27 results about "Chemotherapy resistant" patented technology

The application provides a preparation method of NK cell-derived nanovesicles and application thereof. Specifically, the application provides NK cell-derived nanovesicles (NK-NVs) which are similar to the characteristics and functions of NK cell-derived extracellular vesicles by an extrusion method / stress gradient membrane remodeling technology, and also provides a drug composition, a drug delivery system and corresponding use of the NK-NVs as a delivery carrier for delivering an antitumor drug. The preparation method of the application can mass-produce NK-NVs and kill various types of tumor cells. The NK-NVs have multiple advantages in drug delivery, so that they are expected to be a new choice for tumor immunotherapy, especially for tumor cells with drug resistance, and can significantly improve the sensitivity to chemotherapeutic drugs, and have a wide application prospect.

The invention discloses a nucleolin aptamer modified carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system as well as a preparation method and application thereof, and relates to the field of tumor treatment. The nucleolin aptamer AS1411 is coupled with glycolysis regulation nano-particles through covalent bonds, and the carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system comprises a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system and a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, the glycolysis regulation nano-particles take carboxymethyl chitosan as a carrier skeleton, the carrier skeleton is loaded with a lonidamine derivative through grafting modification, and the nano drug delivery system can synchronously entrap paclitaxel. According to the invention, a synergistic treatment system integrating active targeting, metabolic regulation and chemotherapy is constructed, and by virtue of a multi-mechanism synergistic effect, an antitumor drug for inhibiting tumor cell activity, glycolysis or tumor metabolism reprogramming is prepared; the huge potentials of overcoming the drug resistance bottleneck of traditional chemotherapy, enhancing the curative effect and reducing the toxic and side effects are shown.

The present application relates to the role of UCK1 in promoting the sensitization of colorectal cancer treatment. The present application discloses the key role of UCK1 in the treatment of colorectal cancer. Clinical samples show that the expression of UCK1 in tumor tissues is reduced, and its low expression is related to chemotherapy resistance and poor prognosis. Studies have shown that UCK1 enhances the efficacy of oxaliplatin (OXA) by regulating metabolic pathways, and promotes B cell activation, thereby recruiting CD8 + T cells, and strengthens anti-tumor immunity. UCK1 overexpression can significantly improve OXA sensitivity and produce a synergistic effect with anti-PD-1 therapy. The present application proposes a new strategy centered on activating UCK1, providing a theoretical basis and application prospect for improving the response of colorectal cancer chemotherapy and immunotherapy.

This invention belongs to the field of molecular biology technology, specifically involving tRF5-22-SeCTCA-1, tRF5-22-SeCTCA-1 detection reagents, kits, and their applications. This invention discovers and verifies that tRF5-22-SeCTCA-1 plays a key regulatory role in the process of 5-fluorouracil (5-FU) chemotherapy resistance in colorectal cancer, filling a gap in the research of tRNA-derived fragments (tRFs) in colorectal cancer chemotherapy resistance. It is the first tRF molecule reported to be associated with 5-FU chemotherapy resistance in colorectal cancer, providing a novel molecular target and research direction for predicting chemotherapy resistance in colorectal cancer. This invention also provides a therapeutic strategy targeting tRF5-22-SeCTCA-1 and establishes α-ketoglutarate as an independent reversal agent, providing multi-dimensional technical solutions for the precision diagnosis and treatment of colorectal cancer and the reversal of chemotherapy resistance.

The invention belongs to the technical field of biological medicines, and discloses application of a CCT6A inhibitor in preparation of a medicine for treating colorectal cancer. CCT6A is determined to be a key cancer promoting gene of colorectal cancer for the first time, the CCT6A is remarkably and highly expressed in colorectal cancer tissues and cell lines, and high expression indicates poor prognosis of patients, so that a brand-new specific target is provided for targeted therapy of colorectal cancer. The invention discloses the cancer promoting effect of the compound in colorectal cancer and the association with 5FU drug resistance for the first time, enriches the development of colorectal cancer and the molecular mechanism research of chemotherapy drug resistance, and provides a new theoretical basis and research direction for the fundamental research in the field. Experiments prove that the inhibitor can significantly reduce the mRNA level of CCT6A in colorectal cancer cells so as to strongly inhibit tumor cell proliferation and increase the sensitivity of the colorectal cancer cells to 5-FU, and a novel therapeutic drug with high specificity and high curative effect is provided for treatment of colorectal cancer.

