48 results about "Tissue inhibitor of metalloproteinase" patented technology

The present invention provides a method of diagnosing the presence or severity of liver fibrosis in an individual by detecting α2-macroglobulin (α2-MG) in a sample from the individual; detecting hyaluronic acid (HA) in a sample from the individual; detecting tissue inhibitor of metalloproteinases-1 (TIMP-1) in a sample from the individual; and diagnosing the presence or severity of liver fibrosis in the individual based on the presence or level of α2-MG, HA and TIMP-1.

Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in the affected joint of a mammal is accomplished by administering a chondroprotective compound of Formula (I):where A is hydroxy, (C1-C4)alkoxy, amino, hydroxy-amino, mono-(C1-C2)alkylamino, di-(C1-C2)alkylamino; X and Y are independently H or (C1-C2)alkyl; and n is 1 or 2; R6 is halogen, (C1-C3)alkyl, trifluoromethyl, or nitro; R9 is H; (C1-C2)alkyl; phenyl or phenyl-(C1-C2)alkyl, where phenyl is optionally mono-substituted by fluoro or chloro; -C(=O)-R, where R is (C1-C2)alkyl or phenyl, optionally mono-substituted by fluoro or chloro; or -C(=O)-O-R', where R1 is (C1-C2)alkyl.This treatment ameliorates, diminishes, actively treats, reverses or prevents any injury, damage or loss of articular cartilage or subchondral bone subsequent to said early stage of said degeneration. Whether or not a mammal needs such treatment is determined by whether or not it exhibits a statistically significant deviation from normal standard values in synovial fluid or membrane from the affected joint, with respect to at least five of the following substances: increased interleukin-1 beta (IL-1beta); increased tumor necrosis factor alpha (TNFalpha); increased ratio of IL-1beta to IL-1 receptor antagonist protein (IRAP); increased expression of p55 TNF receptors (p55 TNF-R); increased interleukin-6 (IL-6); increased leukemia inhibitory factor (LIF); decreased insulin-like growth factor-1 (IGF-1); decreased transforming growth factor beta (TGFbeta); decreased platelet-derived growth factor (PDGF); decreased basic fibroblast growth factor (b-FGF); increased keratan sulfate; increased stromelysin; increased ratio of stromelysin to tissue inhibitor of metalloproteases (TIMP); increased osteocalcin; increased alkaline phosphatase; increased cAMP responsive to hormone challenge; increased urokinase plasminogen activator (uPA); increased cartilage oligomeric matrix protein; and increased collagenase.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Cytoplasmic aspartate aminotransferase, soluble Tumor necrosis factor receptor superfamily member 5, soluble CD40 Ligand, soluble C-X-C Motif chemokine 16, S100-A12, Eotaxin, soluble E-selectin, Fibronectin, Granulocyte colony-stimulating factor, Granulocyte-macrophage colony-stimulating factor, Heparin-binding growth factor 2, soluble Hepatocyte growth factor receptor, Interleukin-1 receptor antagonist, Interleukin-1 beta, Interleukin-10, Interleukin-15, Interleukin-3, Myeloperoxidase, Nidogen-1, soluble Oxidized low-density lipoprotein receptor 1, Pappalysin-1, soluble P-selectin glycoprotein ligand 1, Antileukoproteinase, soluble Kit ligand, Tissue inhibitor of metalloproteinase 1, Tissue inhibitor of metalloproteinase 2, soluble Tumor necrosis factor, soluble Vascular cell adhesion molecule 1, and Vascular endothelial growth factor A as diagnostic and prognostic biomarkers in renal injuries.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Cytoplasmic aspartate aminotransferase, soluble Tumor necrosis factor receptor superfamily member 5, soluble CD40 Ligand, soluble C-X-C Motif chemokine 16, S100-A12, Eotaxin, soluble E-selectin, Fibronectin, Granulocyte colony-stimulating factor, Granulocyte-macrophage colony-stimulating factor, Heparin-binding growth factor 2, soluble Hepatocyte growth factor receptor, Interleukin-1 receptor antagonist, Interleukin-1 beta, Interleukin-10, Interleukin-15, Interleukin-3, Myeloperoxidase, Nidogen-1, soluble Oxidized low-density lipoprotein receptor 1, Pappalysin-1, soluble P-selectin glycoprotein ligand 1, Antileukoproteinase, soluble Kit ligand, Tissue inhibitor of metalloproteinase 1, Tissue inhibitor of metalloproteinase 2, soluble Tumor necrosis factor, soluble Vascular cell adhesion molecule 1, and Vascular endothelial growth factor A as diagnostic and prognostic biomarkers in renal injuries.

