50 results about "Anti angiogenic" patented technology

The invention relates to the technical field of tumor biomedical engineering and organ chips, in particular to a vascularized gastric cancer organ chip and a preparation method thereof.The chip is composed of an integrated micro-fluidic main body, an annular micro-column array and an optical sealing film, and a central culture cavity is divided into a tumor area and a blood vessel area by micro-columns; the preparation method comprises the following steps: injecting a fibrous protein solution containing human umbilical vein endothelial cells and cancer-related fibroblasts into a vascular region, and adding thrombin for in-situ gelation to form a pre-vascularized network; the method comprises the following steps: mixing a patient-derived gastric cancer organ with a methacrylic acid esterified gelatin pre-polymerized solution, injecting the mixture into a tumor area, and carrying out photo-crosslinking immobilization; culturing for 7-14 days under the dynamic perfusion condition of a mixed culture medium to obtain a three-dimensional gastric cancer organ model containing a capillary network; the method is expected to be used for rapid, low-cost and high-throughput screening of chemotherapy or anti-angiogenesis drugs and accurate prediction of individual curative effects of patients.

The invention belongs to the technical field of medical diagnosis, and discloses a marker for evaluating the curative effect of treating hepatocellular carcinoma by combining TACE with Czodili monoclonal antibody and bevacizumab, and a construction method and application of an FAAP prognostic scoring model. The invention develops and verifies an FAAP prognostic scoring system, and a novel composite model integrates four indexes of fibrin degradation product / cholinesterase ratio * 1000 (FCR), aspartate aminotransferase (AST), alpha fetoprotein (AFP) and portal vein tumor thrombus (PVTT), and is used for predicting the survival condition of uHCC patients subjected to TACE-Czodimab-bevacizumab triple therapy. The tool has an instant clinical value, can optimize patient selection, guides adaptive treatment upgrading, and provides a standardized curative effect evaluation basis for a clinical test for exploring a TACE-immunotherapy-anti-angiogenesis combined scheme.

This disclosure provides a method for treating a subject afflicted with a renal cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an anti-cancer agent which is an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) another anti-cancer agent. The other anti-cancer agent may be an anti-angiogenic tyrosine kinase inhibitor or an anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) antibody. The disclosure also provides a kit for treating a subject afflicted with a renal cancer, the kit comprising a dosage of an anti-PD-1 antibody, a dosage of another anti-cancer agent which is an anti-angiogenic tyrosine kinase inhibitor or an anti-CTLA-4 antibody, and instructions for using the anti-PD-1 antibody and the other anti-cancer agent in any of the disclosed methods for treating a renal cancer.

Disclosed herein are polypeptides and fusion polypeptides that have anti-angiogenic activity that can be used to inhibit tumor growth and tumor metastasis. The polypeptide consists of 9 or less consecutive amino acid residues (e.g., 8, 7, 6, 5, or 4) comprising the active core amino acid sequence DWLP, or an amino acid substitution variant thereof. Specific amino acid substitutions are disclosed herein. In some embodiments, the peptide consists essentially of 4-6 mers identified as exhibiting the activity of prosaposin A. Also disclosed herein are therapeutic compositions comprising the polypeptides and fusion polypeptides, and their use in the treatment, prevention, and inhibition of angiogenesis-related diseases and disorders such as cancer and cancer metastasis.

The invention relates to the technical field of biological medicines, and particularly discloses an application of Dehydrovomigol sensitized bevacizumab in treatment of cervical cancer. The invention further relates to a preparation method of the Dehydrovomigol sensitized bevacizumab. Compared with a bevacizumab single drug, the effect of the bevacizumab on growth and proliferation inhibition, invasion blocking and angiogenesis inhibition of cervical cancer cells can be remarkably enhanced by combining the Dehydrovomifolol, and the drug resistance of the bevacizumab is reversed. In different experimental models, the Q value of the combination scheme is greater than or equal to 1.15, and the stable synergistic anti-cervical cancer effect is shown. Dehydrovomifolol realizes the effect of enhancing the anti-cervical cancer activity of the bevacizumab by virtue of triple mechanisms of reversing drug resistance, enhancing anti-angiogenesis and regulating an immune microenvironment. According to the combination scheme, the anti-cervical cancer curative effect can be improved, the clinical medication dosage of bevacizumab is reduced, the occurrence risk of toxic and side effects such as hypertension and proteinuria is reduced, and a novel, safe and efficient treatment strategy is provided for cervical cancer treatment.

