Abstract: The present invention relates to a method for differentiating between i) a severe form of cancer and ii) a mild form of cancer, comprising a) determining the amounts of gene product of at least the genes coding for ribosomal protein S6 (RPS6), nucleoside diphosphate kinase (NME/NDKA), and caveolin-1, in a sample from a subject, b) comparing the amounts obtained in step a) to reference amounts, and c) differentiating between a severe form of cancer and a mild form of cancer, wherein an increased amount of products of the genes coding for RPS6 and NME/NDKA and a decreased amount of product of the gene coding for caveolin-1 are indicative of a severe form of cancer. The invention further relates to the use of antibodies specifically recognizing a polypeptide selected from the list consisting of RPS6, NME/NDKA, and caveolin-1, for differentiating between a severe form of cancer and a mild form of cancer.

Abstract: The present invention relates to monoclonal antibodies that bind or neutralize anthrax lethal factor (LF), edema factor (EF), and/or protective antigen (PA). The invention provides such antibodies, fragments of such antibodies retaining anthrax toxin-binding ability, fully human or humanized antibodies retaining anthrax toxin-binding ability, and pharmaceutical compositions including such antibodies. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. Additionally, the invention provides for prophylactic, therapeutic, and diagnostic methods employing the antibodies and nucleic acids of the invention.

Abstract: Methods and composition for tumor therapy, especially esophageal adenocarcinoma (EAC), are described. For example, in certain aspects methods for determining Hedgehog and mTOR signaling pathway status to select patients for administering a combination therapy of Hedgehog and mTOR signaling inhibitors are described. Furthermore, the invention provides compositions that involve testing kits for determining signaling status.

Abstract: Methods and kits for characterizing a subject having a steroid-dependent disease such as prostate cancer are described. A method of treating a steroid-dependent disease in a subject by obtaining a biological sample from the subject, determining if the HSD3B1(1245C) gene or 3?HSD1(367T) protein is expressed in the biological sample, and providing treatment other than or in addition to steroid ablation to the subject if the HSD3B1(1245C) gene or 3?HSD1(367T) protein is expressed is also described.

Abstract: Methods and compositions for using the MHC class II invariant chain polypeptide, Ii (also known as CD74), as a receptor for macrophage migration inhibitory factor (MIF), are disclosed. These include methods and compositions for using this receptor, as well as agonists and antagonists of MIF which bind to this receptor, or which otherwise modulate the interaction of MIF with CD74 or the consequences of such interaction, in treatment of conditions characterized by locally or systemically altered MIF levels, particularly inflammatory conditions and cancer.

Abstract: In some aspects, methods of inhibiting survival or proliferation of a tumor cell are provided, the methods comprising inhibiting the glycine cleavage system (GCS) of the tumor cell. In some aspects, methods of treating a subject in need of treatment for a tumor, the method comprising inhibiting the GCS in the tumor. In some embodiments, the methods comprise contacting a tumor cell or tumor with a GCS inhibitor. In some embodiments, the tumor cell or tumor has elevated expression of serine hydroxymethyltransferase 2 (SH1VIT2). In some aspects, methods of identifying a tumor cell or tumor that is sensitive to inhibiting the GCS are provided, the methods comprising determining whether the tumor cell or tumor overexpresses SHMT2. In some aspects, methods of identifying a candidate anti-cancer agent are provided, the methods comprising identifying or modifying a GCS inhibitor.

Abstract: Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. The ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is “turned on” only under such conditions.

Abstract: Phosphorylation of histones was observed at certain tyrosine residues which have not been associated with epigenetic modification. These sites include H2B Tyr37, H4 Tyr88 and Tyr 51 and H3 Tyr99. Kinases responsible for the phosphorylation as well as downstream genes regulated by such phosphorylation were also identified. Antibodies that are specific to such phosphorylated histones have been generated, which are useful for detecting the phosphorylation and related events. With such findings, the present disclosure provides compositions and methods for disease diagnosis, prognosis and therapy selection, in particular for cancer, obesity and diabetes.

Abstract: The invention provides methods and systems for detecting a biomarker in a synovial fluid wherein the system also includes a control to ensure that the test sample is indeed synovial fluid. The biomarkers and the control for synovial fluid can be identified using proteomic methods, including but not limited to antibody based methods, such as an enzyme-linked immunosorbant assay (ELISA), a radioimmunoassay (RIA), or a lateral flow immunoassay.

