28 results about "Tumor stroma" patented technology

Described herein are methods, systems, and programming for determining a tumor immunophenotype of an image of a tumor. Some embodiments include dividing an image into tiles depicting tumor epithelium and / or tumor stroma. For each tile, an epithelium-immune cell density and a stroma-immune cell density may be calculated based on a number of immune cells identified in the tumor epithelium and the tumor stroma, respectively. Based on the epithelium-immune cell density and the stroma-immune cell density, an inflammation type of the type may be determined, and a tumor immunophenotype may be determined based on each tile's inflammation type.

The invention belongs to the field of biological medicine and ultrasonic medicine, and provides a barium titanate (BTO) piezoelectric material-based ultrasonic responsive targeting nano system (BTO at BAL), which is used for matrix microenvironment remodeling and immunopotentiation of compact tumors such as pancreatic cancer and the like. According to the nanoparticles, oleic acid modified BTO is taken as a core, ROS responsive prodrug molecules containing a small molecule PD-L1 inhibitor BMS1166 and a nitric oxide donor (Arg) 9 are loaded on the surface, and specific targeting on pancreatic cancer cells is realized by combining a targeting peptide LFC131. Under ultrasonic excitation, BTO generates reactive oxygen species (ROS), on one hand, (Arg) 9 is oxidized to release NO, tumor matrix is degraded, tumor hardness is reduced, drug delivery efficiency is improved, and meanwhile, ROS and NO synergistically enhance tumor immunogenicity; on the other hand, the ROS breaks a thioketal bond to release BMS1166, PD-L1 expression is down-regulated, and immunosuppression is reversed. According to the present invention, the significant tumor inhibition and immune activation effects are represented in the animal model, and the clinical transformation potential is provided.

In some embodiments, the present disclosure relates to a method. The method includes accessing digitized pathology imaging data from a cancer patient. The digitized pathology imaging data includes segmented imaging data that identifies one or more regions of interest (ROI) including tumor-stroma regions and / or collagen fibers. A plurality of collagen fiber features are extracted from the one or more ROI. The plurality of collagen fiber features are provided to a machine learning model that is trained to generate a medical prognosis relating to the cancer patient.

This invention discloses an enzyme- and pH-responsive nucleic acid loading and delivery material and its preparation method. The material can be used for efficient loading and delivery of nucleic acid molecules. The preparation method uses amphiphilic zwitterionic monomers to improve the reverse emulsion polymerization system, enhancing polymerization at the two-phase interface and avoiding the extrusion effect of polymerization in the aqueous core on nucleic acid molecules, thereby improving the loading efficiency of nucleic acid molecules. Further preparation of cross-linking agents MP-CL and CB-CL, which can cleave in response to matrix metalloproteinase II or cathepsin B, endows the nanogel with the ability to respond to charge reversal in the tumor matrix and to release nucleic acid molecules from tumor cells. The acid-sensitive blocks on the amphiphilic monomers give the nanogel lysosomal escape capability. The delivery material can efficiently deliver nucleic acid molecules into cells and exhibits excellent stability and biosafety.

The invention discloses an engineered exosome preparation with tumor targeting and specific gripper response release functions as well as a preparation method and application of the engineered exosome preparation. The preparation comprises a myocardial cell exosome, an NK cell biotinylation activation antibody, a tumor disease biotinylation antibody, streptavidin, a tumor fiber matrix FAP targeting peptide and a tumor matrix enzyme response peptide, and anchoring is carried out through an acetamide compound-polyethylene glycol anchor point platform. The engineering bispecific exosome preparation with good tumor targeting and barrier breakthrough ability and immune cell activation effect is prepared, and the preparation breaks a solid tumor compact fiber barrier and increases NK cell infiltration by utilizing the fibrosis treatment ability of the myocardial cell exosome and the capture and targeting effects of an anchor point platform; the natural killer cells are in close contact with tumor cells, the lasting tumor cell killing effect is achieved, and the tumor matrix environment is fundamentally changed.

The invention belongs to the technical field of biological medicines, and particularly relates to a pharmaceutical composition containing carboxamide triazole or pharmaceutically acceptable salts thereof and application of the pharmaceutical composition in preparation of medicines for preventing or treating fibrosis-related diseases. Specifically, the invention discovers that the carboxylamine triazole orotate (CTO) can directly inhibit fibroblast collagen generation and cross-linking maturation, so that the fibrosis degree is reduced; when the polypeptide is combined with a PD-1 antibody, collagen deposition in tumor tissues can be reduced by inducing normalization of a tumor matrix in a synergistic manner, the tumor permeation concentration of chemotherapeutic drugs is remarkably enhanced, and the anti-tumor curative effect is improved. The invention can be applied to the treatment of various matrix dense solid tumors including pancreatic cancer, breast cancer, colorectal cancer and lung adenocarcinoma, and is expanded for intervention of fibrosis-related diseases, thereby providing a new treatment strategy for improving the efficacy of chemotherapeutic drugs and improving immunotherapy response through targeted matrix remodeling.

