57 results about "Stat3 signaling" patented technology

The subject invention pertains to the treatment of tumors and cancerous tissues and the prevention of tumorigenesis and malignant transformation through the modulation of JAK / STAT3 intracellular signaling. The subject invention concerns pharmaceutical compositions containing cucurbitacin I, or a pharmaceutically acceptable salt or analog thereof, to a patient, wherein the tumor is characterized by the constitutive activation of the JAK / STAT3 intracellular signaling pathway. The present invention further pertains to methods of moderating the JAK and / or STAT3 signaling pathwaysin vitro or in vivo using cucurbitacin I, or a pharmaceutically acceptable salt or analog therof. Another aspect of the present invention concerns a method for screening candidate compoudns for JAK AND / or STAT3 inhibition and anti-tumor activity.

Signal Transducer and Activator of Transcription (STAT) proteins have a fundamental role cell signaling, and are activated by a large number of cytokines and growth factors. One member of the STAT family, STAT3, has a critical role in oncogenesis. The present invention relates generally to disruption of the pathway of STAT3 signaling in the treatment of human cancer. STAT3 activation is shown to be present in diverse tumor cell lines and tumors, to promote oncogenesis, to inhibit apoptosis, and to reduce sensitivity to chemotherapeutic agents. Inhibition of STAT3 signaling induces apoptosis specifically in tumor cell lines, and increases sensitivity to chemotherapeutic agents. The invention relates more particularly to methods, compositions, means of administering such compositions, and means for identifying such compositions for the inhibition of STAT3 intracellular signaling in the treatment of human cancers.

Methods of enhancing antitumor activity of an immune cell comprising contacting the immune cell with a Stat3 inhibitor are described. Also described are methods of killing a tumor cell or inhibiting tumor growth in a subject comprising contacting an immune cell of the subject with a Stat3 inhibitor.

The present invention relates to a set of biomarkers, microarrays that provide for detection thereof, an expression signature comprising 16 genes or a subset thereof, and the use thereof in determining the regulation status of IL-6 / STAT3 signaling pathway in a cell sample or subject, as well as compositions for the detection thereof. The regulation status of IL-6 / STAT3 signaling pathway in a cell sample or subject may be assayed based on the level of expression of one or more of these genes. The methods and compositions provided herein may be used to evaluate IL-6 / STAT3 pathway regulation status in a sample; classify a cell sample as having a deregulated or regulated IL-6 / STAT3 signaling pathway; determine whether an agent modulates the IL-6 / STAT3 signaling pathway; predict the response of a subject to an agent that modulates the IL-6 / STAT3 signaling pathway; assign treatment to a subject; and / or evaluate the pharmacodynamic effects of therapies designed to regulate IL-6 / STAT3 pathway signaling. Expression of the biomarkers is preferably determined by RT-PCR using SYBR Green methods, and the expression data analyzed and compared to a control sample by use of the random forest method.

The invention discloses an STAT3 (Signal Transducer and Activator of Transcription 3)-targeting small molecular compound as well as a preparation method and application thereof. The STAT3 inhibitor is a compound shown as a general formula I in the specification, wherein R<1> is 5-chloro-2-hydroxyphenyl, (E)-3-(6-bromo-2-pyridine)-2-cyan or 4-(2-phenylquinoline); R<2> is hydrogen or C1-C6 linear alkyl or branched alkyl. The compound has the advantages that the proliferation and the survival of various tumor cells of breast cancer, lung cancer, liver cancer, cervical cancer, prostate cancer and the like can be remarkably inhibited; the STAT3 signal channel of the tumor cells is inhibited; therefore, the tumor cell apoptosis is induced and the effect of treating the tumor diseases is achieved.

