36 results about "Tumor-Associated Fibroblasts" patented technology

Disclosed are a novel therapeutic agent and a novel treatment method for cancer. Specifically disclosed are: a targeting agent for a cell selected from the group consisting of a cancer cell and a cancer-associated fibroblast, which comprises a retinoid; a substance delivery carrier for the cell, which comprises the targeting agent; an anti-cancer composition utilizing the targeting agent or the carrier; an anti cancer-associated fibroblast composition; and a method for treatment of cancer.

The invention belongs to the field of pharmaceutic preparation, and relates to a targeted drug-carrying liposome of a tumor associated fibroblast. The surface of the targeted drug-carrying liposome is modified with a high-affinity ligand of a specific expression protein of the tumor associated fibroblast. The targeted drug-carrying liposome is capable of realizing targeted delivering of drugs into the tumor associated fibroblast, realizing intervention on tumor microenvironment via action on the tumor associated fibroblast, and realizing tumor treatment. And in addition, the tumor associated fibroblast targeted preparation can be combined with routine tumor cell targeted nano preparations so as to improve antitumous effects of the routine tumor cell targeted nano preparations.

Disclosed are a novel therapeutic agent and a novel treatment method for cancer. Specifically disclosed are: a targeting agent for a cell selected from the group consisting of a cancer cell and a cancer-associated fibroblast, which comprises a retinoid and / or derivative thereof; a substance delivery carrier for the cell, which comprises the targeting agent; an anti-cancer composition utilizing the targeting agent or the carrier; an anticancer-associated fibroblast composition; and a method for treatment of cancer.

The invention relates to a culture method of breast cancer organoids and a co-culture method of tumor-related fibroblasts. According to the invention, a more efficient and convenient improved system for key technical links such as PDO culture, passage, maintenance and the like of tumor tissue organoids of breast cancer patients is established, operation steps and methods for establishing and passage of a PDO cell line are simplified in multiple aspects, components of a culture medium, digestive juice, a washing solution and the like are optimized, and finally, a breast cancer PDO culture system is successfully established. Compared with the prior art, the culture method has the advantages that the success rate and the passage frequency are basically consistent, but the operation is simpler, the required time is shorter, a good foundation is laid for a PDO model to have better clinical and scientific research applications in the future, and the corresponding cost is saved. The inventionalso establishes a stable co-culture system of breast cancer PDO and tumor-associated fibroblasts (CAFs), simultaneous culture, amplification and passage of PDO and CAFs can be realized, and the PDOand the CAFs do not produce obvious influence on each other.

The invention belongs to the field of biomedicine, and relates to a 3D co-culture model based on a tumor cell and a tumor-associated fibroblast. The tumor cell is labeled with a green fluorescent protein, the tumor-associated fibroblast is labeled with a red fluorescent protein, and the two cells and a prepared methylcellulose gel medium are used to construct the 3D co-culture model. The 3D modelprepared in the invention simulates the anaerobic environment of in-vivo tumors, and the tumor cell and the tumor-associated fibroblast are co-cultured to construct the mutual promotion effect of thetwo cells in the in-vivo tumor microenvironment. The 3D co-culture model formed by the tumor cell and the tumor-associated fibroblast simulates the anaerobic environment of the in-vivo tumor, providesa similar effect to the in-vivo tumor microenvironment, and has application prospects in basic researches and clinical drugs.

Compositions of matter, of production, and treatment modalities are disclosed for the prevention and / or therapeutic reduction of tumors through induction of immunity against tumor associated fibroblasts and components of tumor microenvironment. In one embodiment of the invention, placentally derived fibroblast cells are cultured under conditions replicating tumor microenvironment. Expression of CD248 on said cultured fibroblasts is used as a marker of effective manipulation. Cells expressing CD248 are utilized a immunogens for stimulation of immunity towards cancer associated fibroblastic cells.

The invention discloses a culture method of human colorectal cancer tissue organoid, which comprises the following steps: washing human colorectal cancer tissues and putting them into a transfer culture medium, cleaning and shearing; further cleaning, centrifuging, carrying out enzyme digestion, filtering, and collecting cell clusters; and mixing the cell clusters with hydrogel, adding DMEM culture medium to culture after solidification to obtain the human colorectal cancer tissue organoids. According to the invention, gentamicin, amphotericin B, primocin and other antibiotics are added into the transfer culture medium, the digestion solution and the culture medium, so that microbial contamination can be reduced, and the method for obtaining the human colorectal cancer organoids through in-vitro culture is simple, convenient, rapid, high in success rate and good in organoid growth state. The invention further discloses application of the human colorectal cancer organoid in drug testing, and the co-culture model of human colorectal cancer tissue organoids and tumor-associated fibroblasts can be used as a patient individualized drug testing platform.

