234 results about "Resistant cell" patented technology

The invention discloses a pharmaceutical composition for reversing pancreatic cancer gemcitabine drug resistance and application of the pharmaceutical composition, and belongs to the technical field of biological medicine. The composition comprises a generic FGFR inhibitor delatinib and gemcitabine, the concentration of the delatinib is 25 to 50 mg / kg, and the concentration of the gemcitabine is 20 to 30 mg / kg. By inhibiting an FGFR2 / FGFR3 signal channel and reducing the expression of FGFR protein in drug-resistant cells, the chemosensitivity of gemcitabine is synergistically enhanced, the apoptosis induction rate is increased by more than two times, and the synergic index (CI) is less than 1. In-vitro and nude mouse transplantation tumor experiments prove that the composition can significantly inhibit the proliferation of gemcitabine drug-resistant pancreatic cancer cells. The Gemcitabine drug-resistant pancreatic cancer drug can be used for preparing a drug for treating Gemcitabine drug-resistant pancreatic cancer with high FGFR3 expression, patients are screened through immunohistochemistry or gene sequencing, intravenous injection or oral administration is adopted, dosage forms comprise freeze-dried powder injection, capsules or tablets, and a new strategy is provided for pancreatic cancer drug-resistant treatment.

The invention relates to the field of molecular targeted therapy, and discloses an application of an SLC16A5 (MCT6) small-molecule inhibitor MCT6-Ai7-2 in preparation of a medicine for treating acute myeloid leukemia (AML). The inhibitor takes an SLC16A5 protein structure predicted by Alphafold as a target spot, and is obtained through compound database screening, molecular docking and druggability optimization. An in-vitro experiment proves that MCT6-Ai7-2 can remarkably inhibit proliferation of AML cell lines such as U937 and MOLM-13, induce cell apoptosis and retard a cell cycle, has an inhibiting effect on a primary AML patient specimen and is relatively low in toxicity to normal cells; in-vivo experiments show that the compound is effective and has good safety in AML model mice. In addition, the MCT6-Ai7-2 and the vinca can be combined to synergistically enhance the inhibition effect on vinca drug-resistant cells, and by reducing the expression of anti-apoptotic protein MCL-1, the activation of pro-apoptotic factors BIM and tBID is promoted to play a role. The invention provides a novel targeting drug and strategy for treatment of AML (especially drug-resistant or recurrent patients).

The invention is applicable to the technical field of biological medicine, and provides a gadolinium-based nano-composite and application thereof in preparation of a medicine for reversing NSCLC radiation resistance, and a preparation method of the gadolinium-based nano-composite comprises the following steps: synthesizing NaYF4: Yb / Er; synthesizing NaYF4: Yb / Er (at) NaGdF4; synthesizing NaYF4: Yb / Er (at) NaGdF4 (at) mSiO2; 3-aminopropyltrimethoxysilane is added into a NaYF4: Yb / Er (at) NaGdF4 (at) mSiO2 aqueous solution, stirring is performed overnight, washing is performed, shSPARC plasmids are added, and a reaction is performed at the room temperature. The gadolinium-based nanocomposite prepared by the invention has both gene intervention and radiation sensitization functions, is good in biocompatibility, and can regulate the ferroptosis sensitivity of radiation-resistant tumors in a targeted manner, improve the ferroptosis inhibition effect, reverse the radiation resistance of resistant cells and improve the radiotherapy effect.

The invention discloses a drug-resistant marker for treating prostatic cancer olaparib and application of the drug-resistant marker, and relates to the technical field of medicine, and the marker is a PCAR1 gene. Research finds that the PCAR1 gene is remarkably and highly expressed in prostate cancer Olaparil drug-resistant cells and clinical drug-resistant samples, and can be used as a key marker for judging the drug resistance of prostate cancer patients to Olaparil. By detecting the expression level of the PCAR1 gene, the treatment reaction of a patient to the olaparil can be effectively predicted, and a basis is provided for clinically and accurately selecting a treatment scheme. Meanwhile, the specific siRNA designed aiming at the PCAR1 gene can obviously inhibit the expression of the PCAR1 gene, and can effectively reduce the drug resistance of cancer cells to olaparione, promote the apoptosis of the cancer cells and inhibit the proliferation of the cancer cells when being combined with the olaparione for use. Based on the siRNA, the invention prepares a pharmaceutical composition containing the siRNA and olaparil, and provides a new drug combination scheme for the treatment of prostatic cancer.