The invention discloses a bionic photo-thermal nano motor for targeted regulation and control of a solid tumor matrix-immunosuppression microenvironment and a preparation method and application thereof, and belongs to the technical field of biomedical materials.The preparation method comprises the steps that polydopamine nanoparticles and a K2PtCl4 aqueous solution are subjected to condensation reflux, and asymmetric PDA-Pt is prepared; and preparing a cancer-related fibroblast and breast cancer cell fusion membrane and coating the surface of PDA-Pt with the cancer-related fibroblast and breast cancer cell fusion membrane. The nano-motor realizes dual targeting of matrix cells and tumor cells through a surface modified fusion cell membrane, targeted ablation CAFs regulates and controls a tumor matrix microenvironment, a good tumor permeation effect is realized by cooperating with H2O2 responsive self-driving of the nano-motor, a mild photo-thermal-catalytic synergistic effect is formed by a photo-thermal effect of PDA and peroxidase-like activity of Pt nano-enzyme, and a good tumor permeation effect is achieved. And finally, the tumor immunosuppression microenvironment is remarkably improved, and the tumor immunotherapy effect is improved.

The invention discloses hydrogel for culturing tumor organoids as well as a preparation method and application of the hydrogel. The preparation method comprises the following steps: mixing norbornene functionalized hyaluronic acid, enzyme digestion polypeptide matched with tumor matrix degradation, cell adhesion peptide and a photoinitiator, and carrying out a cross-linking reaction to obtain the hydrogel for culturing tumor organoids. The hydrogel prepared by the method disclosed by the invention is clear in component, and a three-dimensional network structure is obtained by gelatinizing hyaluronic acid, tumor characteristic enzyme digestion polypeptide and cell adhesion mimic peptide through a sulfydryl-olefin chemical reaction. The hydrogel prepared by the invention has the characteristics of fast gelation, enzyme sensitivity, adjustable mechanical properties and good biocompatibility under the action of the modified peptide, can be used as a substitute of matrigel for three-dimensional culture of tumor organs, and is applied to sensitivity detection of chemotherapeutic drugs.

Disclosed in the present invention are a FAP-targeting compound and a preparation method therefor. By means of a meticulously designed molecular structure containing a plurality of variable substituents, the compound can precisely target fibroblasts in tumor stroma, thereby providing a new approach for cancer treatment. The Z group of the compound can be flexibly replaced by a radioactive agent, fluorescent agent or contrast agent, thus broadens the application range for tumor diagnosis and treatment. In the preparation method, starting from a starting material, a high-purity and high-yield FAP-targeting compound is ultimately obtained via a plurality of efficient reaction steps. Such compound has good metabolic stability and pharmacokinetic properties, which reduce the side effects of medications and increase the therapeutic effect. The diverse substituents and linker arms of the compound further optimize the physicochemical properties and improve the overall therapeutic effect. When combined with a pharmaceutical carrier, the compound achieves efficient delivery to tumor tissues and reduces non-target side effects, which provides a precise and effective personalized treatment regimen for cancer patients, and significantly improves the therapeutic effect and the quality of life of patients.

The dual therapy involving tumor stroma-binding IL-7 and IL-12 variants led to synergistic antitumor efficacy through suppression of immune exhaustion and promotion of immune memory without compromised tolerability. The disclosure describes a polypeptide comprising an IL-7 polypeptide, or a functional fragment thereof, linked to a extracellular matrix (ECM)-affinity domain. Also described is a nucleic acid encoding a polypeptide of the disclosure and cells comprising the polypeptide(s) or nucleic acid(s) of the disclosure.