The invention discloses a method for capturing, identifying and culturing circulating tumor cells of sarcoma in vitro. The method comprises a step of filtering a peripheral blood sample of a sarcoma patient by using a flexible microfiltration membrane, and cells obtained by filtration can be directly subjected to multiplication culture on the filtration membrane. Immunomagnetic beads of a monoclonal antibody combination group coupled with the anti-human leukocyte surface antigen CD45 can be used for negative enrichment and then multiplication culture is carried out in a cell culture bottle, and the captured or cultured cells can be subjected to subtype identification, characterization and counting by adopting an iFISH technology. It is found for the first time that the flexible microfiltration membrane can be used for capturing and culturing the sarcoma circulating tumor cells, and the flexible microfiltration membrane has no toxic effect on the sarcoma circulating tumor cells. The invention not only provides an effective means for real-time monitoring of relapse and metastasis processes of sarcoma patients and chemotherapy drug resistance monitoring, but also can perform drug sensitivity experimental verification on CTC after multiplication culture, and provides a powerful weapon for accurate diagnosis and treatment of sarcoma.

This application discloses the application of PLAC8 as a target in the preparation of tumor therapeutic drugs, involving the field of biomedical technology. This application clarifies that the "sympathetic nervous system-β2-AR-PLAC8-cholesterol metabolism-M2 polarization" pathway is the core driving pathway for stress-related tumor progression and chemotherapy resistance. It reveals the molecular mechanism by which PLAC8 inhibits cholesterol synthesis through phosphorylation at the S67 site, binding to the N-terminal domain of SREBP2, recruiting OGT to mediate SREBP2O-GlcNAc glycosylation. Through strategies such as gene silencing, β2-AR antagonist intervention, and targeted delivery of siPLAC8 via mannose-modified lipid nanoparticles (LNPs), the application achieved the effects of inhibiting M2 macrophage accumulation, inhibiting tumor growth, and reversing chemotherapy resistance in various tumor models, including gallbladder cancer, intrahepatic cholangiocarcinoma, and prostate cancer. Furthermore, the LNPs delivery system showed no significant toxicity. This research provides a novel therapeutic target centered on PLAC8 and a safe and effective targeted intervention strategy for stress-related tumors, highlighting its clinical translational value.

The invention discloses an application of brucein D and Vinetoram in preparation of a medicine for treating acute or drug-resistant myelogenous leukemia. Through a large number of experimental screening, the brucein D and the Venotocork are combined for medication, and the test result shows that the brucein D and the Venotocork act on different targets and different signal channels of AML cells to generate a remarkable synergistic anti-tumor effect, and after the brucein D and the Venotocork are combined, the proliferation inhibition and apoptosis induction effects on the AML cells can be directly enhanced, and the anti-tumor effect of the Venotocork D and the AML cells can be improved. The compound can also reverse the drug resistance possibly occurring when the Vinetoram is singly used, and also has a remarkable killing effect on chemotherapy drug-resistant AML cells at the same time. The composition provided by the invention can reduce the dosage of antitumor drugs, reduce drug resistance, reduce adverse reactions and improve the life quality of patients, and has important application prospects.

The invention relates to a 3, 4, 5-trihydroxy phenylacetate compound and a preparation method and application thereof, the 3, 4, 5-trihydroxy phenylacetate compound belongs to a compound shown in a general formula I and a general formula II, R1, R2 and corresponding derivatives thereof can activate a copper death pathway mediated by endogenous copper ions, have an obvious anti-tumor effect, and have a stronger anti-tumor effect in chemotherapy of drug-resistant tumors. The tumors comprise melanoma, liver cancer, gastric cancer, breast cancer, oral squamous cell carcinoma and the like. The compound is a non-copper ion carrier compound with a brand new structure, induced copper death does not depend on exogenous copper ions, and endogenous copper ions are dissociated by reducing the content of glutathione which is a copper ion chelate in cells. The copper ions are further combined with microfilament skeleton related protein to cause disintegration of the microfilament skeleton, so that copper death is induced. The compound disclosed by the invention can be used as a potential lead compound for inducing endogenous copper ion mediated copper death for anti-tumor therapy.

