160 results about "Primary tumor" patented technology

The invention belongs to the cross technical field of nanomedicine, tumor treatment and immunotherapy, and particularly provides tumor mitochondria-targeted copper death selective induction nanoparticles, which are prepared by the following preparation method: S1, specifically coupling TPY and MHI through condensation reaction to obtain MTPY; s2, MTPY and copper ions are subjected to complexation, and an MTPY-Cu complex is obtained; and S3, the MTPY-Cu complex and albumin are subjected to self-assembly, and the MTPY-Cu-coated Alb nanoparticles are formed. The dosage of copper is only 1 / 1000 of that of free Cu < 2 + >, and equivalent immune regulation and killing effects can be achieved; primary tumors and distant tumor focuses can be inhibited, and lung metastasis is reduced; immune memory can be induced, and relapse can be prevented; the traditional Chinese medicine composition is combined with cis-platinum to remarkably enhance the curative effect and reverse the induced immunosuppression; the invention has the advantages of high biological safety and no obvious liver and kidney toxicity or hemolytic reaction.

The invention discloses application of MUC12 gene in preparation of drugs for reducing rectal cancer liver metastasis, and belongs to the technical field of medical biology. According to the invention, the clear relation between colorectal cancer liver metastasis and fructose metabolism reprogramming is revealed from a molecular mechanism for the first time. The invention provides a brand-new therapeutic target and strategy by determining the brand-new transfer promoting factor MUC12 and the mediated fructose metabolism regulation effect thereof. Different from the traditional therapy only aiming at the strategies of tumor cell proliferation, blood supply and the like, the method disclosed by the invention intervenes aiming at a tumor nutrition metabolic pathway, and can weaken the metabolic adaptation and proliferation capacity of metastatic tumor cells in the liver more specifically. Experimental results show that the functions of targeted inhibition of MUC12 or downstream fructose metabolism key enzymes KHK and ALDOB thereof can significantly reduce the invasion and metastasis ability of tumor cells, and at the same time, normal growth of primary tumors cannot be significantly affected.

The invention belongs to the technical field of biological detection, and particularly relates to a prediction model for predicting prognosis after neoadjuvant immunotherapy of non-small cell lung cancer (NSCLC) through primary tumor (PT) and a construction method of the prediction model. According to the invention, a plurality of spatial high-throughput sequencing bioinformatics technologies are utilized to analyze a key immune cell subset, an immune microenvironment topological feature structure and a three-level lymphosome-related functional cell subset of a primary focus after neoadjuvant immunotherapy; the prediction model for predicting prognosis after neoadjuvant immunotherapy aiming at the NSCLC through the primary focus and the construction method of the prediction model are more in line with post-treatment immune microenvironment spatial histological characteristic changes, and compared with a previous transcriptome sequencing method without spatial information, the prediction model has the advantages that the prediction model is more efficient and more efficient; the change of a space tumor immune microenvironment after immunotherapy is more accurately represented, and the prognosis after NSCLC neoadjuvant immunotherapy can be more accurately predicted through cell targets really influencing the immune curative effect.

The invention relates to the related technical field of primary cell (PDC) culture, in particular to a method for culturing primary cells (PDC) from glioma patients, which comprises a series of steps of Swis3T3-J2 cell culture, conditioned medium preparation, brain tumor tissue pretreatment, primary tumor cell digestion and culture and the like. Primary human tumor cells are cultured by a conditioned culture medium generated by fibroblasts irradiated by X-rays (X) and a cobalt-60 radioactive source (60Co), and culture conditions of key features of parent tumors and a modeling process can be most effectively reserved by screening and optimizing the culture conditions. And whether the PDC retains the key characteristics of the parent tumor or not is inspected on the aspects of the cell molecular level, the cell phenotype, the animal intracranial tumor model and the like.