The invention provides a pharmaceutical composition for treating non-small cell lung cancer and a use method, and belongs to the technical field of tumor immunotherapy. The invention formulates a non-small cell lung cancer weak chemotherapy and anti-vascular immunity triple treatment scheme based on the combination of a low-dose chemotherapy drug pemetrexed, an immune checkpoint inhibitor and an anti-angiogenesis drug. According to the scheme, low-dose pemetrexed is combined with the anti-angiogenesis medicine and the immune checkpoint inhibitor for use, the optimal synergistic effect can be achieved, meanwhile, the renal toxicity and the myelosuppression risk are remarkably reduced, and the pemetrexed medicine composition is expected to become one of the optimal choices for driving gene negative and PD-L1 positive expression non-squamous NSCLC patients, and has a wide application prospect. The device is suitable for old people or patients with poor physical states; especially for patients with negative driver genes and positive PD-L1 expression, the traditional treatment blank is filled, and clinical data shows that survival benefits are remarkable.

The present invention provides methods, compositions, and combinations for treating cancer via combined use of a compound of formula I or a pharmaceutically acceptable salt, ester, solvate and / or prodrug thereof, wherein A, Q, n, m, R7, R8, V, X1, X2, X3, X4, X5, X6, and X7 are as defined herein, and at least one therapeutically active agents selected from immunotherapeutics, anticancer agents, and anti-angiogenics.

A manganese-doped mesoporous silica nanomaterial, and a preparation method therefor and the use thereof. The nanomaterial comprises a manganese-doped mesoporous silica nanosphere, an anti-angiogenic drug and a surface delivery system. The anti-angiogenic drug is adsorbed in the pores of the manganese-doped mesoporous silica nanosphere, and the surface delivery system is coated on the surface of the manganese-doped mesoporous silica nanosphere, wherein metal manganese ions are doped on the surface and in the framework of the mesoporous silica nanosphere. The anti-angiogenic drug is an HIF-2α inhibitor. After targeted degradation at a tumor site, the nanomaterial releases the manganese ions and the anti-angiogenic drug to realize the dual anti-tumor effects of activating local anti-tumor immunity and inhibiting angiogenesis within the tumor at a targeted tumor site; and the manganese ions and the anti-angiogenic drug have a synergistic effect. In addition, the nanomaterial has no potential toxic effect, has good biosafety, and provides a new choice for the treatment of tumors, especially pVHL-deleted tumors.

The present disclosure provides methods for assessing responsiveness or non-responsiveness to a therapeutic agent (e.g., ICB therapy and / or anti-angiogenic) in subjects having a cancer or tumor based on angio-immune panel signatures. The methods may further comprise identifying suitable treatment for the subject based on the angio-immune panel.

The invention discloses application of a PLAC8 promoter methylation promoter in preparation of a product for promoting angiogenesis of a pig placenta, and belongs to the technical field of biological medicines. Experiments prove that PLAC8 as an anti-angiogenesis factor can directly inhibit the angiogenesis function, and DNMT3A can promote placenta vascular development and improve sow farrowing performance by regulating the methylation level of a PLAC8 promoter. In addition, it is determined that daily ration supplementation of methyl donors in the pig placenta vascular development peak period is an important nutrition way for improving DNA methylation of the PLAC8 promoter region. According to the method, the placenta injury mechanism under the adverse pregnancy outcome is directly determined through combination of in-vivo and in-vitro experiments, a theoretical basis is provided for analysis of a regulation strategy for promoting pig placenta angiogenesis and improving sow reproductive performance from epigenetics, and the accuracy and credibility of a result are improved.

The application discloses a ROS / GSH responsive hyperbranched zwitterionic micelle and a preparation method and application thereof, and relates to a drug delivery system, ROS responsive zwitterionic micelles and GSH responsive zwitterionic micelles are prepared respectively, the ROS responsive zwitterionic micelles are loaded with anti-angiogenic drugs, and the GSH responsive zwitterionic micelles are loaded with anti-tumor stem cell drugs, so that the combined treatment of blood vessel normalization and tumor stem cell killing is realized, while the blood vessel normalization is realized, the restriction of the small intercellular gap of vascular endothelial cells caused by the blood vessel normalization on the enrichment and penetration of subsequent nano drugs in tumor sites is effectively solved, and the change of the interstitial pressure of tumor tissue caused by the blood vessel normalization is fully utilized to promote the deep penetration of small-size GSH responsive zwitterionic micelles into the internal region of the tumor, so that the killing of tumor stem cells is completed, and the combined treatment of the blood vessel normalization therapy and the tumor stem cell therapy is effectively realized.

