Abstract: The present invention provides a combination of anti-HGF/SF antibodies that specifically bind HGF/SF and inhibits HGF/SF activity. The present invention further provides a combination of anti-HGF/SF antibodies comprising three or more anti-HGF/SF antibodies selected from the group consisting of: antibody #1 produced from hybridoma 1C10-F1-A11, antibody #4 produced from hybridoma 8H2-F2-B10, antibody #5 produced from hybridoma 13B1-E4-E10, antibody #7 produced from hybridoma 15D7-B2, and antibody #10 produced from hybridoma 31D4-C9-D4.

Abstract: The present invention provides a combination of anti-HGF/SF antibodies that specifically bind HGF/SF and inhibits HGF/SF activity. The present invention further provides a combination of anti-HGF/SF antibodies comprising three or more anti-HGF/SF antibodies selected from the group consisting of antibody #1 produced from hybridoma 1C10-F1-A11, antibody #4 produced from hybridoma 8H2-F2-B10, antibody #5 produced from hybridoma 13B1-E4-E10, antibody #7 produced from hybridoma 15D7-B2, and antibody #10 produced from hybridoma 31D4-C9-D4.

Abstract: Geldanamycin derivatives that block the uPA-plasmin network and inhibit growth and invasion by glioblastoma cells and other tumors at femtomolar concentrations are potentially highly active anti-cancer drugs. GA and various 17-amino-17-demethoxygelddanamycin derivatives are disclosed that block HGF/SF-mediated Met tyrosine kinase receptor-dependent uPA activation at fM levels. Other ansamycins (macbecins I and II), GA derivatives, and radicicol required concentrations several logs higher (?nM) to achieve such inhibition. The inhibitory activity of tested compounds was discordant with the known ability of drugs of this class to bind to hsp90, indicating the existence of a novel target(s) for HGF/SF-mediated events in tumor development. Methods of using such compounds to inhibit cancer cell activities and to treat tumors are disclosed.

Abstract: The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.

Abstract: Hepatocyte growth factor/scatter factor (HGF/SF), acting through the Met receptor, plays an important role in most human solid tumors and inappropriate expression of this ligand-receptor pair is often associated with poor prognosis. The molecular basis for the malignant activity imparted by signaling of HGF/SF-Met in cancer cells has been attributed to its mitogenic and invasive properties. However, HGF/SF also induces angiogenesis, but the signaling mechanism has not been understood, nor has this activity been directly associated with HGF/SF-Met mediated tumorigenesis. HGF/SF induces expression in vitro of VEGF, a key agonist of tumor angiogenesis. By contrast, thrombospondin-1 (TSP-1) is a negative regulator of angiogenesis. This application discloses that, in the very same tumor cells, in addition to inducing VEGF expression, HGF/SF dramatically down regulates TSP-1 expression.

Abstract: The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.

Abstract: Inhibitors of the MAPK pathway, including MEK-directed proteases and small molecule inhibitors, are cytotoxic to human melanoma cells in vitro and in vivo via apoptotic mechanisms. These compounds are used to kill melanoma cells and to treat subjects with melanoma, either alone or in combination with other therapeutic modalities.

Abstract: The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.

Abstract: The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.

Abstract: In a wide variety of human solid tumors, an aggressive, metastatic phenotype and poor clinical prognosis are associated with expression of the receptor tyrosine kinase. Met and its agonist ligand HGF. Disclosed herein are (a) mAbs and hybridoma cell lines that produce them, which mAbs antibodies are specific for Met and (b) combinations of anti-Met and anti-HGF mAbs. When detectably labeled, these antibodies are useful for imaging such tumors. Anti-Met mAb compositions and methods for scintigraphic detection, diagnosis, prognosis, monitoring and therapy of Met-bearing tumors are provided.

Abstract: The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.

Abstract: The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.

Abstract: The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.

Abstract: The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.

Abstract: A method of preventing tumor cell metastasis by inhibiting the binding of hepatocyte growth factor/scatter factor ("HGF/SF") with met proto-oncogene protein is described. A method of producing HGF/SF and a cell line for the production of HGF/SF are also described. The met proto-oncogene tyrosine kinase receptor (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), ordinarily constitute a paracrine signalling system in which cells of mesenchymal origin produce the ligand, which binds to the receptor that is predominantly expressed in cells of epithelial origin. The method of the present invention disrupts the Met-HGF/SF autocrine signaling that contributes to the tumorigenic process in tumors of mesenchymal origin, such as sarcomas.