19 results about "STAT1" patented technology

The disclosure provides a method for treating a subject afflicted with a tumor comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or antigen-binding portion thereof or an anti-PD-L1 antibody or anti-gen-binding portion thereof, wherein the subject is identified as having a high inflammatory gene signature score. In some embodiments, the high inflammatory gene signature score is determined by measuring the expression of a panel of inflammatory genes in a tumor sample obtained from the subject, wherein the inflammatory gene panel comprises CD274 (PD-LI), CD8A, LAG3, and STAT1.

This invention discloses the application and method of a STAT1-targeting inhibitor in the treatment of immune thrombocytopenic purpura (ITP). It employs ivermectin, a STAT1 nuclear translocation inhibitor, and fludarabine, a STAT1 activation inhibitor. By injecting either the activation inhibitor or the nuclear translocation inhibitor, the platelet count in a mouse model of ITP is increased. Fludarabine, a fluorinated nucleotide analog of vidarabine, is non-radioactive and a small-molecule phosphorylation inhibitor. Ivermectin is a small-molecule inhibitor of nuclear translocation mediated by α / β1 introgression protein. Both have high bioavailability and are widely used to treat various hematological diseases with good safety profiles. Their application in treating ITP is safe, effective, and shows high compliance.

The invention provides an application of combination of SPRC and a PD-1 or PD-L1 inhibitor in preparation of a lung cancer immunotherapy sensitizing drug, and relates to the technical field of biomedicine.In the application, through in-vitro cell experiments, cell co-culture experiments and in-vivo animal experiments, S-propargyl-L-cysteine (SPRC) can play a sensitizing role in the anti-lung cancer curative effect of the PD-1 inhibitor, and can be used for preparing a sensitizing drug for lung cancer immunotherapy. The core mechanism is as follows: 30 [mu] M SPRC is in a non-cytotoxic dose window and can specifically inhibit IFN-gamma induced STAT1 phosphorylation and PD-L1 up-regulation by depending on a CSE / H2S pathway, while IFN-gamma-STAT1-PD-L1 is a core signal axis of PD-L1 adaptive up-regulation in lung cancer cells, and the induction effect of TNF-alpha on PD-L1 is relatively weak; meanwhile, SPRC can inhibit activation of NF-kB induced by TNF-alpha and expression of inflammatory factors such as IL-6 and IL-8 through the pathway so as to exert the anti-inflammatory effect, the CD8 + T cell depletion proportion can be remarkably reduced by combining SPRC with anti-PD-1, the synergistic tumor inhibition effect is formed, the effect is verified in in-vivo and in-vitro experiments, and a closed loop of an in-vitro mechanism and an in-vivo curative effect is achieved.

The invention discloses application of a targeted Nup85 inhibitor in preparation of a medicine for preventing or treating hepatocellular carcinoma, and relates to the technical field of biological medicine and tumor immunotherapy. The invention provides an application of a targeted Nup85 inhibitor in preparation of a medicine for preventing or treating hepatocellular carcinoma. The inhibitor prevents and / or treats hepatocellular carcinoma by enhancing CD8 + T cell functions, enhancement of the CD8 + T cell functions is realized by regulating STAT1 / CCL5 / CXCL10 pathways, and Nup85 reduces expression of CCL5 and CXCL10 by inhibiting nuclear translocation of phosphorylated STAT1, so that infiltration and activation of CD8 + T cells are inhibited. The invention discloses an immune escape mechanism that Nup85 inhibits CD8 + T cell infiltration by inhibiting p-STAT1 nuclear translocation and down-regulating CCL5 / CXCL10 expression in liver cancer for the first time, provides a new liver cancer immunotherapy target, and broadens the application of nucleopore protein in tumor immunotherapy; the target Nup85 inhibitor can be obtained through a conventional means, a new clinical application direction of the target Nup85 inhibitor is defined, and the target Nup85 inhibitor has good clinical transformation and development prospects.