The invention relates to a predictive gene expression signature of response to antiangiogenic drugs, such as axitinib, in gastro-enteric-pancreatic and pulmonary neuroendocrine tumours. The signature is formed by the gene expression of three genes (SPP1, ATXN7 and REXO1L2P), which is converted by means of a bioinformation packet into a unique score that can predict which patients will benefit from treatment with the drug, this benefit being understood as longer survival without progression and larger tumour volume reductions in response to treatment.

The invention discloses a synthesis method of an anti-tumor and anti-angiogenesis medicine PI-88 and a precursor thereof, which comprises the following steps of: performing glycosylation coupling on a monosaccharide module and a double-chain fluorine carrier by adopting a polytetrafluoroethylene particle assisted purification strategy and a remote acyl and ortho-group participated high-stereoselectivity glycosylation strategy, and then removing a 2-bit protecting group to obtain a monosaccharide receptor; carrying out linear assembly to obtain mannose polysaccharide protected by a double-chain fluorine carrier, and then carrying out non-reducing end deprotection, phosphorylation-oxidation and selective protection group removal to obtain a PI-88 precursor; and carrying out sulfonation on exposed hydroxyl groups in the PI-88 precursor, and then removing other protecting groups to obtain PI-88. According to the method, the anti-tumor and anti-angiogenesis medicine PI-88 and the precursor thereof are rapidly and efficiently synthesized, the average yield of each step can reach 90% or above, only polytetrafluoroethylene particles are needed for purification in the assembly and purification process of target molecules, the product can be rapidly locked, the purification difficulty is reduced, the separation loss is reduced, and the method is suitable for industrial production. And large-scale synthesis is easy to realize.

This invention provides an integrated culture dish and method for dynamic mechanical stimulation and monitoring of live cells, belonging to the field of biotechnology, for simulating the effects of lung micromechanical processes on lung cancer cell growth and the production of anti-angiogenic drugs. It includes: a dish body; a culture medium having a tubular elastic membrane with an internal telescopic support, suspended at one end and with a magnetic traction plate at the other end. The elastic membrane has a first conductive region where only the outer layer is conductive, and a second conductive region where both the inner and outer layers are conductive and connected. Insulated conductors within a wire are electrically connected to the two regions respectively. A base is located on the underside of the dish body, and an adjustable magnet on it generates an adjustable attraction force on the magnetic traction plate. The elastic membrane is stretched and contracted by changes in magnetic force to apply mechanical stimulation to the attached cells. The resistance changes are monitored using the conductive regions and the dish body, thereby simulating the mechanical microenvironment of lung cancer cell growth and evaluating the effects of anti-angiogenic drugs.

The present invention discloses the use of anti-angiogenic drugs in improving the retention rate of soft tissue grafts. By using different types of anti-angiogenic drugs to inhibit the early vascularization of soft tissue grafts, the body's immune response to the soft tissue grafts is weakened, thereby reducing inflammation and immune cells, and improving the retention rate of soft tissue grafts.

The invention discloses an apatinib-immune synergistic nano-drug based on bacterial source vesicles as well as a preparation method and application of the apatinib-immune synergistic nano-drug. The nano-drug is Apatinib-MVs, and the nano-drug takes a membrane vesicle secreted by parabacteroides coumarini as a carrier to entrap an anti-angiogenesis drug apatinib; in-vitro anti-tumor experiment results show that the nano-drug can exert an efficient anti-tumor effect through a dual synergistic mechanism of inhibiting tumor angiogenesis and activating anti-tumor immune response at the same time.

Disclosed herein are nanoparticle conjugates (e.g., anti-angiogenic and / or immunomodulatory nanoparticle conjugates, e.g., high-affinity Designed Ankyrin Repeat Protein (DARPin)-based binders targeting one or more cancer and / or immune receptors). The nanoparticle conjugates are useful for therapeutics and / or diagnostics and have a diameter (e.g., average diameter) no greater than 20 nanometers (e.g., as measured by dynamic light scattering (DLS) in aqueous solution, e.g., saline solution).

