5982 results about "Endothelium" patented technology

The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

The present invention relates to ligands which bind to human tumor necrosis factor alpha (TNF) in a manner such that upon binding of these ligands to TNF the biological activity of TNF is modified. In preferred forms the ligand binds to TNF in a manner such that the induction of endothelial procoagulant activity of the TNF is inhibited; the binding of TNF to receptors on endothelial cells is inhibited; the induction of fibrin deposition in the tumor and tumor regression activities of the TNF are enhanced; and the cytotoxicity and receptor binding activities of the TNF are unaffected or enhanced on tumor cells. The ligand is preferably an antibody, F(ab) fragment, single domain antibody (dABs) single chain antibody or a serum binding protein. It is preferred, however, that the ligand is a monoclonal antibody or F(ab) fragment thereof.

The present invention provides devices, methods and systems for the occlusion of various lumens in a body of a patient including devices and methods for enhancing tissue ingrowth, particularly endothelial tissue growth within an occlusive device. The system includes an occlusive device and a delivery device for placing the occlusive device in a body lumen. The occlusive device is generally a tubular member with a mesh member disposed thereon. The occlusive device is configured to be radially expandable along a longitudinal axis of the tubular member and implantable with a delivery catheter such that the occlusive device is in a collapsed state when positioned in the delivery catheter and in an expanded state when positioned in a lumen of a patient. The mesh member of the occlusive device is configured to promote epithelial tissue ingrowth.

The present invention relates generally to decellularized extracellular matrix of conditioned body tissues. The decellularized extracellular matrix contains a biological material, preferably vascular endothelial growth factor (VEGF), produced by the conditioned body tissue that is in an amount different than the amount of the biological material that the body tissue would produce absent the conditioning. The invention also relates to methods of making and methods of using said decellularized extracellular matrix. Specifically, the invention relates to treating defective, diseased, damaged or ischemic cells, tissues or organs in a subject by administering, injecting or implanting the decellularized extracellular matrix of the invention into a subject in need thereof. The invention is further directed to a tissue regeneration scaffold for implantation into a subject inflicted with a disease or condition that requires tissue or organ repair, regeneration and / or strengthening. Additionally, the invention is directed to a medical device, preferably a stent or an artificial heart, having a surface coated or covered with the decellularized extracellular matrix of the invention or having a component comprising the decellularized extracellular matrix of the invention for implantation into a subject, preferably a human. Methods for making the tissue regeneration scaffold and methods for manufacturing a coated or covered medical device having a component comprising decellularized extracellular matrix of conditioned body tissues are also provided.

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.

Disclosed are ligands that have binding specificity for vascular endothelial growth factor (VEGF), for epidermal growth factor receptor (EGFR), or for VEGF and EGFR. Also disclosed are methods of using these ligands. In particular, the use of these ligands for cancer therapy is described.

A device is disclosed for the securement of dermal tissues. The device provides approximation and eversion of the tissue as well as the placement of a fixation element that bridges a wound. The fixation element may be produced in several fixed or dynamic configurations that may or may not alter the ability to engage tissue in response to stresses placed upon the fixation member post-deployment. The delivery device inserts the fastener percutaneously through the epidermis into the sub-dermal position without entering the wound margins with any part of the approximation portion of the delivery device.

A method for the treatment of a patient for the purpose of lowering blood pressure and / or treating cardiac arrhythmias, particularly atrial fibrillation includes the insertion of an ablation catheter into the lumen of a renal artery. The ablation catheter is equipped with an electrode that can stimulate the wall tissue in the renal artery to help identify the location of a renal nerve. High-frequency stimulation of the renal nerve causes a decrease in the blood pressure of the patient thereby indicating that a renal nerve is nearby. The ablation catheter is used to ablate the renal nerve using radiofrequency, ultrasound, microwave energy or cryogenic cooling. An irrigated ablation catheter may be used to decrease damage to cells in the wall of the lumen of the renal artery other than the renal nerve, such as the endothelial cells.

This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

Endothelial cell attachment to an intravascular stent is promoted by coating the stent with an endothelial cell specific adhesion peptide. Coating is preferably carried out by activating the intravascular stent using plasma glow discharge, applying on the stent a layer or plurality of layers of a polymer such as poly(2-hydroxyethylmethacrylate), applying a tresylation solution containing pyridine and tresyl chloride, and applying a five amino acid peptide having the sequence glycine-arginine-glutamic acid-aspartic acid-valine.

The invention relates generally to methods for inhibiting angiogenesis. More particularly, methods for inhibiting angiogenesis comprise selectively inhibiting phosphoinositide 3-kinase delta (PI3Kδ) activity in endothelial cells. The methods may comprise administration of one or more cytotoxic therapies including but not limited to radiation, chemotherapeutic agents, photodynamic therapies, radiofrequency ablation, anti-angiogenic agents, and combinations thereof.