To provide safe and effective compositions and methods for enhancing the efficacy and / or reducing the side effects of cancer chemotherapy and increasing the sensitivity of chemotherapy-resistant cancer cells.SOLUTION: Nutritional supplements comprising fish oil and selenium have been found to provide various activities that are beneficial in treating cancer and related conditions. The supplement provides a synergistic effect in reducing cancer cell growth when used in combination with a chemotherapeutic agent and can reduce growth in drug resistant cancer cells when used in combination with a chemotherapeutic agent to which the cells are resistant. Effects in reducing angiogenesis, reducing metastasis, decreasing the number of circulating cancer cells, and altering AXL signaling have also been found. The use of the supplement was found to reduce the wasting associated with cachexia and decrease circulating cytokines associated with inflammation. The overall effect was found to prolong survival in a clinical study.SELECTED DRAWING: Figure 1

Various embodiments of the present invention provide compositions of tumor-infiltrating lymphocytes (TILs) enriched with tumor-reactive cells. The embodiments also provide methods for producing tumor-reactive TILs enriched with tumor-reactive cells, and the use of the provided enriched tumor-reactive TILs for treating cancer in humans or other subjects. According to the embodiments, a tumor-reactive T cell enriched pharmaceutical T lymphocyte infiltration (TIL) composition comprises an oligoclonal population of tumor-infiltrating T cells, including tumor-derived CD4+ and CD8+ T cells, with up to 40 clones constituting 40% of the TCR frequency in the population. Embodiments of the present invention are particularly useful for treating tumors that are resistant or refractory to conventional chemotherapy, or that have become resistant or refractory.

The invention discloses application of 19-hydroxybufalin in preparation of a medicine for treating prostatic cancer, and belongs to the technical field of pharmaceutical preparations. The 19-hydroxybufalin is found to be targeted in vivo and in vitro for the first time, and the growth of prostate tumors is remarkably inhibited, so that the survival basis of tumor cells is fundamentally weakened, programmed death of the tumor cells is triggered, and tumor regression is effectively induced; a brand-new treatment approach is provided, namely, a non-classical drug target, namely HELLS, is degraded in a targeted manner, so that a new treatment choice is expected to be provided for a patient lacking existing target mutation; the provided 19-hydroxybufalin can be used for treating advanced prostate cancer, especially castration-resistant prostate cancer, and a new candidate treatment drug with great potential and a brand new treatment strategy are provided for effectively solving the problem that chemotherapy drug resistance and targeted therapy selection are limited in the castration-resistant prostate cancer at present.

The invention is applicable to the technical field of biological medicines, and provides application of 20 (S)-protopanaxatriol in preparation of a medicine for reversing chemotherapy resistance of liver cancer. The invention provides application of 20 (S)-protopanaxatriol (20 (S)-protopanaxatriol, hereinafter referred to as 20S-PPT) which is derived from ginseng in preparation of drugs for reversing chemotherapy resistance of liver cancer, the sensitivity of liver cancer cells to chemotherapy drugs is improved, the chemotherapy-induced apoptosis effect is enhanced, and the in-vivo anti-tumor effect is improved on the premise that safety is guaranteed.

The application discloses a monomer compound DTA and application thereof in preparation of a temozolomide-sensitive glioma inhibiting drug. Through a glioma primary cell model, it is proved that the monomer compound Demethylenedelcoine A (DTA) can produce a better anti-chemotherapy resistant glioma effect than a clinical first-line chemotherapy drug temozolomide and carmustine. Therefore, in clinical treatment of temozolomide chemotherapy resistance and radiotherapy failure recurrent glioma, the monomer compound DTA can have a potential treatment advantage, and therefore has a potential drug development value.

This invention discloses a method, system, and apparatus for computer-aided drug screening based on temozolomide and ADAMTS1. This application is the first to discover that ADAMTS1 is significantly enriched in recurrent gliomas following temozolomide exposure; temozolomide strongly induces a stable senescence program, leading to excessive secretion of ADAMTS1. This senescence-induced protease coordinates significant changes in extracellular matrix composition. The remodeled microenvironment acts as a mechanobiochemical signaling agent, recruiting and polarizing host-derived myeloid cells to transform into the immunosuppressive M2 phenotype, thereby conferring chemotherapy resistance to residual glioma cells through paracrine signaling. This application reveals that the "senescence-ADAMTS1-ECM-M2" axis is a key non-cellular autonomous mechanism of temozolomide resistance. Targeting ADAMTS1-mediated matrix reprogramming can eliminate the immunosuppressive niche in gliomas and overcome chemotherapy resistance, showing broad application prospects.

