71 results about "STAT1" patented technology

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.

Small molecule inhibitors of Stat3 and their derivatives are disclosed. Also described are methods to inhibit cell growth by use of Stat3 inhibitors, and the use of Stat3 inhibitors for the prevention and/or treatment of cancer. Further, inhibitors of Stat3 that also do not inhibit Stat1 are described as well as their derivatives. Methods of screening additional compounds for Stat3 inhibition activity and/or non-inhibition of Stat1 activity are also described herein.

Nucleic acid molecules comprising a SNP site selected from the group consisting of position 1296 of bovine uterine milk protein (UTMP) coding sequence (SEQ ID NO: 1), position 213 of bovine signal transducer and activator of transcription (STAT1) coding sequence (SEQ ID NO: 2), position 8514 of the osteopontin (OPN) gene (SEQ ID NO: 3), or position 1070 of a bovine lectin-like oxidized LDL receptor (OLR1) coding sequence (SEQ ID NO: 4), which SNP indicates a desirable milk production trait in a dairy cattle. Also disclosed are an array or a kit comprising the same, a method for detecting the SNPs, a method for progeny testing of cattle, and a method for selectively breeding of cattle.

The present invention describes methods of producing milligram quantities of three forms of purified Stat1 protein from recombinant DNA constructs. In addition, the Stat proteins may be isolated in their phosphorylated or nonphosphorylated forms (Tyr 701). The proteins can be produced in baculovirus infected insect cells, or E. coli. A compact domain in the amino terminus of Stat1α was isolated and found to enhance DNA binding due to its ability to interact with a neighboring Stat protein. A relatively protease-resistant recombinant truncated form of the Stat protein was isolated in 40-50 mg quantities. Purification of the Stat proteins were performed after modifying specific cysteine residues of the Stat proteins to prevent aggregation. Activated EGF-receptor partially purified from membranes by immunoprecipitation was shown to be capable of in vitro catalysis of the phosphorylation of the tyrosine residue of Stat1 known to be phosphorylated in vivo. Techniques are enclosed to separate the phosphorylated from the nonphosphorylated Stat proteins. The techniques disclosed are general for Stat proteins and may be used to isolate large quantities of purified Stat 2, 3, 4, 5A, 5B and 6. Methods for using purified Stat proteins, truncated Stat proteins, or Stat N-terminal fragments for drug discovery are also disclosed.

The invention belongs to the fields of biotechnology and medicine, and relates to an inhibitor capable of inhibiting the excessive proliferation of keratinocytes, an inhibitor composition, and applications of the inhibitor. The inhibitor taking triptolide, triptonide or tripterine as the representative can inhibit the excessive proliferation of the keratinocytes, specifically, the expression levels of STAT1 and p-STAT1 can be inhibited, then the expression level of miR-17-92mRNA is down-regulated, then, miR-17-92 target gene CDKN2B is regulated, the secretion levels of inflammatory factors CXCL1, CXCL10, CXCL16 and IL-6 in cells are inhibited, and finally, the cell cycle progression and immune function abnormity are inhibited; triptolide, tripterine and triptonide can effectively inhibit the proliferation of the keratinocytes, and the effective doses respectively achieve 60nM, 100nM and 80nM.

The present invention is directed to a method of reducing the viability of a tumor cell involving administering a virus that is not a common human pathogen to the tumor cell. Preferably, the virus exhibits differential susceptibility, in that normal cells are not affected by the virus. This differential susceptibility is more pronounced in the presence of interferon. The tumor cell is characterized by having low levels, or no, PKR activity, or as being PKR−/−, STAT1−/− or both PKR−/− and STAT1−/−. The virus is selected from the group consisting of Rhabdovirus and picomavirus, and preferably is vesicular stomatitis virus (VSV) or a derivative thereof.