The invention discloses a recurrence-resistant cell strain for colorectal cancer large segmentation radiotherapy and application, and relates to the technical field of cell biology. The colorectal cancer large segmentation radiotherapy recurrence-resistant cell strain is preserved in the China Center for Type Culture Collection on January 2, 2025, the preservation address is Wuhan University, Wuhan, China, and the preservation number is CCTCC NO: C202533. By constructing the colorectal cancer large segmentation radiotherapy recurrence-resistant cell strain, a new biological material is provided for studying the radiotherapy recurrence-resistant colorectal cancer. The cell strain is screened in a mouse body with a sound immune system, has better physiological correlation, and is beneficial to research on the influence of an immune microenvironment on tumor cell radiotherapy resistance and the remodeling effect of radiotherapy resistant cells on the immune microenvironment. The cell strain can also monitor tumor recurrence after radiotherapy in real time through fluorescence imaging.

The invention relates to the technical field of cell engineering, and particularly discloses a construction method and application of a sika deer immortalized renal epithelial cell line, and the construction method comprises the following steps: taking renal epithelial primary cells from healthy sika deer renal cortex tissues to obtain primary renal epithelial cells; treating the primary renal epithelial cells with trypsin to obtain a cell suspension; inoculating the cell suspension into a complete culture medium, and transfecting with lentivirus loaded with SV40 large T antigen genes to obtain transfected cells; 3 [mu] g / mL puromycin is applied to the transfected cells for selective culture, so that non-transfected cells are eliminated, and drug-resistant cells are obtained; carrying out continuous passage on the drug-resistant cells for at least 30 generations to obtain the immortalized renal epithelial cell line of the sika deer; according to the invention, through a specific action mechanism (inhibiting a p53 / pRb pathway and blocking cell cycle exit) of the SV40 large T antigen, a proliferation limit caused by inhibition of telomerase activity of primary cells of the cervidae animals is overcome, and a cell resource library capable of realizing continuous passage is established.

The invention discloses application of an SUMO inhibitor 2-D08 in preparation of drugs for treating chronic myelogenous leukemia (CML) and drug resistance of a tyrosine kinase inhibitor (TKI) of the SUMO inhibitor 2-D08. It is revealed for the first time that SUMOylation modification drives disease progression by stabilizing BCR-ABL protein, 2-D08 promotes BCR-ABL protein degradation by inhibiting the modification, and leukemia cell proliferation is remarkably inhibited. In-vitro experiments prove that the compound effectively inhibits the activity of TKI drug-resistant cells, and in-vivo experiments show that 5 mg / kg of the compound can improve liver and spleen infiltration of CML mice. The inhibitor provides a new scheme for overcoming drug resistance, and fills the application blank of SUMOylation modification in CML treatment.

The invention discloses an eccDNAcircATP6V0A1 serving as a predictive marker of cis-platinum drug resistance of hypopharyngeal cancer and an application of the eccDNAcircATP6V0A1. The nucleotide sequence of the predictive marker eccDNA is as shown in SEQ ID NO. 3. According to the invention, a hypopharyngeal carcinoma cisplatin drug-resistant cell line model FaDu / DDP is cultured for the first time, meanwhile, a differential eccDNA expression profile and a circRNA expression profile in hypopharyngeal carcinoma cells FaDu and hypopharyngeal carcinoma cisplatin drug-resistant cells FaDu / DDP are disclosed and analyzed in a combined manner, and the eccDNA circATP6V0A1 is further screened and verified as a predictive marker of hypopharyngeal carcinoma cisplatin drug resistance through combined analysis. And a new treatment strategy diagnosis and treatment thought is provided for cis-platinum chemotherapy of hypopharyngeal carcinoma patients clinically.

