83 results about "Catenin Proteins" patented technology

Cyclin D1 is one of the targets of beta-catenin in breast cancer cells. Transactivation of beta-catenin correlated significantly with cyclin D1 expression both in eight breast cell lines in vitro and in 123 patient samples. More importantly, high beta-catenin activity significantly correlated with poor prognosis of the patients and is a strong and independent prognostic factor in breast cancer (p<0.001). Moreover, by multivariate analyses, the inventors found that activated beta-catenin is a strong prognostic factor which provided additional and independent predictive information on patients survival rate even when other prognostic factors, including lymph node metastasis, tumor size, estrogen receptor and progesterone receptor status, were taken into account (p<0.001). This invention demonstrates that beta-catenin is involved in breast cancer formation and / or progression and may serve as a target for breast cancer therapy.

The present invention relates to methods of modulating epithelial stem cell lineage by regulating the expression of Lef1 or a BMP inhibitor and / or the stability of β-catenin or the expression of a Wnt; regulating the expression or activity of GATA-3; or regulating BMPR1A activity either at the level of receptor expression or at the level of pathway activation. Methods of regulating E-cadherin, GATA-3, BMPR1A and HK1-hair keratin and methods of identifying agents which modulate the epithelial stem cell lineage are further provided. Such agents are useful for inhibiting or stimulating inner root sheath development or hair follicle formation.

The invention relates to β-catenin targeting peptides comprising an a-helical segment that are optionally stapled or stitched, and pharmaceutical compositions thereof. Uses of the inventive β-catenin targeting polypeptides including methods for treatment of disease, such as diseases associated with aberrant Wnt signaling, including cancer, are also provided.

The invention relates to β-catenin targeting peptides comprising an α-helical segment that are optionally stapled or stitched, and pharmaceutical compositions thereof. Uses of the inventive β-catenin targeting polypeptides including methods for treatment of disease, such as diseases associated with aberrant Wnt signaling, including cancer, are also provided.

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.

The invention relates to β-catenin targeting peptides comprising an α-helical segment that are optionally stapled or stitched, and pharmaceutical compositions thereof. Uses of the inventive β-catenin targeting polypeptides including methods for treatment of disease, such as diseases associated with aberrant Wnt signaling, including cancer, are also provided.

The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate β-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and / or RSPO3 and inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

A compound of formula (I) is provided which is able to interact with beta-catenin / TCF-4 binding site, having a structure essentially equivalent to a pharmacophore (IA), as herein described.

Methods and therapeutic compositions for the treatment of cancer are disclosed. Specifically, peptides including beta-catenin binding domains and polynucleotide sequences encoding same, such as cadherins and o-catenins and polynucleotide sequences encoding same, effective in methods and compositions for treating cancers associated with abnormally high levels of beta-catenin, such as colon cancers and melanomas.

The present invention relates to a purified molecules, including antibodies, that bind specifically to murine β-catenin phosphorylated at amino acid position Serine552 and to orthologs thereof, such as mammalian orthologs, including human orthologs. Methods of making and using such purified molecules are also provided. Kits containing such purified molecules are further provided.

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.

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.

The invention relates to method and compositions for treating and diagnosing cancer, in particular β-catenin related cancers. In general, the methods include administering RNAi constructs. The invention further relates to methods of identifying CTNNB1 related cancer therapeutics.

The methods comprise administering cells having properties of stem cells or progenitor cells, to the retina and reprogramming of retinal cells mediated by cell fusion of said cells with said retinal cells, said reprogramming being mediated by activation of the Wnt / β-catenin signalling pathway.

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 methods comprise administering cells having properties of stem cells or progenitor cells, to the retina and reprogramming of retinal cells mediated by cell fusion of said cells with said retinal cells, said reprogramming being mediated by activation of the Wnt / ss-catenin signalling pathway.

The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate β-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and / or RSPO3 and inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

The invention discloses a polypeptide specifically combined with beta-catenin protein with high affinity, and application and a synthesis method of the polypeptide. The amino acid sequence of the polypeptide is LEHRERSLQT(X1)RDIQRML(X2)P, wherein X1 is leucine, norleucine or homoleucine, and X2 is phenylalanine, 1-naphthyl alanine, 2-naphthyl alanine, 2-anthryl alanine or 9-anthryl alanine. The polypeptide is used for inhibiting growth of cancer cells. By the polypeptide, various tumor treatment targets can be achieved. The polypeptide inhibits opening of a beta-catenin protein-mediated Wnt signal pathway by inhibiting mutual combination of the beta-catenin protein and BCL9 in the cancer cells, so that growth of tumors is inhibited, self-apoptosis of the cells is induced, and the tumor disease treatment targets are achieved. The synthesis method of the polypeptide is simple and easy to implement, and the final product has high yield efficiency, has mass production potential, and has great drug clinical transformation potential.

A peptide or peptidomimetic comprising the amino acid sequence KKRLSVXLTSSLFR (SEQ ID NO: 1) or the inverse thereof, or comprising at least eight contiguous amino acids of helix C of β-catenin (SEQ ID NO: 41) or inverse thereof, wherein the peptide or peptidomimetic comprises a total of about 50 or fewer amino acids and inhibits the Wnt pathway, as well as a method of inhibiting the Wnt pathway in a cell, a method of treating or preventing a disease mediated by the Wnt pathway, and related compounds, compositions, and methods.

The present invention relates to a transgenic mouse containing a latent oncogenic β-catenin allele capable of spontaneous activation in vivo. The transgenic mouse is useful for the identification of compounds and immunotherapies for the prevention, treatment and / or cure of various forms of cancer associated with β-catenin activation.

