71 results about "E-selectin" patented technology

The invention relates to C5 inhibitors, which inhibit type II endothelial cell activation, wherein the inhibition is manifested by the suppression of E-selectin. These inhibitors are useful in treatment of delayed xenograft rejection or acute vascular rejection. The inhibitors include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, F(ab')2 and Fv, small molecules, including peptides, oligonucleotides, peptidomimetics and organic compounds. Examples of monoclonal antibodies, which bind to and inhibit C5, were generated and are designated MAb 137-76 and MAb 137-30.

Compounds and methods are provided for modulating in vitro and in vivo processes mediated by selectin binding. More specifically, selectin modulators and their use are described, wherein the selectin modulators that modulate (e.g., inhibit or enhance) a selectin-mediated function comprise a class of compounds termed BASAs (Benzyl Amino Sulfonic Acids, which include a portion or analogue thereof) linked to a carbohydrate or glycomimetic.

An unbranched polylactosamine comprising at least 6 monosaccharides and having terminal alpha 2->3 sialylation and internal alpha 1->3 fucosylation at various N-acetylglucosamine residues except for solely at the penultimate N-acetylglucosamine residue.

Compounds, compositions and methods are provided for treating cancer and inflammatory diseases, and for releasing cells such as stem cells (e.g., bone marrow progenitor cells) into circulating blood and enhancing retention of the cells in the blood. More specifically, heterobifunctional compounds that inhibit both E-selectins and CXCR4 chemokine receptors are described.

This invention relates to whole antibodies of neutral isotype having specificity for E-selectin, process for their preparation (using vectors), pharmaceutical compositions containing them, and their use in therapy and diagnosis. Said antibodies are variants of natural antibodies altered in the Fc region, especially in the CH2 domain, so that the interactions with antibodies Fc receptors and complement are very low.

Compounds and methods are provided for modulating in vitro and in vivo processes mediated by selectin binding. More specifically, selectin modulators and their use are described, wherein the selectin modulators that modulate (e.g., inhibit or enhance) a selectin-mediated function comprise particular glycomimetics linked to a member of a class of compounds termed BASAs (Benzyl Amino Sulfonic Acids).

This invention discloses the use of an E-selectin antagonist and a mobilizer of hematopoietic stem cells or progenitor cells in methods and compositions for treating or preventing immunocompromised conditions resulting from medical treatment. The present invention is particular relevant for prophylaxis and / or treatment of hematopoeitic disorders including neutropenia, agranulocytosis, anemia and thrombocytopenia in individuals receiving or proposed to receive treatments that target rapidly dividing cells or that disrupt the cell cycle or cell division.

Compositions containing one or more peptido-mimetics or modified peptido-mimetics of a carbohydrate ligand of an adhesion molecule in a physiologically acceptable carrier are useful for methods of reducing metastasis in a mammal and for inhibiting inflammatory response in a mammal. Particularly useful are embodiments in which the ligand is a Lewis antigen and / or the adhesion molecule is a selectin, e.g., E-selectin. Methods are disclosed for identifying peptido-mimetics of carbohydrate ligands, which may be involved in binding of tumor cells to other cells, such as endothelial cells.

This invention discloses the use of an E-selectin antagonist in methods and compositions for treating or preventing immunocompromised conditions resulting from medical treatment. The present invention is particular useful for prophylaxis and / or treatment of hematopoietic disorders including neutropenia, agranulocytosis, anemia and thrombocytopenia in individuals receiving or proposed to receive treatments that target rapidly dividing cells or that disrupt the cell cycle or cell division.

This invention relates to a novel herbal composition comprising an extract of flowering and fruiting heads of the plant, Sphaeranthus indicus. The said extract of Sphaeranthus indicus contains a compound, 3a-hydroxy-5a,9-dimethyl-3-methylene-3a,4,5,5a,6,7,8,9b-octahydro-3H-naphtho[1,2-b]furan-2-one (7-Hydroxy-4,11(13)-eudesmadien-12,6-olide) (compound 1), as a bioactive marker. The invention also relates to a composition comprising 3a-hydroxy-5a,9-dimethyl-3-methylene-3a,4,5,5a,6,7,8,9b-octahydro-3H-naphtho[1,2-b]furan-2-one (compound 1) as an active ingredient. The invention also relates to methods of manufacture of the said compositions. The invention also relates to methods of administration of the said compositions to a subject in need of treatment for an inflammatory disorder. The invention also relates to tumor necrosis factor- (TNF-α) and interleukin (IL-1, IL-6, IL-8) inhibitory activity of the said compositions. The invention relates to inhibition of the expression of intercellular adhesion molecule 1 (ICAM-1), vascular-cell adhesion molecule 1 (VCAM-1), and E-Selectin by the said compositions. The said compositions may optionally contain at least one anti-inflammatory agent or can be used in combination with at least one anti-inflammatory agent.

