234 results about "STAT3" patented technology

The present invention provides sets of genes the expression of which is important in the prognosis of cancer. In particular, the invention provides gene expression information useful for predicting whether cancer patients are likely to have a beneficial treatment response to chemotherapy.FHIT; MTA1; ErbB4; FUS; BBC3; IGF1R; CD9; TP53BP1; MUC1; IGFBP5; rhoC; RALBP1; STAT3; ERK1; SGCB; DHPS; MGMT; CRIP2; ErbB3; RAP1GDS1; CCND1; PRKCD; Hepsin; AK055699; ZNF38; SEMA3F; COL1A1; BAG1; AKT1; COL1A2; Wnt.5a; PTPD1; RAB6C; GSTM1, BCL2, ESR1; or the corresponding expression product, is determined, said report includes a prediction that said subject has a decreased likelihood of response to chemotherapy.

This invention relates to compounds, compositions, and methods useful for modulating STAT3 gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of STAT3 gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (mRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of STAT3 genes. Such small nucleic acid molecules are useful, for example, for treating, preventing, inhibiting, or reducing cancer, proliferative, and/or inflammatory diseases, disorders, or conditions in a subject or organism, such as psoriasis, eczema, dermatitis, Crohn's disease, and inflammatory bowel disease, and for any other disease, trait, or condition that is related to or will respond to the levels of STAT3 in a cell or tissue, alone or in combination with other treatments or therapies.

The present invention concerns compounds and their use to treat cell proliferative diseases such as cancer. Compounds of the present invention display significant potency as inhibitors of Jak2/STAT3 pathways and downstream targets and inhibit the growth and survival of cancerous cell lines.

The present invention relates to methods for identifying compounds that can reduce immune rejection, for example, transplant- or autoimmune disorder-related immune rejection. The present invention is based, in part, on the discovery, demonstrated herein, that immune rejection can be monitored by determining the amount of particular members of the Jak/Stat signal transduction pathway present within an affected tissue. The present invention is further based, in part, on the discovery, demonstrated herein, that immune rejection can be reduced and tolerance can be induced by modulating the amount of these particular members of the Jak/Stat signal transduction pathway present, expressed or active within an affected tissue. In particular, the results demonstrate that immune rejection can be monitored by determining the amount of mRNA or protein of Stat1, Stat3, Stat4, Stat6, SOCS1, or SOCS3 present, e.g., in an affected tissue.

The present invention provides nucleic acid molecules that inhibit STAT3 expression. Methods of using the nucleic acid molecules are also provided.

The present invention discloses a method for establishing KI-T2A-luciferase cell line based on CRISPR/Cas9 targeted genome modification technology. A T2A-luciferase reporter gene is integrated in the3<rd> end of the mmp 12 gene in a genome by using CRISPR/Cas9 technology. A knock-in cell line of MMP12-T2A-luciferase is established, the site-specific integration of the source gene in the cell lineon the genome is verified. Meanwhile, a reported transcription factor, STAT3, with activation effect on mpp12-T2A is used to transcribe and active the MMP12-T2A-luciferase cell line. The results showthat the expression level of luciferase in MMP12-T2A-luciferase cell line can accurately and sensitively reflect the expression level of MMP12 protein in the cell line. The establishment of the cellline will contribute to the study of the gene function of mmp12 and the screening of small molecule chemical drugs affecting the expression of mmp12, which provides a new experimental thinking and solution for the migration of cancer cells and related researches thereof.

This invention relates, e.g., to a method for predicting the response of a subject having estrogen-receptor-positive breast cancer to an inhibitor of the estrogen signaling pathway (e.g. tamoxifen), comprising measuring in a cancer sample from the subject the level of phosphorylation, compared to a baseline value, of one or more of the following members of an interconnected intracellular signaling pathway: (a) 4EBP1, and/or (b) p70S6, and/or (c) STAT3, and/or (d) FAK, wherein a significantly elevated level of phosphorylation of 4EBP1, and/or p70S6 and/or STAT3, and/or a significantly decreased level of phosphorylation of FAK, compared to the baseline value, indicates that the subject is likely to be a non-responder to the inhibitor and/or has a poor prognosis. Additional members of the intracellular signaling pathway whose phosphorylation can be measured are also described. Also described is a method for treating breast cancer in a subject in need thereof, wherein the subject exhibits an elevated level of phosphorylation of these markers, comprising administering to the subject an effective amount of one or more inhibitors of members of the interconnected intracellular signaling pathway.

