48 results about "STAT3" patented technology

The present application belongs to the field of cell therapy and immunotherapy, and provides a genetically engineered human trophoblast, a preparation method and application thereof. The human trophoblast takes K562 cells as starting cells, and stably expresses membrane-bound interleukin 21, CD137 ligand and Delta-like ligand 1 after genetic engineering. The constructed K562 three-factor trophoblast can significantly improve the expansion efficiency, activation state and functional stability of NK cells and γδT cells. The synergistic mechanism includes enhancing the proliferation, cytotoxicity and stemness maintenance of NK cells and γδT cells through STAT3, NF-κB and Notch signaling pathways, respectively. The human trophoblast has the advantages of good expression stability, significant functional enhancement, and high activity after freezing and recovery.

Pharmaceutical compositions and therapeutic methods are provided comprising a single-domain antibody consisting of SEQ ID NO:1 and a pharmaceutically acceptable carrier. The antibody inhibits KRAS GTPase activity and inhibits phosphorylation of STAT3. In certain embodiments, inhibition of KRAS results in decreased phosphorylation of ERK1 / 2. The antibody reduces tumor cell surface PD-L1 expression and reduces VEGF production. The antibody crosses the blood-brain barrier following systemic administration and may exhibit sustained biological activity in vivo. Methods are provided for treating KRAS-mutant cancers, including pancreatic cancer and triple negative breast cancer, and for enhancing anti-tumor immunity through reduction of PD-L1 expression.

To provide a method of treating an inflammatory neurological disease or condition that can result in destruction or degeneration of axons or myelin.SOLUTION: Provided is a combination comprising a) a compound of formula (I) or a pharmaceutically or veterinarily acceptable salt thereof; and b) one or more drugs selected from the group consisting of I) a compound of a particular formula or a pharmaceutically or veterinarily acceptable salt thereof; ii) a sphingosine-1-phosphate receptor inhibitor (S1PR modulator); and iii) a signal transducer and activator of transcription 3 (STAT3) inhibitor.SELECTED DRAWING: None

The invention relates to application of WDR74 and / or ALYREF as molecular targets in esophageal squamous cell carcinoma diagnosis and treatment, and belongs to the technical field of biological medicine. Aiming at the problem that the esophageal squamous cell carcinoma lacks an effective targeted treatment means, the invention discovers that the expression quantity of WDR74 in tumor tissues is obviously higher than that in para-carcinoma tissues, and the high expression of WDR74 prompts poor prognosis of a patient, and reveals that WDR74 protein and ALYREF protein have specific binding, and the mRNA stability of EGFR is enhanced through ALYREF-mediated m5C RNA epigenetic modification, so that STAT3 phosphorylation is activated, and the treatment effect of the esophageal squamous cell carcinoma is enhanced. Further, the STAT3 is combined with the promoter region of the apoptosis-inhibiting gene MCL1, and finally cell apoptosis is inhibited and tumor formation is promoted. The invention provides a new molecular target and a solution for developing a WDR74 and ALYREF targeting medicine for treating esophageal squamous cell carcinoma and related diagnosis and prognosis evaluation products.

This invention discloses a compound having the structure shown in general formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. This invention also discloses a composition, formulation, and application containing the above compound. The compound of this invention degrades the transcription factor STAT3, exhibits antiproliferative inhibitory activity against the Karpas299 cell line, and has a favorable tumor / plasma AUC ratio.

Described herein are compositions relating to cell-penetrating conjugates of formula (I) or (IV). The compositions are capable of penetrating cells and recognizing intracellular targets (e.g., STAT3) and are, inter alia, useful for diagnostic and therapeutic purposes.

The invention relates to application of a reagent for inhibiting STAT3 gene expression in treatment of oxidative damage of trabecular meshwork cells. According to the invention, a signal channel STAT3 to EIF4E to TGF-beta-SMAD < 2 / 3 > for regulating and controlling the oxidative damage of the trabecular meshwork cells is innovatively found, and the STAT3 activates the TGF-beta-SMAD < 2 / 3 > channel by combining with EIF4E3, so that the apoptosis, oxidative stress and fibrosis of the trabecular meshwork cells caused by the oxidative damage are promoted. After the expression of the STAT3 gene in trabecular meshwork cells is inhibited, the EIF4E3 level can be reduced, and the apoptosis, oxidative stress and fibrosis of the trabecular meshwork cells induced by EIF4E3 are improved. Therefore, a reagent for inhibiting STAT3 gene expression can be used for treating trabecular meshwork cell oxidative damage and eye diseases related to the trabecular meshwork cell oxidative damage, including glaucoma and the like.