The present invention relates to a multimodal non-invasive in vivo system and related method for the characterization of the tissue microenvironment. The system comprises: a multispectral imaging (MSI) camera for superficial spectral screening; a multispectral optoacoustic tomography (MSOT) module for dynamic vascular and perfusion analysis; a Mueller Matrix Polarimetry (MMP) module for extracellular matrix anisotropy assessment; a Raman spectroscopy module for molecular fingerprinting of fibroblast-associated proteins; an optical coherence tomography (OCT) module for morphological and stratigraphic evaluation; an optional Elastic Scattering Spectroscopy (ESS) module for subcellular scattering biomarkers; and a diachronic analysis module for longitudinal monitoring. Data are integrated by an artificial intelligence processing unit to generate quantitative biomarkers of vascularization, extracellular matrix features, immune activity (Langerhans cells) and fibroblast phenotype, distinguishing physiological myofibroblasts from CAF. The invention enables non-nvasive, biopsy-free evaluation of scars, melanocytic lesions, tumor stroma, wound healing and surgical site monitoring.

Disclosed are methods and systems for selecting one or more candidate regions from a tissue for inclusion in a tissue microarray (TMA). Methods involve determining tissue compositions of regions across the tissue and selecting the candidate regions that have desired tissue compositions for inclusion in a TMA. For example, desired tissue compositions can include one or more tissue classes, examples of which include tumor, stroma, immune, necrosis, other tissue, or combinations thereof. Thus, the disclosed method represents an automated process of selecting candidate regions without involving manual input.

The present application relates to the technical field of digital image processing, in particular to a tumor interstitial proportion quantitative evaluation system based on pathological images. The present application automatically obtains tumor epithelial region, tumor interstitial region, tumor region and tumor infiltration front region based on image segmentation, without pre-selecting histological evaluation position for visual evaluation by artificial selection, avoiding the subjective experience dependence of traditional methods, and improving the efficiency of tumor interstitial proportion evaluation. In addition, the present application comprehensively quantitatively evaluates the first tumor interstitial proportion under the overall scale of the to-be-tested pathological image, the second tumor interstitial proportion under the scale of the tumor infiltration front region and the third tumor interstitial proportion under the scale of the tumor region, and finally obtains the tumor interstitial proportion score value which can reflect the tumor interstitial proportion characteristics of different anatomical positions, further improving the accuracy of the evaluation result. The preset rule is to select the window tumor interstitial proportion with the highest tumor interstitial proportion value.

The present disclosure relates to methods of coupling antic-cancer agents and anti-cancer treatments to improve the efficacy of the overall treatment. The anti-cancer agent reduces stroma in the tumor microenvironment, in part by killing stroma producing cells such as TAFs and TAMs. Reduction of tumor stroma not only improves immune cell function, including immune cells administered in a second treatment, but also allows allowing other anti-cancer treatments to better access to tumor cells.

The present invention relates to methods of obtaining an indication of the prognosis of a breast cancer subject, for classifying breast tumours, and related methods. The methods are based on the production of a signature score which is derived from normalised expression levels of a plurality of specific breast tumour stromal protein or tumour stromal RNA biomarkers.

A tumor stroma imaging agent with a chemical structural formula (I):is provided, where R is hydrogen or fluorine. Compared with the prior art, the tumor stroma imaging agent exhibits significant affinity for fibroblast activation protein (FAP), high uptake for a malignant tumor with high FAP expression in a tumor stroma, and high sensitivity and specificity for the diagnosis of a malignant tumor, and is not prone to false positives. Therefore, the tumor stroma imaging agent can be effectively and safely used for the diagnosis and treatment of various malignant tumors with a prolonged half-life and an extended window period, which is conducive to clinical application.

The invention discloses application of an FMR1 inhibitor in preparation of a medicine for treating immunological rejection type gastric cancer. Experimental studies prove that FTO is continuously and highly expressed in immunological rejection phenotypes and is related to interstitial activation and T cell rejection. Continuous immunohistochemistry and multiple immunofluorescence show that the FMR1 protein is highly expressed in an immunological rejection type tumor microenvironment, and most CD8 + T cells are located in tumor interstitial substances. In mechanism, the FMR1 regulates and stabilizes FTO protein and limits the degradation of proteasome of the FTO protein through post-translation, so that FTO-dependent m6A reprogramming is maintained, and an immunological rejection microenvironment is enhanced. Therefore, the invention discloses a non-classical mechanism that the FMR1 modifies and stabilizes the FTO protein after translation, and the FMR1-FTO axis can be used as a potential intervention target for breaking an immune barrier and sensitizing gastric cancer immunotherapy.