Method and apparatus are provided to treat atherosclerosis wherein the artery is partially closed by dilating the artery while preserving the vital and sensitive endothelial layer thereof Microwave energy having a frequency from 3 GHz to 300 GHz is propagated into the arterial wall to produce a desired temperature profile therein at tissue depths sufficient for thermally necrosing connective tissue and softening fatty and waxy plaque while limiting heating of surrounding tissues including the endothelial laser and / or other healthy tissue, organs, and blood. The heating period for raising the temperature a potentially desired amount, about 20 DEG C., within the atherosclerotic lesion may be less than about one second. In one embodiment of the invention, a radically beveled waveguide antenna is used to deliver microwave energy at frequencies from 25 GHz or 30 GHz to about 300 GHz and is focused towards a particular radial sector of the artery. Because the atherosclerotic lesions are often asymmetrically disposed, directable or focussed heating preserves healthy sectors of the artery and applies energy to the asymmetrically positioned lesion faster than a non-directed beam. A computer simulation predicts isothermic temperature profiles for the given conditions and man be used in selecting power, pulse duration, beam width, and frequency of operation to maximize energy deposition and control heat rise within the atherosclerotic lesion without harming healthy tissues or the sensitive endothelium cells.

An endovascular cellular manipulation and inflammatory response are elicited from implantation in a vascular compartment or any intraluminal location of a separable coil comprised at least in part of at least one biocompatible and absorbable polymer or protein and growth factors. Typically a catheter associated with the separable coil is used to dispose the coil into a selected body lumen. The biocompatible and absorbable polymer or protein is thrombogenic. The coil further is comprised at least in part of a growth factor or more particularly a vascular endothelial growth factor, a basic fibroblast growth factor or other growth factors. The biocompatible and absorbable polymer is in the illustrated embodiment at least one polymer selected from the group consisting of polyglycolic acid, poly~glycolic acid poly-L-lactic acid copolymers, polycaprolactive, polyhydroxybutyrate / hydroxyvalerate copolymers, poly-L-lactide. Polydioxanone, polycarbonates, and polyanhydrides. The biocompatible and absorbable protein is at least one protein selected from the group consisting of collagen, fibrinogen, fibronectin, vitronectin, laminin, and gelatin. In one embodiment the coil is composed of the biocompatible and absorbable polymer or protein with a radio-opaque material is disposed thereon. Alternatively, the coil is composed of a radio-opaque material, and the biocompatible and absorbable polymer or protein is disposed thereon. This apparatus may be positioned within intracranial aneurysms or any aneurysm in the body as well as within other body cavities.

Methods of medical treatment and diagnosis using mediators released by endothelial cells stimulated by external addition of pulses to the circulation are disclosed. The external pulses produce circumferential shear stress in body fluid channels that subsequently stimulates the endothelial cells to produce mediators that become available for therapeutic and diagnostic purposes. The preferred means of adding external pulses is the mechanical inducement of periodic acceleration of the body or parts of the body by a reciprocating motion platform.

Described are conjugates formed by an antibody fragment covalently attached to a non-proteinaceous polymer, wherein the apparent size of the conjugate is at least about 500 kD. The conjugates exhibit substantially improved half-life, mean residence time, and / or clearance rate in circulation as compared to the underivatized parental antibody fragment. Also described are conjugates directed against human vascular endothelial growth factor (VEGF), human p185 receptor-like tyrosine kinase (HER2), human CD20, human CD18, human CD11a, human IgE, human apoptosis receptor-2 (Apo-2), human tumor necrosis factor-α (TNF-α), human tissue factor (TF), human α4β7 integrin, human GPIIb-IIIa integrin, human epidermal growth factor receptor (EGFR), human CD3, and human interleukin-2 receptor α-chain (TAC) for diagnostic and therapeutic applications.

The features of the present invention relate to compounds, compositions and methods useful for modulating the expression of vascular endothelial growth factor (VEGF), such as by the mechanism of RNA interference (RNAi). The compounds and compositions include iRNA agents that can be unmodified or chemically-modified.

A medical device for implantation into vessels or luminal structures within the body is provided. The medical device, such as a stent and a synthetic graft, is coated with a pharmaceutical composition consisting of a controlled-release matrix and one or more pharmaceutical substances for direct delivery of drugs to surrounding tissues. The coating on the medical device further comprises a ligand such as an antibody or a small molecule for capturing progenitor endothelial cells in the blood contacting surface of the device for restoring an endothelium at the site of injury. In particular, the drug-coated stents are for use, for example, in balloon angioplasty procedures for preventing or inhibiting restenosis.

The present invention concerns methods for treating and preventing renal / kidney disease, insulin resistance / diabetes, fatty liver disease, and / or endothelial dysfunction / cardiovascular disease using synthetic triterpenoids, optionally in combination with a second treatment or prophylaxis.

Apparatus and methods for stenting are provided comprising a stent attached to a porous biocompatible material that is permeable to endothelial cell ingrowth, but impermeable to release of emboli of predetermined size. Preferred stent designs are provided, as well as preferred manufacturing techniques. Apparatus and methods are also provided for use at a vessel branching. Moreover, embodiments of the present invention may comprise a coating configured for localized delivery of therapeutic agents. Embodiments of the present invention are expected to provide enhanced embolic protection, improved force distribution, and improved recrossability, while reducing a risk of restenosis and thrombus formation.