The invention discloses an application of a compound as a JAK-STAT3 signal passage inhibitor, and particularly relates to an application of a compound with a formula I or pharmaceutically acceptable salt of the compound in the process of preparing an anti-tumor medicament. The application provides a novel treating candidate medicament for a tumor patient, thereby probably further improving the treatment effect on the patient and improving the prognosis of the patient. The compound with the formula I or the pharmaceutically acceptable salt of the compound has the effect on various tumor cells, which indicates that the compound can be used for treating various cancers including cerebral tumor, genitourinary system tumor, lymphatic system tumor, stomach cancer, laryngeal cancer, nasopharyngeal cancer, skin cancer, bone cancer, blood cancer, leukemia, breast cancer and histiocytic lymphoma, non-small cell lung cancer, small-cell lung cancer, lung adenocarcinoma, lung squamous cell cancer, pancreatic cancer, prostatic cancer, liver cancer, epithelial cell cancer and the like. The definition of genes in the formula refers to description for details.

The invention belongs to the field of medical biology, and specifically provides a designing and preparing method of a class of effective signal transduction inhibition compounds for signal transducerand activator of transcription type3 (STAT3), and applications of the effective signal transduction inhibition compounds mainly in clinical treatment of breast cancer. According to the present invention, a variety of breast cancer cell lines have the abnormal intracellular STAT3 signaling system regulation mechanisms, and the compounds of the present invention can significantly inhibit the signaltransduction of STAT3 so as to provide the potential important significance in the clinical treatment and research of breast cancer.

The present invention relates to a mesenchymal stem cell having immunomodulatory activity and a preparation method therefor and, more specifically, to: a rapamycin-treated mesenchymal stem cell having immunomodulatory activity, which expresses any one or more cell surface factors selected from the group consisting of CCR1, CCR2, CCR3, CCR4, CCR7, CCR9 and CXCR4; a cell therapy composition comprising the mesenchymal stem cell, for preventing or treating immune disorders; and a preparation method for the mesenchymal stem cell having immunomodulatory activity. The rapamycin-treated mesenchymal stem cell having immunomodulatory activity, according to the present invention, has increased expression of IDO, TGF-β and IL-10 which are factors having immunomodulatory activity, has decreased expression of Phospho-mTOR, Rictor and Ractor which are signal transduction factors of mTOR, and has increased expression, in the cell, of autophagic inducer Beclin1, ATG5, ATG7, LC3I or LCII. If this cell is used as a cell therapy in individuals having immune disorders, it is possible to effectively treat immune disorders.

The invention discloses an STAT (Signal Transducer And Activator Of Transcription)3 signal channel small-molecule inhibitor and application thereof. The inhibitor is expressed in a chemical structural formula which is shown in the specification, wherein R1 is halogenated aryl, R2 is halogenated aryl, R3 is oxygen or sulphur. The inhibitor has functions of effectively inhibiting the multiplication of various tumor cells and inducing the apoptosis of the various tumor cells. The newly developed STAT3 signal channel small-molecule inhibitor not only has a remarkable inhibition effect on the phosphorylation of the STAT3, but also has the remarkable inhibition effect on the IL-6-induced STAT3 activation and the activation of the STAT3 upstream signal CrC and Jak2, and therefore, the multiplication of the various tumor cells can be inhibited and the apoptosis of tumor cells can be induced. Besides, the STAT3 signal channel small-molecule inhibitor has an in-vitro and vivo treatment effect on various tumors of acute and chronic leukemia, multiple myeloma, lymphoma, lung cancer, prostate cancer, cervical cancer and the like.

The invention belongs to the technical field of medicine and pharmacy, and discloses an application of a micromolecule compound WZ-2-033 shown as below to medicines for treating breast cancer and stomach cancer. The compound can restrain proliferation, clone formation, migration and invasion of breast cancer cells and stomach cancer cells, and can induce apoptosis of the breast cancer cells and the stomach cancer cells. The compound exerts effects through influencing an STAT3 signal channel, can reduce the phosphorylation level (Y705) of the STAT3, can reduce STAT3 dimer formation, can reduceDNA combining capacity and transcriptional activity of the STAT3, and can further reduce the expression level of STAT3 target genes c-Myc, Bcl-xL and Mcl-1 so as to restrain activation of STAT3 signals and restrain the growth of the breast cancer cells and the stomach cancer cells. In an animal model, the compound can restrain the growth of stomach cancer cell transplanted tumors and has favorableapplication prospects.