Fusion proteins of protease inhibitors are provided, in particular fusion proteins of alpha 1-antitrypsin (AAT) and a second protease inhibitor, such as secretory leukocyte protease inhibitor (SLPI) or tissue inhibitor of metalloproteases (TIMP). Polynucleotides encoding the fusion proteins, vectors comprising such polynucleotides, and host cells containing such vectors are also provided. Methods of making the fusion proteins of the invention are also provide, as well as methods of using the fusion proteins, for example to inhibit protease activity in a biological sample or in the treatment of an individual suffering from, or at risk for, a disease or disorder involving unwanted protease activity.

The present invention provides a method of diagnosing the presence or severity of tissue fibrosis in an individual by detecting α2-macroglobulin (α2-MG) in a sample from the individual; detecting hyaluronic acid (HA) in a sample from the individual; detecting tissue inhibitor of metalloproteinases-1 (TIMP-1) in a sample from the individual; and diagnosing the presence or severity of tissue fibrosis in the individual based on the presence or level of α2-MG, HA and TIMP-1.

A method for the use and delivery of tissue inhibitors of matrix metalloproteinase (TIMPs) to control the activity of the matrix metalloproteinase (MMPs) in the extracellular matrix (ECM) in order to treat and prevent extracellular matrix degradation in an injured tendon or ligament is presented. Accelerated breakdown of the extracellular matrix occurs in various pathological processes, including inflammation, chronic degenerative diseases and tumor invasion. Four members of the tissue inhibitor of metalloproteinase (TIMP) family have been characterized so far, designated as TIMP-1, TIMP-2, TIMP-3, and TIMP-4. Various introduction amounts, timing and combinations are capable of inhibiting the activities of all known matrix metalloproteinase (MMPs) and as such play a key role in maintaining the balance between (ECM) deposition and degradation in different physiological processes.

The present invention provides a method of diagnosing the presence or severity of tissue fibrosis in an individual by detecting α2-macroglobulin (α2-MG) in a sample from the individual; detecting hyaluronic acid (HA) in a sample from the individual; detecting tissue inhibitor of metalloproteinases-1 (TIMP-1) in a sample from the individual; and diagnosing the presence or severity of tissue fibrosis in the individual based on the presence or level of α2-MG, HA and TIMP-1.

A method for the detection of the presence and / or the severity of a liver disease in a patient comprising measuring in an isolated sample TIMP-1 (tissue inhibitor of metalloproteinase I), ferritin, at least one additional parameter selected from the group consisting of A2M (alpha-2-macroglobulin) and PI (prothrombin index) and optionally measuring at least one additional biochemical or clinical parameter and diagnosing the presence and / or severity of a liver disease based on the presence or measured levels of these parameters. The method can be used for monitoring therapeutic treatment of liver fibrosis and staging of liver fibrosis.

Fusion proteins of protease inhibitors are provided, in particular fusion proteins of alpha 1-antitrypsin (AAT) and a second protease inhibitor, such as secretory leukocyte protease inhibitor (SLPI) or tissue inhibitor of metalloproteases (TIMP). Polynucleotides encoding the fusion proteins, vectors comprising such polynucleotides, and host cells containing such vectors are also provided. Methods of making the fusion proteins of the invention are also provide, as well as methods of using the fusion proteins, for example to inhibit protease activity in a biological sample or in the treatment of an individual suffering from, or at risk for, a disease or disorder involving unwanted protease activity.

The invention discloses a reagent for auxiliarily diagnosing lung cancer lymph node metastasis, comprising 8 antibodies which are used for detecting 8 protein markers which are MMP1 (matrix metalloproteinase-1), TIMP1 (tissue inhibitor of metalloproteinases metallopeptidase inhibitor 1), IQGAP1 (IQ motif containing GTPase activating protein 1), TPX2 (targeting protein for Xklp2), uPA (Urokinase-type plasminogen activator), Cathepsin-D, Fascin and pIgR / SC (polymeric immunoglobulin receptor / secretory component). By adopting the 8 antibodies and an immunohistochemical staining result, lung cancer lymph node metastasis can be auxiliarily diagnosed, and the reagent is expected to be used for the risk estimation of lung squamous cell cancer lymph node metastasis and the prognostic prediction. The reagent has high creditability, strong practicability and clinical use value based on the clinical routine immunohistochemical staining technology when the reagent is used for auxiliary diagnosis.