The disclosure provides a method for treating a subject afflicted with a cancer comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antagonist, e.g., an anti-PD-1 or anti-PD-L1 antibody, in combination with an indoleamine 2,3-dioxygenase inhibitor, wherein the subject is identified as exhibiting a combined biomarker comprising (a) a high IFNγ inflammatory signature score and (b) a low tryptophan 2,3-dioxygenase 2 (TDO2) gene expression score. The high IFNγ inflammatory signature score is determined by measuring the expression of a panel of IFNγ related inflammatory genes in a cancer sample obtained from the subject, wherein the gene panel comprises, e.g., IFNγ, CXCL10, CXCL9, HLA-DRA, IDO1, and STAT1. In some aspects, the gene panel further comprises CCR5, CXCL11, GZMA, and PRF1. In some aspects, the gene panel comprises CXCR6, TIGIT, PD-L1, PD-L2, LAG3, NKG7, PSMB10, CMKLR1, CD8A, IDO1, CCL5, CXCL9, HLA.DQA1, CD276, HLA.DRB1, STAT1, HLA.E, and TDO2.

The invention belongs to the technical field of biomedicine, and discloses application of fludarabine combined with a PD-1 antibody in preparation of a medicine for treating tumors and a related pharmaceutical composition. Fludarabine is used as an STAT1 inhibitor, can up-regulate the membrane expression level of PD-1 by inhibiting transcription of PRMT5, and has a synergistic effect with a PD-1 antibody to enhance anti-tumor immune response. In-vitro experiments prove that the combined scheme can significantly improve the killing activity of CD8T cells on tumor cells, and in-vivo experiments show that the combined scheme can effectively reduce the tumor volume and prolong the lifetime of tumor-bearing mice, and does not cause significant influences on blood pressure, blood routine, liver functions and other physiological indexes; and the proportion of immune cell subgroups such as regulatory T cells, myeloid-derived suppressor cells and the like is not interfered. The invention provides a new strategy for tumor immunotherapy with enhanced curative effect and good safety by regulating and controlling the I-type interferon / STAT1-PRMT5 / WDR77-PD-1 signal axis, and has important clinical transformation value.

The invention relates to the technical field of nano-drugs, in particular to a tolbuzumab / lanthanide series metal / nucleic acid nano-composite, a preparation method and application. The mass ratio of the tolbuzumab to the lanthanide series metal to the nucleic acid in the nano-composite is (0.5-5.1): 1: (10-11). The nano compound disclosed by the invention can be used for promoting the activation of a cGAS-STING-STAT1 pathway and blocking an IL6 / IL6R-STAT3 signal pathway at the same time, so that chronic inflammation caused by a CIN phenomenon of tumor cells is converted into anti-tumor immune response.

A neutralizing antibody capable of potent neutralization of SFTSVs and the use thereof. The neutralizing antibody specifically recognizes amino acids at 26th, 39th, 42nd, 46th, 50th and 53rd sites of the sub-domain I and amino acids at 260th, 263rd, 268th, 271st and 301st sites of the sub-domain III of the extracellular domain of SFTSVGn. The neutralization activity of the neutralizing antibody ZS004-1C5 in inhibiting SFTSV(DBV) infection of half of cells is 67 thousands times that of MAb4-5 which is the only one fully-humanized neutralizing antibody known so far. Simply by means of one inoculation, the neutralizing antibody ZS004-1C5 can prevent STAT1- / - immunodeficient mice from a lethal attack caused by viruses with a 10-fold median lethal dose (LD50), and therefore has the potential to be put into clinical treatment, and may improve the survival rate for patients with a severe fever with thrombocytopenia syndrome (SFTS) and reduce the risk for intensive care.

The invention relates to the field of biological medicine, and discloses application of an SMURF1 inhibitor, a synergistic immune composition and application of the synergistic immune composition. The SMURF1 inhibitor can be used for preparing drugs for regulating and controlling CD8 + T cell infiltration in a tumor immune microenvironment, and can up-regulate the STAT1 protein level and promote the expression of CXCL9 and CXCL10, thereby enhancing immune response and inhibiting tumor growth. The SMURF1 inhibitor is combined with the PD-1 and / or PD-L1 inhibitor for use, the anti-tumor curative effect can be further improved, and the SMURF1 inhibitor is suitable for tumor treatment related to SMURF1 expression up-regulation or activity abnormity.

