55 results about "Tumor vessel" patented technology

The invention provides an ultrasonic activated blood coagulation targeting tumor selective prodrug as well as a preparation method and application thereof. The blood coagulation targeting tumor selective prodrug has a structure as shown in a formula I. The blood coagulation targeting tumor selective prodrug can trigger a blood coagulation cascade reaction by utilizing tumor vascular injury generated by ultrasonic induction so as to realize targeted anchoring of the drug and inhibit off-target diffusion of an active drug; meanwhile, the prodrug is activated by ultrasound, so that the limitation of tumor heterogeneity on the activation of the prodrug can be overcome. According to the technical scheme, selective enrichment of active drugs in tumors can be effectively improved, and toxicity caused by drug off-target is reduced while tumor growth is remarkably inhibited.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The present disclosure relates to novel adeno-associated adenovirus (AAV) vectors comprising targeting peptides. More particularly, the present disclosure relates to an adeno-associated serotype 2 virus vector, AAV2, comprising a transgene encoding LIGHT wherein the viral capsid of the AAV2 vector comprises a targeting peptide that alters its tropism to target tumor endothelial cells; and a use of the carrier. The disclosure also relates to the use of said vectors in therapy, in particular in the treatment of cancer.

The invention relates to a noninvasive solid tumor internal hypoxia condition detection method, which comprises: chemically modifying a near-infrared two-region fluorophore, an oxygen sensitive group and a tumor targeting group to construct a composite probe, collecting fluorescence and photoacoustic signals of a tumor region after intravenous injection, carrying out de-noising analysis, and combining with multiple parameters to solve hypoxia concentration change, a four-dimensional space-time distribution map is constructed by fusing vascular topological data, and individualized calibration is realized through microfluidic simulation and Bayesian optimization. Compared with a traditional invasive detection and single-mode imaging technology, the advantages of bimodal signals are integrated in a breakthrough mode, non-invasive, real-time and high-resolution dynamic hypoxia monitoring is achieved, acute and chronic hypoxia areas are accurately distinguished, tumor blood vessel heterogeneity interference is reduced through personalized parameter calibration, and the accuracy of hypoxia monitoring is improved. High-precision spatio-temporal data support based on hypoxia microenvironment monitoring is provided for solid tumor radiotherapy target planning, chemotherapy drug delivery optimization, chemotherapy drug resistance and curative effect prediction and evaluation and tumor metastasis progress risk analysis.

The present application relates to the technical field of pharmaceutical formulations and provides zedoary turmeric oil / oxidized regenerated cellulose embolization microspheres, a preparation method therefor, and use thereof. In the present application, with zedoary turmeric oil as a core solution, a mixed solution of oxidized regenerated cellulose, sodium alginate, and gelatin as a shell layer solution, and a divalent or trivalent metal salt solution as a receiving solution, the zedoary turmeric oil / oxidized regenerated cellulose embolization microspheres are prepared by means of a coaxial electrostatic spraying method. The zedoary turmeric oil / oxidized regenerated cellulose embolization microspheres prepared in the present application have a marked core-shell structure, are uniform in size and good in sphericity, can effectively hide the pungent smell of zedoary turmeric oil, improves the stability of zedoary turmeric oil, and enables directed embolization in tumor blood vessels, thereby reducing toxic and side effects. In addition, the embolization microspheres prepared in the present application have good mechanical properties; therefore, the microspheres can effectively resist deformation under compression and prevent fragmentation within the body, enabling firm embolization of zedoary turmeric oil at the tumor vascular site.

The present invention discloses a method for simulating the tumor blood vessel growth process, comprising constructing a two-dimensional discrete coordinate system based on a two-dimensional tumor model and defining a blood vessel index function that describes the cell grid properties of the cell grid; updating the cell number, oxygen concentration, fibronectin concentration, and growth factor concentration of each cell grid at preset intervals t; predicting the movement direction of the blood vessel tip within the current time period t based on the fibronectin concentration and growth factor concentration; calculating a first predicted extension distance and a second predicted extension distance based on the movement direction within the current time period t and the movement direction within the previous time period t; and updating the cell grid properties of each cell grid in the two-dimensional discrete coordinate system based on the movement direction within the current time period t, the vessel tip's existence time, and the movement extension distance calculated from the vessel tip. The present invention incorporates oxygen concentration and cell number into the tumor blood vessel growth model to achieve accurate simulation and prediction of the tumor blood vessel growth process.

