66 results about "Intelectin" patented technology

The present invention provides liquid formulations of antibodies or antibody fragments that immunospecifically bind to integrin alphaVbeta3, which formulations exhibit stability, low to undetectable levels of aggregation, and very little to no loss of the biological activities of the antibodies or antibody fragments, even during long periods of storage. In particular, the present invention provides liquid formulations of antibodies or fragments thereof that immunospecifically bind to integrin alphaVbeta3, which formulations are substantially free of surfactant, inorganic salts, and / or other common excipients. Furthermore, the invention provides methods of preventing, treating or ameliorating an inflammatory disorder, an autoimmune disorder, a disorder associated with aberrant expression and / or activity of integrin alphaVbeta3, a disorder associated with abnormal bone metabolism, a disorder associated with aberrant angiogenesis or cancer utilizing the liquid formulations of the present invention.

Disintegrin variants and pharmaceutical uses thereof are disclosed. The disintegrin variant includes an isolated polypeptide that has integrin αvβ3 receptor-antagonist activity and substantially reduced integrin αllbβ3 and / or α5β1 receptor-blocking activity as compared to a wild-type disintegrin. The variant is encoded by a modified disintegrin nucleotide sequence that encodes a modified amino acid sequence, resulting in a polypeptide having substantially reduced affinity to integrin αllbβ3 and / or α5β1 as compared to a wild-type disintegrin. The variant is useful for treatment and / or prevention of αvβ3 integrin-associated diseases in a mammal, which include osteoporosis, bone tumor or cancer growth, angiogenesis-related tumor growth and metastasis, tumor metastasis in bone, malignancy-induced hypercalcemia, angiogenesis-related eye diseases, Paget's disease, rheumatic arthritis, and osteoarthritis. The angiogenesis-related eye diseases include age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, ischaemia-induced neovascularizing retinopathy, high myopia, and retinopathy of prematurity.

The invention belongs to the field of pharmacology, and relates to stapled-RGD polypeptide, and applications thereof in tumor targeting delivery. Multifunctional targeting polypeptide molecule stapled-RGD with high combination activity with integrin and biological membrane barrier penetration capacity is designed and prepared based on binding peptide cyclization technology; and preparation of fluorescein, drugs, and high molecule carriers modified by the multifunctional targeting polypeptide molecule stapled-RGD, and applications of the fluorescein, the drugs, and the high molecule carriers in tumor imaging and construction of targeted therapy targeted drug delivery systems are disclosed. It is shown by results that specific uptaking of model drugs carried by stapled-RGD by positive cells, tumor mimicry vessels, and tumor ball tissues of expressed integrin is realized, higher tumor targeting capacity, imaging functions, and membrane barrier cell penetration capacity are achieved; nano targeted drug delivery systems constructed by the high molecule carriers modified by stapled-RGD can be used for delivering carried model drugs to target tissues, antitumor drug effect is improved obviously; and stapled-RGD possesses a promising application prospect in mediating drugs, nano targeted drug delivery system membrane barrier penetration, active target searching, tumor diagnosis, and targeted therapy.

The present application is directed to radiolabeled cyclic polypeptides, pharmaceutical compositions comprising radiolabeled cyclic polypeptides, and methods of using the radiolabeled cyclic polypeptides. Such polypeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

The invention belongs to the fields of bioengineering pharmacy, protein polypeptide drugs and biomedical engineering and relates to a polypeptide having high affinity with a receptor of integrin alpha v beta3 and application of the polypeptide. The sequence of the polypeptide is Arg-Trp-Arg or Arg-Lys-Tyr. The polypeptide disclosed by the invention has higher affinity with the integrin alpha v beta3 than the traditional RGD (Arginine-Glycine-Aspartic acid) peptide and can be used in diagnosis and treatment of cancer.

A transgenic carrier with deal targets (fibroblast growth factor receptor and integrant) is composed of the polypeptide CR16 specifically linked with alkaline fibroblast growth factor receptor, the polypeptide CP9 specifically linked with integrant, and the transgenic non-virus carrier system of CR16 / CP9 / cationic polymer PEI / exogenous DNA. Said carrier can effectively introduce the exogenous DNA to the tumor cell line and tumor tissue with high expression of FGFRs, so suppressing the growth of tumor. It can be used to preparation of the medicine for treating tumor and other diseases.