The application belongs to the technical field of biological medicine, and particularly relates to the use of SH2 domain-containing protein tyrosine phosphatase 1 (SHP1) in the preparation of a drug for treating chronic pain, in particular to the use of SHP1 in the preparation of a drug for treating chronic pain by regulating the morphology of spinal cord astrocytes, the integrity of the blood-spinal cord barrier and the STAT1-CXCL10-CXCR3 neuroimmune signal axis, and a chronic pain treatment strategy based on the signal axis. The application first discloses that SHP1 in spinal cord astrocytes directly dephosphorylates STAT1, inhibits the transcription of CXCL10 and the subsequent infiltration of T lymphocytes into the spinal cord, and discloses the core analgesic mechanism, thereby establishing SHP1 as a new target for treating chronic pain, and opening up a new way for the precise treatment of clinical chronic pain, especially neuropathic pain.

The invention provides a detection kit for detecting interferon-related activating genes in neutrophil in a tumor microenvironment. The detection kit comprises an RNA extraction reagent, a reverse transcription reaction reagent, a quantitative PCR reagent, a probe, a positive reference substance and a negative reference substance. And the quantitative PCR reagent comprises upstream and downstream primers of nine interferon related genes, namely, ISG15 (Interferon Sorting Gene 15), RSAD2 (Registered Sequence Administration 2), IFIT1 (Interferon Institute of Transcription 1), IFI44L (Interferon Institute 44L), MX1, OAS1, STAT1, IRF7 and CXCL10. The detection kit can be used for detecting the expression quantity of nine genes including ISG15, RSAD2, IFIT1, IFI44L, MX1, OAS1, STAT1, IRF7 and CXCL10, accurate curative effect grouping is realized through dynamic monitoring of ISG15 + neutrophile granulocyte subpopulation, and meanwhile, improvement of curative effect prediction capability can be realized through combination with mrTRG.

The invention provides an application of a small molecule compound in preparation of an anti-aging product, and the small molecule compound can effectively intervene in an aging-related pathological process, significantly relieve systemic inflammation existing in an aging body, improve motor function decline caused by aging, and significantly enhance muscle function, coordination and endurance. And the overall exercise ability is improved. In addition, the small molecule compound can also significantly enhance the anti-infection ability of an elderly individual to bacteria, effectively relieve excessive inflammatory response and tissue pathological damage caused by infection and break vicious circle of infection acceleration function decline, and the effect of the small molecule compound is achieved by inhibiting overexpression of an STAT1 signal. The invention provides a new strategy with multiple beneficial effects of improving senescence-related chronic inflammation, motor function decline and bad outcome after infection, and provides a new technical choice for developing intervention means for senile co-diseases.

The present application relates to a composition and application for enhancing mesenchymal stem cell treatment efficiency, and belongs to the technical field of cell drug treatment. The composition for enhancing mesenchymal stem cell treatment efficiency comprises a PARP inhibitor and an inflammatory factor. The mesenchymal stem cells are pretreated by the composition, and the mesenchymal stem cells with enhanced treatment efficiency are obtained, which are used for preparing a therapeutic drug for immune diseases characterized by abnormal inflammatory response. The mesenchymal stem cells are treated by the PARP inhibitor combined with the inflammatory factor in the present application, which can improve the intracellular signal transduction and the phosphorylation level of STAT1, increase the expression of the immune suppressor IDO1 and PD-L1, thereby enhancing the immune regulation function of the stem cells, and realizing the gain effect on the treatment of immune diseases mainly characterized by abnormal inflammatory response.

The application discloses a compound with a structure as shown in formula I or a pharmaceutically acceptable salt thereof, wherein L is selected from n1 is an integer from 2 to 7, n2 is an integer from 1 to 4, n3 is an integer from 4 to 6, and R is selected from the application. The compound only needs a small amount of use to have a significant cell proliferation inhibiting effect on tumor cells, can significantly degrade target proteins STAT3 and pSTAT3, can degrade STAT3 through a ubiquitin-proteasome pathway, and has almost no influence on STAT1 and STAT2. The application further discloses a use of the compound or the pharmaceutically acceptable salt thereof in preparation of a STAT3 degradation targeting agent.