Abstract: Embodiments of the present disclosure provide for enzyme sensors, protease sensors, methods for producing and using the enzyme and protease sensors, methods of detecting and/or measuring protease activity, methods for characterizing protease cellular activity, fusion proteins, polynucleotides, and vectors corresponding to the enzyme and protease sensors, kits, and the like.

Abstract: Two universally conserved sequences from influenza type A neuraminidases were identified by large scale sequence analysis then chemically modified and conjugated to carrier proteins to generate mono-specific and monoclonal antibodies. The two antibodies, one targeting the N-terminus of the type A neuraminidase and the other sequence close to enzymatic active site, were capable of binding to all 9 subtypes of neuraminidase while demonstrating remarkable specificity against the viral neuraminidase sequences since no cross-reactivity against allantoic proteins was observed. Quantitative analyses of NA using slot blot suggest that the antibodies can be used for NA antigen quantitation in vaccines. These represent the first time the antibody-based immunoassay can be used for NA quantitative determination.

Abstract: Disclosed is an assay (method) to quantify the amounts of catecholamine-O-methyltransferase (COMT) protein in samples, such as extracts from cell cultures, body fluids, tissues, and environmental samples. It uses novel agents (anti-NE, COMT-NE, or COMT-epitope-NE) in combination with two previously described agents (anti-COMT and COMT) in a competitive ELISA system to achieve this aim.

Abstract: A protein used as a biomarker for diagnosing IgA nephropathy and TGBM (thin-glomerular-basement-membrane) using urine through a target proteomics method. A diagnosis biomarker protein and a kit for diagnosing IgA nephropathy and TGBM and predicting progress of the nephropathy in advance using the protein are provided. The degree of the progression of the disease can be grasped by detecting IgA nephropathy and TGBM, enabling early diagnosis and confirming progress from the patient's urine. In addition, a monoclonal antibody produced based on the diagnosis biomarker protein can be used for an immunoassay kit (ELISA, antibody coated tube test, lateral-flow test, potable biosensor). The monoclonal antibody is used in early diagnosis and progression detection of IgA nephropathy and development of a novel drug for the purpose of treatment.

Abstract: The present invention relates to the use of thrombomodulin analogues for the manufacture of a medicament for the treatment of coagulopathy with hyperfibrinolysis, such as haemophilia disorders. These thrombomodulin analogues exhibit at therapeutically effective dosages an antifibrinolytic effect. Novel protein modifications together with methods for their identification are disclosed.

Abstract: The present invention provides a method of determining the prognosis of a subject with cancer, or determining the progression of a cancer, or of treating a cancer, wherein the method comprises the step of determining the expression level of PTPN9 in a cancer sample from the subject. Preferably a low level of expression of PTPN9, or no expression of PTPN9, is indicative of a poor prognosis.

Abstract: A peptide is disclosed of the general structure: Z—W—Y, wherein Z and Y are independently a one to eight amino acid sequence wherein the amino acids are selected from glycine and alanine and W is a non-hydrolyzable pHis analogue. Such peptides can be used to produce sequence-independent anti-phosphohistidine antibodies. Also provided are antibodies that specifically bind to a peptide comprising a phosphohistidine (or a non-hydrolyzable pHis analogue) but fail to specifically bind to an identical peptide containing histidine instead of phosphohistidine.

Abstract: The invention relates to the use of choline kinase alpha as predictive marker for the determination of the response to a chemotherapeutic treatment in a subject suffering from cancer, particularly for predicting the clinical response of a subject suffering from non-small cell lung cancer to a platinum-based chemotherapeutic treatment. The invention relates to methods for designing a personalised therapy for subjects suffering from cancer, particularly from non-small cell lung cancer, based on the expression levels of choline kinase alpha as well as to methods for the treatment of non-small cell lung cancer using a platinum-based chemotherapeutic treatment based in a subject wherein the subject is selected based on the expression levels of choline kinase alpha.

Abstract: The present invention relates to the field of fibrosis and inflammation and more particularly to the use of ADAM12 (A Disintegrin and Metalloproteinase 12) inhibitors to prevent or treat inflammation-induced fibrosis. The present invention also relates to the use of ADAM12 as a marker for inflammation-induced fibrosis and to the ablation of ADAM12 expressing cells as therapeutic approach to interfere with the development of pro-fibrotic cells.

Abstract: The present invention relates to methods for treating neoplasias in a mammalian subject. In particular, the invention provides methods for treating lymphomas, including forms of non-Hodgkin lymphoma. In one embodiment, these methods involve reducing tumor necrosis factor signaling.