The invention provides a pharmaceutical composition for treating gastric cancer. The pharmaceutical composition comprises an NAT10 inhibitor and a PD-1 inhibitor. The gastric cancer is treated by combining the NAT10 inhibitor Remodelin with the PD-1 inhibitor, so that the problems of tumor angiogenesis and immunosuppression in existing treatment are solved, and the clinical curative effect of immunotherapy is improved. Research finds that when the Remodelin or the PD-1 inhibitor is independently used, a certain tumor inhibition effect is achieved, but the tumor volume of a combined treatment group is remarkably reduced, and immune cell infiltration is remarkably increased.

This invention belongs to the pharmaceutical field, specifically relating to an anti-tumor angiogenesis drug potentiator, an anti-tumor drug composition, and its application. Firstly, this invention discovers that SHCBP1 inhibitors can enhance the therapeutic effect of anti-tumor angiogenesis drugs and can be used as potentiators for anti-tumor angiogenesis drugs. Secondly, when SHCBP1 inhibitors are used in combination with anti-tumor angiogenesis drugs, or in combination with anti-tumor angiogenesis drugs and PD-1 inhibitors, tumor angiogenesis can be normalized and its window period prolonged, significantly improving the efficacy of immunotherapy, anti-angiogenesis, and anti-tumor therapy, showing broad application prospects.

Provided are a multispecific antibody and the use thereof. Specifically, provided is a multispecific antibody, which contains a first targeting domain that targets a chemokine (C-C motif) receptor 8 (CCR8) molecule highly expressed on the surface of a tumor-infiltrating regulatory T cell (Treg), and a second targeting domain that binds to VEGF and / or a third targeting domain that binds to PD-L1. Various functional domains of the CCR8-related multispecific antibody block a PD-1 / PD-L1 immunosuppressive pathway, etc. by means of killing the tumor-infiltrating Treg, so that a T cell is activated, and the generation of a tumor vessel is inhibited. Therefore, the CCR8-related multispecific antibody can be used as an effective therapeutic agent for tumor treatment.

The present invention relates to the field of medical materials technology, and in particular to an anti-tumor vaccine and its applications. The anti-tumor vaccine comprises anti-tumor nanoparticles comprising a nucleic acid encoding a plasma membrane vesicle-associated protein (PLVAP), a cationic lipid, and a non-cationic lipid. Research has shown that an anti-tumor vaccine based on an antigen molecule specifically expressed on tumor vascular endothelial cells (PLVAP) can effectively activate the immunosuppressive microenvironment of tumor patients, inducing the generation of a large number of cytotoxic T cells. These T cells are capable of targeting and killing tumor vascular endothelial cells expressing the PLVAP protein, effectively destroying tumor blood vessels. This vaccine holds significant value in the field of anti-tumor biomaterials.

The invention relates to a mechanical arm thoracocentesis path planning system and method based on a dynamic adaptive ant colony optimization algorithm, and belongs to the technical field of path planning. The system comprises a data preprocessing module, an image segmentation module, a path planning module and a visualization module; the data preprocessing module is used for performing denoising and contrast enhancement on the chest CT image so as to improve the image quality and facilitate subsequent image segmentation and analysis; the image segmentation module is used for automatically segmenting tumor, blood vessel, trachea and bone areas through DenseNet and providing data support for path planning; the path planning module is used for selecting an optimal path or an approximate global optimal path by using a dynamic adaptive ant colony optimization algorithm; and the visualization module is used for presenting the optimal path or the approximate global optimal path on the original chest CT image. The system uses an image segmentation technology and an improved ant colony algorithm to provide an optimal puncture path for puncture.