The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising i) determining in a tumor sample obtained from the patient the gene expression level of at least 7 genes selected from the group consisting of CCR2, CD3D, CD3E, CD3G, CD8A, CXCL10, CXCL11, GZMA, GZMB, GZMK, GZMM, IL15, IRF1, PRF1, STAT1, CD69, ICOS, CXCR3, STAT4, CCL2, and TBX21, ii) comparing every expression level determined at step i) with their predetermined reference value and iii) providing a good prognosis when all expression levels determined at step i) are higher than their predetermined reference values, or providing a bad prognosis when all expression levels determined at step i) are lower than their predetermined reference values or providing an intermediate prognosis when at least one expression level determined value is higher than its predetermined value. The method is also particularly suitable for predicting the responsiveness of the patient to a treatment.

The present invention relates to a method of reducing the viability of tumor cells comprising administering to the tumor cells a virus that is not a common human pathogen. The virus preferably exhibits a differential susceptibility wherein normal cells are not affected by the virus. The differential susceptibility was more pronounced in the presence of interferon. Tumors were characterized by low or no PKR activity, or PKR-/-, STAT1-/-, or both PKR-/- and STAT1-/-. The virus is selected from baculoviruses and picornaviruses, preferably vesicular stomatitis virus (VSV) or derivatives thereof.

The invention discloses application of PPM1A in the treatment and diagnosis of asthma. To be specific, the invention relates to application of the PPM1A as a detection target in preparation of a diagnostic reagent for bronchial asthma, application of a regent detecting the PPM1A in preparation of a diagnostic reagent for bronchial asthma, application of the PPM1A as a therapeutic target in preparation or screening of a drug for treating bronchial asthma, and application of a substance suppressing PPM1A expression in preparation of a drug for treating bronchial asthma. The invention discloses the application of PPM1A in detecting the plasma of the bronchial patient; expressions of the PPM1A in an asthma patient and a normal person are discovered to be different for the first time; and the indicator can be used as the molecular marker of the bronchial asthma. Besides, the PPM1A acting as a miR-1165-3p target gene is discovered to be able to promote Th2 differentiation through the STAT1,STAT5, and Akt accesses to cause the asthma, so that the PPM1A can used as a therapeutic target for asthma.

The invention relates to application of STAT1 serving as ovarian cancer treatment target point. Experiments prove that the STAT1 directly combines with a TGF-beta receptor (ALK1, ALK5 and TbetaRII), proliferation, migration and invasion of ovarian cancer cells can be promoted after STAT1overexpression, and proliferation, migration and invasion of the ovarian cancer cells can be inhibited after STAT1 knocking-down. Therefore, STAT1 reduction processing is conducted on patients with high ovarian cancer STAT1 expressions, a potential treatment effect exists. An STAT1 signal path mutually acts with a TGF-beta1 signal path to influence the proliferation, migration and invasion capability of ovarian cancers. The STAT1 is a potential novel ovarian cancer treatment target point and has a great clinical application value.

The invention discloses an application of a CDK7 targeting inhibitor in preparation of a medicine for treating cytokine release syndrome, which is verified by biochemical and animal model experiments as follows: (1) under proper concentration, the CDK7 targeting inhibitor inhibits the expression of super enhancers and transcription factors related to inflammatory factors such as stat1, IL-1 and IL-6, and thereby inflammatory signal pathways of immune cells such as macrophages, T cells and endothelial cells can be specifically regulated and controlled; (2) mouse death caused by acute inflammatory storm caused by bacterial or viral infection can be remarkably reduced, functional failure caused by inflammation of related organs is reduced, and obvious toxic and side effects are not found in the period. According to the results, the polypeptide has great significance in treatment of cytokine release syndrome caused by bacteria, viruses or immunotherapy.

