7165 results about "Tumor cells" patented technology

The invention relates to the field of antitumor drugs, in particular to a pharmaceutical composition of a KRAS G12C inhibitor and camptothecin and application of the pharmaceutical composition. The camptothecin and the KRAS G12C inhibitor are combined to play a synergistic effect, a DNA damage repair pathway is inhibited, a better inhibition effect is generated on tumor cells containing KRAS G12C mutation, the dosage required for achieving the same anti-tumor effect is greatly reduced, and the medication safety is improved.

The invention relates to the field of antitumor drugs, in particular to a pharmaceutical composition of a KRAS G12C inhibitor and Ly2090314 and application of the pharmaceutical composition. According to the invention, the Ly2090314 and the KRAS G12C inhibitor are combined to play a synergistic effect, a DNA damage repair pathway is inhibited, a better inhibition effect is generated on tumor cells containing KRAS G12C mutation, the dosage required for achieving the same anti-tumor effect is greatly reduced, and the medication safety is improved.

The invention relates to the field of biological medicine, in particular to a stapled peptide targeting RAS-Raf protein interaction and application of the stapled peptide, the stapled peptide is obtained in the mode that Ac-SLHDCLMKALKVR-NH2 and Ac-SLHDCLMKALKVRGL-NH2 serve as peptide chain templates, amino acid at the i site and amino acid at the (i + 4) site are replaced with S5 and cyclized, and the nitrogen terminal is further modified with stearic acid. The stapled peptide can effectively inhibit proliferation and migration of tumor cells; the serum stability is high, and meanwhile, the cell transmembrane capability is excellent, so that target protein in cells can be better targeted, and the biological function of the target protein can be exerted. Therefore, the alphaH helical conformation of the RBD of the RAF can be stabilized through the stapled peptide and a nitrogen-terminal fatty acid modification strategy, the membrane permeability and stability of the RAF are improved, the binding force of the RAF and RAS is further improved, and proliferation and migration of various tumor cells are inhibited.

The invention provides a circulating tumor cell recognition model training method and system based on deep learning, and the method comprises the steps: obtaining a multi-channel pathological sample image set of circulating tumor cells, carrying out the cross-modal feature extraction of a multi-channel pathological sample image, generating a fusion feature vector containing the morphological features and microenvironment features of the cells, and carrying out the recognition of the circulating tumor cells through the fusion feature vector. A deep convolutional network with a multi-stage training strategy is constructed, network parameters of the deep convolutional network in the training process are verified and adjusted by adopting a hierarchical cross validation mechanism, and finally a final recognition model is generated based on the verified and adjusted network parameters. The final recognition model is configured to receive the clinical pathology image stream and output localization coordinates and classification confidence of circulating tumor cells. According to the method, a circulating tumor cell recognition result can conform to a cell space distribution rule and has clinical pathological diagnosis interpretability, and the problems of high false positive rate and insufficient cell subtype discrimination caused by neglecting of microenvironment interaction in a traditional method are solved.

Disclosed in the present invention are a quinazoline compound, and a pharmaceutical composition thereof and the use thereof. Provided in the present invention is a compound as represented by formula I, a stereoisomer thereof or a pharmaceutically acceptable salt thereof. The compounds of the present invention have a good degradation effect on the KRAS protein with a G12D mutation, have a good inhibitory activity against the proliferation of tumor cells with a KRAS G12D mutation, and exhibit good pharmacokinetic properties.

The invention discloses a double-layer microneedle patch and a preparation method thereof.The preparation method of the double-layer microneedle patch comprises the following steps that firstly, 3D printing is conducted through polydimethylsiloxane, and a PDMS mold similar to a machining microneedle is obtained; dispersing the medicine into the sericin solution to serve as an outer layer solution; dispersing germanium nanoparticles into the polycaprolactone solution to obtain an inner layer solution; and finally, adding the outer-layer solution into the needle-shaped groove of the PDMS mold, so that the needle-shaped groove is filled with the outer-layer solution, drying, adding the inner-layer solution, drying, and demolding to obtain the double-layer microneedle patch. When the double-layer microneedle patch is used for drug delivery, drugs can be dissolved and released in a short time, the inner layer is polycaprolactone (PCL) carrying photo-thermal agent germanium nanoparticles, degradation is slow, a photo-thermal effect is generated under irradiation of 808nm near-infrared light, residual tumor cells are induced to die immunogenicity, an immune microenvironment is programmed in a time sequence, and the double-layer microneedle patch has the advantages of being high in sensitivity, high in sensitivity and good in stability. Postoperative recurrence and metastasis of tumors are efficiently inhibited, and meanwhile operative wound repair is promoted.

