46 results about "Pathway activity" patented technology

The present invention concerns a pyrvinium compound or an analog thereof for the treatment of cancers. This compound inhibits Wnt activity in the cells of cancers such as adrenocortical, hepatocellular, hepatoblastoma, malignant melanoma, ovarian, Wilm's tumor, Barrett's esophageal, glioma, bladder, breast, gastric, head & neck, lung cell, mesothelioma, and cervical cancers. The present invention also provides a method for assaying for compounds that alter Wnt pathway activity. Also provided are methods for treating Wnt-related non-cancer disease states.

Elevated Hedgehog (Hh) pathway activity, including ligand stimulated Hh pathway activity, was detected in digestive tract cancers, including esophagus, stomach, biliary tract, and pancreatic cancer, and determined to be associated with growth and proliferation of the cancer cells. Accordingly, methods are provided for treating a digestive tract cancer associated with elevated Hh pathway activity by reducing or inhibiting the Hh pathway activity. Also provided are methods of determining the responsiveness of a digestive tract tumor to treatment with an Hh pathway antagonist.

Compounds, compositions, kits and methods for modulating hedgehog pathway activity, and treating conditions related to abnormal or aberrant hedgehog pathway activity, are disclosed.

Genes involved in double-stranded RNA interference (RNAi pathway genes) are identified and used to investigate the RNAi pathway. The genes and their products are also useful for modulating RNAi pathway activity.

The present invention provides methods and compositions for modulating polyamine pathway activity as a means for ameliorating neurodegenarative disorders. In particular, for ameliorating the symptoms or onset of amyotrophic lateral sclerosis (ALS) by modulating the gene and protein products involved the polyamine pathway, such as by inhibiting the enzyme, ornithine decarboxylase (ODC), involved in the synthesis of the polyamine, putrescine. Compositions and methods are disclosed for inhibiting the polyamine pathway producing lower polyamine levels resulting in a beneficial effect on ALS. This can be accomplished by using modulating agents such as analogs, or polyamine analogs, and antiproliferative drugs. In particular, the polyamine analog N(1),N(11)-diethylnorspermine (DENSPM) is disclosed as a useful modulating agent in the treatment of ALS. Screening assays for pharmacological agents that are capable of decreasing polyamine levels and/or reducing cell proliferation are also disclosed.

RTP801 represents a unique gene target for hypoxia-inducible factor-1 (HIF-1). Down-regulation of the mTOR pathway activity by hypoxia requires de novo mRNA synthesis and correlates with increased expression of RTP801. The present invention relates to screening systems utilizing RTP801 and/or RTP801 interactors and/or RTP801 biological activity, to drug candidates identified by such screening systems, and to the use of such drug candidates in the treatment of various disorders.

The present invention provides methods and compositions for modulating polyamine pathway activity as a means for ameliorating neurodegenarative disorders. In particular, for ameliorating the symptoms or onset of amyotrophic lateral sclerosis (ALS) by modulating the gene and protein products involved the polyamine pathway, such as by inhibiting the enzyme, ornithine decarboxylase (ODC), involved in the synthesis of the polyamine, putrescine. Compositions and methods are disclosed for inhibiting the polyamine pathway producing lower polyamine levels resulting in a beneficial effect on ALS. This can be accomplished by using modulating agents such as analogs, or polyamine analogs, and antiproliferative drugs. In particular, the ODC inhibitor difuoromethylornithine (DFMO) is disclosed as a useful pharmacological agent in the modulation and treatment of ALS. Screening assays for pharmacological agents that are capable of decreasing polyamine levels and/or reducing cell proliferation are also disclosed.

This invention pertains to the discovery that brain-derived neurotrophic factor (BDNF) and its associated signaling pathway is involved in reversing and/or counteracting neuroadaptations within the mesolimbic system that contribute to the development and/or maintenance of addiction (e.g. alcohol addiction). This invention also pertains to the discovery that ibogaine activity is mediated by changes in mRNA expression of GDNF. Thus, in certain embodiments, this inventioni provides a method of mitigating one or more symptoms of substance abuse in a mammal by increasing the expression or activity of GDNF, BDNF, RACK1, and/or the dopamine D3 receptor (D3R) in said mammal.