The invention discloses a rapid extraction method of fibroblast. The method comprises the following steps that 1, isolated tumor tissue is taken and cut into pieces, and a collagenase solution is added for digestion; 2, the mixture is transferred into a centrifugal tube for oscillation, incubation and centrifuging, and sediments are taken to be placed into a cell incubator for culture; 3, the collagenase solution is added for digestion, and the step 2 is executed again to obtain tumor tissue of the loose organization structure obtained after alternate digestion and culture; 4, a pancreatin solution is added, fetal cattle serum is added after normal temperature standing for terminating digestion, suspended solids are poured away, and attaching-wall tumor single cells obtained after trypsin digestion are obtained; 5, a DMEM complete medium is added for subculture, tumor-associated fibroblast is obtained. The invention further provides application of the extraction method. The fibroblast obtained through the extraction method is high in purity, the fibroblast highly expresses FAP, the expression rate is 99.2%, and the method is suitable for medicine popularization.

The invention provides an adriamycin-carrying lipid nanoscale ultrasound contrast agent targeting tumor-related fibroblasts and a preparation method of the adriamycin-carrying lipid nanoscale ultrasound contrast agent. The surface of the contrast agent is modified by a high affinity ligand (FH short peptide) for specifically expressing a TNC protein by the tumor-related fibroblasts, the FH short peptide is used as a targeting ligand, lipid is used as a shell membrane material, and adriamycin and gaseous fluorocarbon are wrapped inside the shell membrane. The targeted ultrasound contrast agentis in nanoscale, has ultrasound imaging capability, can be used for targeted delivery of drugs into the tumor-related fibroblasts, and specifically kills the tumor-related fibroblasts, and a tumor treatment effect is achieved through intervention on a tumor microenvironment.

The invention relates to the technical field of medicines, in particular to a drug carrier with a tumor cell and tumor-related fibroblast dual-targeting function, a preparation method and application. The drug carrier with the tumor cell and tumor-associated fibroblast dual-targeting function contains hyaluronic acid and Z-glycine-proline which are connected through an acyl group, the hyaluronic acid can target a CD44 receptor on the surface of a tumor cell, and when the drug carrier is loaded with an anti-tumor component, the rapid migration of the anti-tumor component to the tumor center can be promoted; the dipeptide Z-glycine-proline can target FAPalpha receptors on the surfaces of tumor-associated fibroblasts, so that after tumor tissue fibrosis, when tumor cells are hindered by fibroblasts, the drug carrier can still accurately target the tumor center.

The invention discloses novel substituted zinc phthalocyanine and their conjugates with doxorubicin, discloses their preparation methods and applications, and belongs to the field of preparation of photosensitizers and drugs. The compound is a novel high-efficiency photosensitizing drug. The zinc phthalocyanine-doxorubicin conjugate is an anticancer drug with the dual effects of photodynamic therapy and chemotherapy. The zinc phthalocyanine-doxorubicin conjugate is linked through a substrate peptide which can be specifically recognized and hydrolyzed by a tumor-associated fibroblast activationprotein, and can be used as an enzyme-targeting activated anticancer prodrug.

The invention discloses application of p53 gene mutation in cancer-associated fibroblasts, and particularly relates to application of p53 gene mutation in the cancer-associated fibroblasts in screening and preparation of cancer therapy medicines. An experimental result shows that the growth of cancer can be promoted by mouse embryonic fibroblasts (MEF) carrying p53N236S mutation, thus it is suggested that p53 mutation activates the cancer-associated fibroblast characteristic of the MEF, and the favorable microenvironment is provided for multiplication, migration and the like of the cancer. Thenew function of p53 mutation in the cancer-associated fibroblasts is disclosed for the first time, through the discovery, the new idea and research direction are provided for p53 mutation in cancer research, a new action target is provided for cancer therapy, and a new strategy is also provided for cancer therapy.

