61 results about "Nuclear translocation" patented technology

Disclosed is a conjugate comprising a biologically active agent (drug) linked to a subcellular targeting moiety that targets a drug specifically to the nucleus. Targeting is achieved by attaching a steroid hormone (or an analog) to the drug. The steroid hormone attached to the drug binds its corresponding receptor, the formation of the receptor-ligand complex results in the internalization of the complex into the nucleus, thus resulting in nuclear translocation of the drug. Also disclosed is a conjugate (comprising the complex of the drug and the steroid hormone) bound to a polymer by spacers allowing for concurrent passive targeting to the tumor cell (afforded by attachment to the polymer by the EPR effect) and nuclear targeting of the conjugate (due to the presence of the steroid). Using a suitable degradable spacer allows for the release of free drug in the tumor and enhances nuclear targeting efficacy. The polymer can be further linked to a cellular targeting molecule, where the targeting molecule directs the polymer to specific cells. One may thus be able to effectively target drugs to the nucleus of tumor cells. With little or modifications, several therapeutic agents can be targeted using the invention.

Agents that stimulate nuclear translocation of Nrf2 protein and the subsequent increases in gene products that detoxify and eliminate cytotoxic metabolites are provided in a method for treating diabetic retinopathy or drusen formation in age-related macular degeneration. The structurally diverse agents that act on the Nrf2 / ARE pathway induce the expression of enzymes and proteins that possess chemically versatile cytoprotective properties and are a defense against toxic metabolites and xenobiotics. Agents include certain electrophiles and oxidants such as a Michael Addition acceptor, diphenol, thiocarbamate, quinone, 1,2-dithiole-3-thione, butylated hydroxyanisole, flavonoid other than genistein, an isothiocyanate, 3,5-di-tert-butyl-4-hydroxytoluene, ethoxyquin, a coumarin, combinations thereof, or a pharmacologically active derivative or analog thereof.

There is disclosed an isolated cDNA sequence (SEQ ID NO:1) encoding a P4.33 polypeptide and comprising a coding region (SEQ ID NO:2) of the sequence described in SEQ ID NO:1, or a sequence having at least 90% homology with the coding region of SEQ ID NO:1. The P4.33 polypeptide functions as a specific cell-surface receptor for IGFBP-3, and undergoes nuclear translocation in combination with IGFBP-3. In particular aspects, IGFBP-3 and P4.33 (IGFBP-3R) cooperatively suppress DNA synthesis and cell growth, and induce caspase activation and apoptosis in cancer cells, indicating that P4.33 is an important mediator of IGF-independent growth inhibitory actions of IGFBP-3. The P4.33:IGFBP-3 system of the present invention can be used, inter alia, in screening and diagnostic assays, and for therapeutic methods for cancer treatment and tumor suppression.

Agents that stimulate nuclear translocation of Nrf2 protein and the subsequent increases in gene products that detoxify and eliminate cytotoxic metabolites are provided in a method for treating diabetic retinopathy or drusen formation in age-related macular degeneration. The structurally diverse agents that act on the Nrf2 / ARE pathway induce the expression of enzymes and proteins that possess chemically versatile cytoprotective properties and are a defense against toxic metabolites and xenobiotics. Agents include certain electrophiles and oxidants such as a Michael Addition acceptor, diphenol, thiocarbamate, quinone, 1,2-dithiole-3-thione, butylated hydroxyanisole, flavonoid other than genistein, an isothiocyanate, 3,5-di-tert-butyl-4-hydroxytoluene, ethoxyquin, a coumarin, combinations thereof, or a pharmacologically active derivative or analog thereof.

The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-κB in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-κB in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.

The invention provides a new detection index for drug sensitivity under the state of an inflammatory bowel disease and application of the new detection index in the design of a drug therapy scheme, relates to multiple fields of pharmaceutical pharmacokinetics, pharmacology, cytobiology and molecular biology, creatively reveals natural drug-resistant phenomena of the inflammatory bowel disease and expounds related mechanisms. According to the new detection index, the phosphorylation of STAT3 is promoted by virtue of cell factors TNF-a, IL17 and LPS, which are excessively secreted in mice with the inflammatory bowel disease, in a way of STAT3 / Nf-kb, then the phosphorylation and the nuclear translocation of P65 are induced, the expression of peripheral blood monouclear cells P-gp is promoted, and the drug concentration of an immune inhibitor in the cells is reduced, the treatment effect of the immune inhibitor is inhibited, and the natural drug resistance is generated; by administering a P-gp specific inhibitor, the drug resistance phenomenon can be reverted. The new detection index prompts that P-gp expression quantity of peripheral blood lymphocyte can serve as an evaluation index of the natural drug resistance of patients with IBD (inflammatory bowel disease), and by virtue of the combination of the P-gp inhibitor, the decrease of the pharmaceutical effect caused by the natural drug resistance can be reverted, so that a new thought is provided for the treatment scheme of IBD.

The present invention provides a peptide comprising amino acid sequences R I, F I and R I G C and containing 25 or fewer amino acid residues, and capable of transporting a functional molecule into a cell, and also into a nucleus, more efficiently than a previous PTD.

Provided herein are compositions containing photoactivatable caged tamoxifen and tamoxifen derivative molecules. Also provided are kits containing one of these compositions and a light source. Also provided are methods of optically inducing nuclear translocation of a fusion protein containing a mammalian estrogen receptor ligand binding domain in a eukaryotic cell and methods of optically inducing recombination in a eukaryotic cell that include contacting a eukaryotic cell with at least one of these compositions. Also provided are methods of treating breast cancer in a subject that include administering a photoactivatable caged tamoxifen or tamoxifen derivative molecule to a subject having breast cancer.

Heritable pathogenic variants in the mismatch repair (MMR) pathway, also known as Lynch Syndrome (LS), can lead to the development of colon cancer and other cancers. Following mismatch, a complex of proteins consisting of MLH1, MSH2, MSH6 and PMS2 translocate into the nucleus to signal recruitment of repair mechanisms. Flow cytometry-based, functional variant assays (FVAs), were developed to determine whether variants in these MMR repair genes and / or other related genes would augment the nuclear translocation of MLH1 and MSH2 and downstream nuclear phosphorylation of ATM and ATR in response to DNA mismatches. Each assay distinguished pathogenic variants in MMR repair genes (MLH1, MSH2, PMS2 and MSH6) from benign controls. The combination of multiple assays provided robust separation between heterozygous pathogenic variant carriers and benign controls. The ability to produce distinct molecular phenotypes by these assays suggest FVA assays of MMR pathways could be used to identify LS and associated risk of colon and other cancers and could act as an adjunct to MMR gene sequencing panels in categorizing variants.

A peptide which is formed from an amino acid sequence selected from the group comprising amino acid sequences of SEQ ID NO: 1 to SEQ ID NO: 3, according to the present invention, has osteoclast differentiation and activation inhibition and is highly effective for preventing or treating bone diseases related to the destruction of the bone. A peptide, according to the present invention, reduces expression of cathepsin K and TRAP related to osteoclast differentiation, inhibits nuclear translocation of NF-kB, and ultimately inhibits osteoclast differentiation. Provided is a composition, for preventing or treating bone diseases, comprising the peptide.