Abstract: The current invention is a capture-particle comprising: a) a molecular sieve portion; and b) an analyte binding portion; wherein the molecular sieve portion, analyte binding portion or both further comprise a cross-linked region having modified porosity. Capture particles wherein the molecular sieve portion, analyte binding portion or both comprise pore dimensions sufficient to exclude molecules larger than about 60 kDa. These particles are useful in purification and diagnostic methods. Kits comprising the capture particles are also described.

Abstract: Methods are provided for treating cancer metastasis by administering a therapeutic composition targeting a kinase substrate cascade.

Abstract: A method for selecting combinations of drugs for treatment of diseases that arise from deranged signaling pathways is disclosed. The method involves measuring the activity states for signaling proteins in a diseased cell and determining whether the activity states are different from the activity states observed for a reference cell such as a normal cell. Based on the observed differences, combinations of two or more drugs are selected to reduce these differences. Treatment of a subject with the combinations restores the activity states of the signaling proteins of the deranged disease-associated signaling pathways toward the activity states observed in the reference cell. Since the diseased cell and the reference cell can both be obtained from the same subject, combinations of drugs that specifically target patient-specific signaling derangements is possible.

Abstract: A method and device to detect Hepatitis C (HCV) antibodies in oral fluid is provided. This method introduces a non-antibody detection molecule that labels all classes of patient antibodies in oral fluid, followed by the specific concentration of labeled anti-HCV antibodies by selective capture in a trapping zone consisting of peptide antigens derived from the HCV genome. Signal generated by the labeled antibodies present in the trapping zone is proportional to the number of anti-HCV antibodies bound to the antigens present in the trapping zone. Presence of signal derived from the capture of antibody/detection molecule complexes in the trapping zone is indicative of past exposure to HCV.

Abstract: Nanoporous materials can be used to enrich samples for subsequent analysis of substances contained in the sample. The method is shown to enrich the yield of species in the low molecular weight proteome, allowing detection of small peptides in the low nanomolar range.

Abstract: Capture particles for harvesting analytes from solution and methods for using them are described. The capture particles are made up of a polymeric matrix having pore size that allows for the analytes to enter the capture particles. The pore size of the capture particles are changeable upon application of a stimulus to the particles, allowing the pore size of the particles to be changed so that analytes of interest remain sequestered inside the particles. The polymeric matrix of the capture particles are made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. The capture particles may be used to isolate and identify analytes present in a mixture. They may also be used to protect analytes which are typically subject to degradation upon harvesting and to concentrate low an analyte in low abundance in a fluid.

Abstract: The present invention relates to the identification and diagnostic use of biomarkers in primary colorectal cancer tumors whose activation level are predictive of the likelihood of the onset of metastatic disease. These biomarkers may be used to determine the suitability of a patient for aggressive and/or targeted treatments. Kits and compositions of the invention are also provided.

Abstract: This invention relates, e.g., to a method for predicting a subject's response to a chemotherapeutic agent and/or the subject's prognosis, comprising measuring the phosphorylation state of at least one member of the mTOR pathway, and/or of at least one member of an interconnected polypeptide pathway (e.g. a member of the Akt pathway or a member of the IRS pathway), compared to a baseline value, in a cancer tissue or cancer cell sample from the subject, wherein an elevated level of the phosphorylation state compared to the baseline value indicates that the subject is a non-responder to the chemotherapeutic agent and/or has a poor prognosis. Also described is a method for treating a cancer in a subject in need thereof, wherein the subject exhibits an elevated level of the phosphorylation state, comprising administering one or more inhibitors of the mTOR and/or an interconnected pathway.

Abstract: This invention relates, e.g., to a composition that, at room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve cellular morphology, and allow the sample to be frozen to generate a cryostat frozen section suitable for molecular analysis. The composition comprises (1) a fixative that stabilizes the proteins in the sample and that has a sufficient water content for a stabilizer and/or a permeability enhancing agent to be soluble therein; (2) a stabilizer, comprising (a) a kinase inhibitor and (b) a phosphatase inhibitor and, optionally, (c) a protease (e.g., proteinase) inhibitor; (3) a permeability enhancing agent; and (4) lactic acid. Methods and kits are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring protein degradation, including the loss of posttranslational modifications (such as phosphorylation), e.g.

Abstract: The present invention provides compositions and methods for shielding and directing agents to biological targets in cellular systems for therapeutic, prophylactic, and diagnostic uses. Vascular devices are also provided which have coated surfaces that contain proteomic antisense, as well as therapeutic and other biological agents attached thereto.

Abstract: Capture particles for harvesting analytes from solution and methods for using them are described. The capture particles are made up of a polymeric matrix having pore size that allows for the analytes to enter the capture particles. The pore size of the capture particles are changeable upon application of a stimulus to the particles, allowing the pore size of the particles to be changed so that analytes of interest remain sequestered inside the particles. The polymeric matrix of the capture particles are made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. The capture particles may be used to isolate and identify analytes present in a mixture. They may also be used to protect analytes which are typically subject to degradation upon harvesting and to concentrate low an analyte in low abundance in a fluid.