The invention discloses an application of tegaserod or pharmaceutically acceptable salt thereof as a JAK-STAT3 signal channel inhibitor and an immunomodulator and an application of the tegaserod or the pharmaceutically acceptable salt thereof in preparation of antitumor drugs. The tegaserod and the pharmaceutically acceptable salt thereof have a very good inhibition effect on the growth of varioustumor cells in vivo and in vitro, and are expected to be used for treatment of various cancers.

The invention belongs to the field of biotechnology and medical technology, and provides an application of self-designed RNA nucleic acid in enhancing the sensitivity of radiation-resistant lung cancer cells to radiation therapy. The RNA nucleic acid provided by the invention can significantly increase the sensitivity of radiation-resistant lung adenocarcinoma cells to radiation therapy by regulating the STAT3 signal, thereby providing a new idea for the treatment of radiation-resistant lung adenocarcinoma.

The invention belongs to the field of medicines, and discloses a substituted pyridino imidazole compound as shown in the specification and an application thereof in preparation of a medicine for treating lung cancer. Cell level experiments prove that the compound can inhibit proliferation, migration, invasion and clone formation of lung cancer cells, induce apoptosis of the lung cancer cells and inhibit the phosphorylation level of STAT3; mouse in-vivo experiments show that the compound can inhibit growth and metastasis of lung cancer cells, specifically inhibit an STAT3 signal path, inhibit growth of lung cancer cell transplantation tumors and patient PDX tumors in an animal model, lay a foundation for subsequent new drug research and development, and have important theoretical significance and wide application prospects.

The invention discloses an application of cinnamic acid on preparation of medicines for treating cancers. The cancers comprise a prostatic cancer, a non-Hodgkins lymphoma, spongioblastoma, oophoroma and a colorectal cancer. The cinnamic acid can effectively promote apoptosis of malignant cells, adjusts a proliferation cycle of the malignant cells and restrains proliferation of the malignant cells to a certain degree; and moreover, the cinnamic acid can act on an STAT3 signal channel, obviously reduces expression of STAT3 genes and effectively restrains growth of malignant tumors of the prostatic cancer, the non-Hodgkins lymphoma, the spongioblastoma, the oophoroma and the colorectal cancer in bodies of mice. By the application of the cinnamic acid on preparation of the medicines for treating the cancers, novel medicines with antitumor activity can be conveniently researched on the aspects of cell apoptosis and tissue cell proliferation cycle, prevention and treatment on various malignant tumors which are relevant to STAT3 are researched conveniently, and a novel thinking is provided for treatment of the various malignant tumors.

The abnormal adjustment and control of an Stat3 (signal transducer and activator of transcription 3) signal transduction system generally exist in canceration cell strains. The invention provides a compound EGCG (epigallocatechin gallate) which is an effective Stat 3 inhibitor. The Stat 3 inhibitor can be applied to preparation of cancer therapy medicines containing endogenous activated Stat3 signal paths.

The invention provides a new medicinal use of serrate rabdosia herb, particularly application of serrate rabdosia herb extractive serving as an STAT3 signal specificity inhibiter in preparation of an anti-tumor drug. The cell model screening experiment, Western-Blot, the semi-quantitative PCR detection and the animal experiment testify that the serrate rabdosia herb extractive has very good STAT3 inhibition activity, and can effectively inhibit the expression of related genes adjusted and controlled by STAT3, thereby effectively inhibiting the growth of tumor cells on which the STAT3 signal depends. Therefore, the serrate rabdosia herb extractive serves as the STAT3 signal specificity inhibiter, the pharmaceutically acceptable process and auxiliary materials are adopted to prepare the anti-tumor drug preparation based on STAT3 target spot, and a very good development prospect is obtained.