The invention provides a retinal progenitor cell generated by separating and inducing as well as a composition including the cell. The cell is transplanted to a host, so that integration rate and oncogenicity of the retina are greatly improved. The invention further provides a method of preparing the retinal progenitor cell by restraining a classical Wnt signal channel as well as a method of preparing the retinal progenitor cell suitable for transplanting. The invention further provides a composition consisting: (a), a Tcf1 protein, (b), a beta-catenin protein, and (c), a Sox2 protein as well as an application of the composition in screening a drug for lowering cell oncogenicity generated by inducing. The invention further provides a method of screening the drug for lowering cell oncogenicity generated by inducing. The invention opens up a novel way for cell treatment.

The invention relates to the field of the medical wound surface restoration technology. The construction in vitro, which contains that composite skin of self epidermal cells can be used for transplantation, has become the hot point of the research on the field of the wound surface restoration; however, the culture of amplified epidermis cells in vitro has the defects that the culture conditions are stern; the epidermis source is seriously lacking, etc. The object of the invention is to supply composite skin which is constructed by taking hair follicle stem cells as seed cells, and a construction method thereof; the invention cultures the hair follicle stem cell in an isolating way, and the stem cell is inoculated on the surface of a dermis substitute through a plasmid vector transfection mutant Beta-catenin gene to form the composite skin after the culture cultivation in vitro. The invention can control the differentiation of the hair follicle stem cell and promote the multiplication of the hair follicle to multiple the stem cell in a short time; in this way, the stem cell can meet the requirement of application; moreover, the hair follicle stem cell has strong multiplication property which can promote the anti-infection capability after the transplantation of the composite skin.

Provided herein are methods of diagnosing and / or treating malignant or pre-malignant conditions in a subject. Overexpression of copy number variant-dependent genes, e.g., genes encoding a cell surface receptor, resulting from copy number changes compared to control is diagnostic of the condition, such as multiple myeloma or monoclonal gammopathy of undetermined significance. Also provided are methods for treating malignant conditions, such as multiple myeloma or a hyperdiploid subtype, with therapeutic agents, with or without other anti-cancer drugs, to downrregulate the overexpressed CNV genes and / or up-regulate the underexpressed genes. Furthermore, methods for lowering drug resistance in multiple myeloma cells via inhibition of platelet activation or thrombin release and for increasing survivability of a multiple myeloma subject via lithibition of PSMD4 gene to increase b-catenin protein expression are provided.

Human TKT genes are identified as modulators of the beta-catenin pathway, and thus are therapeutic targets for disorders associated with defective beta-catenin function. Methods for identifying modulators of beta-catenin, comprising screening for agents that modulate the activity of TKT are provided.

Provided is a peptide, which has an anti-inflammatory activity and an activity for promoting osteogenic differentiation, formed from the amino acid sequence selected from the group comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3. And provided is a peptide, which has a hair growth promoting activity, formed from the amino acid sequence selected from the group comprising the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 2. A peptide formed from the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, according to the present invention, consequently shows an anti-inflammatory activity by inhibiting an inflammatory cytokine expression and proliferation of inflammatory cells, and consequently promotes osteogenic differentiation by increasing phosphorylation of PI3K, Smad1, Smad5 and Smad8, which contribute to osteogenesis, and by increasing ALP, OPG and BSP expressions. And a peptide formed from the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, according to the present invention, consequently shows efficacy for preventing hair loss and promoting hair growth by promoting proliferation of hair follicle cells and human umbilical vein endothelial cells, increasing phosphorylation of EPK, increasing expressions of PI3K, β-catenin, IGF-1, KGF and Wnt3a which are proteins that contribute to hair growth, and reducing an expression of DKK-1 which is a hairless gene.

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-catenin. 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 method for detecting that LRP6 is the target gene of miR-29a by using a dual-luciferase reporter gene, the purpose of the present invention is to confirm that miR-29a can be negatively expressed by targeting the 3'UTR of the LRP6 gene through a dual-luciferase reporter gene system Regulates the expression of LRP6. A method for detecting LRP6 as a target gene of miR-29a using a dual-luciferase reporter gene, the method comprising the following steps: (1) constructing a plasmid vector and performing point mutations: (2) dual fluorescence detection. The present invention The beneficial effects are as follows: provide a new method for verifying that miR-29a can negatively regulate the expression of LRP6 by targeting the 3'UTR of the LRP6 gene, and contribute to miR-29a, LRP6 and Wnt / -catenin signaling pathways Elucidation of the pathogenesis of osteogenesis-related diseases involved; contribute to the development of potential drugs for osteogenesis-related diseases involved in miR‑29a, LRP6 and Wnt / ‑catenin signaling pathways and the screening of biomarkers.

The invention belongs to the technical field of the preparation and the application of a pig genetic marker, and concretely relates to a technology for detecting the single nucleotide polymorphism (SNP) of the fourteenth exon of a pig CTNNAL1 coding gene. The technology comprises the following steps: extracting genomic DNA from pig blood, designing a primer, carrying out PCR amplification, cloning and sequencing the obtained PCR product, carrying out sequence comparison analysis, detecting the SNP, and analyzing the correlation between the marker and the litter size traits. The invention discloses a DNA sequence of the fourteenth exon of the pig CTNNAL1 gene and an SNP typing detection technology. The nucleotide sequence of the genetic marker is represented by SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3 in a sequence table, there is a base mutation C / G at the 646th base of the sequences represented by the SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3 in the sequence table, and the base mutation causes the AluI-RFLP polymorphism. The invention also discloses a preparation method of the genetic marker, and an application of the genetic marker in the pig litter size marker-assisted selection.