In accordance with at least one aspect of this disclosure, there is provided an imaging agent, a including dye compound conjugated to an antigen specific targeting vector which can be particularly advantageous because their behavior in vivo can contribute to superior optical imaging properties, for example, by significantly increasing the target-to-background ratio of imaged tissues, leading to higher resolution imaging, and ultimately providing for better recognition of malignant tissue for resection and margin assessment and improved visualization during minimal invasive laparoscopic surgery, for example. A method of imaging tumor cells in a subject, can include, administering an imaging effective amount of an imaging agent according at least one embodiment of the invention; 2-4 hours after administration of the imaging agent, irradiating a region in the subject in which tumor cells are expected to be found with at a wavelength absorbed by the imaging agent; and detecting a signal from the imaging agent, thereby imaging the tumor cells, wherein the target-to-background ratio 2-4 hours after administration is from about 2.75 to about 15.

The invention discloses a colorectal cancer drug relocation method based on multi-omics integration. The system comprises a multi-omics data acquisition and preprocessing module, a tumor microenvironment analysis module, a specific disease network construction module, a multi-dimensional drug relocation module and a result evaluation module. And the tumor microenvironment analysis module comprises cell heterogeneity identification, cell map construction, cell annotation and tumor cell subset annotation. The specific disease network construction module comprises tumor feature expression program extraction, expression program screening, meta-program construction, clinical related meta-program recognition and specific disease protein interaction network construction. And the multi-dimensional drug relocation module comprises a module for identifying diseases by using a random walk algorithm, carrying out drug screening based on disturbance data, carrying out drug screening based on network proximity and carrying out comprehensive drug relocation. From the perspective of single cell data, element programs related to colorectal cancer survival are excavated, corresponding modules are designed, and the efficiency and precision of colorectal cancer targeted drug screening are improved.

The invention discloses a nano system for tumor radioimmunotherapy and a preparation method and application thereof, and belongs to the technical field of biological medicines.The system modifies bacteria outer membrane vesicles (OMVs) through engineering to enable the bacteria outer membrane vesicles to carry magnetite nanoparticles (Fe3O4NPs) and an ATR inhibitor VE822, the Fenton reaction activity of the Fe3O4NPs and the synergistic effect of the ATR inhibitor for inhibiting DNA damage repair are utilized, and the tumor radioimmunotherapy effect is improved. DNA damage is amplified, DNA damage reaction (DDR) is inhibited, generation of hydroxyl radicals (. OH) under radiation is enhanced, radiation resistance of tumor cells is reduced, immune reaction is reactivated, infiltration of effector T cells to tumors is improved, growth of mice tumors is remarkably inhibited, and an effective strategy is provided for tumor radioimmunotherapy.

The invention discloses an AIE type fluorescent probe with tumor targeting as well as preparation and application thereof, and belongs to the technical field of medicines, the probe can accurately target HDAC6 high-expression tumor cells, the specific binding capacity of the probe reduces interference to normal cells, and the detection accuracy is improved. The probe is fused with AIE performance dye molecules and emits strong fluorescence during aggregation, so that the imaging sensitivity and definition are remarkably enhanced. By optimizing the structure and synthesis conditions, the fluorescence intensity and stability of the probe are improved, the sensitivity of early tumor detection is ensured, and the survival rate and life quality of patients are improved. The preparation method is simple, convenient, feasible, low in cost and beneficial to practical application. The probe can be used for preparing tumor detection products, assisting in tumor diagnosis and classification, monitoring treatment changes and evaluating the curative effect. High-precision imaging can be realized in the aspect of tumor imaging, the method can be used for evaluating curative effect and guiding formulation of subsequent treatment schemes, and the application prospect is wide.