The invention discloses a phototherapy nano-drug with mitochondrial / STAT3 protein double-site targeting. The phototherapy nano-drug is ATO / CR nano-particles formed by self-assembling a compound CR and atorvaquone under the action of distearoyl phosphatidyl ethanolamine-polyethylene glycol; the structure of the compound CR is shown as a formula I in the specification. The invention discloses an application of the phototherapy nano-drug with mitochondrial / STAT3 protein double-site targeting in preparation of drugs for treating tumors. The phototherapy nano-drug can target mitochondria and STAT3 protein in tumor cells through ATO, and can also passively target tumor sites through the high-permeability long-retention effect of nano-particles, so that more nano-therapeutic agents are enriched around tumors, and the curative effect is improved. The phototherapy nano-drug provided by the invention has good photothermal performance, can effectively enhance the PTT effect of gastric cancer, and exerts the tumor synergistic treatment ability by promoting cell apoptosis, inhibiting angiogenesis and hindering the cell cycle.

This invention belongs to the field of biomedical technology and relates to the application of OSM inhibitors in the preparation of drugs for the prevention or treatment of calcific aortic valve disease. This invention reveals for the first time that OSM drives osteogenic differentiation and calcified nodule formation of valvular interstitial cells through the OSM-OSMR-JAK2 / JAK3-STAT3-RUNX2 signaling axis, which is the core pathogenic mechanism leading to calcific aortic valve disease. This invention utilizes anti-OSM neutralizing antibodies or sulforaphane to effectively block this signaling axis, significantly inhibiting macrophage infiltration, valvular calcification, and improving hemodynamic abnormalities. This invention provides a precise target and a novel strategy for the modification therapy of calcific aortic valve disease, solving the technical problem of the ineffectiveness of traditional broad-spectrum anti-inflammatory therapy in valvular calcification.

This invention discloses a STAT3-mutated cell product and its uses, belonging to the interdisciplinary field of genetic engineering and tumor immunotherapy. Through saturation mutation screening, this invention is the first to discover that STAT3 gain-of-function mutations promote CAR-T anti-tumor responses. Furthermore, through cell and animal experiments, it is demonstrated that activating STAT3 can alleviate CAR-T cell immune exhaustion and significantly enhance the in vivo and in vitro killing ability of CAR-T cells against tumor cells, thereby improving the efficacy of anti-tumor therapy. This invention provides a new therapeutic target and strategy for the field of tumor immunotherapy, possessing significant scientific and clinical application value.

The present invention relates to a single domain antibody specifically binding to STAT3 or an antigen-binding fragment thereof, a fusion protein comprising the single domain antibody or the antigen-binding fragment thereof, and a use of the fusion protein.

The present disclosure provides cytokine signaling receptors to provide STAT3 and STATS signaling in cells such as iPSC-derived CD8+ T cells. The cytokine signaling receptors may be under the control of endogenous or exogenous promoters to regulate their expression in a cell. The present disclosure also provides engineered cells comprising the cytokine signaling receptors, or a combination of a cytokine signaling receptor and a secreted cytokine, as well as methods of use of the engineered cells.

The disclosure is generally directed to spherical nucleic acids (SNAs), nanostructures with a core surrounded by a radial presentation of oligonucleotides, that can activate a cytoplasmic DNA sensor including but not limited to cyclic GMP-AMP synthase (cGAS). In some embodiments, the SNAs also inactivate a transcription factor including but not limited to signal transducer and activator of transcription 3 (STATS). Methods of making and using the SNAs are also provided herein. In some aspects, the present disclosure provides a spherical nucleic acid (SNA) comprising (a) a nanoparticle core; and (b) a shell of oligonucleotides attached to the external surface of the nanoparticle core, the shell of oligonucleotides comprising a double-stranded or single-stranded stem loop DNA oligonucleotide that activates cyclic GMP-AMP synthase (cGAS) and is at least 15 base pairs in length.

