241 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 relates to the use of a novel class of cancer stem cell pathway (CSCP) inhibitors; to methods of using such compounds to treat refractory, recurrent, or metastatic cancers; to methods of selective killing cancer cells by using such compounds with specific administration regimen; to methods of targeting cancer stem cells by inhibiting Stat3 pathway; to methods of using novel compounds in the treatment of conditions or disorders in a mammal related to aberrant Stat3 pathway activity; and to processes for preparing such compounds and intermediates thereof, and to the pharmaceutical composition of relevant compounds, and to the specific methods of administration of these compounds.

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.

Belonging to the field of biotechnology, the invention discloses a non-small cell lung cancer (NSCLC) marker, which is STAT3, and also can include CEA, CA125 and CYFRA21-1. The invention confirms the high expression of STAT3 in peripheral blood and serum, and discloses application of STAT3 in preparation of NSCLC diagnostic reagents by the inventor. Specifically, by making use of a genetic recombination technology and targeting at the gene coding region of STAT3, an eukaryotic expression vector PSUPER-STAT3 able to transcribe in vivo and generate small interference RNA (siRNA) is constructed successfully, and is transfected into an eukaryotic cell, thus laying a foundation for a further experimental study on lung cancer RNAi (RNA interference) and antitumor gene therapy. Utilization of the RNAi technology can effectively inhibit the gene expression of STAT3, induce cell apoptosis, and establish the base for molecular mechanism research and gene therapy of lung cancer, thus providing application of the marker provided in the invention in preparing related targeted medicines.

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.

The present invention relates to a novel naphtho class of compounds as Stat3 pathway inhibitors and as cancer stem cell inhibitors; to methods of using such compounds to treat cancer; to methods of using such compounds to treat disorders in a mammal related to aberrent Stat3 pathway activity; to pharmaceutical compositions containing such compounds.

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 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.

Disclosed herein are chimeric antigen receptors (CARs) comprising an intracellular segment comprising an interleukin receptor chain, a JAK-binding motif, a Signal Transducer and Activator of Transcription (STAT) 5 association motif and / or a CD3ζ intracellular signaling domain comprising an exogenous STAT3 association motif, as well as cells and 5 compositions comprising said CARs and uses thereof.

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.

Disclosed is a protein having the ability to inhibit the function of a STAT in a mammalian JAK / STAT signal transduction pathway, which is induced by STAT3 or STAT6, which has the ability to inhibit tyrosine phosphorylation of gp130 or STAT3 and which comprises an SH2 domain; and also disclosed is a DNA coding for the same. Further disclosed is a method for screening a substance having the capability to regulate cytokine activity, in which the protein of the present invention is used. Still further disclosed are an antisense DNA and an antisense RNA capable of inhibiting the biosynthesis of the above-mentioned protein; a monoclonal antibody capable of binding to the above-mentioned protein; and a DNA probe and an RNA probe capable of hybridizing to the above-mentioned DNA. Still further disclosed are a replicable recombinant DNA molecule comprising a replicable expression vector and, operably inserted therein, the DNA of the present invention; a cell of a microorganism or cell culture, transformed with the replicable recombinant DNA molecule; and a method for screening a substance having the capability to regulate cytokine activity in which the transformant is used.

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.).

Embodiments of the invention include methods of treating, preventing, and / or reducing the risk of fibrosis in an individual in need thereof. In some embodiments, particular small molecules are employed for treatment, prevention, and / or reduction of the risk of fibrosis. In at least particular cases, the small molecules are inhibitors of STAT3.

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.

The invention relates to a combined diagnostic marker for inflammation-associated HCC and an application thereof. Combined application of an STK4 protein in a peripheral blood monocyte or plasma, phosphorylated p65 (p-p65) and phosphorylated STAT3 (p-STAT3) in the peripheral blood monocyte and an IL-6 protein in the plasma as the marker for inflammation-associated HCC is provided for the first time, and a theoretical basis and a simpler detection method are provided for fast and early diagnosis and monitoring of HCC.

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.