A method of in vitro fucosylation of selectin ligands on cord blood-derived hematopoietic stem cells for bone marrow transplantation is disclosed. In this method, an effective amount of an α1,3-fucosyltransferase, e.g., α1,3-fucosyltransferase VI, is used in vitro to treat cord blood-derived hematopoietic stem cells to convert non-functional PSGL-1 or other ligands on the cell surface into functional forms that bind selectins, especially P-selectin or E-selectin. The treated cells have enhanced effectiveness in reconstituting bone marrow in patients in need of such therapy.

The invention relates to C5 inhibitors, which inhibit type II endothelial cell activation, wherein the inhibition is manifested by the suppression of E-selectin. These inhibitors are useful in treatment of delayed xenograft rejection or acute vascular rejection. The inhibitors include antibody molecules, as well as homologues, analogues and modified or derived forms thereof, including immunoglobulin fragments like Fab, F(ab')2 and Fv, small molecules, including peptides, oligonucleotides, peptidomimetics and organic compounds. Examples of monoclonal antibodies, which bind to and inhibit C5, were generated and are designated MAb 137-76 and MAb 137-30.

Compounds, compositions and methods are provided for inhibiting in vitro and in vivo processes mediated by E-selectin binding. More specifically, particular glycomimetic compounds are described, wherein the compounds are E-selectin antagonists.

The invention feature methods and compositions for treating hematopoietic disorders, inflammatory conditions, and cancer and providing stem cell therapy in a mammal.

The invention relates to an amphiphilic polysaccharide derivative carrier for targeting tumor new blood vessels. According to the derivative, a polysaccharide skeleton is coupled with functional polypeptide targeting E-selectin by virtue of a disulfide bond to ensure that polysaccharide has amphipathy, and is assembled into nano particles for targeting the tumor new blood vessels after carrying an antitumor drug or a tumor new blood vessel inhibitor in an aqueous medium. The nano particles deliver medicines to the tumor new blood vessels in an active targeting manner by virtue of the high affinity between the functional polypeptide targeting the E-selectin and the E-selectin on the surface of the tumor new blood vessels, then a disulfide bond connecting arm can be specifically degraded by a strong reducing environment in endothelial cells of the tumor new blood vessels to cause that the functional polypeptide targeting the E-selectin is separated from polysaccharide, and the medicines are quickly released to treatment target points, so that the concentration of free medicines at tumor new blood vessel parts can be significantly improved and the antitumor curative effect is enhanced. An auxiliary material can be used as a carrier for water-insoluble, indissolvable or amphiphilic antitumor drugs and the tumor new blood vessel inhibitor, and is administrated by injecting into blood vessels or muscles, or is administrated orally or externally. The amphiphilic polysaccharide derivative carrier provided by the invention is simple in preparation method, mature in process and suitable for large-scale production.

Methods for treating and / or preventing mucositis comprising administering to a subject in need thereof an effective amount of at least one compound chosen from E-selectin antagonists, pharmaceutically acceptable salts of E-selectin antagonists, prodrugs of E-selectin antagonists, and pharmaceutically acceptable salts of prodrugs of E-selectin antagonists, and compositions comprising at least one of such compound.

Compounds, compositions, and methods for treatment and / or prevention of cancer and inflammatory diseases, and for releasing cells such as stem cells (e.g., bone marrow progenitor cells) into circulating blood and enhancing retention of the cells in the blood are disclosed. For example, heterobifunctional compounds that inhibit both E-selectins and CXCR4 chemokine receptors are described and pharmaceutical compositions comprising at least one of the same.

A method of in vitro fucosylation of selectin ligands on cord blood-derived hematopoietic stem cells for bone marrow transplantation is disclosed. In this method, an effective amount of an α1,3-fucosyltransferase, e.g., α1,3-fucosyltransferase VI, is used in vitro to treat cord blood-derived hematopoietic stem cells to convert non-functional PSGL-1 or other ligands on the cell surface into functional forms that bind selectins, especially P-selectin or E-selectin. The treated cells have enhanced effectiveness in reconstituting bone marrow in patients in need of such therapy.

This invention relates to whole antibodies of neutral isotype having specificity for E-selection, process for their preparation (using vectors), pharmaceutical compositions containing them, and their use in therapy (e.g. for inflammatory disorders) and diagnosis. Said antibodies are variants of natural antibodies altered in the Fc region, especially in the CH2 domain, so that the interactions with antibodies Fc receptors and complement are absent or very low.

The invention discloses application of a serum molecular marker combination as a lung cancer diagnosis and curative effect monitoring marker, belonging to the field of immunodetection. The content of protein (OPN, SAA, CRP, CEA, CYFRA21.1, MIF, AGP, HGF, E-selectin, GRO and NSE) in 11 serums is measured through a Luminex protein chip diagnosis technology. The eight serum protein molecular markers are OPN, SAA, CRP, CYFRA21.1, CEA, NSE, AGP and HGF. The eight serum protein molecular markers have significant promotion effect on a non-small cell lung cancer (NSCLC) and a small cell lung cancer (SCLC). A three-protein detection combination formed by OPN, CEA and another protein (CRP, SAA, CYFRA21.1 or NSE) has excellent diagnosis potential on NSCLC. Compared with the prior art, the serum molecular marker combination has the beneficial effects that the content of multiple protein molecular markers of serum of a patient with lung cancer is detected, and the serum molecular marker combination can be used for lung cancer diagnosis and curative effect monitoring through coordinated comparative analysis of the multiple protein molecular markers.