The invention discloses a tumor cholesterol metabolism regulation microneedle patch and a preparation method, the microneedle patch comprises a needle tip and a backing which are connected, the needle tip comprises a needle tip body and nanoparticles loaded on the needle tip body, the nanoparticle is a manganese ion-doped organic metal framework, the outer layer of the manganese ion-doped organic metal framework is modified with a targeting agent, cholesterol oxidase and superoxide dismutase are carried on the manganese ion-doped organic metal framework, the targeting agent can target a CD44 receptor, and the organic metal framework can carry drugs. The targeted drug can enter tumor cells in a targeted mode, superoxide dismutase catalyzes superoxide anions overexpressed in the tumor cells to generate H2O2 and O2, O2 needed by catalysis is provided for cholesterol oxidase, cholesterol at the tumor site is consumed by the cholesterol oxidase, accumulation of 7-DHC is reduced, meanwhile H2O2 can be generated, and the cholesterol oxidase can be used for catalyzing the tumor site. H2O2 is catalyzed by manganese ions through a Fenton-like reaction to generate OH to induce tumor cells to generate ferroptosis, so that ferroptosis-immune synergistic treatment is realized.

The invention relates to application of a targeted inhibition circPDK1 reagent in preparation of an anti-esophageal cancer drug, and belongs to the field of biological medicines. The reagent for targeted inhibition of circPDK1 expression provided by the invention is shRNA or siRNA, and in-vivo and in-vitro experiments prove that the reagent can significantly inhibit circPDK1 expression and inhibit growth and migration of esophageal cancer tumor cells; after siRNA of targeted annular circPDK1 is packaged into efficient and low-toxicity LNP-siRNA, circPDK1 expression is specifically silenced, proliferation and migration of esophageal cancer tumors can be remarkably inhibited, and a basis is provided for clinical treatment and scientific research of esophageal cancer related circRNA.

The invention discloses a PROTACs compound for targeted degradation of PRMT5 and application of the PROTACs compound. The PROTACs compound comprises a compound as shown in the following formula, and related analogues or pharmaceutically acceptable salts, metabolites or prodrugs of the compound: in the # imgabs0 # formula, X represents a ligand bound to PRMT5 protein, Z represents a ligand of E3 ubiquitin ligase, and Y represents a linking group for linking X and Z; according to the invention, CRBN is used as E3 ligase, and a series of PRMT5-targeted PROTAC degradation compounds are designed and synthesized. The compound can effectively induce PRMT5 degradation, significantly inhibit proliferation, growth, migration, infiltration, clone formation and metastasis of tumor cells, promote apoptosis of cancer cells, promote autophagy of the tumor cells, prevent or overcome drug resistance of BTK inhibitors and / or prolong the lifetime of tumor patients, and has wide application prospects.

The invention discloses an anti-PD-L1 antibody coupling drug and a preparation method thereof, belongs to the field of biological medicines, and is used for preparing anti-cancer drugs. The antibody coupling medicine is formed by coupling an anti-PD-L1 antibody and a payload through a linker, a light chain variable region sequence of the antibody is a sequence recorded by SEQ ID NO: 1, a heavy chain variable region sequence of the antibody is a sequence recorded by SEQ ID NO: 2, the payload is an avixatecan derivative Dxd, and the ratio (DAR) of the payload to the antibody is 6-8. The antibody-conjugated drug has a better killing effect on PD-L1 positive tumor cells of human and dogs, and has fewer dimers and higher thermal stability at a high DAR value (DAR6-8), and an accelerated stability test shows that the antibody-conjugated drug has good structural stability and binding activity.