The invention relates to a novel human derived monoclonal antibody for identifying activated integrin alpha 4 beta 7. The monoclonal antibody for specifically identifying activated integrin alpha 4 beta 7 is obtained by screening by an inventor. Based on the identification specificity, the monoclonal antibody can be used as a carrier for targeting transportation to take a medicament to positions of pathological tissues so as to fulfill an aim of treating diseases; and the monoclonal antibody also can be used as a tool for researching the activation status of the integrin alpha 4 beta 7.

The invention provides a tumor dual target liposome mediated by integrin and a preparation method thereof. The composition of the invention comprises the components of an antitumor medicament, polypeptide with tumor new vessel target function and tumor cell target function, polyethylene glycol and derivates thereof and a vector for preparing liposome medicaments.

The invention belongs to the field of pharmacy, and relates to a multi-purpose targeting molecule, and applications of a compound and a drug delivery system modified by the multi-purpose targeting molecule in brain tumor diagnosis and treatment. According to the invention, the multi-purpose targeting molecule RGD-pHA being compatible to brain capillary endothelial cells and crossing the blood-brain barrier, being highly compatible to integrin and crossing the blood-brain tumor barrier, and targeting to the brain tumor cells is prepared by adopting a molecule splicing method; the invention further relates to preparation of fluorescein and a medicine modified by RGD-pHA, and a macromolecular carrier material, and applications of RGD-pHA in construction of the drug delivery system. The experimental result shows that the RGD-pHA can be specifically taken by brain capillary endothelial cells expressing the dopamine receptor for mediating the model drug or the nanometer drug delivery system to enter the brain, so that the model drug or the nanometer drug delivery system is specifically taken by the positive cells and the tumor sphere tissue expressing the integrin, the good brain tumor targeting effect is shown in vitro and vivo, and the efficiency in resisting brain tumor is obviously improved.

The invention relates to the technical field of medicine, in particular to an exosome carrier of a target integrin alpha v beta 3 and a preparation method and application of the exosome carrier. Mononuclear suspension cells THP-1 are adopted and stimulated by PMA of the certain concentration to obtain the exosome carrier, the surface of an exosome after separating contains an RGD target molecule metalloprotease disintegrin family 15, and the target integrin receptor alpha v beta 3 can be obtained. The in-vitro releasing experiment shows that the prepared exosome can slowly release loaded chemotherapeutic medicine, and the better capacity of jointly loading genes and the chemotherapeutic medicine is achieved. In the tumor treatment process, the exosome can enhance the effects of cells of aspecificity target overexpression integrin alpha v beta 3 on tumor cells through the chemotherapeutic medicine or gene medicine, apoptosis of tumor cells is promoted, and therefore the exosome carrierforms a targeted and efficient low-toxicity bionic nanoscale delivery system of tumor treatment.

The invention discloses the application of nucleic acid aptamers in identifying and being bound with integrin alpha4. According to the application of the nucleic acid aptamers in identifying and being bound with the integrin alpha4, it is initiatively found that the nucleic acid aptamers Sgc-4e can identify and be bound with the integrin alpha4 in a specific mode, and the specific binding effect of the nucleic acid aptamers Sgc-4e and the integrin alpha4 is utilized for establishing a method for detecting the integrin alpha4. Experimental results show that the nucleic acid aptamers Sgc-4e have the advtanges of being high in affinity, great in specificity, free of immunogenicity and toxicity and the like, and by means of the method for detecting the integrin alpha4 which is established based on the nucleic acid aptamers Sgc-4e, a new strategy for treating multiple sclerosis can be provided.

Provided is a cell culture vessel characterized in that a surface to be in contact with cells is coated with a laminin fragment having integrin α6β1 binding activity or a modified form thereof in a dry state,the laminin fragment being derived from at least one kind selected from laminin α5β1γ1 and laminin α5β2γ1,the cell culture vessel being any of the following:(1) a cell culture vessel of which a surface to be in contact with cells is coated only with a laminin fragment having integrin α6β1 binding activity or a modified form thereof in a dry state;(2) a cell culture vessel of which a surface to be in contact with cells is coated with a laminin fragment having integrin α6β1 binding activity or a modified form thereof in combination with a laminin fragment having no integrin α6β1 binding activity in a dry state; and(3) a cell culture vessel of which a surface to be in contact with cells is coated with a laminin fragment having integrin α6β1 binding activity or a modified form thereof in combination with a protein that is neither a laminin nor a laminin fragment, in a dry state.