The invention disclosed herein provides methods for diagnosing and treating diseases and/or conditions associated with dysregulated Stat3-mediated activity.

The present invention relates to methods for treating and/or preventing cancer. In particular the present invention relates to ex vivo immunotherapeutic methods. The methods comprise decreasing Stat3 (signal transducer and activator of transcription3) expression and/or function in tumor cells and the administration of such cells to a subject in need of treatment and/or prevention. Other methods of the invention comprise activating T-cells by co-culturing the T-cells with the tumor cells with decreased Stat3 expression or function. The invention further encompasses methods comprising decreasing Stat3 expression or function in antigen-presenting cells and co-administering tumor cells and the antigen-presenting cells with decreased Stat3 function to a patient. The invention further relates to methods for stimulating dendritic cell differentiation.

Compounds, compositions, and methods for inhibiting STAT3 expression are provided. The compositions comprise antisense oligonucleotides targeted to a nucleic acid encoding STAT3. Methods of inhibiting STAT3 expression and promoting apoptosis using these oligonucleotides are provided. Also provided are methods of treating diseases, particularly inflammatory diseases and cancers associated with STAT3 overexpression or constitutive activation or insufficient apoptosis.

The invention discloses an application of miltirone in preparation of antitumor drugs. The miltirone has a structure of formula I; the miltirone serves as an inhibitor of STAT3 (Signal Transducer and Activator of Transcription 3) and is capable of inhibiting growth and proliferation of tumor cells which are abnormally activated by STAT3 so as to cause the apoptosis of the tumor cells and also capable of improving sensibility of cytotoxic drugs and inhibiting formation of tumor vessels. The miltirone with the structure of formula I can inhibit STAT3 kinase Tyr705 phosphorylation level to achieve the functions of accelerating the apoptosis of the tumor cells, improving the sensibility of chemotherapy drugs and inhibiting formation of new vessels; and the proliferation of tumor cells can be significantly inhibited due to the combined combination of the miltirone with low toxicity or non-toxic concentration and adriacin doxorubicin with low toxicity or non-toxic concentration and the combined application of the miltirone and cis-platinum with low toxicity or non-toxic concentration. The functions of the miltirone with the structure of formula I have positive significance to prevention and treatment of tumors.

The present invention relates to uses of cucurbitacins and compositions comprising cucurbitacin B. The present invention also relates to methods for preventing or treating various diseases and disorders by administering to a subject in need thereof cucurbitacin B. The invention also encompass methods of developing a therapeutic that comprises a cucurbitacin using the signaling molecules in the Ras-Raf-Mek-Elk-STAT3 pathway.

The invention provides application of miR-1246 and/or TERF2IP in diagnosis and treatment of glioma. The fact that that microRNA-1246 (miR-1246) is the most abundant microRNA expressed in glioma-derived exosomes (GDEs) and is significantly up-regulated in anoxic glioma-derived exosomes (H-GDEs) is disclosed for the first time. In addition, the miR-1246 is also enriched with exosomes isolated from cerebrospinal fluid (CSF) of a patient with preoperative glioblastoma (GBM), and the exosomes miR-1246 in cerebrospinal fluid of the patient with GBM after tumor resection are significantly reduced. The MicroRNA-1246 is shown to have the strongest capability to induce polarization of M2 macrophages. In addition, studies find that H-GDEs-induced M2 macrophage polarization is mediated by the miR-1246/TERF2IP/STAT3 and miR-1246/TERF2IP/NF-kappa B pathways.