Provided are: a targeting molecule targeting a target cell which is selected from the group consisting of a stellate cell, a myofibroblast, a cancer-associated fibroblast, a tumor cell and a cell expressing STRA6, said targeting molecule being selected from the group consisting of (1) a peptide containing an amino acid sequence in the cell-binding region of RBP, (2) a variant peptide of the aforesaid peptide (1), said variant peptide having a comparable targetability to peptide (1), and (3) a peptide mimetic having a comparable targetability to peptide (1) or peptide (2); a targeting agent, a carrier, a complex and a medicinal composition each comprising the targeting molecule; a method for treating, examining, diagnosing or monitoring a disease related to the aforesaid target cell; a method for labeling, detecting or imaging the target cell, etc.

The invention provides a pharmaceutical composition for mild photothermal therapy of tumors as well as a preparation method and application of the pharmaceutical composition. The pharmaceutical composition is composed of a dual-targeting amphiphilic glucan derivative carrier, a material (PTA) with photo-thermal conversion performance and an autophagy inhibitor. The dual-targeting amphiphilic glucan derivative carrier can be self-assembled in water to form nano-micelles, and is physically loaded with PTA and an autophagy inhibitor for tumor photothermal therapy. The preparation is mainly characterized in that: 1) the preparation has active dual-targeting capability of tumor cells and tumor-related fibroblasts, and can efficiently enter the cells through the action of receptor ligands, so that the transfer efficiency of the preparation is improved; 2) under the irradiation of 808nm laser, PTA absorbs light energy and efficiently converts the light energy into heat, and the autophagy inhibitor inhibits the autophagy behavior of tumor cells and sensibilizes photo-thermal, so that an excellent mild photo-thermal treatment effect is realized, and the physical barrier of a tumor matrix can be weakened; tumor photothermal can further induce tumor cells to generate immunogenic cell death, generated tumor fragments can further activate an immune system, and the tumor photothermal treatment effect is greatly improved.

The invention provides an amphiphilic dextran derivative carrier for targeting tumor-associated fibroblasts and preparation and application of a pharmaceutical composition of the amphiphilic dextran derivative carrier. The amphiphilic dextran derivative carrier comprises a derivative skeleton modified by hydrophilic dextran carboxyl, an FAP-alpha responsive peptide fragment connecting arm and a hydrophobic group molecule. The amphiphilic derivative is self-assembled in an aqueous solution to form nanoparticles, and molecules with pharmacological activity can be physically loaded for tumor treatment. The amphiphilic dextran derivative carrier is mainly characterized in that: (1) after the nanoparticles reach a focus part, a specific peptide fragment connecting arm can be subjected to enzyme digestion by FAP-alpha which is specifically and highly expressed on the surface of tumor-associated fibroblasts, so that the nanoparticles are rapidly degraded; and (2) the pharmacological active molecules which are physically loaded are quickly released from the disintegrated nanoparticles, tumor-associated fibroblasts can be effectively killed or the function thereof can be inhibited, the physical barrier of a tumor matrix can be weakened, and the permeation of an anti-tumor preparation can be promoted when the nano-particles are combined with other anti-tumor preparations, so that the treatment effect of the anti-tumor preparation can be effectively improved.

The invention provides an application of an miR-10a-mediated tumor-associated fibroblast to a product with at least one of the following functions (1) to (6): (1) inhibiting tumor cell proliferation,(2) promoting tumor cell apoptosis, (3) inhibiting tumor cell migration, (4) inhibiting tumor cell invasion, (5) inhibiting tumor cell sphere formation, and (6) preventing and / or treating a tumor, wherein the tumor is a colorectal cancer; a tumor cell is a colorectal cancer cell; and a nucleotide sequence of miR-10a is as shown in SEQ ID NO:1. According to the application, the effect of the overexpressed miR-10a on liver fibroblast activity in vitro is known and understood from a new perspective, and the effect of a change of the liver fibroblast activity on formation of metastasis in liver bythe colorectal cancer cell is thoroughly discussed, so as to provide a molecular mechanism of hepatic metastasis in the colorectal cancer with an epigenetic basis and to provide a new idea and targetfor prevention and treatment of the colorectal cancer.

The invention belongs to the field of pharmaceutical preparations, relates to a novel medicine delivery system, and particularly relates to a medicine delivery system for regulating tumor microenvironment and active targeting and use thereof. The medicine delivery system adopts an FDA-approved biodegradable polymer polylactic acid material; a natural drug monomer alpha-mangostin (alpha-M) is physically occluded by an emulsion solvent evaporation method to prepare a medicine-loaded nano-delivery system (alpha-M NP); functional polypeptides are further modified on a surface of the alpha-M NP bycovalent binding; tumor-associated fibroblasts abnormally activated in the tumor microenvironment can be actively targeted so as to prepare a nano medicine delivery system with functions of active targeting and regulating the tumor microenvironment. In-vitro and in-vivo experiments show that the delivery system can inhibit excessive activation of the tumor-associated fibroblasts, effectively improves the tumor microenvironment, increases accumulation of medicines in tumor locations, and has greater clinical application prospects.