Abstract: A diagnostic method for determining prognosis of a myocardial infarcted patient, wherein the amounts of FXIII protein are determined on the day of myocardial infarction (t0) and at least on the following three days (t1 to t3), wherein a lowering of FXIII amount on any one of t0 to t3 below a threshold value is indicative of an increased risk of poor prognosis.

Abstract: The present invention relates to a method for labeling or targeting cells whose plasma membrane has lost integrity, such as dead cells, such as for discriminating between live cells and cells whose plasma membrane has lost integrity; to an embodiment of the method for determining one or more values of one or more parameters of cells of a biological sample; to use of the method in an assay for screening drugs for therapy such as cancer therapy; to use of the method to monitor and/or determine the effectiveness of a therapy; to an assay kit; to a complex; to the complex for use as a medicament; to the complex for use in treatment of cancer(s) and/or plaque(s) and/or regeneration and/or supporting the immune system; and, to a dead cell.

Abstract: LKB1 mutation status and/or expression, YES expression and phosphorylation level; and/or CD24 expression are employed to predict melanoma prognosis and response to therapeutics. Inhibitors (including targeted inhibitors) of SRC family kinases (especially YES) are employed to treat melanoma.

Abstract: The present invention is directed towards methods for measuring and assaying PAS Kinase activity. The methods are useful, for example, for detecting PASK activity in a cell, and for screening for small molecule regulators of PAS kinase activity, as well as characterizing endogenous factors and stimuli that modulate PAS kinase activity, and identifying and optimizing the activity of potential PAS kinase inhibitors.

Abstract: This invention is based in part on the discovery that miR-34 is independent of p53. It has been discovered that miR-34 functions in a TP53-independent tumor suppression pathway. Specifically, miR-34-induced inhibition of cancer cell growth was found to be the same in p53-normal and p53-deficient cells. Thus, miR-34 has a more central role during tumor suppression that is uncoupled from p53. In the absence of p53, miR-34, unlike certain other miRNAs, is sufficient to induce an up-regulation of genes known to be regulated by p53, including but not limited to p21CIP1/WAF1 (CDKN1A), PUMA, BAX, NOXA, PHLDA3, and MDM2 and a down-regulation of HDAC1. Therefore, these biomarkers can be used as biomarkers of miR-34 activity. The invention is further based on the discovery that some of these biomarkers are indispensable for a therapeutic response to miR-34 activity, and are thus prerequisite biomarkers of miR-34 activity.

Abstract: Methods for treating a subject determined to have a cancer comprising a heterozygous inactivation of a housekeeping gene (or a homozygous deletion of a functionally redundant housekeeping gene) by treating the subject with an inhibitor of the gene. For example, a subject having a cancer with an ENO gene deletion can be treated with a glycolysis inhibitor, such as an enolase inhibitor. In some aspects, a subject having a cancer with an ARS gene deletion can be treated with an ARS inhibitor.

Abstract: The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in sepsis patients. In particular, the invention relates to using assays that detect one or more biomarkers selected from the group consisting of Insulin-like growth factor-binding protein 7, Beta-2-glycoprotein 1, Metalloproteinase inhibitor 2, Alpha-1 Antitrypsin, Leukocyte elastase, Serum Amyloid P Component, C-X-C motif chemokine 6, Immunoglobulin A, Immunoglobulin G subclass I, C-C motif chemokine 24, Neutrophil collagenase, Cathepsin D, C-X-C motif chemokine 13, Involucrin, Interleukin-6 receptor subunit beta, Hepatocyte Growth Factor, CXCL-1, -2, -3, Immunoglobulin G subclass II, Metalloproteinase inhibitor 4, C-C motif chemokine 18, Matrilysin, C-X-C motif chemokine 11, and Antileukoproteinase as diagnostic and prognostic biomarker assays of renal injury in the sepsis patient.

Abstract: The present invention relates to specific markers capable of detecting the development of colorectal cancer and the colorectal cancer inhibitory effect of SeMet (selenomethionine) having a chemopreventive effect against colorectal cancer. When the expressions of the biomarkers according to the present invention are measured and the expression levels thereof are analyzed in combination, whether SeMet (selenomethionine) is to be administered to prevent colorectal cancer can be determined and the development of colorectal cancer and the inhibitory effect of SeMet (selenomethionine) against the development of colorectal cancer can be monitored. Thus, these markers can be effectively used to observe the colorectal cancer inhibitory effect of SeMet (selenomethionine) and the prognosis of colorectal cancer resulting from the intake of SeMet (selenomethionine).