The invention belongs to the field of biotechnology and medicine and relates to an inhibitor capable of inhibiting a killing effect of CD8<+>T cells on melanocytes, inhibitor composition and an application to vitiligo preventing and treating drugs. When dose of triptolide, celastrol or wilforlide A are in 5-10 nM, the inhibitor capable of inhibiting the killing effect of the CD8<+>T cells on the melanocytes can inhibit the expression level of STAT1 (signal transducer and activator of transcription 1) in keratinocytes, then the expression level of IRF1 is down-regulated, secretion of CXCL10 and CXCL16 in the keratinocytes is inhibited, and chemotaxis of CXCL10 and CXCL16 on the CD8<+>T cells is further reduced, so that the killing effect of the CD8<+>T cells on the melanocytes is inhibited; the inhibitor capable of inhibiting the killing effect of the CD8<+>T cells on the melanocytes is a tripterygium wilfordii terpenoid and particularly is triptolide, celastrol or triptonide.

Nucleic acid constructs, vectors, and recombinant cells harboring the nucleic acid constructs or vectors are disclosed. The nucleic acid constructs include genes encoding a chimeric antigen receptor (CAR) and/or one or more transcription factors, optionally mutated. The transcription factors include those that mediate proinflammatory cytokine expression, e.g., T-bet, STAT1, or STAT4. Methods are disclosed of co-expression of the CAR and the transcription factor in a human or non-human immune cell, preferably human T cells. Also disclosed are methods for using these cells for immunotherapy, e.g., in treating cancer, infection, autoimmunity, allergy or inflammation diseases by the administration of a prophylactically or therapeutically effective amount of one or more of the nucleic acid constructs, vectors, and/or immune cells, e.g., human CAR-T cells, described herein.

Methods of enhancing cellular responses to interferons are disclosed. These methods comprise administering to a subject a vector comprising a Stat1-CC transgene, such as an AAV5 vector comprising a reporter operably linked to a nucleic acid sequence encoding a Stat1-CC polypeptide. The methods can be used in the treatment of diseases that involve interferon responses, such as multiple sclerosis, amyotrophic lateral sclerosis, and lupus; viral infections such as infection by hepatitis C virus, influenza A virus, cowpox virus, Sendai virus or Encephalomyocarditis virus; respiratory disorders; and cancers.

The subject invention concerns compositions and methods for blocking cancer cell growth or proliferation and/or inducing cancer cell death. Compositions of the present invention are peptidomimetics that inhibit STAT function. Peptidomimetics of the invention display selective inhibition of specific STAT isoform homo-dimerization. The peptidomimetic probes of STAT1 function, described herein, provide the means to preferentially inhibit STAT1 over STAT3 through the exploration of the C-terminus.

The invention belongs to the field of biotechnology, and particularly relates to a research method of application of wedelolactone to preparation of lung cancer treating products. The invention researches influence of the wedelelactone on the activity, the cycles and the apoptosis of non-small cell lung cancer A549 cells as well as intervention to p-Caspase3, p53, p-STAT1 and STAT1 gene expressionof the cells, explores the anti-tumor effect of the wedelolactone on the A549 cells and the mechanism thereof, provides the research method of the application of the wedelolactone to the preparationof the lung cancer treating products, and provides a theoretical basis for future research on the non-small cell lung cancer treating mechanism of the traditional Chinese medicine. The research methodcomprise the following steps: performing cell culture, detecting the cell proliferation inhibiting rate by a CCK-8 method, detecting the cycles and the apoptosis of the cells through propidium iodideand Annexin-PI staining and detecting gene transcription and translation of the cells through RT-PCR and Western blot.

The invention provides an application of prussian blue in preparation of a medicine for treating vascular restenosis and a preparation method of prussian blue nanoparticles. At present, no special-effect medicine exists for vascular restenosis, so that the providing of the medicine with special effects for preventing and treating vascular restenosis has certain practical significance. The prussianblue provided by the invention can inhibit activation of a phosphorylation signal transduction element and a transcription activator 1 (p-STAT1), significantly targets macrophages, and polarizes themacrophages into M2, thereby effectively relieving long-term prognosis of restenosis. Besides, the prussian blue provided by the invention can significantly reduce pro-inflammatory cytokines, accelerate repair of endothelial cells and reduce migration and proliferation of vascular smooth muscle cells, thereby inhibiting the progress of restenosis.

