The United States of America, As Represented by the Secretary, Department of Health and Human Services

Paul K Goldsmith

Xin Wei Wang

Vivian Takafuji

Urszula Wojda

Jeffery L Miller

Based on the observation of the cooperation of osteopontin (OPN) and matrixmetalloproteinase-9 (MMP-9) in the promotion of the metastatic phenotype, therapies and diagnostic assays are disclosed for the treatment of a tumor that overexpresses OPN, such as hepatocellular carcinoma (HCC), for example metastatic HCC. In one example, methods of treating a tumor include administration of an agent that reduces cellular invasion resulting from the interaction between a fragment of OPN (OPN-5kD) generated by MMP-9 cleavage and CD44 receptor. Examples of such agents include fragments of OPN-5kD and antibodies specific for OPN-5kD. Therapeutic compositions are also provided that include such agents. Also provided are methods of diagnosing or prognosing a tumor, for example by detecting expression of OPN-5kD peptide or OPN-c mRNA in a biological sample obtained from the subject. Also provided are antibodies that specifically bind OPN-5kD.

Compositions and methods for diagnosis and treatment of tumors

Methods for delivering a biologically active molecule into a cell by linking a molecule to the cell surface, wherein the molecule can act as a surface receptor, then complexing the biologically active molecule with a ligand for the surface receptor, and finally contacting the biologically active molecule-ligand complex with the cell surface are disclosed. Delivery of any biologically active molecule, e.g. proteins, enzymes, nucleic acids, hormones, nucleic acids, and oligonucleotides, is contemplated. The use of biotin or biotinylated antibodies as the surface receptor is disclosed. The use of PEI and PEI-avidin conjugates complexed with oligonucleotides for delivery into a directly or indirectly biotinylated cell surface, along with the PEI-avidin-nucleic acid compositions, are disclosed. Primary and cultured cells with a covalently linked surface receptor molecule, such as biotin, on their surfaces are also disclosed.

Growing community of inventors

Rockville, MD, United States of America

Paul K Goldsmith