Abstract: This invention relates, e.g., to a composition that, at room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve cellular morphology, and allow the sample to be frozen to generate a cryostat frozen section suitable for molecular analysis. The composition comprises (1) a fixative that is effective to fix the phosphoproteins, and that has a sufficient water content to be soluble for a stabilizer and/or a permeability enhancing agent); (2) a stabilizer, comprising (a) a kinase inhibitor and (b) a phosphatase inhibitor and, optionally, (c) a protease (e.g., proteinase) inhibitor; and (3) a permeability enhancing agent (e.g. PEG). Methods are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring protein degradation, including the loss of posttranslational modifications (such as phosphorylation), e.g.

Abstract: The invention relates to a one-step chemical composition that preserves animal tissue, cells, and biomolecules, such as human tissue, human cells, and biomolecules therein. It improves the fidelity and morphologic structure of cells, organelles, and nuclear chromatin, and maintains and enhances the cellular antigenicity for immunohistochemistry and flow cytometry, while preserving proteins, post-translational modifications of proteins, and nucleic acids. In one embodiment, the composition comprises a) a non-aldehyde precipitating fixative at a concentration below 25% (volume/volume), b) a reversible/cleavable protein cross-linker that targets lipid-associated molecules, and c) a c reversible/cleavable protein cross-linker that targets water soluble molecules. In another embodiment, the composition further includes a kinase inhibitor, a phosphatase inhibitor, and a permeation enhancer.

Abstract: The invention relates to both a sensitive method for the capture and detection of low-abundance Borrelia burgdorferi (Bb) bacterial antigens allowing for the diagnosis of Lyme Disease using standard immunoassays. Furthermore, this invention allows the antigen to be identified in a sample of urine, serum, or other biological fluids isolated from humans and animals. The invention provides a method to capture, concentrate, separate and specifically quantify the abundance of Bb antigens using immunoassays. The detection of Bb Outer Surface Protein A is presented as an example of the disclosed invention. High sensitivity levels, low cost and easily collected biofluids allow this technology to reach patients in clinics as well as POC applications for the early detection of Lyme disease prior to seroconversion. A kit containing necessary reagents and the method for diagnosis, monitoring or assessing lyme disease using an immunoassay such as an ELISA, western blot or RPPMA is disclosed.

Abstract: Capture particles for harvesting analytes from solution and methods for using them are described. The capture particles are made up of a polymeric matrix having pore size that allows for the analytes to enter the capture particles. The pore size of the capture particles are changeable upon application of a stimulus to the particles, allowing the pore size of the particles to be changed so that analytes of interest remain sequestered inside the particles. The polymeric matrix of the capture particles are made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. The capture particles may be used to isolate and identify analytes present in a mixture. They may also be used to protect analytes which are typically subject to degradation upon harvesting and to concentrate low an analyte in low abundance in a fluid.

Abstract: Methods and kits for identifying and/or monitoring neurological conditions in a patient using ratios of biomarkers are disclosed. The neurological conditions may include, for example, Alzheimer's disease or mild cognitive impairment. The particular biomarkers that may be useful in identifying and/or monitoring neurological conditions may include, for example, biliverdin reductase, biliverdin reductase, estrogen receptor alpha, superoxide dismutase, S100A7, hemeoxygenase 1, matrix metalloproteinase 9 and platelet derived growth factor receptor. In particular, ratios of these biomarkers are useful.

Abstract: Disclosed herein is a method for predicting the prognosis, the likelihood of metastasis in, or the desirability of administering an aggressive therapy to, a subject with colorectal cancer, comprising determining, in a sample from the subject, the level of phosphorylation of one or more of certain proteins compared to a positive and/or negative reference standard; or the total amount of COX-2 protein compared to a positive and/or negative reference standard. Also described are methods for treating subjects likely to develop metastatic colorectal carcinoma, and pharmaceutical compositions and kits for implementing the methods of the invention.

Abstract: A method and device to detect Hepatitis C (HCV) antibodies in oral fluid is provided. This method introduces a non-antibody detection molecule that labels all classes of patient antibodies in oral fluid, followed by the specific concentration of labeled anti-HCV antibodies by selective capture in a trapping zone consisting of peptide antigens derived from the HCV genome. Signal generated by the labeled antibodies present in the trapping zone is proportional to the number of anti-HCV antibodies bound to the antigens present in the trapping zone. Presence of signal derived from the capture of antibody/detection molecule complexes in the trapping zone is indicative of past exposure to HCV.

Abstract: Capture particles for harvesting analytes from solution and methods for using them are described. The capture particles are made up of a polymeric matrix having pore size that allows for the analytes to enter the capture particles. The pore size of the capture particles are changeable upon application of a stimulus to the particles, allowing the pore size of the particles to be changed so that analytes of interest remain sequestered inside the particles. The polymeric matrix of the capture particles are made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. The capture particles may be used to isolate and identify analytes present in a mixture. They may also be used to protect analytes which are typically subject to degradation upon harvesting and to concentrate low an analyte in low abundance in a fluid.

Abstract: This invention describes the identification of novel organic dye chemistries that can be used as affinity baits to capture proteins and other biomolecules useful in the fields of medical diagnostics, environmental science, toxicology, and infectious disease. Incorporation of unique affinity dye compounds within hydrogel capture particles improves analyte yield and preanalytical precision, and stabilizes the analyte against degradation, while increasing measurement sensitivity. The particles in this invention can be used for routine clinical testing as well as for discovery of low abundance disease biomarkers. Example hydrogel particles containing new high affinity bait chemistries were used to identify a new set of human serum biomarkers.