The invention relates to composition and a method of using the composition for modulating proliferation, invasiveness, the expression of a biomarker of an abnormal cell, of reducing the risk of a patient cell becoming abnormal, or of modulating proliferation of a carcinoma-associated fibroblast or of a tumor-associated macrophage. The invention also relates to a method of culturing the composition to produce molecules that modulate abnormal cell proliferation, invasiveness, or metastasis. The composition comprises a biocompatible matrix and cells engrafted thereon.

The invention belongs to the field of genetic engineering, and particularly relates to application of a novel miRNA (micro-ribonucleic acid) composition to preparing non-small cell lung cancer resisting medicines. Transformation of lung tumor-associated fibroblasts of non-small cell lung cancer to normal fibroblasts can be promoted by means of changing expression level of the miRNA composition; the novel miRNA composition includes miR-1, miR-206 and miR-31. The application has the advantages that the miR-1 / miR-206 are simultaneously over expressed in the lung tumor-associated fibroblasts of the non-small cell lung cancer, the miR-31 is expressed at low level in the lung tumor-associated fibroblasts of the non-small cell lung cancer, accordingly, transformation of the lung tumor-associated fibroblasts to the normal fibroblasts can be promoted, anti-tumor effects can be realized at cell and animal level, and the miRNA composition has potential anti-tumor application value.

The invention discloses medicinal use of NRK in lung cancer therapy and prognosis. The invention particularly discloses application of the NRK in preparation of products for diagnosing prognosis of alung cancer and application of the NRK in preparation of drugs for treating the lung cancer; and the invention relates to application of an NRK neutralizing antibody in preparation of products for diagnosing the lung cancer and application of the NRK neutralizing antibody in preparation of drugs for treating the lung cancer. According to the medicinal use, CAFs and NFs derived from tissue of LUADI, II and III are analyzed by using RNA-seq and a comprehensive bioinformatics method, it is discovered that the NRK is specifically expressed in lung-cancer-tumor-related fibroblasts, can serve as aclinical diagnosis biomarker of the lung cancer and can provide a better diagnosis prognosis index; and the NRK in LUAD-related CAFs is increased remarkably, so that the NRK can serve as a target point of combined treatment on LUAD.

The invention belongs to the technical field of drug targeting carriers, and discloses a co-drug-loading cell microparticle preparation and a preparation method thereof, the co-drug-loading cell microparticle preparation comprises microparticles secreted from tumor cells, and a photosensitizer and a tumor-associated fibroblast deactivator together entrapped in the microparticles. The detailed composition and the structure of the preparation are improved, microparticles secreted from tumor cells are taken as carriers, and the photosensitizer and the tumor-related fibroblast deactivator are simultaneously entrapped in the carriers, so that the obtained co-drug-loading cell microparticle preparation has the advantages that on one hand, the tumor matrix microenvironment is transformed, the enrichment of the photosensitizer in tumors is enhanced, and the tumor-related fibroblast deactivator can be effectively inhibited; on the one hand, the direct killing effect of photothermal therapy on tumor cells can be improved, on the other hand, tumor immunogenic death caused by photothermal therapy can be enhanced, CD8 + T cell infiltration can be promoted, CD8 + T cell death induced by antigen-dependent activation caused by tumor-related fibroblasts can be reduced, and the tumor immune microenvironment can be improved.

The invention discloses a co-loaded liposome based on simultaneous killing of tumor cells and CAFs and a preparation method thereof and belongs to the technical field of liposome medicaments. The co-loaded liposome is a liposome co-loaded with a micromolecular toxic drug and a macromolecular antibody drug and comprises the following components: phospholipid, cholesterol, the micromolecular toxic drug and the macromolecular antibody drug, and the phospholipid is composed of an anionic lipid and a cationic lipid. The mass ratio of the micromolecular toxic drug to the phospholipid is (1: 5)-(1: 100), the molar ratio of the cationic lipid to the phospholipid is (0.05: 1)-(0.5: 1), the mass ratio of the anionic lipid to the cholesterol is 19: 5, and the mass ratio of the macromolecular antibody drug to the cationic lipid is (1: 45)-(1: 900). According to the co-loaded liposome and the preparation method thereof, specific adsorption and responsive shedding of the macromolecular antibody drug can be achieved, the tumor cells and tumor-related fibroblasts (CAFs) can be killed at the same time, and the treatment effect on colorectal cancer is improved.