Abstract: This invention relates to methods of treating cancer in a subject such as a human and determining at least one of the following in a sample from the subject, such as a human: (a) the presence or absence of a mutation at the alanine 677 (A677) residue in EZH2; or (b) the presence or absence of a mutation at the tyrosine 641 (Y641) residue in EZH2; or (c) the presence or absence of an increased level of H3K27me3 as compared to a control, and administering to said human an effective amount of an EZH2 inhibitor or a pharmaceutically acceptable salt thereof if at least one of the A677 mutation, Y641 mutation, or increased level of H3K27me3 is present in the sample.

Abstract: The invention relates to a method for diagnosing cancer, particularly bladder or prostate cancer using compounds of general formula (I): wherein R1, R2, R3, R4, R5 X, Y and z are as defined herein.

Abstract: This invention provides novel biomarkers for Niemann-Pick disease, type C (NPC). In an exemplary embodiment, the invention provides methods for identifying a subject as having NPC. In embodiments, the methods involve detecting the level of biomarker selected from the group comprising i) galectin-3 (LGALS3); ii) cathepsin D (CTSD); iii) LGALS3 and CTSD; and iv) LGALS3 and/or CTSD in combination at least one additional NPC associated biomarker in a sample obtained from the subject. In embodiments, the methods involve comparing the level of biomarker to a reference.

Abstract: An aspect of the invention provides a method of selectively necrosing cells, comprising: providing a plurality cells, including at least one cancer cell and at least one non-cancerous cell; and administering to the cells a compound, including an HDM-2 targeting component and a cytotoxic component attached to the HDM-2 targeting component, wherein said compound comprises a membrane-active form.

Abstract: A method for characterizing the risk a subject will develop an autoimmune and/or alloimmune disease following tissue transplant includes obtaining a biological sample from the subject, wherein the subject has received the tissue transplant determining in the biological sample a level of at least one protein selected from Tables 1-4, comparing the measured level of the at least one protein to a control value, and characterizing a subject as at greater risk of developing an autoimmune disease and/or alloimmune disease if the level of at least one protein determined is increased or decreased compared to the control value.

Abstract: The invention generally relates to methods for identifying protein-protein interactions. In certain aspects, methods of the invention involve conducting a protein-fragment complementation assay on a sample to form a protein-protein complex between two proteins in the sample that only transiently interact under physiological conditions, separating the complexes from the sample, and analyzing a protein of the complex using a mass spectrometry technique.

Abstract: The technology described herein is directed to methods, assays, and systems relating to determining the level of SAKT signaling activity in a sample obtained from a subject as well as methods relating to administering inhibitors and/or agonists of SAKT signaling.

Abstract: A method for producing organic-inorganic composite materials includes at least one biomineralising protein and/or polypeptide-encoding recombinant polynucleotide being introduced into at least one host cell, preferably from the class of slime moulds, and the expressed protein and/or polypeptide influencing the formation of inorganic particles in an extracellular matrix of the host cell.

Abstract: A method of reducing blood glucose in a subject has been developed. In preferred embodiments, the method involves administering to the subject a specific activator of endogenous mitogen-activated protein kinase kinase 6 (MKK3), mitogen-activated protein kinase kinase 6 (MKK4), mitogen-activated protein kinase kinase 6 (MKK6), p38 mitogen-activated protein kinase (p38MAPK), mitogen-activated kinase-activated protein kinase 2 (MK2), or a combination thereof, in an effective amount to reduce blood glucose in a subject. In other embodiments, the method involves administering to the subject a specific activator to increase X-box binding protein 1 (XBP1) phosphorylation on Thr48 and Ser61 in an effective amount to reduce blood glucose in the subject. Methods of identifying agents for reducing blood glucose in a subject are also provided.

Abstract: The present invention relates to the field of recombinant toxin protein production in bacterial hosts. In particular, the present invention relates to production processes for obtaining high levels of a recombinant CRM197, Diphtheria Toxin, Pertussis Toxin, Tetanus Toxoid Fragment C, Cholera Toxin B, Cholera holotoxin, and Pseudomonas Exotoxin A, from a bacterial host.