The invention relates to an application of oligonucleotide based on NAT10 gene in preparation of drugs for reversing platinum drug resistance of non-small cell lung cancer. The antisense oligonucleotide provided by the invention not only can reverse platinum drug resistance, but also can inhibit proliferation of non-small cell lung cancer drug-resistant cells, and cell proliferation experiments prove that proliferation of chemotherapy drug-resistant cells is inhibited after treatment; according to the present invention, the tumor cell lipid metabolism abnormality is regulated, the lipid droplet staining results prove that the number of the treated cell lipid droplets is significantly reduced, and the tumor growth can be significantly inhibited, the expression of NAT10 in the tumor tissue can be reduced, the malignant development and metastasis of the tumor can be inhibited, and the anti-tumor effect can be provided in the animal experiment;

The inventors establish a role for primary cilia in human TNBC chemotherapeutic resistance. They developed patient-derived organoids, and showed that these recapitulated the cellular heterogeneity of TNBC biopsies. They treated their TNBC organoids with chemotherapeutics and observed partial killing. The surviving cells with organoid-reconstituting capacity showed selective enrichment for the quasi-mesenchymal ciliated cell subpopulation. They developed a family of small-molecule inhibitors of ciliogenesis and show that these, or genetic ablation of primary cilia, suppress chemoresistance. In particular, the present invention relates to a method of preventing therapeutic resistance in a patient suffering from a cancer comprising administering to the patient a therapeutically effective amount of an inhibitor of ciliogenesis. The present invention also relates to a method of treating a therapy-resistant cancer in a patient suffering from a cancer comprising administering to the patient a therapeutically effective amount of an inhibitor of ciliogenesis.

The invention belongs to the technical field of biological medicines, and particularly relates to an epirubicin-resistant human breast cancer cell strain, an exosome and application of the epirubicin-resistant human breast cancer cell strain and the exosome in construction of a mouse chemotherapy drug-resistant breast cancer model so as to solve the problem that an existing animal model is difficult to simulate the occurrence and transmission process of epirubicin drug resistance in clinic. The exosome is secreted by an epirubicin-resistant human breast cancer cell strain, the epirubicin-resistant human breast cancer cell strain is preserved in the China Center for Type Culture Collection, and the preservation number is CCTCC NO: C2025338. The exosome secreted by the cell strain can reduce the accumulation of chemotherapeutic drugs in tumor tissues and up-regulate the expression of P-gp and MRP1 drug-resistant proteins, thereby promoting the formation of tumor chemotherapeutic drug resistance. The mouse chemotherapy drug-resistant breast cancer model constructed by the invention is closer to a real pathological generation process of clinical breast cancer drug resistance, and has important basic scientific research value and application prospect for researching a chemotherapy drug-resistant mechanism, screening drugs for reversing chemotherapy drug resistance and exploring new therapeutic targets.

Methods are provided for treating cancers in subjects in need of such treatment. Such methods include methods of treating cancers, including VHL-expressing cancers and chemotherapy-resistant solid tumor cancers, such as malignancies reliant on BCL-xL, with combinations of chemotherapeutic agents and DT2216. These methods include treatment of malignancies which utilize any mechanism which drives resistance by BCL-xL.

The present invention provides a method and composition for performing bone marrow transplantation. [Solution] This disclosure relates, as a whole, to methods and compositions for performing bone marrow transplantation using non-myeloablative chemotherapeutic agents and chemotherapeutic-resistant cells. Using the methods and compositions described herein, a patient's bone marrow can be reconstituted, and the patient can avoid adverse side effects, including myeloablative and / or immune system disorders.

The invention belongs to the technical field of biological medicine, and particularly relates to a kit for breast cancer drug resistance detection and application of the kit. The kit comprises a primer pair for amplifying the NOL7 gene, an upstream primer sequence of the primer pair for amplifying the NOL7 gene is as shown in SEQ ID NO. 1, and a downstream primer sequence is as shown in SEQ ID NO. 2. Experiments prove that high expression of the NOL7 gene is related to breast cancer drug resistance, and the NOL7 gene can be used as a marker for breast cancer drug resistance detection. Meanwhile, the marker for breast cancer drug resistance detection is applied to preparation of the kit, and the kit can specifically, sensitively and accurately detect the expression level of NOL7 in a tumor sample, so that a brand new tool is provided for clinically evaluating the chemotherapy drug resistance risk of a patient, and the application prospect is wide.

The application relates to the technical field of data processing, and discloses a PRAK signal pathway analysis method and system. The method comprises the following steps: collecting circRNA expression profiles, miRNA regulation data and PRAK pathway protein phosphorylation data by high-throughput sequencing technology to form a comprehensive data set, mining molecular interaction relationships to construct a pathway connection matrix containing three regulation axes of P38-PRAK-HSP27, VEGFA-PRAK and PRAK-GTPBP4-RhoA, predicting the PRAK pathway activation strength value by using a graph neural network algorithm, extracting the response characteristic markers of a chemotherapy-resistant type, an apoptosis-sensitive type and a proliferation regulation type, and matching an optimal PRAK pathway intervention target point combination. The application solves the technical problem that the existing PRAK signal pathway analysis method cannot intelligently process multi-omics data and accurately predict the pathway activity state.