The invention discloses a mouse-derived gastric adenocarcinoma cell line MKC1 and application thereof. The mouse gastric adenocarcinoma cell line MKC1 (Mus musculus) is preserved in the China Center for Type Culture Collection, the preservation date is June 15, 2024, and the preservation number is CCTCC (China Center for Type Culture Collection) NO: C2024183. The cell line belongs to a murine gastric adenocarcinoma cell line, can be stably passaged, is high in growth speed, and can form primary tumors in a C57BL / 6 mouse body with a sound immune system. In addition, the cell line has the advantages of being high in repeatability, stable and single in property and the like, and is suitable for related research of gastric cancer immune microenvironment, tumor drug resistance, invasion and metastasis and the like.

The invention relates to the field of immunotherapy, more in particular to a composition for use in the treatment of cancer. The invention also relates to a composition obtainable by such a method, such as a pharmaceutical composition. More in particular, the invention relates to an ex vivo method for obtaining a composition suitable for the treatment of cancer in a subject, comprising the steps of providing primary tumor cells derived from the subject, and ex vivo contacting the tumor cells with an inhibitor of a bromodomain and extra-terminal domain family member (BET inhibitor).

The invention relates to the technical field of medicines, in particular to a composite nano vaccine and application thereof. The composite nano vaccine is prepared by coupling a natural compound with endoplasmic reticulum stress induction capability on the surface of Ga-MOF nano particles. The composite nano vaccine can significantly enhance the anti-tumor effect through a ferroptosis mechanism, an endoplasmic reticulum stress and immunogenic cell death mechanism and a cryoablation technology synergistic effect mechanism, reverses an immunosuppressed tumor microenvironment, inhibits the growth of primary tumors and distant metastatic tumors, and has a good anti-tumor effect. A brand new strategy is provided for comprehensive treatment of tumors, and the application prospect is wide.

The present invention discloses a pH / GSH program-responsive photothermal nanocomposite hydrogel co-drug-carrying system and a preparation method and application thereof, and belongs to the field of anti-tumor materials. The nanocomposite hydrogel co-drug-carrying system of the present invention is a pH-sensitive chitosan hydrogel co-carrying GSH stimulus-responsive drug-carrying nanoparticles encapsulated by hyaluronic acid and indocyanine green. The drug-carrying nanoparticles encapsulate tyrosine kinase inhibitors, and the chitosan hydrogel is obtained by cross-linking chitosan with polyethylene glycol-4-formylbenzoic acid. The nanocomposite hydrogel is easy to administer in situ, and the photothermal conversion of indocyanine green under near-infrared light irradiation is used to accurately thermally ablate the primary tumor; at the same time, the drug-carrying nanoparticles escape from the gel, respond to the release of the loaded tyrosine kinase inhibitor by GSH in the tumor cells, and inhibit tumor recurrence and metastasis. The nanocomposite hydrogel can achieve chemotherapy-photothermal synergistic therapy, enhance the therapeutic effect on tumors and reduce toxic side effects.

Methods are provided for enhancing immune responses comprising providing an immunogenic composition comprising a cocktail of an intracellular agonist, an immunosuppressive antagonist, and a cytostatic / damage-inducing agent. Further provided herein are methods for treating primary tumors and preventing metastasis.

The present invention relates to the field of radiopharmaceutical chemistry, and more particularly to a radioactive probe that targets fibroblast activation protein (FAP), a preparation method, and applications thereof. The structural formula of the compound targeting FAP provided by the present invention is: #imgabs0#. This compound possesses excellent radionuclide labeling properties. The resulting radioactive probe, a FAP inhibitor, can simultaneously target tumor-associated fibroblast activation protein (FAP) and bone metabolism-related targets, thereby improving diagnostic accuracy and specificity, increasing retention time and effectiveness, and enhancing treatment outcomes. This allows for more comprehensive diagnosis and evaluation of tumors and bone metastases, and is particularly suitable for patients with both primary tumors and bone metastases.