The application provides a pancreatic cancer deep penetration ferroptosis nano preparation and a preparation method and application thereof, the nano preparation comprises a drug-loaded core and a MOF shell, the drug-loaded core is formed by polymerization of a ferroptosis inducer Erastin and a polymer material, and the MOF is formed by coordination of iron ions and tannic acid. The preparation method is as follows: iron ions, the polymer material and Erastin are mixed to form an organic phase solution, the solution is slowly dropped into a tannic acid aqueous phase solution, and the nano preparation is obtained through ultrasonic and stirring. The nano preparation constructed in the application can regulate the re-polarization of tumor-associated macrophages, thereby reducing the activation and collagen deposition of tumor-associated fibroblasts to regulate the dense tumor stroma, achieving deep penetration of the nano preparation, after reaching the deep part of the tumor, the iron ions and Erastin synergistically act to destroy the redox balance of tumor cells, improve the ferroptosis effect of tumor cells, and realize ferroptosis treatment of pancreatic cancer cells.

The present invention relates to a multispecific antibody containing an LRRC15 antigen-binding domain and the use thereof. Particularly, provided in the present invention is a multispecific antibody, which contains a first targeting domain that targets to a leucine-rich repeat containing 15 (LRRC15) molecule highly expressed on the surface of a tumor cell, also contains a second targeting domain that binds to a CD40 molecule on the surface of an antigen presenting cell (APC) or a CD3 molecule on the surface of a T cell, and optionally, contains a third targeting domain that targets to PD-1, CLDN18.2 or FAP, and / or a fourth targeting domain that targets to TGF-β. The LRRC15-related multispecific antibody of the present invention can effectively activate T cells and reduce tumor stroma impact, thereby providing effective treatment for tumors and fibrotic diseases.

The invention discloses application of fibroblast-MMP11 in pancreatic cancer angiogenesis and tumor cell heterogeneity and metastasis, relates to the technical field of biological medicine, and discloses application of fibroblast-MMP11 in pancreatic cancer angiogenesis and tumor cell heterogeneity and metastasis. Preferably, the drug targets the FbMMP11 or the VEGF and NOTCH signal channels activated by the FbMMP11. According to the application of the fibroblast-MMP11 as the pancreatic cancer diagnosis marker, prognosis and metastasis risks of patients are evaluated by detecting the expression level of the FbMMP11. The invention relates to a pharmaceutical composition for inhibiting angiogenesis and metastasis of pancreatic cancer. The pharmaceutical composition comprises an inhibitor targeting FbMMP11 and a VEGF / NOTCH signaling pathway blocker. In the invention, the molecular basis of the FbMMP11 subgroup for promoting tumor matrix fibrosis through high expression of collagen synthesis genes such as COL1A1 and INHBA is defined; secondly, a new mechanism that FbMMP11 promotes tumor angiogenesis by activating VEGF and NOTCH signal pathways in EnCOL15A1 endothelial cells is disclosed.

The tumor stroma, which occupies a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, particular emphasis is on a subset of stromal cells, called cancer-associated fibroblasts, which are present in more than 90% of epithelial cancers, including pancreatic, colon, and breast cancers. Cancer-associated fibroblasts are characterized by high expression of FAP, which is not detectable in normal adult tissues but is associated with poor prognosis in cancer patients. The present invention provides small molecule radiopharmaceuticals and imaging agents based on FAP-specific inhibitors.

A method for preparing biomimetic nanocomposite materials based on thylakoid membranes is disclosed, belonging to the field of bionanomaterials technology. This invention addresses the problems of existing nano-manganese oxide, which is easily cleared by the immune system, has difficulty penetrating complex tumor matrixes, and suffers from complex synthesis methods and high costs; it also addresses the issues of insufficient rigidity, instability, inability to accurately reach tumor sites, and limited functionality in existing single-membrane structures. The method comprises: 1. Dispersing a thylakoid membrane in pure water, then heating and adding hydrochloric acid solution to obtain a Mg-removed Nks system; 2. Adding an aqueous manganese chloride solution to the Mg-removed Nks system, then adjusting the pH and continuing stirring. This invention is used for the preparation of biomimetic nanocomposite materials based on thylakoid membranes.

The application discloses a pathological section tumor stroma ratio quantification method, and steps are as follows: (1) a weakly supervised neural network training process based on an image block: firstly, block a full section image scanned by a digital scanner, then assign a unique label, i.e., tumor or non-tumor, to each image block, and finally, train a neural network added with a two-dimensional random inactivation layer using cross-entropy loss and translation invariance loss; (2) a tumor stroma ratio quantification algorithm based on a neural network: generate a class activation mapping graph using a previously trained model to identify a section, calculate a stroma region using a morphological algorithm, and further calculate a tumor stroma ratio. The application is suitable for making an accurate quantitative judgment on the tumor state of a patient in a clinic, and compared with existing methods, the application has the characteristics of high repeatability, low execution cost and high calculation accuracy, can help a pathologist to quantize a prognosis factor difficult to manually calculate, and significantly reduces the workload of the pathologist.