The present application provides a lung cancer type prediction method and system based on a fusion deep learning network. It dynamically segments CT images of lung cancer patients, extracts tumor vascular distribution data and calculates three-dimensional density parameters and vascular rupture direction parameters, and simultaneously obtains a necrotic area volume ratio sequence; separates circulating tumor cells through spiral sorting of blood samples and fluid control, and generates stiffness change parameters and deformation recovery parameters derived from deformation trajectories; combines three-dimensional density, vascular rupture direction and stiffness parameters to extract the vascular rupture direction time series offset, and dynamically and synchronously matches the stiffness change response to generate a synchronization set; constructs a lag correlation between the vascular rupture direction offset and the deformation recovery period, and determines the weight matching through cross-modal analysis; combines the spatiotemporal characteristics of the necrotic area volume to output the lung cancer subtype classification results. The present application integrates a cross-modal correlation model of vascular dynamic offset and cell mechanical response to achieve accurate discrimination of lung cancer subtypes.

The invention belongs to the technical field of biological medicine, and discloses application of THY1 in diagnosis and prognosis of glioblastoma. According to the invention, a THY1-positive cancer-related fibroblast (THY1 + CAF) subgroup is identified in glioblastoma for the first time, and it is found that the subgroup and tumor blood vessels are highly co-localized in spatial distribution, and the abundance of the subgroup and the blood vessel density are significantly positively correlated; tHY1 + CAF is a key cell component for promoting angiogenesis in a GBM tumor microenvironment; tHY1 can be used as a marker of GBM specific CAFs, and is used for auxiliary diagnosis, prognosis evaluation (high THY1 + CAF may indicate worse prognosis and stronger angiogenesis phenotype) and curative effect monitoring of GBM. Meanwhile, the target THY1 or THY1 + CAF provides a brand-new and potential action target for developing a GBM new therapy for resisting angiogenesis and even remodeling an immunosuppressive microenvironment.

The invention provides a lung cancer type prediction method and system based on a fusion deep learning network, and the method comprises the steps: carrying out the dynamic segmentation of a CT image of a lung cancer patient, extracting tumor blood vessel distribution data, calculating a three-dimensional density parameter and a blood vessel fracture direction parameter, and synchronously obtaining a necrotic region volume ratio sequence; circulating tumor cells are separated through blood sample spiral sorting and fluid control, and rigidity change parameters and deformation recovery parameters derived from a deformation track are generated; combining the three-dimensional density, the blood vessel fracture direction and the rigidity parameters, extracting the time sequence offset of the blood vessel fracture direction, and dynamically and synchronously matching the rigidity change response to generate a synchronous set; establishing lag correlation between the blood vessel fracture direction offset and the deformation recovery period, and determining weight matching through cross-modal analysis; and outputting a lung cancer subtype classification result in combination with the necrotic region volume spatial-temporal characteristics. According to the application, the cross-modal correlation model of the blood vessel dynamic migration and the cell mechanical response is fused, and accurate discrimination of the lung cancer subtype is realized.

The present invention discloses a method for improving the solid tumor enrichment ability of red blood cell carriers, specifically: a small molecule compound RRx-001 is loaded into the red blood cell carrier, RRx-001 causes the PS molecules on the surface of the red blood cells to be everted, which can mediate the targeted adhesion of red blood cells to tumor vascular endothelial cells expressing PSR protein, thereby achieving active targeting of tumors. In addition, the present invention transforms red blood cells by RRx-001, thereby enhancing the ability of red blood cells to produce NO, dilates tumor blood vessels by NO, and increases blood flow in tumor blood vessels. The present invention transforms red blood cells by RRx-001 so that they have the performance of both tumor targeting and generating NO to dilate tumor blood vessels, thereby achieving effective enrichment of chemotherapy drugs at the tumor site, and is applicable to all solid tumors, so the present invention is of great significance for drug delivery to tumors.