The invention belongs to the cross technical field of veterinary medicine and biomedicine, and relates to a construction and evaluation method of a dog spontaneous breast cancer organoid model, which specifically comprises the following steps: (1) obtaining dog spontaneous breast cancer tissues through operation or biopsy, separating tumor tissues under sterile conditions, and carrying out fine enzymolysis digestion treatment to obtain dog spontaneous breast cancer tissues; obtaining a single-cell suspension; and (2) inoculating the single-cell suspension into a three-dimensional culture system, carrying out three-dimensional culture by adopting a culture medium containing EGF, FGF and B27 in combination with a growth factor, promoting the growth and amplification of the breast cancer organs, and carrying out timely passage according to the growth condition so as to maintain the activity of the model. The model constructed by the invention completely retains genetic heterogeneity and pathological microenvironment of primary tumors, does not need gene editing, is simple and convenient to operate and low in cost, is particularly suitable for individual drug sensitivity detection of pet dogs, and provides an efficient and high-simulation experimental platform for dog breast cancer mechanism research and clinical precise medication.

The application belongs to the technical field of nanomedicine, tumor treatment and immunotherapy, and specifically provides a copper death selective induction nanoparticle targeting tumor mitochondria, which is prepared by the following preparation method: S1, TPY is specifically coupled with MHI through a condensation reaction to obtain MTPY; S2, MTPY is complexed with copper ions to obtain an MTPY-Cu complex; and S3, the MTPY-Cu complex is self-assembled with albumin to form an MTPY-Cu@Alb nanoparticle. The copper dose of the application is only 1 / 1000 of that of free Cu 2+ , and the equivalent immune regulation and killing effects can be achieved; the primary tumor and distant tumor foci can be inhibited, and lung metastasis can be reduced; and the application can induce immune memory and prevent recurrence; the application is combined with cisplatin to significantly enhance the therapeutic effect and reverse the induced immunosuppression; and the application has high biological safety, and has no obvious hepatorenal toxicity or hemolytic reaction.

The application discloses a kind of nanoparticles for tumor sonodynamic combined individualized immunotherapy and its preparation method and application, belong to the field of biological medicine.The nanoparticles for tumor sonodynamic combined individualized immunotherapy are double-shell core structure nanoparticles formed by inner core and shell, and the inner core is formed by self-assembly of TLR3 agonist Poly (I:C), L-arginine and polylysine, and the shell is hyaluronic acid layer HA-Ce6 conjugated with photosensitizer Ce6.It is found through experiment verification that the nanoparticles can target tumor, generate reactive oxygen species to kill tumor cells under the action of ultrasound, promote M1 macrophage polarization and produce NO release at the same time, play the role of antitumor and immune effect, and realize the combined application of sonodynamic and NO gas therapy.The nanoparticles for tumor sonodynamic combined individualized immunotherapy can trigger systemic immune response, inhibit primary tumor, produce immune memory effect, and prevent tumor metastasis and recurrence.

An embodiment of the present invention relates to: a cancer antigen peptide nanostructure comprising an assembly of cancer antigen peptides conjugated with deoxycholic acid; a method for preparing same; and use thereof. The inventors of the present invention confirmed that the nanostructure of the present invention effectively stimulates the maturation of dendritic cells, migrates to lymph nodes, and activates T cells. Also, in a cancer cell model, significant infiltration of cytotoxic T lymphocytes into primary tumors was observed, and an anti-metastatic effect was confirmed. Therefore, the nanostructure according to the present invention can be effectively used as a promising immunotherapy platform that can be applied to various intractable cancers.

The present invention relates to the provision of vaccines which are specific for a patient's tumor and are potentially useful for immunotherapy of the primary tumor as well as tumor metastases. In one aspect, the present invention relates to a method for providing an individualized cancer vaccine comprising the steps: (a) identifying cancer specific somatic mutations in a tumor specimen of a cancer patient to provide a cancer mutation signature of the patient; and (b) providing a vaccine featuring the cancer mutation signature obtained in step (a). In a further aspect, the present invention relates to vaccines which are obtainable by said method.