The invention provides application of a copper death inducer in preparation of a medicine for treating osimertinib-resistant non-small cell lung cancer, and belongs to the technical field of treatment of non-small cell lung cancer. According to the invention, through high-throughput drug screening, the copper death inducer copper diethyl dithiocarbamate (CuET) and osimertinib are combined for use, so that a remarkable synergistic anti-cancer effect is achieved; furthermore, through detection of a wild type and osimertinib drug-resistant cell line model, an osimertinib sensitive and drug-resistant patient-derived organoid and a mouse xenotransplantation model, it is found that the anti-tumor effect of osimertinib can be remarkably enhanced through copper death induction, and osimertinib drug resistance is overcome. According to the technical scheme provided by the invention, osimertinib drug-resistant non-small cell lung cancer cells can be effectively killed, the curative effect of osimertinib in sensitive and drug-resistant models is remarkably enhanced, and an application scene is provided for copper death in tumor treatment.

The invention relates to the technical field of biology, in particular to a human cholangiocarcinoma drug-resistant cell line HuCCT1-GEM-2 and application thereof.The human cholangiocarcinoma drug-resistant cell line HuCCT1-GEM-2 is preserved in the China Center for Type Culture Collection on May 11, 2023, the preservation number is CCTCC NO: C2023103, the IC50 value of the human cholangiocarcinoma drug-resistant cell line HuCCT1-GEM-2 to gemcitabine is 314.5 mu M, the IC50 value of a parent cell HUCCT1 to gemcitabine is 12.7 mu M, the drug-resistant index is up to 24.8, and the human cholangiocarcinoma drug-resistant cell line HuCCT1-GEM-2 can be used as a drug-resistant cell line. The cell body is obviously enlarged and rounded or is more irregular in shape, the specific volume of the cell cytoplasm is larger, binuclear or multinuclear appears in the cell, and the drug-resistant cell presents obvious bulk aggregation growth; after 24 hours, the growth rate of the HuCCT-1-GEM-2 cell is obviously slower than that of a parent cell, and the HuCCT-1-GEM-2 cell can be used for researching the drug resistance mechanism of bile duct cancer.

The invention discloses an application of an engineered exosome rich in RHOT1 in preparation of a medicine for improving insulin resistance. The engineering exosome RHOT1-Exo rich in RHOT1 is obtained by the following steps: screening to obtain a polypeptide P15 targeting CD81, forming a recombinant protein RHOT1-P15 from the P15 and RHOT1, then constructing a recombinant plasmid for expressing the recombinant protein, transfecting cells, culturing, and extracting the exosome, thereby obtaining the engineering exosome RHOT1-Exo rich in RHOT1. The RHOT1-Exo is used for treating insulin-resistant cells, and the research shows that the RHOT1-Exo can effectively improve the ATP content of mitochondria, improve the oxidative phosphorylation level, enhance the antioxidant enzyme activity of cells and reduce ROS (reactive oxygen species), finally improve the mitochondrial network structure and improve the expression of insulin signal channel related proteins, and can be used for treating insulin-resistant cells. The obvious mitochondrial function repairing potential and the insulin resistance improving effect are shown. According to the invention, the RHOT1 protein is successfully applied to the treatment of insulin resistance in the form of exosome, and a scientific strategy is provided for the application of the medicine for clinically treating insulin resistance.

The invention provides application of tipirfarb in reversing osimertinib drug resistance, and relates to the technical field of medicines. The research of the inventor finds that the high expression of the MAST1 protein induces the targeted drug resistance of lung cancer, and the MAST1 protein can be used as an anti-drug-resistance action target. A new MAST1 inhibitor tipirfarb is obtained through virtual screening, and the antitumor activity of osimertinib on drug-resistant cells can be enhanced. The invention lays a foundation for subsequent development of an MAST1-targeted anti-drug-resistance strategy, provides brand new anti-drug-resistance targets and candidate molecules for targeted therapy of lung cancer, and has clinical value.

This invention discloses a butyrolactone compound with multidrug resistance reverse transcription activity, its preparation method, and its uses. The compound's structural formula is shown in Figure I. The preparation method includes the following steps: fermenting *Aspergillus pyrolyticus* (accession number CCTCC NO: M2014086) to obtain a butyrolactone fermentation product; extracting the fermentation product with ethyl acetate to obtain a crude extract; degreasing the crude extract with hexane and dichloromethane to obtain a final extract; and purifying the final extract using normal-phase silica gel column chromatography, reversed-phase medium-pressure column chromatography, and reversed-phase semi-preparative high-performance liquid chromatography. The advantage of this butyrolactone compound is that it possesses multidrug resistance reverse transcription activity and the ability to regulate P-gp-mediated drug efflux in multidrug-resistant cell lines, making it a potential drug for treating multidrug-resistant cancers.