Methods of medical treatment and diagnosis using mediators released by endothelial cells stimulated by external addition of pulses to the circulation are disclosed. The external pulses produce circumferential shear stress in body fluid channels that subsequently stimulates the endothelial cells to produce mediators that become available for therapeutic and diagnostic purposes. The preferred means of adding external pulses is the mechanical inducement of periodic acceleration of the body or parts of the body by a reciprocating motion platform.

A medical device coated with one or more antibodies and one or more layers of a matrix is disclosed. The antibodies or fragments thereof react with an endothelial cell surface antigen. Also disclosed are compositions and methods for producing the medical device. The matrix coating the medical device may be composed of a synthetic material, such as a fullerene, or a naturally occurring material. The fullerenes range from about C60 to about C100. The medical device may be a stent or a synthetic graft. The antibodies promote the adherence of cells captured in vivo on the medical device. The antibodies may be mixed with the matrix or covalently tethered through a linker molecule to the matrix. Following adherence to the medical device, the cells differentiate and proliferate on the medical device. The antibodies may be different types of monoclonal antibodies. By facilitating adherence of cells to the surface of the medical device, the disclosed methods and compositions will decrease the incidence of restenosis as well as other thromboembolic complications resulting from implantation of medical devices.

Methods and compositions for recruiting cells circulating in the blood stream of a subject to a blood contacting surface, and in particular, devices and methods for recruiting endothelial cells to a blood contacting surface of a prosthesis as well as engineering a self-endothelializing graft in vivo by recruitment of circulating endothelial progenitor cells (EPCs) to form a neo-endothelium on a prosthetic structure.

This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

The present invention provides compositions and methods for enhancing transport of biologically active compounds across biological membranes and across and into animal epithelial or endothelial tissues. The composition includes a biologically active agent and a transport moiety. The transport moiety includes a structure selected from the group consisting of (ZYZ)nZ, (ZY)nZ, (ZYY)nZ and (ZYYY)nZ. Subunit “Z” is L-arginine or D-arginine, and subunit “Y” is an amino acid that does not comprise an amidino or guanidino moiety. Subscript “n” is an integer ranging from 2 to 10. The method for enhancing transport involves the administration of the aforementioned composition.

A device and method to dissolve or eliminate blood clots from a patient relies upon a non-rapid moving mechanism to physically dissolve clots without damaging endothelium of the arteries and veins of a patient. In one embodiment, in addition to mechanical agitation of a clot, a thrombolytic agent is administered simultaneously with such agitation. Preferably, intermittent agitation is utilized over a prolonged period of time to effectuate clot removal.

Method and apparatus are provided to treat atherosclerosis wherein the artery is partially closed by dilating the artery while preserving the vital and sensitive endothelial layer thereof. Microwave energy having a frequency from 3 GHz to 300 GHz is propagated into the arterial wall to produce a desired temperature profile therein at tissue depths sufficient for thermally necrosing connective tissue and softening fatty and waxy plaque while limiting heating of surrounding tissues including the endothelial layer and / or other healthy tissue, organs, and blood. The heating period for raising the temperature a potentially desired amount, about 20° C. within the atherosclerotic lesion may be less than about one second. In one embodiment of the invention, a radically beveled waveguide antenna is used to deliver microwave energy at frequencies from 25 GHz or 30 GHz to about 300 GHz and is focused towards a particular radial sector of the artery. Because the atherosclerotic lesions are often asymmetrically disposed directable or focussed heating preserves healthy sectors of the artery and applies energy to the asymmetrically positioned lesion faster than a non-directed beam. A computer simulation predicts isothermic temperature profiles for the given conditions and may be used in selecting power, pulse duration, beam width, and frequency of operation to maximize energy deposition and control heat rise within the atherosclerotic lesion without harming healthy tissues or the sensitive endothelium cells.

Compositions and methods are provided for producing a medical device such as a stent, a stent graft, a synthetic vascular graft, heart valves, coated with a biocompatible matrix which incorporates antibodies, antibody fragments, or small molecules, which recognize, bind to and / or interact with a progenitor cell surface antigen to immobilize the cells at the surface of the device. The coating on the device can also contain a compound or growth factor for promoting the progenitor endothelial cell to accelerate adherence, growth and differentiation of the bound cells into mature and functional endothelial cells on the surface of the device to prevent intimal hyperplasia. Methods for preparing such medical devices, compositions, and methods for treating a mammal with vascular disease such as restenosis, artherosclerosis or other types of vessel obstructions are disclosed.

The present invention concerns methods and reagents useful in modulating vascular endothelial growth factor (VEGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D) and / or vascular endothelial growth factor receptor (e.g., VEGFR1, VEGFR2 and / or VEGFr3) gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against VEGF and / or VEGFr gene expression and / or activity. The small nucleic acid molecules are useful in the diagnosis and treatment of cancer, proliferative diseases, and any other disease or condition that responds to modulation of VEGF and / or VEGFr expression or activity.