The invention discloses preparation and application of a PD-L1 nano-inhibitor capable of enhancing the immunotherapy effect of cervical cancer, and belongs to the field of nano-drugs. According to the invention, PDA-coated double-high-Z metal nanoparticles, GdPt-coated PDA for short, are synthesized by using a solvothermal method and a solution oxidation method. Compared with the prior art, the GdPt-coated PDA has an excellent immunotherapy effect and good biological safety. The GdPt (at) PDA not only can realize immunotherapy by down-regulating the expression level of PD-L1, but also can improve the tumor immunosuppression microenvironment and promote immune cell infiltration in tumors through combined radiotherapy, and cooperates with alphaCTLA-4 to realize dual-immune checkpoint blocking therapy, thereby successfully inhibiting the growth of primary tumors and distant tumors.

The application discloses a novel AIE photosensitizer and a preparation method and application thereof. The AIE photosensitizer of the application comprises TDQ shown in the following structural formula, has superior photo-thermal conversion performance and photodynamic performance, and can be used for preparing a tumor diagnosis reagent or a tumor treatment drug. The co-loading liposome of TDQ and a senescence-inducing molecule (Ali) can be used as a multi-modal light diagnosis and treatment agent to realize efficient delivery of drugs to tumor tissues, and the photo-thermal therapy and the photodynamic therapy based on TDQ not only induce cell apoptosis through oxidative stress and mitochondrial dysfunction, but also trigger cancer cell senescence and promote the secretion of SASPs, so that the anti-tumor immunity is significantly enhanced, and finally the growth of primary tumors, tumor recurrence and re-metastasis are inhibited. The material of the application has simple preparation process, low cost, and is suitable for scale production and clinical medical use.

This invention discloses a T-cell training method based on tumor organ-on-a-chip. The method includes: preparing an organ-on-a-chip with a micropillar array and a biomimetic fishbone structure; introducing primary tumor cells from a patient into the chip, causing them to spontaneously form uniform three-dimensional tumor spheroids; dynamically pumping pre-activated peripheral blood lymphocytes from the same patient into the chip and co-culturing them with the tumor spheroids; collecting the co-cultured lymphocytes and repeating the co-culture process multiple times to obtain a lymphocyte population with enhanced anti-tumor activity. This invention utilizes organ-on-a-chip technology to highly simulate the dynamic tumor immune microenvironment in vivo. Through multiple cycles of "training," it effectively activates and expands tumor-specific T cells, avoiding immune exhaustion, and providing a highly efficient and controllable new platform for personalized immunotherapy of solid tumors.

To provide vaccines which are specific to a patient's tumor and are potentially useful for immunotherapy of a primary tumor and tumor metastasis.SOLUTION: In one aspect, the present invention relates to a method for producing individualized vaccines for cancer, comprising (a) identifying cancer specific somatic mutation in a tumor sample of a cancer patient to provide a patient's cancer mutation signature, and (b) providing a vaccine characterized by the cancer mutation signature obtained in step (a). In a further aspect, the invention relates to a vaccine that can be obtained by the method.SELECTED DRAWING: None

Disclosed is a method for determining the expression of PD-L1 that is based on a RT-qPCR in a RNA sample of, for example, Circulating Tumor Cells (CTC) or fresh frozen primary tumor tissues. In particular, a method is disclosed for the detection of PD-L1 mRNA positive CTCs or primary tumor tissues (fresh frozen) based on the quantitative determination of the molecular marker (PD-L1) in biological samples of patients suffering from cancer. In use, detection can take place before, during or after immune therapy or any other treatment in order to provide significant information concerning the guiding or the monitoring of the anti-PD-L1 agents effectiveness. This RT-qPCR assay could comprise a promising companion diagnostic test in order to evaluate the PD-L1 expressional status on CTC or tumor tissue, providing clinical applications, which could have an important impact on therapeutic interventions since the expression of PD-L1 is associated with response to immunotherapy.

As cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we assessed the cerebrospinal fluid (CSF) that bathes the CNS for tumor DNA, here termed CSF-tDNA. The results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

The invention provides a conformation-locked amphibian skin peptide derivative or a pharmaceutically acceptable salt thereof. The conformation-locked amphibian skin peptide derivative or the pharmaceutically acceptable salt thereof has a structural formula shown in the specification or a structural analogue thereof, x is derived from one amino acid in TLa, the sequence of the TLa is LLRHVVKILEKYL, and (X) 3 is composed of any continuous sequences in three TLa. The invention also provides a preparation method of the tumor microenvironment response type TLa derivative-STING agonist MSA-2 conjugate and an application of the tumor microenvironment response type TLa derivative-STING agonist MSA-2 conjugate in tumor immunotherapy. In-vivo experiments show that the conjugate can effectively inhibit primary tumor growth and distal pulmonary metastasis in a melanoma model, and tumors of part of mice can completely fade away. The conjugate disclosed by the invention is expected to be developed into a novel efficient and low-toxicity tumor immunotherapy drug.

The invention discloses a bionic hybrid nano regulator for enhancing cell copper death and a preparation method and application thereof, and belongs to the technical field of biomedical materials. The invention designs a bionic nano-platform which simultaneously loads a lactic acid regulator cyclostilbene Su 3118 and a copper ion carrier disulfiram DSF, and the bionic nano-platform is combined with hybrid macrophages and tumor cell membranes to construct a nano-regulator SCTDM. The nano regulator can exert multiple functions, including tumor targeting, in-situ photothermal therapy, lactic acid regulation and enhanced copper death. The nano regulator provided by the invention is simple and convenient to manufacture, is combined with in-situ photothermal therapy and lactic acid regulation and is used for enhancing cell death immunotherapy of copper death so as to eliminate primary tumors and delay relapse, and a technical support is provided for regulating immunity by enhancing copper-induced cell death through metabolic reprogramming.

Provided herein are methods for enhancing an immune response comprising providing an immunogenic composition comprising a mixture of an intracellular agonist, an immunosuppressive antagonist, and a cell inhibitor / damage inducer. Further provided herein are methods of treating a primary tumor and preventing metastasis.

The preparation method comprises the following steps: firstly, screening out No.3 polypeptide with the most obvious tumor cell migration promoting effect from supernatant proteins of cancer-related fibroblast (CAF) cells of primary tumor lesions and metastatic tumor lesions of an ovarian cancer patient, and naming the No.3 polypeptide as POCMM1; scratch experiments confirm that the POCMM1 promotes migration of ovarian cancer cells and has concentration dependence, and further prove that the matrix factor POCMM1 promotes development of tumors and has the potential of serving as a biomarker for ovarian cancer diagnosis. The expression level of the matrix factor POCMM1 in serum of an ovarian cyst patient, an ovarian cancer patient without metastasis and an ovarian cancer patient with metastasis is subsequently detected, and compared with the expression level of the matrix factor POCMM1 in the serum of the ovarian cyst patient, the expression level of the matrix factor POCMM1 in the serum of the ovarian cancer patient is increased; the expression in serum of a metastatic ovarian cancer patient is the highest, so that the matrix factor POCMM1 can be confirmed to be used as a biomarker for ovarian cancer diagnosis.

The invention discloses a culture medium for in-vitro adherent culture of primary tumor cells and application, and relates to the technical field of tumor cell culture. Comprising a basic culture medium, fetal calf serum FBS with the concentration of 5 ng / mL-15 ng / mL, an epidermal growth factor EGF with the concentration of 1 ng / mL-10 ng / mL, a basic fibroblast growth factor bFGF with the concentration of 0.5 ng / mL-5 ng / mL, an insulin-transferrin-selenium ITS supplement with the final volume concentration of 0.1%-1%, L-glutamine with the final volume concentration of 0.5 mM-2 mM, ascorbic acid with the final volume concentration of 0.1%-0.5% and non-essential amino acid with the final volume concentration of 1%-5%. The kit comprises 10 [mu] g / mL-50 [mu] g / mL of heparin and 1 [mu] g / mL-5 [mu] g / mL of an Rho kinase inhibitor. The culture medium overcomes the defects that in the prior art, when primary tumor cells are subjected to adherent culture, apoptosis or dedifferentiation is prone to occurring, in-vivo tumor characteristics are difficult to simulate, the tumor growth speed is low, the proliferation effect is poor, and the adherent rate is low.

