflamed tissues and in tumor tissues and metastases using therapeutic compositions containing ?v?3 antagonists.

Abstract: The invention provides methods for treating tumors and tumor metastases in a mammal comprising administering, to a mammal in need of treatment, a therapeutic amount of an antagonist sufficient to inhibit angiogenesis in combination with a therapeutic amount of anti-tumor immunotherapeutic agent, such as a anti-tumor antigen antibody/cytokine fusion protein having a cytokine and a recombinant immunoglobulin polypeptide chain sufficient to elicit a cytokine-specific biological response.