Radiolabeled cyclic polypeptides, pharmaceutical compositions comprising radiolabeled cyclic polypeptides, and methods of using the radiolabeled cyclic polypeptides. Such polypeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

The invention belongs to technical field of genes, and relates to a long non-coding RNA AY927503 and application thereof. It is proved through experiments that the long non-coding RNA AY927503 can adjust migration of human hepatocellular carcinoma cells, sulfatide can adjust migration of the human hepatocellular carcinoma cells through the long non-coding RNA AY927503, express of integrin alpha V can be adjusted, and the long non-coding RNA AY927503 can adjust migration of the cells through the integrin alpha V; it is proved through experiments that the long non-coding RNA AY927503 is mainly located in cytoplasm and also exists in cell nuclei, the long non-coding RNA AY927503 can adjust the activity of a promoter of the integrin alpha V, and the long non-coding RNA AY927503 is not combined with a transcription factor on the promoter of the integrin alpha V but is directly combined with the promoter of the integrin alpha V. According to the long non-coding RNA AY927503 and the application thereof in gene control, the long non-coding RNA AY927503 can be directly combined with the promoter of the integrin alpha V, adjust the transcriptional activity of the integrin alpha V and then influence the behavior of the cells; the long non-coding RNA AY927503 can be used for preparing a target molecule of the human hepatocellular carcinoma cells.

The invention relates to disubstituted phenyl biguanide compounds and application containing the same to inducing malignant tumor cell for anoikis and inhibiting tumor growth and transfer. Proved by in vitro-in vivo experiments, the disubstituted phenyl biguanide compounds show the remarkable functions of inducing the malignant tumor cell for anoikis, starting caspase cascade and inhibiting tumor growth and transfer and also have the characteristics of high efficiency and low toxicity, so the disubstituted phenyl biguanide compounds as pharmaceutical compounds are expected to be applied to a plurality of malignant tumor medicaments for inhibiting the tumor growth, invasion and metastasis and treating human melanoma, neurospongioma, lung cancer, gastric cancer, prostate cancer, ovarian cancer and the like.

Provided herein are antibodies with high affinity for the β8 subunit of αβ8.

The invention discloses a 131I-labelled c(RGDyk)-targeting doxorubicin thermosensitive nanoliposome and its preparation and application and belongs to the field of medical technology. The structure of the 131I-labelled c(RGDyk)-targeting doxorubicin thermosensitive nanoliposome is as follows: 131I and c(RGDyk) are coupled, and c(RGDyk) is inserted through DSPE-PEG-NHS activation into the DPPC molecular layer of the liposome which wraps doxorubicin and magnetic particles. The 131I-labelled c(RGDyk)-targeting doxorubicin thermosensitive nanoliposome is mainly applied in therapeutic diagnosis and prevention of breast-cancer tumor. The advantages are as follows: by using liposome as a vector and integrin alpha v beta3 as an action target, by organically combining chemotherapy, radiotherapy and thermotherapy and through c(RGDyk) targeting action on tumor, kill rate of tumor can be raised, influence on normal body is little, and requirements on aspects of specificity, safety, effectiveness and the like are met to the greatest extent.

The invention discloses application of an integrin beta4 gene DNA methylation site to the preparation of biomarkers for early diagnosis of asthma and / or COPD.

Treatment and diagnostic methods are provided for pulmonary disease, including chronic obstructive pulmonary disease, Arhgef1, a leukocyte signaling molecule, functions normally to suppress integrin-mediated MMP production by alveolar macrophages. MMP9 production by fibronectin-stimulated monocytes and macrophages depends on autocrine thromboxane receptor signaling and this signaling pathway is attenuated by Arhgef1. Expression of ARHGEF1 by human peripheral blood monocytes varies between individuals and inversely correlates with fibronectin-mediated MMP9 production. Arhgef1 levels can function as a predictor for a pulmonary disease candidate and a thromboxane receptor antagonist can treat a pulmonary disease condition resulting from low Arhgef1 levels.

The invention relates to a polypeptide-drug conjugate with a tumor directed therapy effect, and a preparation method and an application thereof. The polypeptide-drug conjugate can specifically convey PD0325901 analog to cancer cells over-expressing integrin alphavbeta3 in order to realize the directed therapy effect of tumors.