The invention concerns a method for the detection of the presence and / or the severity of a liver disease in a patient comprising measuring in an isolated sample TIMP-1 (Tissue Inhibitor of Metalloproteinase I), A2M (a-2-macroglobulin), PLT (number of blood plateletes, PI (prothrombin index), optionally at least one additional parameter selected from the group consisting of urea and GGT (γ-glutamyltranspeptidase) and optionally measuring at least one additional biochemical or clinical parameter and diagnosing the presence and / or severity of a liver disease based on the presence or measured levels of these parameters. The method can be used for monitoring therapeutic treatment of liver fibrosis and staging of liver fibrosis.

The invention discloses the construction of a si RNA expression vector of the tissue inhibitor of metalloproteinases (TIMPs) and application in treatment of cirrhosis, which belong to the technical field of genetic engineering. In the invention, according to the design principle of siRNA, a corresponding si RNA sequence is designed by selecting nucleotide sequences of TIMP-1 and TIMP-2 coding areas respectively to perform BLAST comparison, so that isogenesis with other genes is avoided; single-stranded oligonucleotides chemically synthesized and the double stranded DNA formed by annealing in vitro are connected with a eukaryotic expression vector pGeneil-1; and enzyme digesting identification and sequence assay prove that the si RNA expression vector of the TIMP-1 and TIMP-2 is constructed successfully. The vector transfects a hepatic stellate cell (HSC) through liposome and can inhibit the expression of the TIMP-1 and the TIMP-2 obviously; cirrhosis animal model assay shows that the expression vector can reduce the collagenous fiber deposition of liver tissues considerably and is expected to be used as a novel anti-hepatic fibrosis genetic therapy in clinical treatment.

Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in the affected joint of a mammal is accomplished by administering a chondroprotective compound of Formula (I): where A is hydroxy, (C1-C4)alkoxy, amino, hydroxy-amino, mono-(C1-C2)alkylamino, di-(C1-C2)alkylamino; X and Y are independently H or (C1-C2)alkyl; and n is 1 or 2; R6 is halogen, (C1- C3)alkyl, trifluoromethyl, or nitro; R9 is H; (C1-C2)alkyl; phenyl or phenyl-(C1- C2)alkyl, where phenyl is optionally mono-substituted by fluoro or chloro; -C(=O)-R, where R is (C1-C2)alkyl or phenyl, optionally mono-substituted by fluoro or chloro; or -C(=O)-O-R1, where R1 is (C1- C2)alkyl. This treatment ameliorates, diminishes, actively treats, reverses or prevents any injury, damage or loss of articular cartilage or subchondral bone subsequent to said early stage of said degeneration. Whether or not a mammal needs such treatment is determined by whether or not it exhibits a statistically significant deviation from normal standard values in synovial fluid or membrane from the affected joint, with respect to at least five of the following substances: increased interleukin-1 beta (IL-1beta), increased tumor necrosis factor alpha (TNFalpha); increased ratio of IL-1beta to IL-1 receptor antagonist protein (IRAP); increased expression of p55 TNF receptors (p55 TNF-R), increased interleukin-6 (IL-6); increased leukemia inhibitory factor (LIF); decreased insulin-like growth factor-1 (IGF-1); decreased transforming growth factor beta (TGFbeta); decreased platelet-derived growth factor (PDGF); decreased basic fibroblast growth factor (b-FGF); increased keratan sulfate; increased stromelysin; increased ratio of stromelysin to tissue inhibitor of metalloproteases (TIMP); increased osteocalcin; increased alkaline phosphatase; increased cAMP responsive to hormone challenge; increased urokinase plasminogen activator (uPA); increased cartilage oligomeric matrix protein; and increased collagenase.

The present invention provides methods of promoting arteriogenesis in a subject. Embodiments include methods comprising: administering an effective dose of tocotrienol to the subject; causing an increase in Tissue Inhibitor of Metalloproteinase Metallopeptidase Inhibitor 1 (TIMP1) in vessels of cerebrovascular collateral circulation in the subject; attenuating the activity of Matrix Metalloproteinase-2 (MMP2); thereby promoting arteriogenesis.