The present invention provides a method for reducing stroke-related tissue damage by treating a mammal with E-selectin. Preferably, this treatment induces E-selectin tolerance in the mammal. Another aspect of the invention is a method for inducing E-selectin tolerance in a mammal through intranasal administration of E-selectin, preferably including booster administrations. The present methods are especially adapted for use in patients at increased risk of stroke or who may become at increased risk of stroke.

Provided herein are E-selectin antagonist therapeutic agents and improvements thereto and compositions comprising these E-selectin antagonists. Methods are also provided for using these E-selectin antagonist therapeutic agents to treat and / or prevent diseases and disorders treatable by inhibiting binding of an E-selectin to an E-selectin ligand. Also provided herein improvements to E-selectin antagonist glycomimetic compounds that improve the oral bioavailability of the glycomimetic compounds.

Methods and compositions using E-selectin antagonists are provided for the treatment and prevention of diseases and disorders treatable by inhibiting binding of E-selectin to an E-selectin ligand. Described herein are E-selectin antagonists including, for example, glycomimetic compounds, antibodies, aptamers and peptides that are useful in methods for treatment of cancers, and treatment and prevention of metastasis, inhibiting infiltration of the cancer cells into bone marrow, reducing or inhibiting adhesion of the cancer cells to endothelial cells including cells in bone marrow, and inhibiting thrombus formation.

Compounds, compositions and methods are provided for inhibiting in vitro and in vivo processes mediated by E-selectin binding. More specifically, particular glycomimetic compounds are described, wherein the compounds are E-selectin antagonists.

The invention provides a three-dimensional bionic nanometer material for capturing circulating tumor cells and a preparation method thereof.The material is composed of porous graphene, microballoon spheres and a silicon substrate, a three-dimensional array structure is formed through electrostatic adsorption and self-assembly, chemical modification is carried out on the surfaces of the graphene and the microballoon spheres, E-selectin protein molecules and ligands used for cell capturing are modified and fixed, and a bionic structure for enhancing cell recognition is achieved.The material can be integrated in a micro-fluidic chip, recognition and capturing of the chip for the circulating tumor cells is are enhanced, separation efficiency is improved, and the captured cells can be detected and analyzed conveniently; a fixed recognition ligand is changed, the material can also be used for effectively capturing different types of cells, and rare tumor cells can be recognized and captured from peripheral blood samples.

An isolated and purified glycoprotein and functional analogues thereof are disclosed. The glycoproteins are characterized by being expressed on at least primitive hematopoietic cells, and being a ligand for L-selectin. The binding activity of the ligand of the present invention to L-selectin is not sulfation-dependent and it is neither inhibited by anti-CD34 antibodies nor by MECA-79 monoclonal antibody and the ligand is resistant to O-sialoglycoprotein endopeptidase activity. Further, the present invention provides a method of performing an overlay adherence assay by using isolated cells or cell lines as a substrate. The cells are prepared as the substrate for the assay using a cytocentrifuge with a modified sample chamber allowing placement of the cytocentrifuged cell pellet to any selected location on the slide as required by the shear conditions employed for any given assay.

As illustrated herein, cholesterol is oxidized when it is present in atherosclerotic plaques. This reaction generates cholesterol oxidation or ozonation products that can act as chemotactic attractants of macrophages, can promote differentiation of monocytes into macrophages and can increase expression of E-selectin and Class A scavenger receptor (SR-A). The present application is directed to methods of using such cholesterol ozonoation products to identify agents that can be used to treat atherosclerosis and other inflammatory artery diseases.

Provided herein are glycomimetic E-selectin antagonist compounds of formula (I)) and pharmaceutical compositions comprising at least one of the same. The compounds of the present disclosure include trisaccharide domain mimics comprising at least one macrocycle created through the 2nd and 3rd positions on a galactose within the mimic. Methods are also provided comprising using at least one of such compounds and compositions comprising at least one of the same to treat and / or prevent diseases and disorders treatable by inhibiting binding of an E-selectin to an E-selectin ligand.

Compounds, compositions and methods are provided for treating cancer and inflammatory diseases, and for releasing cells such as stem cells (e.g., bone marrow progenitor cells) into circulating blood and enhancing retention of the cells in the blood. More specifically, heterobifunctional compounds that inhibit both E-selectins and CXCR4 chemokine receptors are described.

The invention belongs to the field of biological detection, and relates to a reagent for predicting micro-bleeding of an acute cerebral infarction patient. The reagent consists of reagents for detecting any one or more of adiponectin, E-selectin, S100B proteins and soluble advanced glycation end product receptors sRAGE. The content of the adiponectin, the E-selectin, the S100B proteins and the soluble advanced glycation end product receptors in the venous blood of the acute cerebral infarction patient is detected, so that the occurrence possibility of micro-bleeding of the patient is judged in an early stage, and a basis is provided for early intervention.