The invention relates to an anti-CD3 nano antibody, an anti-CD38 antibody and a bispecific antibody containing the anti-CD3 nano antibody and the anti-CD38 antibody. According to the invention, an anti-CD3 nano antibody and an anti-CD38 monoclonal antibody are excavated and prepared, humanized design is carried out to obtain antibodies with high affinity and specificity, and different configurations of bispecific T cell conjugation antibodies targeting CD3 and CD38 are further designed, so that the CD3 and CD38 dual-specificity T cell conjugation antibodies are obtained. The antigen binding activity, the T cell-mediated tumor cell killing effect and the T cell proliferation and activation function of the antibody are systematically evaluated in vitro, and experimental results show that the T cell conjugation antibody can effectively recruit and activate T cells and has a remarkable killing effect on CD38 positive tumor cells, and it is further verified that the antibody has remarkable in-vivo anti-tumor activity and has a good application prospect. Therefore, the polypeptide has high affinity, good pharmacological characteristics and development potential.

The present invention relates to magnetic, catalytically active, and radiosensitizing nanoparticles (NanoXcats) and the method for their production. A method is disclosed for the production of functionalized greigite nanoparticles with a narrowband size distribution (10-30 nm) for use in multimodal cancer therapy. NanoXcats are superparamagnetic Fe3S4 nanoparticles whose surfaces are equipped with polar functional groups. The surface structures of NanoXcats are suitable for conjugation with, or for covalent or electrostatic binding of, active substances, which may be cancer drugs, cell growth inhibitors, or NO donors. Due to the EPR effect, NanoXcats are preferentially internalized by tumor cells. The targeted accumulation of NanoXcats in tumor tissue is achieved by an external inhomogeneous magnetic field. NanoXcats exhibit enhanced catalytic activity in tumor cells.The catalytic activity of intracellular NanoXcats can be triggered, controlled, and enhanced by low-dose X-rays. Surface-bound drugs are additionally activated in tumor cells by the catalytic activity of NanoXcats. NanoXcats act as superoxide dismutase, nitric oxide synthase, and Fenton catalyst. They catalyze, for example, reactions of the superoxide anion radical to hydrogen peroxide, of L-arginine to NO, and of hydrogen peroxide to the hydroxyl radical.

A method for qualifying a specimen prepared on one or more hematoxylin and eosin (H&E) slides by assessing an expected yield of nucleic acids for tumor cells and providing associated unstained slides for subsequent nucleic acid analysis is provided.

The invention provides a tumor cell exosome, an anti-tumor immune drug delivery system and a preparation method and application of the anti-tumor immune drug delivery system, the tumor cell exosome is derived from starved and stimulated tumor cells, the tumor cell exosome is coated with nano drug particles for delivery, and the exosome has the effects of enhancing immune cell infiltration and remodeling an immune microenvironment; due to the homing effect of the exosome, the medicine and the exosome are more easily accumulated in the tumor, and the targeting property is improved; due to coating and camouflage of the biological membrane of the exosome membrane, the exosome membrane is prevented from being recognized, attacked and removed by an organism, and the biological safety is improved, so that the exosome and the nano-drug act on the tumor together to achieve a synergistic effect.

The invention relates to the field of bioelectricity data processing, and discloses a tumor cell metabolite distribution three-dimensional reconstruction method and system based on artificial intelligence, and the method comprises the steps: collecting the multi-modal data of tumor cells, recognizing the entity elements of the tumor cells and the corresponding entity relationship from the multi-modal data, and obtaining the entity relationship of the entity elements of the tumor cells; constructing a metabolite knowledge map of the tumor cells; according to the space coordinates of the metabolites and the microenvironment characteristic data of the tumor cells, analyzing a space aggregation mode of the metabolites in the tumor cells; in combination with the spatial distribution mode and the biological metabolic pathway of the metabolites, key features of the metabolites in the tumor cells are extracted, and a metabolite distribution discrimination network of the tumor cells is established; and identifying an abnormal distribution mode of the metabolite in the tumor cells, constructing a metabolite distribution three-dimensional model of the tumor cells, and outputting a metabolite three-dimensional distribution result of the tumor cells. According to the method, the accuracy and comprehensiveness of the three-dimensional distribution result of the tumor cell metabolites can be improved.