The disclosure relates to adoptive cell therapy compositions including a population of isolated immune cells that are obtained from a donor subject. The immune cells can be modified to suppress Bruton's tyrosine kinase (BTK), interleukin-2-inducible T cell kinase (ITK), delta isoform of phosphoinositide 3-kinase (PI3Kδ), helios, blimp1, SOCS1, GATA3, IL-10, STAT3, TOX, CD25, foxp3, Ezh2, TGF-beta Receptor II, LAG-3, PD-1, TNF-alpha, or combinations thereof. The immune cells are optionally depleted of CD8+ T cells by about 10-fold or greater relative to un-depleted leukocytes.

This invention discloses a triphenylamine-based D-A type AIE molecule targeting STAT3, its preparation method, and its application in the diagnosis and treatment of colorectal cancer. This molecule uses triphenylamine as a donor and pyridinium as an acceptor, linked by a rigid conjugated trans-vinyl group, exhibiting aggregation-induced emission (AIE) properties. The preparation method employs a Knoevenagel condensation reaction, using 4-(diphenylamino)benzaldehyde and 1,4-dimethylpyridinium iodide as raw materials, and proceeds via a nucleophilic addition-dehydration reaction catalyzed by pyrrolidine, with a yield of 50±3% and a purity ≥98%. This molecule exhibits a fluorescence emission wavelength of 640 nm, demonstrates a significant AIE effect, can penetrate the colorectal cancer cell membrane and specifically aggregate, and shows activity against the IC50 of HCT116 and DLD1 cells. 50 The concentrations were 6.41 μM and 11.46 μM, respectively, which exerted anti-tumor effects by inhibiting STAT3 phosphorylation, enabling integrated diagnosis and treatment of colorectal cancer.

The invention relates to the technical field of tumor early warning, and discloses an LAMA-IL-6-JAK-STAT3 axis-targeted uveal melanoma micro-metastasis early warning and immune escape blocking system, which comprises a micro-metastasis early warning module, a cooperative control module and an immune escape blocking module, the system executes the following steps: S1, target anchoring and sample collection: the micro-transfer early warning module specifically binds LAMA protein, IL-6 cell factors and JAK / STAT3 kinase in a sample through a targeting probe, and collects uveal melanoma nidus tissue cells and a peripheral blood sample to complete target anchoring. In the system, an LAMA-IL-6-JAK-STAT3 axis is used as a specific action target, an LAMA antagonist, an IL-6 receptor inhibitor and a JAK kinase inhibitor in the composite targeting preparation respectively and accurately act on key nodes of a signal axis, and down-regulation of STAT3 activity is realized through stepped regulation, so that non-specific damage of traditional treatment to normal cells is avoided, toxic and side effects of intraocular tissues are reduced, and the treatment effect is good. The local diagnosis and treatment requirements of uveal melanoma are particularly met.

The invention relates to siRNA targeting TRIM29, the sequence of the siRNA is shown as SEQ ID NO.1. Through cell level and animal level experiment detection, the siRNA can inhibit expression of the TRIM29, and the sensitivity of gallbladder cancer to gemcitabine is remarkably improved; the invention further relates to gemcitabine and TRIM29 siRNA co-loaded lipid nanoparticles and a preparation method and application thereof, the preparation method comprises the steps that firstly, gemcitabine and TRIM29 siRNA wrapped lipid nanoparticles are constructed, then the gemcitabine and TRIM29 siRNA are co-incubated to obtain GSL, the GSL is oval in microcosmic shape and good in stability, through cell level and animal level experiment detection, the GSL has a good anti-tumor effect, and the GSL has a good anti-tumor effect on the gemcitabine and TRIM29 siRNA co-loaded lipid nanoparticles. The GSL can significantly reduce the protein expression level of TRIM29, significantly improve the sensitivity of gallbladder cancer to gemcitabine, inhibit tumor growth, and inhibit STAT3 pathway, and the GSL prepared by the method has good biological safety, and opens up a new channel for treatment of gallbladder cancer.

Methods of inducing rejuvenation in a population of adult glial progenitor cells, and methods of treating a subject having a myelin deficiency are disclosed in this patent application. The method of inducing rejuvenation in a population of adult glial progenitor cells, may comprise: administering, to the population of adult glial progenitor cells, one or more nucleic acid molecules encoding microRNAs, wherein administering suppresses the signal transducer and activator of transcription 3 (STAT3) signaling pathway; and / or administering microRNAs, wherein administering suppresses the E2F transcription factor 6 (E2F6) signaling pathway; and / or administering microRNAs, wherein administering suppresses the Myc-associated factor X (MAX) signaling pathway, wherein the one or more nucleic acid molecules are administered in an amount sufficient to induce rejuvenation in the population of adult glial progenitor cells.