The invention provides a marker for auxiliary diagnosis of colorectal cancer and application of the marker, and belongs to the technical field of disease diagnosis and treatment. The research of the invention finds that the LncRNA-AC145123.2 is significantly down-regulated in tissue and serum samples of a colorectal cancer patient. Due to high sensitivity and specificity in diagnosis, the kit becomes a powerful tool for early diagnosis of colorectal cancer. In addition, the invention also finds that proliferation, migration and angiogenesis of colorectal cancer cells can be effectively inhibited by up-regulating the expression of the LncRNA-AC145123.2. Therefore, the LncRNA-AC145123.2 and the activator thereof not only can be used for auxiliary diagnosis, but also provide important molecular targets for developing novel colorectal cancer treatment drugs, especially anti-angiogenesis drugs.

The invention belongs to the technical field of tumor treatment, and particularly relates to a recombinant Newcastle disease virus as well as a preparation method and application thereof in tumor resistance. According to the recombinant gene provided by the invention, the GGTA1P coding gene can express heterologous alpha-Gal epitopes in tumor cells, so that immune escape is reduced, an immune system is enhanced, and the tumor cells are recognized and killed; cSF2, TP53 and IL12 expressed by the CSF2 coding gene, the TP53 coding gene and the IL12 coding gene respectively have the functions of immunoregulation, apoptosis promotion or angiogenesis resistance, and can enhance the anti-tumor effect by cooperating with GGTA1P. Furthermore, the Newcastle disease virus (NDV) has a natural oncolytic characteristic, the recombinant gene is inserted between the P gene and the M gene of the Newcastle disease virus, and the recombinant Newcastle disease virus obtained after transfection can infect tumor cells in a targeted manner and activate immune response.

The invention relates to an application of 2-methyl-4 (3H)-quinazolinone in preparation of an anti-angiogenesis medicine. The invention discloses the application of the 2-methyl-4 (3H)-quinazolinone compound as an angiogenesis inhibitor in anti-angiogenesis drugs for the first time, and the 2-methyl-4 (3H)-quinazolinone compound has a remarkable inhibition effect on internode blood vessels and dorsal longitudinal anastomosis angiogenesis of a Tg (flk: mCherry) fluorescent transgenic zebrafish strain. Meanwhile, the growth of the zebrafish embryos of the strain is not obviously influenced, and the toxicity is extremely low. The compound not only can be extracted from streptomyces, but also can be obtained through an artificial synthesis process, has a reliable and stable source, and has a good application prospect in the field of anti-angiogenesis drugs.

This invention provides a 3-amino-5-phenyl-pyrazole derivative microtubule inhibitor, its preparation, and its pharmaceutical uses. The structure of the 3-amino-5-phenyl-pyrazole derivative is shown in formula (I): In formula (I), R1 is independently selected from 3,4,5-trimethoxyphenyl, 3,4-dimethoxyphenyl, or dioxolane[1,3-d]phenyl; R2 and R3 are independently selected from methyl, methoxy, fluorine, chlorine, or bromine. This type of compound not only possesses strong antitumor activity but also anti-angiogenic effects, effectively inhibiting the proliferation of tumor cells and can be used to prepare tumor proliferation inhibitors. Furthermore, it has a strong ability to inhibit microtubule aggregation, providing a novel microtubule inhibitor for inhibiting tumor cell proliferation.

The invention discloses a traditional Chinese medicine composition for treating targeted drug related proteinuria, a pharmaceutical preparation and application. The traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials or extracts thereof: angelica sinensis, radix paeoniae alba, raw astragalus membranaceus, radix pseudostellariae, radix ophiopogonis, schisandra chinensis, raw atractylodes macrocephala koidz and divaricate saposhnikovia roots. The traditional Chinese medicine composition treats the anti-angiogenesis targeted drug related proteinuria through the treatment rules of activating blood and nourishing liver, and invigorating spleen and tonifying kidney, so that the patients can be treated by drugs, and the risk of drug withdrawal of the hepatocellular carcinoma patients due to the anti-angiogenesis targeted drug related proteinuria such as a vascular endothelial growth factor inhibitor is further reduced; the long-term prognosis of hepatocellular carcinoma patients is improved, and the lifetime of the hepatocellular carcinoma patients is prolonged.