The disclosure relates generally to methods and compositions for performing bone marrow transplants using a non-myeloablative chemotherapeutic agent and chemotherapeutic-resistant cells. Using the methods and compositions described herein, a patient's bone marrow may be reconstituted and the patient avoids adverse side effects, including myeloablation and / or an impaired immune system.

The inventors establish a role for primary cilia in human TNBC chemotherapeutic resistance. They developed patient-derived organoids, and showed that these recapitulated the cellular heterogeneity of TNBC biopsies. They treated their TNBC organoids with chemotherapeutics and observed partial killing. The surviving cells with organoid-reconstituting capacity showed selective enrichment for the quasi-mesenchymal ciliated cell subpopulation. They developed a family of small-molecule inhibitors of ciliogenesis and show that these, or genetic ablation of primary cilia, suppress chemoresistance. In particular, the present invention relates to a method of preventing therapeutic resistance in a patient suffering from a cancer comprising administering to the patient a therapeutically effective amount of an inhibitor of ciliogenesis. The present invention also relates to a method of treating a therapy-resistant cancer in a patient suffering from a cancer comprising administering to the patient a therapeutically effective amount of an inhibitor of ciliogenesis.

The invention discloses a nano-selenium-phellinus igniarius polysaccharide composite carrier and a preparation method and application thereof.The composite carrier takes nano-selenium particles as a core and phellinus igniarius polysaccharide as a coating layer, the phellinus igniarius polysaccharide coats the surface of nano-selenium through electrostatic interaction and / or chemical bonding, the nano-selenium particles are spherical particles of 20-100 nm, a characteristic ultraviolet absorption peak exists at 250 nm, the coating rate is not lower than 80%, and the nano-selenium particles are spherical particles of 20-100 nm. The phellinus igniarius polysaccharide is prepared by adopting a chemical reduction method, taking phellinus igniarius polysaccharide, sodium selenite and ascorbic acid as raw materials, and performing liquid-phase reduction and process optimization. The composite carrier induces iron overload and lipid peroxidation by excessively activating a colorectal cancer cell ROS / Nrf2 / HO-1 pathway, specifically induces ferroptosis, can bypass a chemotherapy drug resistance mechanism, and is high in targeting property and low in toxicity. The preparation method is simple, convenient and controllable, the composite carrier is high in stability and bioavailability and remarkable in tumor inhibition effect, various dosage forms can be prepared, a novel efficient and low-toxicity strategy is provided for treatment of colorectal cancer, especially chemotherapy drug-resistant colorectal cancer, and the clinical transformation prospect is good.

The invention provides an application of RASSF10 as a therapeutic target in preparation of a medicine for treating gastric cancer, and relates to the technical field of biomedicine, verification experiments prove that the RASSF10 as the therapeutic target can enhance the sensitivity of the gastric cancer to docetaxel after being up-regulated, so that the autophagy activity of a xenograft of the gastric cancer is increased, the proliferation is reduced, and the apoptosis is enhanced. The reagent for promoting RASSF10 expression is combined with docetaxel and can be used for preparing the medicine for treating gastric cancer, and the medicine can contain medically acceptable auxiliary agents. The RASSF10 methylation can be used as a minimally invasive biomarker for predicting the stomach cancer docetaxel sensitivity, and related products comprise a detection reagent or a detection kit. The compound cRGD-LipoatrR10 can deliver recombinant RASSF10 to gastric cancer cells in a targeted mode, the sensitivity of docetaxel is enhanced, the preparation method comprises the steps of lipid membrane formation, hydration ultrasonic treatment, extrusion, purification and freeze-drying, and a new scheme is provided for precise treatment of gastric cancer and overcoming of chemotherapy drug resistance.

The present application relates to the technical field of targeted nanoparticles, in particular to a bone-targeting metabolic-driven chemotherapy resistance relieving polymer, a dual-drug inhibitor nano delivery particle and a preparation method and application thereof. The nano delivery particle comprises the bone-targeting metabolic-driven chemotherapy resistance relieving polymer MALss ALN , the polymer MALss Gi , and an MCT1 inhibitor. The present application discloses a metabolic reprogramming nano therapeutic system targeting osteosarcoma and a preparation and application method thereof, aiming to solve the problem of poor sensitivity of cisplatin, cope with the complex immune microenvironment of osteosarcoma, and propose a new nano therapeutic strategy for overcoming chemotherapy resistance and immune inactivation by precisely regulating the metabolic-immune axis.