Pharmaceutical compositions and compounds comprising a phosphorothioated CpG oligodeoxynucleotide linked to a DNA oligonucleotide that is hybridized an RNA aptamer are useful in methods of treating cancer (such as leukemia) and methods of inhibiting DNA methyltransferase. In embodiments, the RNA aptamer binds to an intracellular target such as DNMT1, NF-kB, RUNX1, MYC, MYB, ETS, PAX5, MDM2, F0XM1, PU.l, STAT3, STATS. STAT6, FAD, ATP5B, or beta-catenin.

The invention discloses an application of sanguinarine chloride (SGC) in preparation of a medicine for treating a PRCC-TFE3 rearranged renal cell carcinoma (rRCC), and belongs to the technical field of biological medicine, in particular to an application of sanguinarine chloride (SGC) in preparation of a medicine for treating a PRCC-TFE3 rearranged renal cell carcinoma (rRCC). According to the application, it is found for the first time that SGC has a specific killing effect on PRCC-TFE3 rRCC cells and has extremely low toxicity on normal kidney cells; the SGC has multiple anti-tumor action mechanisms: on one hand, the SGC is directly combined with and antagonizes a VEGFR2 receptor on a cell membrane to block autocrine signal transduction of VEGFB; on the other hand, the SGC inhibits transcription of VEGFB (vascular endothelial growth factor B) through ROS / p-STAT3 axis epigenetics; besides, the SGC can inhibit the production of lactic acid and the acylation of H3K18, and down-regulate the secretion of chemotactic factors, so that the infiltration of polymorphic myeloid-derived suppressor cells (PMN-MDSCs) in a tumor microenvironment is remarkably inhibited; in an immune sound mouse model, the SGC shows an excellent in-vivo anti-tumor effect, and a brand new targeting and immunoregulation double-effect candidate drug is provided for clinically treating the PRCC-TFE3 rRCC lacking an effective standard therapy.

The application relates to the fields of biological medicine and antibody engineering technology, and particularly relates to a STAT3 hybridoma-derived antibody affinity maturation method based on computational biology, which comprises the following steps: (1) obtaining an antibody variable region sequence; (2) constructing STAT3 antigen and antibody models and evaluating; (3) performing antigen-antibody molecular docking and optimization, and screening out models; (4) performing docking model analysis, and obtaining potential saturation mutation sites; (5) performing site saturation mutation, and obtaining mutation results; (6) performing mutation site analysis, and determining final mutation sites; (7) amplifying a target fragment containing the mutation sites; (8) constructing a recombinant expression vector, and obtaining a reformed STAT3 recombinant antibody through eukaryotic expression and purification; and (9) performing relative affinity determination.

The subject matter disclosed herein is directed to modulating gene expression using siRNA compositions and methods directed to affecting key cell populations supporting the growth and metastasis of cancer to affect the beneficial treatment, remission or removal of the underlying tumor in a patient.

The present invention relates inter alia to pharmaceutical compositions and kits comprising (i) an inhibitor of the expression, activity and / or function of c-Raf, (ii) an inhibitor of the expression, activity and / or function of EGF Receptor (EGFR), or (iii) an inhibitor of the expression, activity and / or function of STAT3, for use in combination in the prevention and / or treatment of cancer.

The application relates to the field of health assessment, and particularly discloses a ZNF281-based gastric cancer prognosis value evaluation system, which comprises a ZNF281 expression quantification module, which is used for detecting the protein / RNA expression level of ZNF281 in tumor tissue through immunohistochemistry, real-time fluorescent quantitative PCR or Western blot technology; a stemness feature and signal path analysis module, which is used for acquiring the protein expression or cell positive rate of stemness genes CD44 and SOX9; then evaluating the activation state of an IL6 / JAK / STAT3 path, including Western blot detection of a p-STAT3 / STAT3 ratio, ELISA determination of IL6 and CXCL5 cytokine levels; then analyzing the cancer-associated fibroblast infiltration in a tumor microenvironment, quantifying the CAF density through alpha-SMA immunofluorescence staining, and combining single-cell sequencing analysis of the interaction strength of a CXCL5 / CXCR2 signal shaft. The technical scheme of the application can integrate the expression amount of ZNF281, signal path activity and clinical pathological data, and precisely stratify the chemotherapy sensitivity and prognosis of gastric cancer patients.