The invention provides a human bladder cancer vedicetumab drug-resistant cell strain as well as a construction method and application thereof. The cell strain is named as a human bladder cancer drug-resistant cell strain T24-RC48, and the preservation number of the cell strain is CCTCC (China Center For Type Culture Collection) NO: C2024180. During construction, a method of continuously inducing at low concentration and gradually increasing the drug concentration and the treatment time of the RC48 is adopted, so that the formation of the RC48 drug-resistant cells is effectively induced, and the construction method is simple to operate and can effectively make up for the defects of the existing method. The human bladder transitional cell carcinoma RC48 drug-resistant cell strain T24-RC48 constructed by the invention can be used for researching a bladder cancer drug-resistant mechanism, promoting the development of predictive biomarkers, evaluating the antitumor activity of drugs and preparing a tumor cell model or a tumor animal model; a cell research model is provided for screening, researching and developing effective drugs and methods for overcoming bladder cancer drug resistance, and good application prospects are achieved.

The invention discloses an 8-hydroxyl dictamnine platinum complex with high activity in vitro and vivo as well as a synthesis method and application thereof. According to the invention, 8-hydroxy dictamnine is used as an active ligand and reacts with cis-Pt (DMSO) 2Cl2 platinum salt to synthesize the 8-hydroxy dictamnine platinum complex. The 8-hydroxyl dictamnine platinum complex can inhibit the growth of human ovarian adenocarcinoma cis-platinum drug-resistant cells SK-OV-3 / DDP in a targeted manner, shows excellent anti-tumor activity, has potential medicinal value, and is expected to be used for preparing various anti-tumor drugs.

The invention relates to application of SMARCC1 in preparation of a medicine for treating carfilzomib-resistant multiple myeloma, and belongs to the technical field of biological medicine. According to the invention, direct association between SMARCC1 and the drug resistance of multiple myeloma to carfilzomib is determined for the first time, and the sensitivity of drug-resistant cells to carfilzomib can be significantly enhanced by down-regulating the expression of the gene. Specifically, through systematic analysis on clinical data, SMARCC1 is found to be remarkably and highly expressed in relapse / refractory MM patients and is closely related to poor survival. The SMARCC1 knock-down obviously inhibits the multiplication capacity of multiple myeloma drug-resistant cells, so that the SMARCC1 not only promotes the multiplication capacity of the drug-resistant cells, but also is closely related to the drug resistance of the multiple myeloma cells to carfilzomib, which prompts that the SMARCC1 can be used as a potential therapeutic target and is used for reversing the carfilzomib drug resistance of multiple myeloma.

The application discloses application of Ophisaurus apodus in preparation of a drug for reversing drug resistance of gastric cancer and belongs to the technical field of medicines. The application can reduce tumor volume and size, promote drug resistance cell apoptosis, and reverse the chemotherapeutic drug resistance of a nude mouse with gastric cancer by jointly using Ophisaurus apodus in different parts of the body and cisplatin, by down-regulating P-gp, MRP1 and Bcl-2 protein expression, and by up-regulating Bax protein expression. The effect of the tail + cisplatin group is the most significant.

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 invention relates to application of a KRT7-AS inhibitor in preparation of a medicine for treating ovarian cancer or paclitaxel drug resistance of the ovarian cancer. The invention discloses a mechanism of KRT7-AS for promoting ovarian cancer progression by inhibiting ferroptosis for the first time. After KRT7-AS is knocked down by utilizing an shRNA (short hairpin ribonucleic acid) inhibition technology, biological behaviors of ovarian cancer cells and ovarian cancer paclitaxel drug-resistant cells are influenced: proliferation, migration and invasion capabilities are reduced to different degrees, and meanwhile, ferroptosis is activated to inhibit tumor growth. The invention provides a new thought and a potential target for precise treatment of ovarian cancer, and is expected to bring good news to ovarian cancer patients. Long-chain non-coding RNA KRT7-AS is novel carcinogenic lncRNA of ovarian cancer, and the effect of KRT7-AS knockout in the ovarian cancer cell process is researched. By targeting KRT7-AS, ferroptosis of ovarian cancer cells is regulated and controlled, so that tumor progression is influenced. The KRT7-AS inhibitor is used for targeting KRT7-AS, can be used as a treatment method for treating ovarian cancer, and is an innovative strategy for treating ovarian cancer.