The invention relates to a target anti-cancer medicine based on an STAT3 (Signal Transducers and Activators of Transcription type 3) protein target spot. Cell lines of a plurality of types of breast cancers have an abnormal regulation and control mechanism of an intracellular STAT3 signal conduction system. The invention provides one type of compound, which is an effective regulator of STAT3 signal conduction, and can be applied to preparation of medicines for treating breast cancer.

The invention provides a preparation method and application of a tegaserod water-soluble organic acid salt. Specifically, the invention provides a water-soluble organic acid salt of a compound as shown in a structural general formula (I). The organic salt can be used as a PI3K / Akt / mTOR and JAK-STAT3 signal channel inhibitor and an immunomodulator for use of developing drugs for treating tumors and inflammations. In the tegaserod organic acid salt provided by the invention, the solubility of the tegaserod D-pyroglutamate in water is greater than 600 mg / mL, and is improved by more than 3000 times compared with that of maleate. Therefore, obvious advantages are generated in the aspects of in-vivo pharmacokinetic behaviors of medicines, development of new dosage forms of the medicines and the like, and the compound can be used for improvement of a preparation process and development of the new dosage forms and has practicability. In the study of antitumor activity in mice, the tegaserod D-pyroglutamate has obvious inhibitory activity on prostatic cancer and melanoma, and the growth inhibitory activity on melanoma B16F10 reaches 50.6%.

The invention relates to a naphthoquinone-fused triazole core skeleton derivative compound, relates to a preparation method and application of the naphthoquinone-triazole core skeleton derivative compound, and belongs to the field of organic chemistry. The provided naphthoquinone-triazole core skeleton derivative compound has a structural formula represented by the following formula (I) in the specification, wherein X is a C or N atom; R1, R2, R3, R4, R5, R6, R7 and R8 are separately independently any one of hydrogen, halogens, hydroxyl, cyano, sulfydryl, amino, nitro, nitroso, alkyl, alkoxy,ester group, carboxyl and sulfonyl. The application of the provided naphthoquinone-triazole core skeleton derivative compound or a pharmaceutically acceptable salt or hydrate thereof in preparation ofdrugs for treating diseases in which STAT3 signal transduction is abnormal is provided.

The invention relates to an application of atopaxar hydrobromide as a novel JAK-STAT3 signal channel inhibitor. The atopaxar hydrobromide can be used for inhibiting STAT3 activity and STAT3 downstreamgene expression to control cell proliferation; the atopaxar hydrobromide has an inhibition effect on STAT3 activation induced by cytokines and JAKs self-phosphorylation; in computer molecular simulation, the atopaxar hydrobromide can be combined with an SH2 structural domain of STAT3 and has very high affinity with a JAK kinase JH1 structural domain; and the atopaxar hydrobromide can horizontallyinhibit the tumor cell growth. A research method of the atopaxar hydrobromide as a novel JAK-STAT3 signal pathway inhibitor comprises the following steps: cell culturing; protein extraction; western-Blot; RNA extraction; RT-PCR (Reverse Transcription-Polymerase Chain Reaction) and fluorescent quantitative PCR; luciferase activity analysis; cell viability analysis; cell cycle detection by flow cytometry; cell apoptosis detection by flow cytometry; nude mouse transplantation tumor experiments; computer molecular dynamics simulation docking analysis; and data calculation and processing. The invention lays a foundation for further cell cycle detection and subsequent research and development of novel small molecule drugs.