The invention belongs to the technical field of genes, and particularly relates to an application of a TIMP-1 (tissue inhibitor of metalloproteinase-1) gene in preparation of a product for treating diabetic skin ulcers. The application comprises the following steps: building a recombinant expression vector with the TIMP-1 gene with the TIMP-1 gene or an adenovirus vector or a lentiviral vector; co-transfecting HEK293 cells with the recombinant expression vector with the TIMP-1 gene and adenovirus vector shuttle plasmids, and obtaining a recombinant adenovirus with the TIMP-1 gene; and transfecting the recombinant adenovirus with the TIMP-1 gene into skin cells of diabetes patients or animal models; and improving the TIMP-1 expression level. The application proves that the TIMP-1 is capable of inhibiting excessive fibroblast apoptosis caused by high glucose, in skin of the diabetes patients, thus healing of the diabetic skin ulcers is accelerated; and a basis is provided for inventing the TIMP-1 gene as a new therapeutic target and medicine for preventing and treating chronic diabetic foot ulcers.

The invention belongs to the field of therapies for solid cancers, in particular, skin cancer. Compositions comprising tissue inhibitors of metalloproteinases (TIMPs) linked to anchors for anchoring TIMP into a cell membrane and heatlabile vesicles are provided. Also provided are uses of TIMP or TIMP constructs for treating solid cancers in combination with hyperthermic treatment.

The present invention relates in general to metalloproteinase inhibitors and to polynucleotides encoding such inhibitors. In particular, the invention relates to novel mammalian inhibitors of metalloproteinase, which are designated as type three or TIMP-3, to fragments, derivatives, and analogs thereof, and to polynucleotides encoding the same. Novel methods of producing such compositions and novel methods of using such compositions are also provided.

The invention relates to the technical field of medical detection and in particular to a myocardial damage marker MMPs (Matrix Metalloproteinases), TIMPs (Tissue Inhibitor of Metalloproteinases) and cTnI (Cardiac Troponin I) detection kit and a detection method. The kit mainly consists of a fluorescence labeling probe, an anti-MMPs, TIMPs and cTnI monoclonal antibody, an anti-mouse IgG antibody, asolid-phase membrane and a detection card. According to the kit, MMps and TIMPs are firstly established and cTnI detection is combined for combined detection and diagnosis schemes of myocardial damage, the kit is prior to a conventional congestive heart failure marker group, accurate scientific bases are provided for clinical diagnosis of myocardial infarction and stroma reconstruction related congestive heart failure, secondly, by using an immunochromatography fluorescence quantitative determination detection method based on a fluorescence latex immunochromatography quantitative technique, MMPs, TIMPs and CtNI are combined and respectively detected, a myocardial damage detection system is established, immunochromatography is established, a fluorescence quantitative determination method is implemented, conventional euzymelinked immunosorbent assay (ELISA) is broken through, a myocardial damage detection system based on the fluorescence latex immunochromatography quantitative techniqueis established in China for a first time, and the kit has the characteristics of rapidness, accuracy, high sensitivity and good specificity.

The present invention relates to fusion constructs of glycosylphosphatidylinositol (GPI)-anchored tissue inhibitors of metalloproteinases (TIMPs) and their use for the treatment of cancer and in regenerative medicine. By this approach, the GPI-anchored TIMP proteins are incorporated into the surface membrane of tumor cells and render tumor cells sensitive to FAS-induced apoptosis. Furthermore, the fusion constructs of the present invention are effective agents useful in wound healing applications. In one embodiment, the TIMP is linked to mucin followed by GPI in order to enhance surface presentation. The use of GPI to link TIMP renders the resulting fusion protein particularly useful as an anti-cancer agent for the treatment of cancer, and, in particular, any residual cancer following an incomplete surgical resection of primary tumors in an individual.

The present invention relates to the diagnosis of colorectal cancer. It discloses the use of protein TIMP-1 (tissue inhibitor of metalloproteinase 1) as a marker molecule in the diagnosis of colorectal cancer. It relates to a method for diagnosis of colorectal cancer from a stool sample, derived from an individual, the method involving measuring TIMP-1 in the sample. Measurement of TIMP-1 can, e.g., be used in the early detection or diagnosis of colorectal cancer.