Disclosed herein are systems, methods, and compositions useful for determining cellular pathway disruption comprising the use of RNA expression level information. This determined level of disruption can assist in the identification of genetic variants that alter pathway activity, to correlate these variants with disease state and disease progression, and to identify those therapeutics most likely to be effective and which should be avoided.

RTP801L represents a unique gene target for hypoxia-inducible factor-1 (HIF-1) that may regulate hypoxia-induced pathogenesis; down-regulation of the mTOR pathway activity by hypoxia requires de novo mRNA synthesis and correlates with increased expression of RTP801L.

The present invention relates to screening systems utilizing RTP801L and/or RTP801L interactors and/or RTP801L biological activity, and to the potential drugs and methods of treatment identified by such screening systems.

The invention discloses a kind of human gene CTRP4 and its coding CTRP4 protein. The invention also relates to the application of an antagonist of the gene and protein in the preparation of NF-kappaB and/or IL6-STAT3 pathway activity inhibiting drug, and relates to the application of an agonist of the gene and the protein in the preparation of hematopoiesis promoting drug and GP130 molecule up-regulating drug.

A bioinformatics process which provides an improved means to detect NFkB cellular signaling pathway in a subject, such as a human, based on the expression levels of at least six unique target genes of the NFkB cellular signaling pathway measured in a sample. The invention includes an apparatus comprising a digital processor configured to perform such a method, a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and a computer program comprising program code means for causing a digital processing device to perform such a method. Kits are also provided for measuring expression levels of unique sets of NFkB cellular signaling pathway target genes.

The invention provides an abnormal tumour cell pathway identification method capable of overcoming signal distortion. The abnormal tumour cell pathway identification method comprises the following steps: performing pathway deconstruction of a gene expression profile image matrix by utilizing a non-negative matrix decomposition algorithm so as to obtain a pathway expression profile matrix; drawing an abnormal activity curved line of each pathway according to an operation characteristic curved line of a receiver and the pathway expression profile matrix; calculating an abnormal activity value of each pathway according to the abnormal activity curved line of each pathway; and comparing the abnormal activity value of each pathway with a pre-set threshold value, and taking the pathway as an abnormal tumour cell activity pathway when the abnormal activity value of the pathway is higher than the pre-set threshold value. According to the invention, distortion defects to pathway activity modelling in the traditional method are overcome; influence of pathway related noise to pathway activity evaluation is eliminated; the abnormal tumour cell pathway identification method has high precision, stability and reliability for detecting abnormal tumour cell pathways; and the abnormal tumour cell pathway identification method disclosed by the invention can be applicable to detecting and identifying drug targets in research and development of drugs and personalized medication.

The present application mainly relates to specific method for determining a risk score that indicates a risk that a subject will experience a clinical event within a defined period of time. The risk score is determined based on a combination of inferred activities of two or more cellular signaling pathways in a subject, wherein the cellular signaling pathways comprise a TGF-beta pathway and one ormore of a PI3K pathway, a Wnt pathway, an ER pathway, and an HH pathway. The present application also relates to an apparatus, to a non-transitory storage medium, and to a computer program for determining a risk score that indicates a risk that a subject will experience a clinical event within a defined period of time. The present invention also relates to a kit for measuring expression levels ofthree or more target genes of each of two or more cellular signaling pathways in a sample of a subject, to kits for determining a risk score that indicates a risk that a subject will experience a clinical event associated with a disease within a defined period of time, and to uses of the kits in performing the method.

The present application relates to a method for determining a risk score that indicates a risk that a clinical event will occur within a certain period of time. The risk score is based at least in part on a combination of inferred activities of two or more cellular signaling pathways in a tissue and/or cells and/or a body fluid of a subject. The cellular signaling pathways comprise a Wnt pathway, an ER pathway, an HH pathway, and/or an AR pathway. The risk score is defined such that the indicated risk that the clinical event will occur within the certain period of time decreases with an increasing P_ER and increases with an increasing max(P_Wnt, P_HH), wherein P_ER, P_wnt, and P_HH denote the inferred activity of the ER pathway, the Wnt pathway, and the HH pathway, respectively.