The invention discloses a cycloalkane thiophthene derivative and pharmaceutically acceptable salts, metabolic products or prodrugs thereof. A compound can be used for treating diseases related with STAT3 (Signal Transducer and Activator of Transcription 3) activation, such as ovarian cancer, endometrial cancer, cervical cancer, breast cancer, colon cancer, pancreatic cancer, lung cancer, brain cancer, prostate cancer, kidney cancer, liver cancer, bladder cancer, oral cancer, sarcoma, prostate cancer, head and neck squamous cell carcinoma, neuroglioma, melanoma, lymphoma, leukemia, and renal fibrosis, pulmonary fibrosis, rheumatoid arthritis, hair growth, arthritis, psoriasis, lupus erythematosus, inflammatory lung diseases and inflammatory bowel diseases. (The formula is shown in the description.).

The invention relates to construction and screening as well as applications for a siRNA expression carrier of a stomach cancer target STAT3 gene. Two expression plasmids STAT3-siRNA1/2 in mammal cells for expressing siRNA are constructed by mainly utilizing an RNA interference technology aiming at different target sequences of an STAT3 gene. The siRNAs expression carrier of the stomach cancer target STAT3 gene provided by the invention can inhibit STAT3 gene expression efficiently with specificity, and can be used for preparing gene medicaments for treating high-expression STAT3 gene stomach cancer.

An adenoviral vector which expresses a dominant negative form of Stat3 called Stat3-EVA for the treatment of non-small cell lung carcinoma. This construct has two mutations in the DNA binding site of Stat3 which prevents binding to DNA but has no effect on tyrosine phosphorylation or dimerization.

The invention discloses a method for electromagnetically detecting the activation level of an STAT 3 protein through a DNA probe ligand and application. By use of STAT3 which is an important transcription factor and dynamic reversible and controllable mutual action between two natural ligands which are DNA and polypeptide, a DNA probe capable of specifically identifying a protein is designed; the polypeptide is used for controlling reversible combination and dissociation between the target protein STAT3 and the DNA probe; by stable coordination interaction between Zr<4+> and a phosphate group and a phosphorylated nano-graphene composite beacon, catalytic signal amplification is realized. According to the method, by introduction of the phosphorylated nano-graphene composite beacon serving as a signal amplification strategy, the phosphorylated nano-graphene composite beacon is stable and difficult to inactivate, thus finally realizing sensitive, efficient and stable detection for the activated STAT3 protein.

The invention discloses an application of STAT3 in porcine ovarian granulosa cells. STAT3 is taken as a research object, and a porcine STAT3 gene promoter double-luciferase reporter gene recombinationplasmid is constructed, and the core promoter region of the STAT3 is found through the expression activity of the STAT3 gene promoter in the porcine ovarian granulosa cell; and then the interaction between the transcription factor C/EBP beta and the core promoter region of the STAT3 is verified; then C/EBP beta superexpression vector is constructed and small interfering RNA (C/EBP beta-siRNA) issynthesized, the effect of C/EBP beta on STAT3 is detected, finally, the expression vector of C/EBP beta and C/EBP beta-siRNA were transfected respectively to the granulosa cells in order to detect the apoptosis and proliferation of the cells. The application of STAT3 in porcine ovarian granulosa cells finds the application of the transcription factor C/EBP beta in the ovarian granulosa cell by finding the transcription factor C/EBP beta in the STAT3 promoter region, and has good application value for researching the ovarian follicular atresia mechanism.

The invention relates to an SiRNA lentivirus vector of human STAT3 gene and a construction method thereof. The SiRNA lentivirus vector comprises a segment of sequence and a lentivirus vector pLenti6.3/V5-DEST; the nucleotide sequence comprises an interference target sequence SiRNA aming at an mRNA sequence of the human STAT3 gene; the registry number of the mRNA sequence of the human STAT3 gene in the Gene bank is NM_139276; and the interference target sequence SiRNA is selected from SEQ ID NO:1, SEQ IDNO:2, SEQ ID NO:3 and SEQ ID NO:4. The lentivirus vector expresses sense chains and anti-sense chains of siRNA molecules of the human STAT3 gene when the lentivirus vector is in target cells, so that the mRNA of the human STAT3 is subjected to specific degradation and the expression is silent; and the invention provides an effective method for knocking out STAT3 gene expression in vivo, and opens up a new way for treating tumors.