The invention belongs to the field of tumor biology, and relates to human tumor-associated fibroblast cell lines and an application thereof. The human tumor-related fibroblast cell lines have the following biological characteristics: long fusiform or astral shape, rich cytoplasm and eosinophilic property, cell nucleus positioned in the center of the cell body in circular or oblong shape, radial or beam arrangement of cells , part of the cells disordered in arrangement, polarity disappearance, obvious crossing and overlapping phenomena, and stable passage in ten generations. The proteins of alpha-SMA, FAP, E-cadherin and Vimentin expressed by the cells are positive. The human tumor-associated fibroblast cell lines have the advantages of achieving long-term in-vitro culture while keeping cell characteristics unchanged. The human tumor-associated fibroblast cell lines are a powerful tool for related researches of tumor-related fibroblast cells, and a powerful tool for researching generation and development of tumor-related fibroblast mediated tumors and related molecular action mechanisms, developing drug targets for treating tumors, novel tumor biological treatment technologies and detecting related bioengineering product researches.

The invention discloses preparation and application of a targeted hypersensitive broad-spectrum oncolytic virus. The targeted hypersensitive broad-spectrum oncolytic virus is a recombinant virus containing a recombinant Newcastle disease virus, a hypersensitive gene alpha-1, 3GT, a heparanase gene HPSE for dissolving an extracellular matrix, and a FAP scFv gene (NDV-GT-HPSE-FAP scFv, called NDV-GHF for short) plasmid for targeting tumor-associated fibroblasts; and the recombinant virus is obtained by co-transfecting a BSR cell with a recombinant Newcastle disease virus NDV-GHF plasmid and a helper plasmid and rescuing. The recombinant Newcastle disease virus NDV-GHF plasmid is a recombinant Newcastle disease virus NDV-GHF plasmid obtained by recombining NDV with alpha-1, 3GT, HPSE and FAP scFv genes; the sequence of the HPSE gene is as shown in SEQ ID NO: 1; the sequence of the FAP scFv gene is as shown in SEQ ID NO: 2; and the sequence of the alpha-1, 3GT gene is as shown in SEQ ID NO: 3. The invention also discloses a preparation method of the recombinant virus and an application of the recombinant virus in melting a tumor physical barrier.

The invention belongs to the technical field of biomedicine, and particularly discloses a nucleic acid aptamer for targeting tumor-associated fibroblasts and application of the nucleic acid aptamer. The sequence of the nucleic acid aptamer is 5 '-AGCGTGGAGGATAATTAGGCATCGTTCCGCCTAGGAAATTATTCAATCTACGC-3', and the sequence of the nucleic acid aptamer is shown in the description. The nucleic acid aptamer has high specificity and high affinity to tumor-associated fibroblasts, can be used as a molecular probe for imaging of tumor-associated fibroblasts, can be used as a drug carrier to participate in targeted transportation and fixed-point release of drugs in a targeted drug delivery system, and can be used for imaging of tumor-associated fibroblasts, tumor-associated fibroblasts, tumor-associated fibroblasts, tumor-associated fibroblasts, tumor-associated fibroblasts, tumor-associated fibroblasts and tumor-associated fibroblasts. The method can be used for identification and functional research of tumor-associated fibroblast specific target molecules. The nucleic acid aptamer can keep good activity at the temperature of 4 DEG C and 37 DEG C, and has the advantages of being easy and convenient to operate, low in cost, short in period, high in accuracy and the like in research and detection of tumor-related fibroblasts.

The invention belongs to the technical field of medicine preparation, and particularly relates to a traditional Chinese medicine decoction for treating tumors and an application thereof. In the application of the present invention, acronychia pedunculata and the components contained in a compounded medical and edible plant can improve the overall immunity, can change the tumor microenvironment (TEM), and activates a part of the subgroups in tumor-associated fibroblasts (CAF) which inhibit tumors, and the decoction synergistically play a role in inhibiting tumors and preventing recurrence and metastasis. The clinical data confirms that the composition can effectively inhibit tumors, improves clinical symptoms, and prevents co-morbidity and complications.