This invention relates to drug-resistant breast cancer cells and their applications, belonging to the field of tumor cell technology. The drug-resistant breast cancer cells of this invention are human mammary ductal carcinoma cells T47DR and / or human breast cancer cells MCF7R. The human mammary ductal carcinoma cells T47DR were deposited at the Guangdong Provincial Microbial Culture Collection Center on October 25, 2024, with accession number GDMCC No: 65348; the human breast cancer cells MCF7R were deposited at the same center on October 25, 2024, with accession number GDMCC No: 65347. This invention demonstrates that the clonogenic ability, migration ability, anti-apoptotic ability, and spheroidization ability of drug-resistant breast cancer cells are significantly enhanced. They can form tumors independently of estrogen and metastasize throughout the body in a short period of time. The tumor stemness of the drug-resistant cells is enhanced, and they exhibit resistance to apelexifen and / or tamoxifen.

The invention discloses an application of MetAP2 as a target spot in a drug for reducing drug resistance of multiple myeloma cells. According to the invention, expression of mRNA and protein of MetAP2 in MM drug-resistant cells is increased; when the protein expression of MetAP2 in the MM cells is exogenously changed, the sensitivity of the MM cells to BTZ can be changed; the lifetime of a myeloma mouse model established by using the MM cell for knocking down the MetAP2 is obviously prolonged, and the bone destruction condition is effectively improved. The invention provides a new solution thought for clinically inhibiting tumor growth and improving drug resistance of multiple myeloma, and has important clinical significance and transformation value.

A method for identifying a protein associated with a receptor-ligand interaction is described. The method comprises providing a population of engineered cells comprising a targeting library targeting specific gene expression, contacting the population of cells with a recombinant toxin fusion for sufficient time, and identifying proteins in the selection pool of cells by sequencing one or more of the nucleic acid molecule comprised in the selection pool of cells, thereby identifying the target gene. Toxin-resistant cell lines, toxin-producing cell lines, recombinant toxin fusions, probes and methods producing same, and kits thereof, are also provided.

The invention belongs to the technical field of biological medicine, and particularly relates to application of an anti-HIV drug in inhibition of non-small cell lung cancer drug resistance. The invention finds that the combined use of the anti-HIV drug and EGFR-TKI can effectively and specifically target the MRD drug-resistant cells, inhibit the formation of the MRD drug-resistant cells, significantly improve the curative effect of EGFR-TKI and delay tumor recurrence.

Embodiments disclosed herein use forward genetics tools (e.g., ORF libraries, perturbation libraries) to study fitness advantages under immune pressure, including resistance mechanisms. Once the resistance mechanisms are identified, vulnerabilities (i.e., dependencies) in resistant cells can be identified (e.g., synthetic lethality screens in resistant cancer cells). For example, drug or CRISPR screening can be performed in cells with an identified resistant state. Embodiments disclosed herein also provide targets for resistance to IFN-y treatment.

Chemotherapy resistance is the major therapeutic barrier in acute myeloid leukemia (AML). To address this issue, the inventors generated a syngeneic mouse model of AML, which we evolved to develop resistance to a front-line chemotherapy regimen. The inventors identified SRRM1 as a critical vulnerability of chemoresistant leukemic cells and identified that PAK1 and CLK kinases are regulators of SRRM1 in chemoresistant AML cells. Human and murine chemoresistant cells were found to be markedly more sensitive to inhibitors of PAKs (FRAX597) and CLKs (TG003 and ML 167) compared to their naive counterparts, an effect which was even further enhanced by treatment with cytarabine and daunorubicin. Simultaneous suppression of Clk1 and Pak1 or Clk-4 and Pak1 using validated shRNAs and combinations of FRAX597 and TG003, or FRAX597 and ML 167 synergized to reduce the growth and the colony-forming capacity of chemoresistant AML cells and sensitized them to chemotherapy. The combined treatment improved overall mouse survival and reduced disease burden in the chemoresistant AML mouse models. Moreover, AML patient cells that were primarily refractory or from a post chemotherapy relapse (n=21 ) exhibited a higher ex vivo sensitivity to the FRAX597 + TG003 combination in comparison with chemosensitive patients at diagnosis (n=28). Finally, combined PAK1 and CLK inhibition more effectively reduced disease progression in animals transplanted with the relapse sample than in those engrafted with the sample taken at diagnosis. Thus, the present invention relates to combination of PAK1 inhibitors and CLK inhibitors for preventing resistance to chemotherapy in patients suffering from acute myeloid leukemia.