Provided are a camptothecin compound, an antibody drug conjugate, and a preparation method therefor and the use thereof. Specifically provided is a camptothecin compound as represented by formula (K) or a pharmaceutically acceptable salt thereof. The provided camptothecin compound and the antibody drug conjugate thereof have a good cytotoxic activity and can inhibit the proliferation of tumor cells.

The invention relates to the technical field of medical image processing and tumor diagnosis, in particular to a tumor recognition method based on multi-modal information fusion. The method comprises the following steps: acquiring tumor multi-modal information of a target object, wherein the multi-modal information comprises tumor image data, tumor genomics data and individual tumor related information; the tumor-related information comprises a vascular structure, a blood flow velocity, fluid viscosity and fluid pressure of the target object; determining a tumor cell density, a diffusion coefficient and a cell proliferation rate according to the tumor image data and the tumor genomics data; predicting a diffusion path of the tumor in the local tissue according to the tumor cell density, the diffusion coefficient and the cell proliferation rate; predicting a metastasis path of tumor cells through a vascular system according to the individual tumor related information; and according to the diffusion path of the tumor in the local tissue and the metastasis path of the tumor cells through the vascular system, identifying the potential metastasis site of the tumor.

The invention discloses a tumor evolution trajectory prediction method and system based on image feature learning, and the method comprises the steps: obtaining the whole-process pathological section image data of a target type tumor patient, carrying out the analysis and screening of the image quality, constructing a pathological section screening strategy, and extracting a standard image; extracting tumor cell characteristics based on the standard image, performing grouping analysis on the cell characteristics of different time periods through a clustering algorithm, and determining tumor cell development characteristics; further constructing the cell development characteristics of multiple patients into a heterogeneity propagation network, simulating the tumor evolution process by using a random walk algorithm, and identifying the multi-branch evolution trajectory of the tumor; and finally, establishing a tumor evolution trajectory prediction model to predict the tumor development trend of the current patient. According to the method, the accuracy and interpretability of tumor evolution trajectory modeling can be improved, and reliable support is provided for clinical individualized diagnosis and treatment.

The invention discloses a preparation method and application of a manganese-based amino acid coordination polymer, and belongs to the technical field of nano-enzymes and nano-drugs. Divalent manganese salt, histidine and other amino acids are subjected to a co-precipitation reaction to prepare the manganese-based amino acid coordination polymer, and the polymer is of a nanoparticle structure, small in size and high in stability, has enzyme-like activity, catalyzes hydrogen peroxide to generate high-toxicity hydroxyl free radicals and is used for specifically killing tumor cells. The catalyst has the capability of catalytically generating singlet oxygen in the presence of hydrogen peroxide. Meanwhile, the manganese-based amino acid complex has glutathione oxidase-like activity, consumes glutathione to overcome the resistance of tumors to oxidative stress, improves the chemical kinetic curative effect, and has anti-tumor application potential.

The invention discloses a cationic polymer-based proteolysis targeting chimera as well as preparation and application thereof, and belongs to the fields of targeting protein degradation and nanotechnology. According to the chimera, a cationic polymer is used as a connecting arm to connect a target protein ligand and an E3 ubiquitin ligase ligand to form a ternary complex, so that efficient degradation of target protein is realized. By adjusting the ligand proportion, chimeras with different degradation efficiencies can be synthesized, and accurate regulation and control are realized. The pH-responsive nano-drug obtained by hydrolyzing the targeting chimera by using the targeting protein can respond to an acidic tumor microenvironment, specifically release the chimera, and improve the targeting property and the treatment effect of the drug. Compared with the traditional PROTACs, the compound has higher bioavailability and tumor permeation effect; the preparation method of the nano-drug is simple and easy to implement, provides possibility for preparation of high-performance nano-drugs, shows potential in preparation of anti-tumor cell drugs, provides new thoughts and methods for tumor treatment, and has important clinical application value.