Provided herein are methods for simultaneously determining the functional status of multiple signaling pathways in a diseased cell sample obtained from a subject to thereby select for therapeutic use in the subject a targeted therapeutic agent that affects the signaling pathway with the highest level of aberrant activity in the subject's cells. Also provided are methods for determining whether a signaling pathway is ultrasensitive in a diseased cell sample from a subject, also allowing for selection of an effective targeted therapeutic agent for therapeutic use in the subject. Methods of administering a selected targeted therapeutic agent to the subject are also provided.

A bioinformatics process which provides an improved means to detect a MAPK-AP-1 cellular signaling pathway in a subject, such as a human, based on the expression levels of at least three unique target genes of the MAPK-AP-1 cellular signaling pathway measured in a sample. The invention includes an apparatus comprising a digital processor configured to perform such a method, a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and a computer program comprising program code means for causing a digital processing device to perform such a method. Kits are also provided for measuring expression levels of unique sets of MAPK-AP-1 cellular signaling pathway target genes.

A bioinformatics process which provides an improved means to detect a JAK-STAT3 cellular signaling pathway in a subject, such as a human, based on the expression levels of at least three unique target genes of the JAK-STAT3 cellular signaling pathway measured in a sample. The invention includes an apparatus comprising a digital processor configured to perform such a method, a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and a computer program comprising program code means for causing a digital processing device to perform such a method. Kits are also provided for measuring expression levels of unique sets of JAK-STAT3 cellular signaling pathway target genes.

The present application mainly relates to specific method for determining a risk score that indicates a risk that a subject will experience a clinical event within a defined period of time. The risk score is determined based on a combination of inferred activities of two or more cellular signaling pathways in a subject, wherein the cellular signaling pathways comprise a PI3K pathway and one or more of a Wnt pathway, an ER pathway, and an HH pathway. The present application also relates to an apparatus, to a non-transitory storage medium, and to a computer program for determining a risk score that indicates a risk that a subject will experience a clinical event within a defined period of time. The present invention also relates to a kit for measuring expression levels of three or more target genes of each of two or more cellular signaling pathways in a sample of a subject, to kits for determining a risk score that indicates a risk that a subject will experience a clinical event associated with a disease within a defined period of time, and to uses of the kits in performing the method.

The methods, compositions, and kits of the invention are related to the discovery that lestaurtinib reduces levels and pathway activity of an SPOP substrate. Accordingly, described herein are methods and compositions for the use of lestaurtinib in downregulating one or more SPOP substrates or signaling pathway activities thereof in a subject in need thereof.

The invention is directed to in silico method to identify novel combinatorial oncoproteins that inhibit hedgehog pathway activity in various cancer cell lines required for the treatment of cancer. The invention in particular relates to in silico method to identify combinatorial oncoproteins as potential drug targets in the treatment of Glioma, Colon and Pancreatic Cancer.

The present invention relates to a method comprising inferring activity of a PI3K cellular signaling pathway in a tissue and/or cells and/or a body fluid of a medical subject based at least on expression levels of one or more target gene(s) of the PI3K cellular signaling pathway measured in an extracted sample of the tissue and/or the cells and/or the body fluid of the medical subject. The present invention further relates to an apparatus comprising a digital processor configured to perform such a method, a non-transitory storage medium storing instructions that are executable by a digital processing device to perform such a method, and a computer program comprising program code means for causing a digital processing device to perform such a method.

The invention belongs to the fields of medicine and genetic engineering, and relates to an application of a traditional Chinese medicinal monomer, namely shizukaol D, in preparing medicines and an application method of the shizukaol D. The invention provides the application of the traditional Chinese medicinal monomer, namely the shizukaol D, in preparing the anti-tumor target medicines, in particular an application in preparing a Wnt pathway inhibitor. The invention also provides a corresponding kit for testing activity of a Wnt pathway, a method for inhibiting Wnt signal pathway of in-vitro tumor cells and a pharmaceutical composition for inhibiting the Wnt pathway. According to the application provided by the invention, a novel lead compound is provided for the Wnt pathway inhibitor, a novel method and a novel approach are offered for inhibiting the Wnt pathway of the cells and a novel application is provided for the traditional Chinese medicinal monomer, namely the shizukaol D; therefore, medicinal value of a plant source, namely chloranthus japonicus, of the shizukaol D is enhanced.