The invention discloses application of an antagonist of integrin alpha M beta2 to preparation of a medicine for treating blood platelet quantity related diseases. The blood platelet quantity related diseases include idiopathic or secondary thrombocytopenia and idiopathic or secondary thrombocytosis. The antagonist of the integrin alpha M beta2 can be an anti-integrin alpha M beta2 antibody, amino acid sequence polypeptide and oligopeptide of the integrin alpha M beta2, derivatives and analogues of the amino acid sequence polypeptide and oligopeptide of the integrin alpha M beta2, and a small-molecular compound antagonist of the integrin alpha M beta2. The invention discloses the application of the antagonist of the integrin alpha M beta2 to the preparation of the medicine for treating the blood platelet quantity related diseases for the first time.

The invention relates to a chemical structure and a preparation method of a tumor imaging agent, and in particular relates to a single photon emission computed tomography (SPECT) technetium (99mTc)-labeled RGD polypeptide trimer medicine, namely 99mTc-4P-RGD3. The tumor imaging medicine is combined with an integrin alphavbeta3 in a ligand mode so as to achieve an application of imaging a tumor part. The preparation method comprises the following implementing steps: linking HYNIC-Osu to 4P-RGD3 so as to obtain a ligand HYNIC-4P-RGD3, and chelating the HYNIC in the ligand with 99mTc so as to obtain the 99mTc-4P-RGD3 tumor imaging agent. A research on animal in-vivo distribution and a tumor imaging step proves that the tumor imaging agent is relatively high in tumor uptake and lower in background uptake to normal organs in a whole body, and the definition of tumor image of the whole body is improved; a drug metabolism experimental step shows that the 99mTc-4P-RGD3, after metabolized in an animal body, can be still discharged out of the body in a prototype mode. The technetium-labeled integrin alphavbeta3 tumor imaging agent (99mTc-4P-RGD3) prepared by the technical means disclosed by the invention can be used for solving a problem of high background uptake of other technetium-labeled RGD medicines in animal body, so that the technetium-labeled RGD medicine is more suitable for the assessment of tumors in whole body.

The invention discloses integrin alpha 6 target polypeptide and application, and the sequence motif of the polypeptide is RWYXXXA. The integrin alpha 6 target polypeptide has very good affinity with integrin alpha 6, is relatively stable in vivo, and can serve as a target carrier. The integrin alpha 6 target polypeptide can be applied to molecular imaging of multiple kinds of integrin alpha 6 overexpression tumors, and has an important value in the molecular imaging of tumors. By coupling the polypeptide with a molecular imaging probe, the molecular imaging can be carried out on the multiple kinds of integrin alpha 6 overexpression tumors, and can be applied to diagnosis and screening of tumors very well.

Foot and out disease virus (FMDV) is worldwide problem. Rapid isolation, serotyping and vaccine matching of FMDV from infected animals is critical to enable the implementation of effective vaccination programs and to stop the spread of infection during outbreaks. Current virus isolation protocols use primary cells, known to be susceptible to FMDV, or baby hamster kidney cells (BHK-21) and other cell lines that are not highly sensitive to some strains of FMDV. The αVβ6 integrin is a principal receptor for FMDV. We therefore transduced the porcine kidney cell line, LFBK, to stably express both the αV and β6 bovine integrin subunits. The LFBK-αVβ6 cell line showed both β6 expression and enhanced susceptibility to FMDV infection for at least 100 cell passages. LFBK-αVβ6 cells are highly sensitive for detecting all serotypes of FMDV from experimentally infected animals, including the porcinophillic strain O / TAW / 97 and are thus a sensitive tool for FMDV isolation.

The invention disclsoes a method for synthesizing cyclic peptides through an enzyme method and belongs to the technical field of cyclic peptide synthesis. The method comprises: mixing linear peptides and sortase A at the mol ratio of 25 to 1, and reacting at 37 DEG C to prepare the cyclic peptides. The yield of the cyclic peptides is 70 percent to 93 percent; the method has the advantages of high yield, simple steps and the like and is green and environmentally friendly. The prepared RGD (arginine-glycine-aspartic acid) linear peptides and the cyclic peptides have a property of inhibiting the mutual effect of integrin alphavbeta3 and extracellular matrixes; the prepared AKRHHGYKRKFH linear peptides and cyclic peptides have a property of inhibiting candida albicans, pseudomonas aeruginosa and staphylococcus aureus and have wide application value.