The invention belongs to the technical field of biology, and relates to a biomarker for early diagnosis of non-small cell lung cancer and application of the biomarker. The biomarker comprises a combination of secretory phosphoprotein 1, epithelial cell adhesion molecules and matrix metallopeptidase 14, and / or a combination of coding nucleic acid of the secretory phosphoprotein 1, coding nucleic acid of the epithelial cell adhesion molecules and coding nucleic acid of the matrix metallopeptidase 14. The coding nucleic acid comprises mRNA or cDNA. In a test set, a non-small cell lung cancer circulating tumor cell scoring diagnosis model constructed by taking the biomarker as the characteristic has the diagnosis accuracy of 87.5% and the sensitivity and specificity of 92.5% and 82.5% respectively. Compared with existing clinical tumor indexes, cancer can be found more early, and early screening of the non-small cell lung cancer is facilitated.

Provided herein are novel anti-CD20 x anti-CD28 antibodies and methods of using such antibodies for the treatment of B-cell malignancies. Subject anti-CD20 x anti-CD28 antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and CD20 on tumor cells. Thus, such antibodies enhance anti-tumor activity at tumor sites. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies (e.g., anti-CD3 x anti-CD20 x anti-CD79b antibodies) for the treatment of B-cell malignancies.

The invention provides an LRC58 monoclonal antibody and a preparation method and application of a kit of the LRC58 monoclonal antibody. The monoclonal antibody hybridoma cell strain LRC58 is preserved in the China General Microbiological Culture Collection Center (CGMCC) with the preservation number of CGMCC No.46113, and the prepared monoclonal antibody can effectively recognize the LRC58. The invention further discloses a method for preparing the monoclonal antibody.

Provided are methods for identifying and treating patients with cancer, where the cancer expresses CEACAM5. The methods include measuring circulating CEA to identify patients likely to benefit from treatment with an agent specific for CEACAM5. Such patients can have high circulating CEA and only low or medium expression of CEACAM5 on tumor cells as measured by immunohistochemistry (IHC). The agent specific for CEACAM5 can be tusamitamab ravtansine. Such agent can be used in combination with one or more additional agents to treat the cancer. In certain embodiments the cancer is non-squamous non-small cell lung cancer (NSQ NSCLC).

The invention discloses a PEI and targeting peptide modified magnetic nano-carrier and a preparation method and application thereof. The nano-carrier is regular in morphology and uniform in particle size and has good crystallinity and magnetic performance. E5 polypeptide and RGD cyclic peptide on the surface of the nano-carrier are respectively combined with CXCR4 protein and integrin on the surface of a tumor cell, and the nano-carrier and CXCR4 are internalized into lysosome through an integrin-mediated way, so that the target protein CXCR4 is degraded. The PEI in the nano-carrier can load and deliver siRNA into tumor cells to silence the expression of CXCR4 mRNA (messenger Ribonucleic Acid). Through nucleic acid delivery and a protein targeted degradation strategy, the CXCR4 level of tumor cells is jointly reduced, the migration ability of the tumor cells is inhibited, and meanwhile, the anti-tumor effect of M1 type polarization of macrophages is activated.

The invention provides a whole-process targeting polypeptide, a drug compound thereof, a drug delivery system and application of the whole-process targeting polypeptide. The whole-process targeting polypeptide comprises pHA and VAP which are covalently connected through a bridging structure; the VAP is LVAP, a reverse sequence polypeptide of the LVAP, DVAP or SVAP; wherein the amino acid sequence of the LVAP is as shown in SEQ ID NO: 1; the SVAP is a D-configuration polypeptide of the LVAP; the DVAP is a D-configuration polypeptide of the LVAP inverted sequence polypeptide; the bridging structure is amino-monoethylene glycol-carboxylic acid or a derivative thereof. The whole-process targeting polypeptide not only can cross a blood-brain barrier, target tumor neovascularization, cross a blood-tumor barrier, target tumor mimicry vessels, tumor cells and stem cells thereof, but also has better tumor cell affinity, anti-tumor treatment and in-vivo safety effects. Meanwhile, the drug compound or the drug delivery system has a synergistic effect after being combined with a chemotherapeutic drug, and the anti-tumor drug effect can be remarkably improved.