The application discloses a kind of nanomedicine for tumor hypoxia, which is prepared by mPEG-SS-PLGA wrapping drug IR-1048, PFOB and 4-MU.The nanomedicine of the application is constructed by wrapping perfluorooctyl bromide (PFOB), 4-methyl umbelliferone (4-MU) and IR-1048 in tumor microenvironment-responsive amphiphilic polymer mPEG-SS-PLGA, and in response to high GSH in tumor area, 4-MU, PFOB and IR-1048 are released; 4-MU makes the dense tumor extracellular matrix loose, so that tumor vessels are normalized, which is conducive to PFOB carrying oxygen into the tumor interior, long-term solution of tumor hypoxia, remodeling of tumor microenvironment, and reduction of myeloid-derived suppressor cell (MDSC) infiltration; and under the action of 980nm laser in vitro, IR-1048 responds, and the effect of photothermal therapy of tumor is improved.

A pharmaceutical composition for tumor vascular occlusion according to an exemplary embodiment may include alkaline 5-fluorouracil and glucose. For example, the composition may include glucose which exerts a synergistic effect on inducing apoptosis of vascular endothelial cells with alkaline 5-fluorouracil, thereby significantly enhancing the anti-cancer effect.

The invention provides a bispecific antibody capable of binding to PD-L1 and VEGF (vascular endothelial growth factor). The bispecific antibody comprises a first binding domain capable of binding to PD-L1 and a second binding domain capable of binding to VEGF. The bispecific antibody provided by the invention is combined with PD-L1, so that the immunosuppression of tumor cells on T cells can be relieved, and the anti-tumor function of an immune system can be recovered; meanwhile, by combining the bispecific antibody with VEGF, the growth of the tumor can be slowed down, the blood supply of the tumor can be reduced, and even the tumor blood vessel can be normalized, so that the immune environment is improved, and the attack ability of immune cells on the tumor is enhanced.

The invention provides a soft elastic polyurethane-based hydrophobic drug-loaded developable magnetic vascular embolism microsphere and a preparation method thereof, the microsphere takes polyurethane as a matrix, magnetic particles, a developing agent and an anti-tumor hydrophobic drug are compounded through a microfluidic method, and the microsphere has good soft elasticity. The blood vessel embolism microsphere provided by the invention has good biocompatibility and safety, controllable particle size, uniform size and soft elasticity, can enter blood vessels with different diameters and embolism tumor peripheral blood vessels, is higher in filling rate and more complete in embolism, meets the requirement of stable embolism, and has a good application prospect. According to the preparation method, efficient loading and long-acting slow release of anti-tumor hydrophobic drugs can be effectively achieved, developing and precise positioning can be achieved, and the magnetic-thermal therapy and targeted drug use can be achieved.

The present application belongs to the technical field of ultrasonic molecular imaging and biomedical engineering, and particularly relates to a nano-ultrasound contrast agent for enhancing immunotherapy and a preparation method and application thereof. The nano-ultrasound contrast agent for enhancing immunotherapy provided by the present application is a novel ultrasonic nano-vesicle formed by loading a protein drug for blocking an immune checkpoint into a nano-carrier with a special composition. The nano-ultrasound contrast agent has high biological safety, small and uniform particle size, can be long-circulated in vivo, has good imaging effect on the extravascular field of a tumor, has good penetration, is highly targeted, has high drug utilization rate, can improve the delivery efficiency of a tumor immunotherapy drug and the immunotherapy effect, can realize tumor diagnosis and immunotherapy integration under ultrasonic guidance, and effectively solves the current problems of difficult tumor ultrasonic diagnosis, low tumor responsiveness of an immunotherapy drug, weak targeting, and inability to be regulated in vitro.

In combination with conventional therapies (e.g., targeted therapy, chemotherapy, and angiogenesis inhibitors etc.), immunotherapies targeting checkpoint molecules have shown promise in the treatment of solid or liquid tumors. However, apoptotic regulatory T cells (Treg) induced by such therapies often become more suppressive in the tumor microenvironment (TME), through increased generation of adenosine tightly controlled by ectonucleotidases, viz. CD39 and CD73. CD39 / ENTPD1, a novel checkpoint molecule, is highly expressed and activated on the tumor vasculature and infiltrating immune cells, promoting tumor growth. Deletion or blockade of CD39 enhances anti-tumor activity by augmenting anti-tumor immune responses and inhibiting tumor angiogenesis. The present invention is based at least in part on the development of anti-CD39 antibodies which mediate CD39 downregulation on immune cells, such as T-cells with markers of T-cell exhaustion, and the demonstrated utility of these antibodies in blocking tumor growth with minimal side effects in pre-clinical models.