The invention provides a new application of acevaltratum, and particularly relates to an application of the acevaltratum to preparation of a medicine for preventing and / or treating tumors. The inventor finds that the acevaltratum has an obvious inhibiting effect on tumor cells, and the inhibiting effect is verified on cells and animal living bodies. Tests prove that the acevaltratum can induce thedegradation of c-Maf, CCND1 and JAK2 oncoproteins and inhibit Otub1, c-Maf, USP10 and STAT3 signal channels, so that the proliferation of tumor cells is effectively controlled, the apoptosis of the tumor cells is induced, and the acevaltratum has inhibiting and treating effects on tumors. Besides, as a plant extract, the acevaltratum also has the advantage of low toxicity.

The invention provides a novel medical application of picrasma quassioides alkaloid, i.e., an application of picrasma quassioides alkaloid serving as a STAT3 (Signal Transducer and Activator of Transcription 3) signal specificity inhibitor. As proved by a cell model screening experiment and Western-Blot detection, the picrasma quassioides alkaloid has high STAT3 inhibiting activity and can be used for effectively inhibiting the expression of relevant genes regulated and controlled by STAT3, so that the growth of tumor cells dependent on STAT3 signals can be inhibited effectively. The picrasma quassioides alkaloid is taken as an active ingredient for preparing an antitumor medicament based on the target spot of STAT3; and antitumor medicaments such as various oral preparations, injections and the like of various dosage forms are prepared from pharmaceutically-acceptable processes and auxiliary materials by taking picrasma quassioides alkaloid as an active ingredient.

The invention discloses a polypeptide for promoting angiogenesis and pharmaceutical use of the polypeptide. The polypeptide comprises an amino acid sequence as shown in SEQ ID No. 1. The polypeptide of the invention is a short fragment peptide chain of NLRC5 protein, and can promote tissue repair and prevent and treat ischemic diseases through angiogenesis; the polypeptide can play roles in combining with STAT3 and regulating and controlling, and remarkably inhibits an IL-6-STAT3 signal channel, so that angiogenesis is promoted; and the molecular weight of the peptide chain of the polypeptide is 60kDa and is 1 / 4 of the molecular weight of the NLRC5 protein, the protection effect of the NLRC5 protein in vivo is facilitated by adopting a short peptide form, tissue permeation can be better exerted without influencing the main activity, and the problems of weak absorption of in-vivo injection administration, easy generation of immune reaction and the like which are caused by large molecular weight of the protein are avoided.

The invention relates to an application of a GATA4 inhibitor in inhibiting an NF-[kappa]B / STAT3 signal channel, and according to earlier-stage research, USP28 regulates the stability of MYC through deubiquitination so as to promote up-regulation of the expression quantity of MYC; then a GATA4 promoter region is demethylated, so the expression of GATA4 is up-regulated; The process of 'inflammatory cancer transformation' of pancreas is promoted by activating two inflammation-related signal channels, namely NF-[kappa]B / SASP and Reg3[beta] / STAT3. The application has the advantages that the transcription factor GATA4 is taken as an entry point, the discussion that USP28 / MYC / GATA4 signal axis promotes pancreas inflammatory cancer transformation is taken as the center, the formation cause of pancreas cancer is understood from the new perspective of transformation, and a new method and thought are provided for preventing and treating pancreas cancer.

Methods of enhancing antitumor activity of an immune cell comprising contacting the immune cell with a Stat3 inhibitor are described. Also described are methods of killing a tumor cell or inhibiting tumor growth in a subject comprising contacting an immune cell of the subject with a Stat3 inhibitor.

The invention belongs to the technical field of biology, and discloses a novel marker for judging a malignant tumor of bile duct cancer, and the novel marker for judging the malignant tumor of bile duct cancer is Gankyrin. According to the novel marker for judging the malignant tumor of the cholangiocarcinoma, provided by the invention, the expression of the Gankyrin in human CCA tissues and cell lines is evaluated, and the influence of the Gankyrin on the growth and metastasis of the CCA is detected in vivo and in vitro respectively. The invention finds that the Gankyrin can be used as an important prognostic marker of the CCA, and meanwhile, the Gankyrin has important enlightenment for the treatment of the CCA in the future by exploring the action mechanism of the Gankyrin. The invention finds that the Gankyrin has important significance for evaluating the prognosis of the CCA, activates an IL-6 / STAT3 signal channel by down-regulating an Rb protein, plays a key role in the generation and the metastasis of the CCA, and can be used for carrying out targeted therapy aiming at the important way which influences the generation and the metastasis of the CCA in the future.