Abstract: The invention relates to a method for evaluating kits for rapid diagnosis of malaria, in order to determine or to test the sensitivity and specificity thereof. To that end, the reactive strips of the diagnostic kits are exposed to different concentrations of the malaria parasite in a method that allows data on sensitivity and specificity indicated on the technical sheet of the kit to be ascertained.

Abstract: Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.

Abstract: The present invention relates to inhibitors of antithrombin III and the medical use thereof in treating or preventing bleeding. The inhibitors are preferably used in subjects suffering from an acquired or genetic bleeding disorder, such as haemophilia, or in a subjects having a clinical condition characterised by excessive bleeding, such as surgery, trauma and internal bleeding. The inhibitor of antithrombin III can e.g. a peptide, an aptamer or an antibody or antibody fragment that specifically binds to and inhibits antithrombin III.

Abstract: This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

Abstract: The present disclosure relates to isolated antibodies against human SPLA2-V and uses thereof.

Abstract: Methods and kits for diagnosing the presence of and prognosing the appearance of tissue remodelling-associated conditions, involving the presence of enzyme complexes in a biological sample, are disclosed. In particular, the method pertains to diagnosing the presence of or prognosing appearance of metastatic cancer by the identification of high molecular weight enzyme complexes comprising MMPs.

Abstract: Provided herein are methods directed to the prediction and early assessment of the efficacy of cancer treatment regimens, in particular in patients undergoing therapy with a DNA-damaging chemotherapeutic agent, by determining expression levels of certain proteins found to be useful as biomarkers in circulating tumor cells obtained from the patient both prior to and post-treatment.

Abstract: The present disclosure provides innovative methodology and related compositions and kits for preventing and treating various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, by using an inhibitor of processed forms of lysyl oxidase or lysyl oxidase-like proteins, an inhibitor of LOX and an inhibitor of a LOXL, or a synergistic combination of an inhibitor of LOX or LOXL combined with other therapeutic agents. Also provided are innovative methods for selecting agents that prevent or inhibit tumor invasion, angiogenesis and metastasis, by contacting cells that are in an epithelial-mesenchymal transition (EMT) state with a candidate agent and detecting a change in the EMT state of the cells. Methods and related compositions and kits for diagnosing or monitoring various diseases associated with abnormal cell proliferation, angiogenesis and fibrosis, by using molecules or agents that specifically recognize processed forms of LOX or LOXL are also provided.

Abstract: The subject invention pertains to materials and methods for diagnosing and/or predicting pathologic infant conditions. A method of the invention comprises obtaining a biological sample from an infant and analyzing the sample to detect at least one protein biomarker of necrotizing enterocolitis (NEC), wherein a patient is diagnosed with NEC or determined to have a likelihood of developing NEC following detection of the biomarker. In another method of the invention, the likelihood of a patient developing NEC is determined. In certain embodiments, treatment is administered to the patient following diagnosis of NEC or determination that the patient has a likelihood of developing NEC.

Abstract: This present invention describes the derivation and selection of antibodies capable of neutralising the major exotoxins; TcdA and TcdB of Clostridium difficile. The invention also describes novel neutralisation and antigen binding properties of individual Mabs and mixtures thereof.

Abstract: Methods are described for the production and use of fluorescence resonance energy transfer (FRET)-based competitive displacement aptamer assay formats. The assay schemes involve FRET in which the analyte (target) is quencher (Q)-labeled and previously bound by a fluorophore (F)-labeled aptamer such that when unlabeled analyte is added to the system and excited by specific wavelengths of light, the fluorescence intensity of the system changes in proportion to the amount of unlabeled analyte added. Alternatively, the aptamer can be Q-labeled and previously bound to an F-labeled analyte so that when unlabeled analyte enters the system, the fluorescence intensity also changes in proportion to the amount of unlabeled analyte.

Abstract: Provided is a monoclonal antibody, or antigen-binding fragment thereof that binds to c-Met. Such antibodies, or antigen-binding fragments thereof, are useful in in vivo, ex vivo or in vitro immunochemical and other imaging methods for detecting cell surface c-Met receptor levels for diagnostic, prognostic and predictive purposes, and for optimizing therapeutic regimens in patients harboring tumors in which c-Met is implicated in pathogenesis.

Abstract: The present invention relates to methods for treating endoplasmic reticulum (ER) stress-related conditions (e.g., cancer, protein folding/misfolding disease, diabetes mellitus) and for identifying compounds for treating ER stress-related conditions in a subject (e.g., a human). The invention also provides methods for diagnosing an ER stress-related condition in a subject and kits for the treatment of same.