The invention discloses a traditional Chinese medicine composition for treating hepatic fibrosis and a preparation method and an application thereof, and belongs to the field of traditional Chinese medicines. The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 10 to 20 parts of asiatic moonseed rhizome, 5 to 15 parts of rhizoma arisaematis, and 10 to 20 parts of waternut herb. The traditional Chinese medicine composition has the advantages that according to pharmacological experiment results, the ALT (alanine transaminase), AST (aspertate aminotransferase) and AKP (alkaline phosphatase) contents of serum biochemical indexes of a hepatic fibrosis Kunming mouse can be improved, the Hyp (hydroxyproline) content of the liver tissue is improved, the visceral indexes of spleens, livers and thymus of the hepatic fibrosis mouse model are improved, the HA (hyaluronic acid), LN (laminin), PCIII (type III procollagen) and CIV (type IV collagen) contents of the hepatic fibrosis mouse model are improved, the protein expression levels of TGF-beta 1 (transforminggrowthfactorbeta - beta 1), RLX (raloxifene) and TIMP-1 (tissue inhibitor of metalloproteinase-1) of the liver tissue of the hepatic fibrosis are improved, the super-micro structure of the liver tissue of the hepatic fibrosis is improved, and the obvious influence on the weight of the mouse is avoided; the effect of treating the hepatic fibrosis is obvious, and the toxic effect is avoided.

The invention relates to the diagnosis and treatment of diseases, including inflammatory disorders, proliferative disorders and autoimmune diseases. The invention provides, and involves the use of, antibody molecules that bind: i) lysozyme, ii) neutrophil elastase, iii) tissue inhibitor of metalloproteinase-1 (TIMP-1), or iv) the D domain of Tenascin-C. The invention also relates to the use of antibody molecules that bind v) the IIICS isoform of fibronectin, vi) the Extra Domain-B (ED-B) of fibronectin, vii) matrix-metalloproteinase 3 (MMP3), or viii) the A1 domain of tenascin-C in the diagnosis and treatment of inflammatory disorders such as inflammatory bowel disease.

The present invention relates to cancer therapies. More specifically, the present invention relates to oncolytic adenoviral vectors and cells and pharmaceutical compositions comprising said vectors. The present invention also relates to a use of said vectors in the manufacture of a medicament for treating cancer in a subject and a method of treating cancer in a subject. Furthermore, the present invention relates to methods of producing peptidylarginine deiminase and TIMP in a cell and increasing anti-tumor effect and induction of specific immune response in a subject, as well as uses of the oncolytic adenoviral vector of the invention for producing transgenes in a cell and increasing anti-tumor effect and generation of specific immune response in a subject.

The present invention provides methods and compositions for identifying patients at risk of kidney injury. A risk score, which is a composite of a urinary concentration of IGFBP7 (insulin-like growth factor-binding protein 7) and a urinary concentration of TIMP-2 (tissue inhibitor of metalloproteinase 2), is determined obtained from the patient, and is used to manage patient treatment.

The invention relates to the use of the plasma concentration of the polypeptide “tissue inhibitor of metalloproteinase-4” (TIMP-4) as a biomarker for the diagnosis of heart failure.

The present invention provides methods and compositions for managing renal replacement therapy. A risk score, which is determined from a urinary concentration of IGFBP7 (insulin-like growth factor-binding protein 7) and / or a urinary concentration of TIMP-2 (tissue inhibitor of metalloproteinase 2), is determined obtained from the patient, and is used to manage patient treatment.

The present invention relates to fusion constructs of glycosylphosphatidylinositol (GPI)-anchored tissue inhibitors of metalloproteinases (TIMPs) and their use for the treatment of cancer and in regenerative medicine. By this approach, the GPI-anchored TIMP proteins are incorporated into the surface membrane of tumor cells and render tumor cells sensitive to FAS-induced apoptosis. Furthermore, the fusion constructs of the present invention are effective agents useful in wound healing applications. In one embodiment, the TIMP is linked to mucin followed by GPI in order to enhance surface presentation. The use of GPI to link TIMP renders the resulting fusion protein particularly useful as an anti-cancer agent for the treatment of cancer, and, in particular, any residual cancer following an incomplete surgical resection of primary tumors in an individual.