The invention relates to methods for identifying compounds which modulate the interaction between STAT3 an SP1. A peptide is provided which is able to bind STAT3 and interfere with the interaction of STAT3 and SP1. The invention provides methods for identifying compounds which are capable of binding to the peptide and thus release interference with the interaction between STAT3 and SP1, as well as methods for identifying inhibitors and enhancers of the STAT3 SP1 interaction. Compounds identified by the methods of the invention are useful in the repression or stimulation of appetite in a patient, useful for the treatment of leptin resistance, obesity and anorexia.

The invention discloses application of an iridoid compound in preparation of a medicine for treating acute lung injury or pulmonary fibrosis. The application comprises the steps that RLE-6TN and Raw264.7 are used for constructing an acute lung injury cell model, an LPS-induced mouse acute lung injury model and a bleomycin-induced mouse pulmonary fibrosis model; from the aspects of proinflammatory cytokine expression, lung histopathology, oxidation resistance, NF-kappa B / Stat3 signal channel related protein expression and the like, the protection effect and the action mechanism of the iridoid compound, especially morroniside and loganin on acute lung injury are discussed; by copying a pulmonary fibrosis model, the protection effect of loganin and morroniside on pulmonary fibrosis is preliminarily proved; and it is preliminarily proved that the protection effect of loganin and morroniside on acute lung injury is possibly achieved through an NF-kappa B / Stat3 signal channel.

The invention discloses a peptide and application thereof in regulating megakaryocyte differentiation and treating platelet-related diseases. The invention discloses application of AGK as a marker for preventing / relieving / treating platelet-related diseases, and the deficiency of AGK significantly damages platelet generation and further leads to thrombocytopenia; the AGK plays an important role in megakaryocyte differentiation and platelet formation by regulating and controlling JAK2 / STAT3 signal pathway; the peptides 617V and 617F enhance JAK2 / STAT3 signal transduction by promoting combination of the AGK and the JAK2, so that megakaryocyte differentiation is accelerated; the megakaryocyte differentiation can be inhibited by blocking the combination of the AGK and the JAK2; regulating the combination of the AGK and the JAK2 can be used to treat thrombocytopenia and thrombocythemia. The invention discloses an application of a medicament for regulating combination of AGK and JAK2 in preparation of a medicine for treating platelet-related diseases, the AGK plays an important role in megakaryocyte differentiation and thrombopoiesis, and prompts that a new strategy may be provided for treatment of thrombocytopenia or thrombocythemia through interaction of targeted AGK and JAK2.

The invention discloses application of amentoflavone in preparation of a drug for treating glioma. The amentoflavone is used for influencing activation of a JAK2STAT3 pathway of glioblastoma and apoptosis and proliferation of tumor cells. The method comprises the following steps: treating glioblastoma cell lines U87MG 24, 48 and 72 hours by using 0 [mu]M, 50 [mu]M, 100 [mu]M, 150 [mu]M and 200 [mu]M amentoflavone, then respectively detecting the influence of the glioblastoma cell lines on cell proliferation and apoptosis by using CCK8 and Annexin V / PI staining, and detecting the influence of the glioblstoma cell lines on cell JAK2-STAT3 pathway activation and the apoptosis related protein of the downstream regulation by using Western blotting. The amentoflavone is used for blocking a JAK2-STAT3 signal path, promoting tumor cell apoptosis and inhibiting proliferation of tumor cells, and is a novel method for glioblastoma treatment or adjuvant therapy.