The invention belongs to the technical field of biomedicine, and particularly relates to a diagnosis and treatment integrated nano composite material for targeting tumor blood vessels as well as a preparation method and application of the nano composite material. The invention aims to provide the diagnosis and treatment integrated nano composite material for targeting tumor blood vessels, so that organic integration of multi-mode molecular imaging and targeted therapy is successfully realized, an innovative solution is provided for constructing a novel diagnosis and treatment integrated platform, the technical blank of existing blood vessel targeting drugs is filled, and the application prospect is wide. And meanwhile, the treatment and monitoring functions are innovatively integrated to meet the urgent clinical requirements. According to the present invention, based on the precise evaluation requirement of tumor blood vessel targeting treatment, the MRI imaging agent and the blood vessel targeting drug are grafted and integrated on the POSS through the chemical bond for the first time, such that the treatment-monitoring integration is achieved, the targeting property and the synergistic treatment effect of the nanoparticles are systematically evaluated, the pain point that the action process cannot be evaluated in real time by using the traditional drug is solved, and the application prospect is broad. And a basis is provided for clinical individualized treatment.

The invention provides an Escherichia coli outer membrane vesicle with a tumor targeting effect and a construction method thereof, and relates to the technical field of engineering transformation of Escherichia coli outer membrane vesicles. According to the invention, the tumor vascular targeting peptide GX1 is modified on the surface of the bacterial outer membrane vesicle, so that the escherichia coli outer membrane vesicle with a tumor targeting effect is successfully obtained. The escherichia coli outer membrane vesicle not only can realize a specific targeting effect on cancer cells, but also remarkably improves the problem of insufficient targeting of the tumor blood vessel targeting peptide GX1. The Escherichia coli outer membrane vesicle provided by the invention is expected to be used as a carrier for targeted delivery of antitumor drugs for further development and research.

Pathogenic blood vessels are blood vessels that are not involved in the vascularization of normal organs but are in the pathogenic tissues such as the new blood vessels that drive vision diseases or the blood vessels in tumors that tumors depend on to survive. The current disclosure provides an advancement over typical anti-angiogenic strategies that target the generation of new blood vessels by providing compositions and methods that can selectively target and kill existing pathogenic blood vessels. The conventional antiangiogenic drugs or factors inhibit angiogenesis (the growth of new blood vessels), but cannot effectively kill existing pathogenic blood vessels. Agents, including small molecule compounds and antibodies, have been identified that bind to and activate PLXDC1 and PLXDC2 proteins, leading to effective killing of the endothelial cells in pathogenic blood vessels in vision diseases and in tumors that express these proteins. The disclosure thereby provides a novel modality for eliminating or reducing existing pathogenic blood vessels, thereby treating diseases such as diabetic retinopathy, age-related macular degeneration (AMD), retinopathy of prematurity, and cancer.

A technology is described which provides a platform for improving the penetration into tumors in a subject of cancer treatment and cancer imaging agents for greater patient benefit. The invention in particular overcomes two challenges for use of tumor targeting methods for solid tumors: poor penetration and the immunosuppressive nature of the tumor microenvironment. The platform described here allows long-term, in vivo production of iRGD. In a preferred embodiment, CAR-T cells are engineered to secrete iRGD, a tumor-penetrating peptide to achieve tissue-penetrating delivery of drugs and imaging agents in a tumor-specific manner. The peptide acutely permeabilizes the tumor vasculature by binding to αv integrins and neuropilin, but in a tumor-specific manner. This method produces a modification in the tumor microenvironment that enhances drug access into the tumor, prevents distant metastasis of the tumor cells, and allows long-term iRGD therapy without the need for repeated injections of iRGD.