The invention relates to the technical field of bladder cancer treatment, and particularly discloses a method for inducing necrotic apoptosis of bladder cancer cells by inhibiting ADM up-regulation of STAT1, and the method comprises the following steps: resuscitating a cell cryopreservation tube filled with a human bladder cancer cell strain T24, and then adding the cell cryopreservation tube into a complete culture medium for cell culture; when the growth density of the human bladder cancer cells reaches 80%, pancreatin is added for digestion to prepare a cell suspension, then centrifugation is performed, a supernatant is discarded, and subculture is performed after resuspension; the method comprises the following steps: preparing cells in subculture into a cell suspension, inoculating the cell suspension into a 6-well plate for culture, then discarding a culture medium, adding a 1640 culture medium, adding ADM-siRNA and LipofectamineTM3000 for transfection, collecting the cells, and detecting the apoptosis condition. According to the invention, ADM-SiRNA is transfected in bladder cancer cells to knock down the expression of ADM and up-regulate the expression of STAT1, so that an STAT1-mediated RIPK1 / RIPK3 / MLKL signal channel is activated, and bladder cancer cell apoptosis is promoted, so that the invention provides an important theoretical basis and practical guidance for developing accurate and efficient anti-tumor therapy.

The invention provides application of fludarabine in preparation of a medicine for preventing and / or treating corneal epithelium lesion, and belongs to the technical field of biological medicine preparation. The invention discloses application of fludarabine in preparation of a medicine for preventing and / or treating corneal epithelium lesion. Experiments show that diabetes can cause increase of expression of STAT1 in corneal epithelium cells and delay healing of mouse corneal epithelium wounds, and the exogenous STAT1 antagonist fludarabine can reverse the healing delay phenomenon of diabetic mouse corneal epithelium wounds and promote repair of the corneal epithelium wounds. Therefore, the technical scheme provided by the invention provides a new treatment means for repairing the corneal epithelium lesion.

The application belongs to the technical field of pharmaceutical chemistry, and discloses a small-molecule inhibitor targeting PARP11 and application thereof in preparation of an antitumor drug. Through systematic optimization of the skeleton structure of ITK7, a new type of PARP11 inhibitor with high efficiency, high selectivity and high safety is obtained. The compound can effectively activate the IFN-gamma / STAT1 signal pathway, inhibit AKT signal activation, improve the tumor immune microenvironment, and significantly inhibit tumor growth and metastasis, thereby providing a new chemical entity and treatment strategy for development of a new type of immunomodulatory antitumor drug.

The invention belongs to the technical field of medicinal chemistry, and discloses a targeted PARP11 small-molecule inhibitor and application thereof in preparation of antitumor drugs, and the novel PARP11 inhibitor with high efficiency, strong selectivity and high safety is obtained through systematic optimization of an ITK7 skeleton structure. The compound can effectively activate an IFN-gamma / STAT1 signal channel, inhibit AKT signal activation, improve a tumor immune microenvironment and significantly inhibit tumor growth and metastasis, and a new chemical entity and a treatment strategy are provided for development of novel immunoregulation type antitumor drugs.

Inventors demonstrated that an epigenetic regulator CBX3 antagonizes IFNγ signalling via directly repressing the transcription of two key interferon-stimulated immune genes, STAT1 and PD-L1. The key role of CBX3 in repressing STAT1 and PD-L1 transcription suggests that CBX3 is an important checkpoint to control immune genes' activation in response to different ligands' stimulation, such as the important immune modulator IFNγ, which placed CBX3 in a key position to keep colon immune homeostasis. This role placed also CBX3 in a key position to keep colon immune homeostasis. These studies have started to reveal a new role of CBX3 in controlling the colon epithelium inflammatory response, in addition to its classical role in the formation and stabilization of heterochromatin. Particularly, low CBX3 expression is associated with better CRC patients' overall survival. Corresponding to this result, CBX3 depletion makes IFNγ-insensitive CRC cells dramatically regain IFNγ sensitivity, which significantly increases CRC cells' chemosensitivity under IFNγ stimulation. Accordingly, the invention relates to a Chromobox protein homolog 3(CBX3) inhibitor for use in the treatment of cancer in a subject in need thereof.