Abstract: The increased efficacy and reduced unwanted side effects of drugs can be insured by treating only responsive patients. In an embodiment of the invention, signaling pathways that a particular drug interferes with, are derive together with predictive biomarkers and dynamic biomarker that can read the activity of these pathways before and after drug treatment in order to select a responder patient population. In an alternative embodiment of the invention, certain core pathways that the drug does not interfere with and that are known to be causally involved in a particular disease(s) can be identified, and derive the biomarkers for those to be able to exclude these patients that suffer from a disease in which those drug non effected pathways are involved from being treated with the specific drug in question.

Abstract: Provided herein are polymers, pH-sensitive polymers and/or linkers; conjugates comprising said polymers and/or linkers, optionally, coupled to one or more agents and/or targeting moieties; and particles (e.g., nanoparticles comprising the aforesaid polymers, linkers and/or conjugates), which can be used to enhance the delivery and/or efficacy of one or more agents in a subject.

Abstract: Provided herein are methods, e.g., computer-implemented methods or automated methods, of evaluating a cancer sample, e.g., a prostate tumor sample, from a patient. Also provided are biomarker panels for prognosticating prostate cancer. Also provided are methods of treating prostate cancer by identifying aggressive prostate cancer or prostate cancer that may have lethal outcome.

Abstract: The increased efficacy and reduced unwanted side effects of drugs can be insured by treating only responsive patients. In an embodiment of the invention, signaling pathways that a particular drug interferes with, are derive together with predictive biomarkers and dynamic biomarker that can read the activity of these pathways before and after drug treatment in order to select a responder patient population. In an alternative embodiment of the invention, certain core pathways that the drug does not interfere with and that are known to be causally involved in a particular disease(s) can be identified, and derive the biomarkers for those to be able to exclude these patients that suffer from a disease in which those drug non effected pathways are involved from being treated with the specific drug in question.

Abstract: Provided herein are polymers, pH-sensitive polymers and/or linkers; conjugates comprising said polymers and/or linkers, optionally, coupled to one or more agents and/or targeting moieties; and particles (e.g., nanoparticles comprising the aforesaid polymers, linkers and/or conjugates), which can be used to enhance the delivery and/or efficacy of one or more agents in a subject.

Abstract: Methods and compositions for improving the delivery and/or efficacy of a therapy (e.g., an anti-cancer, anti-fibrotic or anti-inflammatory therapy) are disclosed. The invention is based, at least in part, on the discovery that metformin, a widely prescribed anti-diabetic drug, can affect the tumor microenvironment (e.g., directly, i.e., independent of its effects on cancer cells themselves or tumor metabolism). In embodiments described herein, metformin has been shown to reduce the amount of extracellular matrix, including collagen 1 and hyaluronan, in the fibro-inflammatory tumor microenvironment in a subject (e.g., a subject with a desmoplastic tumor).

Abstract: The increased efficacy and reduced unwanted side effects of drugs can be insured by treating only responsive patients. In an embodiment of the invention, signaling pathways that a particular drug interferes with, are derive together with predictive biomarkers and dynamic biomarker that can read the activity of these pathways before and after drug treatment in order to select a responder patient population. In an alternative embodiment of the invention, certain core pathways that the drug does not interfere with and that are known to be causally involved in a particular disease(s) can be identified, and derive the biomarkers for those to be able to exclude these patients that suffer from a disease in which those drug non effected pathways are involved from being treated with the specific drug in question.

Abstract: Provided herein are methods, e.g., computer-implemented methods or automated methods, of evaluating a cancer sample, e.g., a prostate tumor sample, from a patient. Also provided are biomarker panels for prognosticating prostate cancer. Also provided are methods of treating prostate cancer by identifying aggressive prostate cancer or prostate cancer that may have lethal outcome.

Abstract: The increased efficacy and reduced unwanted side effects of drugs can be insured by treating only responsive patients. In an embodiment of the invention, signaling pathways that a particular drug interferes with, are derive together with predictive biomarkers and dynamic biomarker that can read the activity of these pathways before and after drug treatment in order to select a responder patient population. In an alternative embodiment of the invention, certain core pathways that the drug does not interfere with and that are known to be causally involved in a particular disease(s) can be identified, and derive the biomarkers for those to be able to exclude these patients that suffer from a disease in which those drug non effected pathways are involved from being treated with the specific drug in question.

Abstract: The increased efficacy and reduced unwanted side effects of drugs can be insured by treating only responsive patients. In an embodiment of the invention, signaling pathways that a particular drug interferes with, are derive together with predictive biomarkers and dynamic biomarker that can read the activity of these pathways before and after drug treatment in order to select a responder patient population. In an alternative embodiment of the invention, certain core pathways that the drug does not interfere with and that are known to be causally involved in a particular disease(s) can be identified, and derive the biomarkers for those to be able to exclude these patients that suffer from a disease in which those drug non effected pathways are involved from being treated with the specific drug in question.

Abstract: The invention provides substituted pyrazolidinone compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are useful for a variety of therapies, including treating or preventing various cancers, inflammation, septic shock, preterm labor, infertility, pain, and ischemia, and other diseases and disorders associated with MEK-1 and/or ERK-2 activation.

Abstract: The invention provides substituted pyrazolidinone compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are useful for a variety of therapies, including treating or preventing various cancers, inflammation, septic shock, preterm labor, infertility, pain, and ischemia, and other diseases and disorders associated with MEK-1 and/or ERK-2 activation.

Abstract: The present invention relates to cell-based assays useful for screening for modulators, such as inhibitors, of activated mutant KIT tyrosine kinase receptors, which are associated with mast cell-related disorders, such as mastocytosis and various types of cancer. The invention further provides for the treatment of mast cell-related disorders with an inhibitor identified by the screening method.

Abstract: The invention provides substituted pyrazolidinone compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are useful for a variety of therapies, including treating or preventing various cancers, inflammation, septic shock, preterm labor, infertility, pain, and ischemia, and other diseases and disorders associated with MEK-1 and/or ERK-2 activation.

Abstract: The invention provides substituted pyrazolidinone compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are useful for a variety of therapies, including treating or preventing various cancers, inflammation, septic shock, preterm labor, infertility, pain, and ischemia, and other diseases and disorders associated with MEK-1 and/or ERK-2 activation.

Abstract: The invention described herein relates to modulation of fertility in male mammals. A genetically altered mouse having a mutation in the Kit/stem cell factor receptor protein is described. In addition, antibodies that specifically bind to a Kit/stem cell factor receptor are described. Methods to diagnose Kit-mediated fertility defects; methods to identify agents that modulate Kit-mediated activation of phosphatidylinositol 3′-kinase and thereby modulate spermatogenesis; and pharmaceuticals that modulate spermatogenesis by effecting Kit-mediated activation of phosphatidylinositol 3′-kinase are also described.