The invention relates to application of an HOXB9 inhibitor in a medicine for reversing oxaliplatin resistance of gastric cancer, and belongs to the field of biological medicine. The invention discloses for the first time: HOXB9 is remarkably high in expression and is positively correlated with poor prognosis in tissues of patients with gastric cancer, which are poor in curative effect after chemotherapy containing oxaliplatin; by constructing an oxaliplatin drug-resistant gastric cancer cell strain and a patient-derived organ model, the HOXB9 is proved to specifically mediate the survival of the drug-resistant cell strain by activating a focal adhesion signaling pathway (p-FAK / AKT), and the HOXB9 is irrelevant to cell proliferation. Aiming at the mechanism, shRNA nucleic acid molecules (SEQ ID NO: 1-2) targeting HOXB9 are provided, and drug-resistant cell strains can be selectively killed through lentiviral vector delivery, so that the drug-resistant cell IC50 is reduced by more than 50%, the apoptosis rate is increased by 3 times, and the chemotherapy resistance of organoids is reversed. The invention provides a brand-new target spot and a treatment scheme for overcoming the drug resistance of oxaliplatin for gastric cancer.

The invention discloses a 2-amino-4-anilino pyrimidine compound as well as a preparation method and application of the 2-amino-4-anilino pyrimidine compound. The compound has a strong inhibition effect on EGFR (epidermal growth factor receptor) gene mutation targets and c-MET and has a strong inhibition effect on osimertinib drug-resistant cells; and the compound can inhibit proliferation of various tumor cells, and provides excellent application prospects for treatment of EGFR gene mutation and MET amplified malignant tumors.

The invention relates to application of a proteasome inhibitor in preparation of a medicine for treating tumors resistant to a tyrosine kinase inhibitor, and in the application, a plurality of strains of liver cancer cells with drug resistance to lenvatinib or regorafenib are constructed by utilizing a plurality of human liver cancer cell lines with different genetic backgrounds; a high-throughput CRISPR (clustered regularly interspaced short palindromic repeats) gene knockout screening technology and a patent medicine gene CRISPR library are utilized, and gene targets of which the gene knockout or inactivation can better kill drug-resistant cells are specifically identified from thousands of patent medicine genes. Wherein the function inactivation of a plurality of genes in the proteasome family shows more obvious cell killing activity in a plurality of drug-resistant cell models compared with non-drug-resistant cells. The invention discovers and verifies that the proteasome inhibitor has a specific killing effect on tyrosine kinase inhibitor drug-resistant liver cancer for the first time.

The present disclosure relates generally to lipid nanoparticles (LNPs) and compositions comprising the same, and their use for delivering agents, such as nucleic acid-based therapeutic agents, particularly to transfected resistant cells and / or lung tissue.

The invention provides a bicyclic heteroaryl BRAF negative allosteric modulator and a preparation method and application thereof.The structural general formula of the bicyclic heteroaryl BRAF negative allosteric modulator or pharmaceutically acceptable salt of the bicyclic heteroaryl BRAF negative allosteric modulator is shown as I. The bicyclic heteroaryl BRAF negative allosteric modulator targeting BRAF kinase is high in effect and good in druggability and can be used for preparing BRAF kinase. The drug resistance phenomenon caused by BRAF protein dimerization is overcome. A test example verifies that the compound synthesized by the invention shows remarkable cell proliferation inhibition activity on BRAFWT, BRAFV600E and a p61-BRAFV600E tumor drug-resistant cell line constructed by slow virus transient transfer, has remarkable kinase inhibition activity, and has a good application prospect; and # imgabs0 # I is adopted.