234 results about "Catenin" patented technology

Methods and compositions are provided for the identification of stem cells and cancer stem cells. β-catenin is also identified as a target for the development of therapeutic moieties against hematopoietic tumors, i.e. leukemia and lymphoma cells, which may include screening assays directed at β-catenin, or members of the β-catenin signaling pathway. Cellular proliferation in hematopoietic cells can be altered by introducing stabilized β-catenin into a hematopoietic cell that is altered in its ability to undergo apoptosis but which is not fully transformed. The immortalized cells are useful in screening assays, and in the analysis of pathways by which hematopoietic cells undergo transformation.

Methods for generating high-yield, high-purity cardiomyocyte progenitors or cardiomyocytes from pluripotent cells are described. Wnt/β-catenin signaling is first activated in pluripotent cells, e.g., by inhibition of Gsk-3 to obtain a first population of cells. Wnt/β-catenin signaling is then inhibited in the first cell population to induce cardiogenesis under fully defined, growth factor free culture conditions.

Interaction between MUC1 and β-catenin can be interrupted using polypeptides or antibodies that specifically bind to the binding site on MUC1. Interruption provides the beneficial effect of inhibiting, reducing, and/or retarding invasiveness and metastasis. Fusion polypeptides and antibodies are provided to achieve a therapeutic effect.

Methods and agents are disclosed for modulating the interaction of β-catenin or γ-catenin with CBP or p300. Agents that increase the binding of CBP to β-catenin are associated with enhancing the β-catenin-related proliferation of adult stem cells, including hematopoietic stem cells, neural stem cells, skin stem cells, and pancreatic stem cells.

Methods and agents are disclosed for modulating the interaction of β-catenin or γ-catenin with CBP or p300. Agents that increase the binding of CBP to β-catenin are associated with enhancing the β-catenin-related proliferation of adult stem cells, including hematopoietic stem cells, neural stem cells, skin stem cells, and pancreatic stem cells, as well as embryonic stem cells.

The present invention provides methods for the prevention, treatment and/or amelioration of fibrosis or fibrotic conditions. The present invention further provides small molecule inhibitors of Wnt- and TGF-p-mediated β-catenin signaling to prevent, treat and/or ameliorate fibrosis or fibrotic conditions. Kits comprising small molecule inhibitors of Wnt- and TGF-p-mediated β-catenin signaling and methods of identifying small molecule inhibitors of Wnt- and TGF-p-mediated β-catenin signaling are also provided.

The present invention is directed to methods and compositions for cancer therapy, particularly cancers resulting from a defective Wnt/beta-catenin signaling pathway. In specific embodiments, a T-cell factor (Tcf)-responsive promoter regulating expression of a therapeutic gene is administered to an individual having the cancer. In a specific embodiment, the Tcf-responsive promoter comprises a minimal CMV promoter and is present on an adenovirus vector. The promoter regulates expression of a therapeutic gene.

The present invention relates to the fields of cell biology, molecular biology, and medicine. More specifically, the invention is directed to generating cardiomyocyte cells from non-cardiomyocyte cells by enhancing the activation of the Wnt/β-catenin signaling pathway. The cardiomyocyte cells that are generated in the present invention are then used as cardiac disease therapy.

Aspects of this invention are related, at least in part, to the use of chemical compounds able to inhibit GSK-3 and/or to stabilize β-catenin and formulations thereof. Some aspects of this invention relate to compositions comprising such compounds. Some aspects of the invention provide methods of using such compounds and/or compositions in the treatment of subjects having a neurological disease and/or psychiatric disorder. Some aspects of this invention provide methods of using ruboxistaurin, enzastaurin, sunitinib, midostaurin, lestaurtinib, 7-hydroxystaurosporine, and/or Chir99021 in the treatment of subjects having a neurological disease and/or psychiatric disorder. In some embodiments, compounds are administered in combination with Lithium.

Methods for generating high-yield, high-purity cardiomyocyte progenitors or cardiomyocytes from pluripotent cells are described. Wnt/β-catenin signaling is first activated in pluripotent cells, by, for example, inhibiting Gsk-3 to obtain a first population of cells. Wnt/β-catenin signaling is then inhibited in the first cell population to induce cardiogenesis. One or more of these steps is performed under defined, albumin-free culture conditions.

The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. The invention is based, at least in part, on the results provided herein demonstrating that hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, possess superior pharmacokinetic properties compared to the corresponding unmodified peptides, and are highly effective in binding to β-catenin in vitro, in cellulo, and in vivo, disrupting the BCL-9/β-catenin interaction, and thereby interfering with deregulated Wnt/β-catenin signaling for therapeutic benefit in a variety of human diseases including human cancer.

The invention relates to oligomer compounds (oligomers), which target beta-catenin mRNA in a cell, leading to reduced expression of beta-catenin. Reduction of beta-catenin expression is beneficial for a range of medical disorders, such as hyperproliferative disorders, such as cancer. The invention provides therapeutic compositions comprising oligomers and methods for modulating the expression of beta-catenin using said oligomers, including methods of treatment.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond expressed/synthetic to the modulation of PHD2 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short inter-fering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsR-NA), micro-RNA (miRNA), and short hair-pin RNA (shRNA) molecules that are capa-ble of mediating or that mediate RNA inter-ference (RNAi) against PHD2 gene expres-sion.

Disclosed herein are isoxazole derivaties and uses thereof. Serving as agonists of Wnt, the isoxazole derivatives activate Wnt/β-catenin signaling and thus can be used in the treatment and prevention of diseases related to the signal transduction. Also, pharmaceutically acceptable salts of the isoxazole derivatives are disclosed.

Methods for detecting, diagnosing and monitoring thyroid cancer in a subject are described comprising measuring in a sample from the subject markers including Ep-ICD and β-catenin. The invention also provides kits and compositions for carrying out the methods of the invention.

A method of preventing and/or treating a cancer including co-administering a c-Met inhibitor and a beta-catenin inhibitor to a subject in need thereof, a pharmaceutical composition comprising a c-Met inhibitor and a beta-catenin inhibitor, and a kit comprising a pharmaceutical composition comprising a c-Met inhibitor, and a pharmaceutical composition comprising a beta-catenin inhibitor packaged together.

The invention discloses a system for indicating the active state of a Wnt signal in a cell by using BiFC (Bimolecular Fluorescence Complementation) and application of the vector composition. The invention provides a fusion protein group which consists of fusion protein A and fusion protein B, wherein the fusion protein A comprises a core effector beta-catenin fragment and a fluorescent protein fragment A located at a fragment C of the core effector beta-catenin fragment; the fusion protein B comprises a transcription factor (TCF) and a fluorescent protein fragment B located at a fragment N of the TCF. Proved by experiments, a complex formed by the core effector beta-catenin and the TCF in a Wnt signal channel is visualized by using a strategy on the basis of BiFC, so that the active state of Wnt in the cell is directly displayed; a BiFC system is used for instantaneously transfecting cells or constructing a stable expression cell line, so that specific signals formed in a cell nucleus can be observed and can specifically display and reflect the active state of the Wnt signal channel in a living cell and variation thereof.

A series of oxazole and thiazole compounds are shown herein to be small molecule inhibitors of the Wnt pathway that specifically target the activity of the stabilized pool of β-cat oxazole and thiazole compounds are disclosed that have a formula represented by the following:

The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, cancer, and others.

The present invention relates to amino-substituted quinazoline derivatives as inhibitors of β-catenin/tcf-4 pathway, which can be useful in the treatment of cancer; to processes for their preparation; to pharmaceutical compositions comprising them; and to methods of using them.