The present invention relates to mouse antibodies that bind to angiopoietin-2 (Ang2), humanized anti-Ang2 antibodies derived therefrom, and the use thereof. The anti-Ang2 antibodies have a dual function of activating the Tie2 receptor together with neutralizing Ang2. The anti-Ang2 antibodies show the property of normalizing abnormal and pathological blood vessels, and thus exhibits therapeutic efficacy against various diseases and disorders associated with abnormal blood vessels. The present invention further provides an angiogenesis inhibitor and a composition for treatment of diseases associated with abnormal Ang2 expression and Tie2 dysregulation, which comprise the antibody as an active ingredient, and a composition for diagnosing diseases associated with Ang2 inhibition and Tie2 activation, which comprises the antibody.

Disclosed herein are polypeptides and fusion polypeptides that have anti-angiogenic activity that can be used to inhibit tumor growth and tumor metastasis. The polypeptide consists of 9 or less consecutive amino acid residues (e.g., 8, 7, 6, 5, or 4) comprising the active core amino acid sequence DWLP, or an amino acid substitution variant thereof. Specific amino acid substitutions are disclosed herein. In some embodiments, the peptide consists essentially of 4-6 mers identified as exhibiting the activity of prosaposin A. Also disclosed herein are therapeutic compositions comprising the polypeptides and fusion polypeptides, and their use in the treatment, prevention, and inhibition of angiogenesis-related diseases and disorders such as cancer and cancer metastasis.

The invention discloses a temozolomide and Boc-1-methyl-D-tryptophan axial asymmetric disubstituted silicon phthalocyanine conjugate as well as a preparation method and application of the temozolomide and Boc-1-methyl-D-tryptophan axial asymmetric disubstituted silicon phthalocyanine conjugate. 1, 3-diimino isoindoline is used as an original raw material, dichlorosilicon phthalocyanine is generated through a ring formation reaction, silicon phthalocyanine with double chains being tetraethylene glycol is obtained through a nucleophilic reaction, and finally, a target product DTPC is generated through an esterification reaction. The target product DTPC can enhance targeting and killing effects on cancer cells, can resist angiogenesis and effectively and synergistically promote anti-tumor immunity, and provides a new thought for improving photodynamic therapy.

The invention provides a drug resistance marker of an anti-angiogenesis drug and application of the drug resistance marker, and particularly provides application of gamma-synuclein (SNCG) as the drug resistance marker of the anti-angiogenesis drug, especially bevacizumab.

The invention relates to a predictive gene expression signature of response to antiangiogenic drugs, such as axitinib, in gastro-enteric-pancreatic and pulmonary neuroendocrine tumours. The signature is formed by the gene expression of three genes (SPP1, ATXN7 and REXO1L2P), which is converted by means of a bioinformation packet into a unique score that can predict which patients will benefit from treatment with the drug, this benefit being understood as longer survival without progression and larger tumour volume reductions in response to treatment.

Provided are systems and methods for assessing the presence or risk of obstetrical complications, particularly those related to an angiogenic and anti-angiogenic imbalance. Also provided are methods of treating an angiogenic and anti-angiogenic imbalance with water-soluble statins, such as pravastatin.

This invention relates to the field of medical data analysis, and more particularly to a method for assessing the risk of pregnancy outcomes in pregnant women based on multifactor feature analysis. The method includes: acquiring individual measured time-series datasets and baseline reference data for physiological expectations; obtaining a gestational age-specific pathological surge penalty factor by weighting the ratio of angiogenic factors to anti-angiogenic factors; obtaining a cross-system pathological cascade time coupling factor by temporally tracing and coupling abnormal deviations in vascular system indicators and blood system indicators; obtaining a fused feature vector by correcting and fusing the initial linear regression slope features; and obtaining the pregnancy outcome risk assessment result by performing machine learning prediction on the fused feature vector. This method solves the problem that existing prediction methods based on linear regression slope extraction and feature splicing cannot effectively identify gestational age-specific early high-risk signals and cross-system short-term pathological cascade signals.

Provided include methods, compositions and kits for treating metastatic cancer in a subject. The method can comprise administering to a metastatic colorectal cancer patient an effective amount of a PLK1 inhibitor (for example, onvansertib) and an effective amount of bevacizumab, wherein the patient has not received any treatment comprising bevacizumab within at least three months prior to the administration of the PLK1 inhibitor and bevacizumab in a manner sufficient to reduce or inhibit progression of the metastatic cancer.