The invention relates to the technical field of biological materials, in particular to a combretastatin targeted lipid drug delivery system and a preparation method thereof. According to the method, AS1411 and ApoE peptides are adopted to carry out joint modification on CA4 / HM-Fe lipidosome. Fe < 3 + > is introduced on the basis of the sound-sensitive agent HMME, so that the sound-sensitive agent HMME and the sound-sensitive agent HMME are self-assembled to form an HM-Fe complex, CA4 and free HMME are entrapped in a hydrophobic region, and HM-Fe is entrapped in a hydrophilic core, so that the HM-Fe complex can be used as a good carrier for delivering CA4, and the problem of poor water solubility of CA4 is effectively solved. The liposome is co-modified by AS1411 and ApoE peptide, so that dual active targeting of liver cancer cells and tumor vascular endothelial cells can be realized, the in-vitro uptake efficiency is effectively improved, and the enrichment efficiency of a drug at a tumor part is remarkably improved; the system is high in stability, low in toxicity, efficient, good in biocompatibility, high in tumor inhibition rate and good in tumor inhibition effect and safety.

The invention discloses a medical image automatic positioning system based on deep learning, which comprises an image preprocessing module, a feature extraction module, a positioning optimization module and a post-processing module, and is characterized in that multi-level spatial features are extracted by constructing a five-layer multi-scale feature pyramid network, and accurate positioning is realized by adopting a three-level cascade attention mechanism; and finally, a positioning result is optimized through a self-adaptive post-processing algorithm. According to the invention, a space and channel dual attention mechanism is innovatively designed, so that the positioning precision Dice coefficient reaches 0.92 + / -0.03, and the positioning precision is improved by more than 40%. The system is particularly suitable for positioning key parts such as tumors and vasculopathy, and reliable technical support is provided for precise medical treatment.

The invention belongs to the technical field of biomedicine, and provides a breast pad in-situ tumor animal model blood flow velocity prediction method for solving the problem that an existing solid tumor blood flow velocity detection method is difficult to be widely applied to conventional research, and the method comprises the steps that the blood flow velocity and the tumor volume of in-situ tumor blood vessels are continuously collected; analyzing the animal plasma sample to obtain the plasma cell factor concentration related to the blood vessel function; and fitting the morphological characteristics of the tumor tissue, the cell factor concentration and the blood flow velocity of the tumor blood vessel to construct a blood flow velocity prediction model based on the tumor volume and a blood flow velocity prediction model based on the plasma cell factor concentration. Through the constructed prediction model, a researcher can conveniently predict the blood flow velocity of the tumor blood vessel through the obtained data only by obtaining tumor volume data or concentration data of a certain plasma cell factor, additional animal experiments are not needed for measurement, and the method can be widely applied to conventional research.

The invention discloses a tumor treatment system based on an ultrasonic fatigue effect, which directly damages a cancer cell membrane structure and destroys the integrity of the cancer cell membrane structure through the continuous action of low-intensity ultrasonic energy, specifically targets a disordered tumor extracellular matrix by utilizing the ultrasonic fatigue effect, and simultaneously causes mechanical damage to tumor blood vessels. The tumor core hypoxia caused by nutrition delivery is blocked, so that cell apoptosis is induced. And the multi-layer mechanical-biological effect jointly inhibits tumor growth. The tumor treatment system is combined with temozolomide for use, can synergistically amplify the anti-tumor effect, and is suitable for hypoxic tumors tolerated by a traditional therapy. According to the treatment system, a non-invasive and controllable tumor treatment mode is achieved through accurate regulation and control of energy, and a new thought is provided for tumor treatment.

The invention discloses an application of an AZD2858 compound in preparation of a synergist of a chemotherapeutic drug for brain glioma. The invention discloses application of an AZD2858 compound in preparation of a reagent or a medicine for inducing tumor vessel normalization. The invention further discloses a pharmaceutical composition for treating brain glioma. The pharmaceutical composition comprises the AZD2858 compound and a brain glioma chemotherapy drug. The AZD2858 compound disclosed by the invention can induce tumor blood vessel normalization so as to improve the delivery and effect of the brain glioma chemotherapeutic drug, and the problems that the current brain glioma chemotherapeutic drug is poor in treatment effect and delivery effect are solved.