The invention relates to a CSF1R family inhibitor with a structure as shown in a formula (Ia) or a formula (Ib) and application of the CSF1R family inhibitor in pharmacy. The compound disclosed by the invention can be widely applied to preparation of drugs for treating tumors, autoimmune diseases, metabolic diseases or metastatic diseases related to CSF1R, PDGFRa and KIT kinase; the compound can be used for preparing medicines, especially medicines for treating ovarian cancer, pancreatic cancer, prostate cancer, breast cancer, cervical cancer, glioblastoma, multiple myeloma, metabolic diseases, neurodegenerative diseases, metastasis of primary tumor sites or bone metastatic cancer, and is expected to be developed into a new generation of CSF1R, PDGFRa and KIT kinase inhibitor medicines. # imgabs0 #

The present invention discloses an application of RARRES2 gene in the diagnosis and treatment of brain metastasis of breast cancer. We first compared the gene expression differences between primary tumors of human breast cancer and brain metastases by mining public databases such as GEO and MET500, screened and compared the RARRES2 gene, and compared the expression of the RARRES2 gene in breast cancer bone metastasis, lung metastasis and liver metastasis. Secondly, single-cell transcriptome sequencing was performed on brain metastases of breast cancer patients. The results showed that the expression level of RARRES2 in brain metastasis of breast cancer was significantly lower than that in primary tumors, but the expression of RARRES2 in bone, lung and liver metastases of breast cancer was not significantly different from that in primary tumors, suggesting that it is specifically related to brain metastasis of breast cancer. By constructing RARRES2 overexpression and knockdown human breast cancer brain metastasis cell (MDA-MB-231) lines, it was found that RARRES2 overexpression significantly inhibited the proliferation and invasion of the cells. By constructing a luciferase-labeled RARRES2 overexpression breast cancer brain metastasis mouse model, it was found that RARRES2 overexpression can significantly inhibit the proliferation of breast cancer cells in the brain.

The application belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating lung cancer bone metastasis and application thereof. The main active ingredients of the traditional Chinese medicine composition include, in mass parts, 20-40 parts of radix codonopsis, 20-40 parts of poria, 20-40 parts of astragalus, 10-30 parts of atractylodes, 10-20 parts of licorice, 10-30 parts of curcuma, 10-20 parts of pinellia, 5-10 parts of dried tangerine or orange peel, 20-40 parts of oldenlandia, 10-30 parts of psoralea, 10-30 parts of drynaria, 10-30 parts of epimedium, and 10-20 parts of jackinthepulp. Animal experiments show that the traditional Chinese medicine composition can not only inhibit primary tumor growth, but also slow down tumor progression of bone metastasis. When combined with a chemotherapy drug, the traditional Chinese medicine composition can not only significantly enhance the tumor inhibition effect of the chemotherapy drug, but also significantly prolong the survival time of mice, relieve weight loss and organ toxic side effects caused by the chemotherapy drug.

The invention belongs to the technical field of microorganisms, and particularly discloses an anesthesia coating spore as well as a preparation method and application thereof. The coating spore comprises a spore and a ferric iron-propofol coating attached to the body surface of the spore, and the coating is formed through metal-phenol complexing and pi-pi stacking. The spores are dormant bodies of collagenase-producing bacteria. The coating spores can be selectively germinated and colonized in a tumor hypoxic microenvironment, Fe < 3 + > can promote bacterial proliferation, loaded propofol inhibits tumor metastasis by inhibiting migration and invasion of tumor cells, generated collagenase degrades tumor collagen, meanwhile, Fe < 3 + > is reduced into Fe < 2 + > by glutathione in the cells, and the coating spores can be selectively colonized in the tumor hypoxic microenvironment. Therefore, a powerful Fenton reaction is induced to trigger lipid peroxidation, and ferroptosis of tumor cells is initiated. The injection of the anesthetic coating spores in the single tumor not only effectively ablates the primary tumor and inhibits the growth of the tumor, but also significantly inhibits the distal pulmonary metastasis of the in-situ tumor model.