The invention discloses an application of tripterine in preparation of a medicine for enhancing bladder cancer resisting activity of an MEK inhibitor, the Western blot experiment proves that the tripterine can effectively reduce p-STAT3 and p-Akt compensatory expression increase caused by the MEK inhibitor for the first time, so that STAT3 and Akt signal channel compensatory activation caused by the MEK inhibitor is reversed; in-vivo animal experiments show that the combination of the tripterine and the MEK inhibitor has a remarkable synergistic anti-tumor effect, and the anti-tumor effect of the tripterine is superior to that of any single drug; the pharmaceutical composition provided by the invention can effectively block the escape path of tumor cells by simultaneously inhibiting the three key signal paths of MEK / ERK, STAT3 and PI3K / Akt, overcomes or delays the drug resistance of the MEK inhibitor mediated by compensatory pathway activation, and provides a new drug combination strategy for the treatment of malignant tumors.

The invention provides a method and system for detecting the malignant degree of endometrial cancer cells, and the method comprises the following steps: judging the influence mechanism of leptin on the malignant degree of cancer cells by detecting parameters such as leptin concentration, JAK2 / STAT3 pathway activation degree, cell proliferation activity, migration and invasion ability and the like; the dynamic association between the leptin concentration change and the activation state of the JAK2 / STAT3 signal channel can be systematically evaluated, the regulation and control effect of the channel on the proliferation, migration and invasion ability of cancer cells is effectively quantified, and a scientific basis is provided for developing treatment schemes and drugs for endometrial cancer.

The application discloses a method for analyzing active ingredients of Xuanhushan against liver cancer based on multi-target affinity ultrafiltration, and the method comprises the following steps: preparing water extract of Xuanhushan; respectively incubating with four target proteins of COX-2, HKDC1, STAT3 and NGF; identifying the combined ingredients after ultrafiltration separation through LC-MS / MS and calculating the binding degree; verifying the HepG2 cell proliferation inhibition activity through a CCK-8 method; simulating the binding mode and free energy through molecular docking, and constructing an active ingredient-multi-target interaction network; the application integrates experimental and calculation technologies, systematically clarifies the active ingredients and molecular mechanisms of Xuanhushan against liver cancer, and provides a new strategy for multi-target analysis of traditional Chinese medicine compounds.

The present invention relates to a single domain antibody specifically binding to STAT3 or an antigen-binding fragment thereof, a fusion protein comprising the single domain antibody or the antigen-binding fragment thereof, and a use of the fusion protein.

The application belongs to the technical field of biological medicine, and provides an application of E3 ubiquitin ligase TRIM40 in preparation of a drug for treating myocardial hypertrophy, wherein the application first discloses that E3 ubiquitin ligase TRIM40 is highly expressed in pathological myocardial hypertrophy and promotes myocardial cell hypertrophy, thereby providing a theoretical basis for the E3 ubiquitin ligase TRIM40 as a therapeutic target. In addition, the application finds that the E3 ubiquitin ligase TRIM40 regulates the function of STAT3 by directly combining and ubiquitinating STAT3, thereby expanding the upstream regulation mechanism of STAT3 in myocardial hypertrophy, and providing a potential target and a theoretical basis for developing a novel anti-myocardial hypertrophy drug targeting the TRIM40-STAT3 pathway.

The present invention discloses an monoclonal antibody, which can bind to HyIL-6 with the binding constant 2.86×10−10 and significantly inhibit IL-6 / IL-6R / gp130 complex formation. In addition, the monoclonal antibody of the present invention effectively inhibits HyIL-6-stimulated signal transducer and activator of transcription 3 (STAT3) activation and related vascular endothelial growth factor (VEGF) induction. Data from hydrogen deuterium exchange mass spectrometry (HDX-MS) demonstrate that the antibody of the present invention mainly binds to site IIIa of IL-6 and blocks the final step in the interaction between gp130 and IL-6 / IL-6R complex. Additionally, data from ELISA binding assays and kinetics assays indicate that the antibody of the present invention interacts simultaneously with IL-6 and IL-6R, while it does not interact with IL-6R alone. The unique features of the antibody of the present invention offer a novel alternative for IL-6 blockade and illuminate a better therapeutic intervention targeting IL-6.