This invention belongs to the field of pharmaceutical technology, specifically relating to a method for isolating ovarian cancer-related mesenchymal stem cells and their application in anti-tumor treatment. The isolation method includes the following steps: (S1) extracting and isolating mesenchymal stem cells from fresh tumor samples from ovarian cancer patients using the direct tissue block method; (S2) sequentially screening and confirming the mesenchymal stem cells as tumor-derived through cell morphology identification, surface marker analysis, iterative stemness detection, and tumor and / or fibroblast marker exclusion experiments. Experiments have demonstrated that ovarian cancer-related mesenchymal stem cells can be used to evaluate the anti-tumor efficacy of drugs, their anti-invasive ability against tumor matrix support, and / or their anti-globulinization ability against tumor matrix support.

The invention belongs to the technical field of nano-drugs, and discloses a method capable of enhancing deep penetration of tumors based on NO gas nano-drugs, and the method comprises the following specific steps: step 1, selection and pretreatment of a starting material for preparing a nano-drug carrier: selecting Boc-NH-PEG-NH2 as a starting material of a PEG chain; according to the present invention, with the accurately prepared nano-drug carrier, the NO donor can be efficiently loaded and the responsive release can be achieved, the effective accumulation of the NO gas at the tumor site can be ensured so as to provide the anti-tumor effect, the release of the NO gas can trigger the expression and the activity enhancement of the matrix metalloproteinase (MMPs), and the tumor matrix collagen can be degraded so as to achieve the anti-tumor effect; compared with the prior art, the nano-drug provided by the invention has the advantages that the penetration barrier of tumor tissues is obviously reduced, favorable conditions are provided for the deep penetration of the nano-drug, in addition, the deep penetration of the nano-drug is further promoted by the responsive disintegration of the nano-drug in a tumor microenvironment, the anti-tumor effect is enhanced, and finally, the nano-drug has a selective toxic effect and is relatively low in toxicity to normal cells.

The invention discloses a serratia marcescens anti-tumor fungicide and a preparation method and application thereof, and relates to the field of biological medicine, the serratia marcescens anti-tumor fungicide comprises a recombinant serratia marcescens strain SM-IL12-PDG, the strain integrates a prodigiosin synthetic gene cluster (pigA-N) driven by an anoxic response type promoter (PgldE) and an IL-12 expression unit driven by a low pH response type promoter (PhoP / PhoQ) in an attenuated strain; according to the serratia marcescens anti-tumor fungicide as well as the preparation method and the application thereof, efficient prodigiosin in-situ synthesis and immune factor targeted delivery are synchronously realized under a tumor microenvironment specific activation condition through a synthetic biological gene loop synergistic regulation mechanism; and triple synergistic effects of direct toxin killing, immune response enhancement and tumor matrix remodeling are formed.

Disclosed herein are systems and methods based on tumor infiltrating leukocyte (TIL) fractal geometry to predict clinical implications in breast cancer samples. Using machine learning techniques, an algorithmic classifier is constructed and trained on a cohort of tumor images (e.g. radiographic, immunohistochemical (IHC), and H&E images) to discriminate between TILs and cancer cells, and breast cancer samples are classified based on TIL fractal geometry / anatomic distribution in the tumor stroma. Fractal geometry-directed reassessment of classifications may prompt tumor type reclassification resulting in altered cancer therapy.

The invention provides a dual-channel organ-like dynamic co-culture micro-fluidic chip and application thereof. The chip comprises at least one group of parallel micro-fluidic channels, namely a micro-fluidic channel I and a micro-fluidic channel II; the distance between the parallel micro-fluidic channels is 50 to 2000 [mu] m; at least one semispherical concave structure is arranged at the bottom of the microfluidic channel, and the semispherical concave structure is used for directly fixing the organoid or embedding the organoid by hydrogel; a gap structure is arranged between the hemispherical concave structures on the microfluidic channel I and the microfluidic channel II, and allows organoid in the microfluidic channel I and the microfluidic channel II to be in direct contact and secreted cell factors to be diffused. The microfluidic chip solves the problems of controllable contact, independent nutrition supply and dynamic microenvironment simulation of heterologous organs in a three-dimensional space, and provides a precise technical platform for drug interaction research, tumor-matrix interaction analysis, organ development model construction and the like.