The invention provides the use of an antibody reactive with RNase L or a fragment thereof for the preparation of a medicament for diagnosing a rheumatoid arthritis (RA) disease. The invention also provides the use of a ribonuclease L gene as a biomarker for the preparation of a medicament for diagnosing a rheumatoid arthritis disease. The RNase L is significantly highly expressed in the joint synovial membrane of a RA patient and is positively correlated with the secretion of TNF[alpha]. After RNase L gene knockout, a CIA mouse model incidence and arthritis score are significantly inhibited. The above results confirm that the RNase L promotes the occurrence and development of the RA. The RNase L is mainly expressed in macrophages, and promotes the differentiation of macrophages into proinflammatory M1 by activating a JAK/STAT1 pathway, thereby promoting a RA inflammatory response. In summary, the RNase L can be used as a biomarker of the rheumatoid arthritis diseases.

The present invention provides a method for predicting the treatment response to anti-cancer immunotherapy of a mammalian cancer patient, the method comprising: a) measuring the gene expression of at least 2 the following cancer promoting genes: PTGS2, VEGFA, CCL2, IL8, CXCL2, CXCL1, CSF3, IL6, IL1B and IL A in a sample obtained from the tumour of the patient; b) measuring the gene expression of at least 2 of the following cancer inhibitory genes: CXCL11, CXCL10, CXCL9, CCL5, TBX21, EOMES, CD8B, CD8A, PRF1, GZMB, GZMA, STAT1, IFNG, IL12B and IL12A in a sample obtained from the tumour of the patient; c) computing a ratio of the gene expression of said at least 2 cancer promoting genes and the gene expression of said at least 2 cancer inhibitory genes; and d) making a prediction of the treatment response and/or prognosis of the patient based on the gene expression ratio computed in step c). Also provided are related methods for stratifying patients and for treating patients, including with immune checkpoint blockade therapy.

The invention discloses a capture probe and a kit for primary atopic disease related genes and application of the kit. The primary atopic disease related genes captured by the capture probe are selected from two or more of FLG, CDSN, DSG1, DSP, SPINK5, PLCG2, ADGRE2, TPSAB1, FOXP3, IL2RA, TGFBR1, TGFBR2, WAS, MALT1, CARD11, WIPF1, ARPC1B, DOCK8, CARMIL2, ERBIN, ZNF341, RAG1, RAG2, DCLRE1C, ADA, IL7RA, CHD7, LIG4, ZAP70, STAT3, STAT1, STAT5B, JAK1, IL4RA, IL6ST, IL6R and PGM3. The capture probe effectively improves the diagnosis efficiency of primary atopic diseases, and can provide a diagnosis basis for treatment. Mutation sites of the primary atopic diseases can be accurately and quickly detected.

The invention discloses application of RFPL1S-201 in the preparation of drugs for inhibiting the proliferation, invasion and/or metastasis of ovarian cancer, application of RFPL1S-201 or substances that promote the expression of RFPL1S-201 in the preparation of drugs for inhibiting the proliferation, invasion and/or metastasis of ovarian cancer, and application of expression plasmids overexpressing RFPL1S-201 in the preparation of drugs for inhibiting the proliferation, invasion and/or metastasis of ovarian cancer. It is found that lncRNA RFPL1S-201 can inhibit the proliferation, invasion andmetastasis of ovarian cancer cells, and meanwhile lncRNA RFPL1S-201 can inhibit the liver metastasis of ovarian cancer in vivo. A mechanism of action is mainly to inhibit tumor progression and promotetumor chemotherapy sensitivity by inhibiting an IFN-STAT1 signal channel.