65 results about "P53 protein" patented technology

Various embodiments of the present invention are directed to the field of Oncology, and in particular embodiments directed to a method of ameliorating, treating, or preventing a malignancy in a human subject wherein the steps of the method assist or boost the immune system in eradicating cancerous cells. In certain embodiments, administration of beneficial bacteria to an individual's microbiome that have been modified so as to produce effective amounts of desired compositions, compounds, agents, e.g. tomatidine, p53 protein, statins, etc., is employed to address cancerous conditions. In several embodiments, the administration of such beneficial bacteria and microbes to an individual's microbiome invokes either an active (or a passive) immune response to destroy, weaken or render less invasive certain cancerous cells, and preferably maintains muscle tissue to combat cancer cachexia.

Compounds of formula (I): wherein X is selected from CR^X and N; R^N1 is selected from H and C_1-4 alkyl, which may be substituted by SH or halo; R^G1 is selected from H and SH; R^C2 is selected from H and optionally substituted C_1-7 alkyl; R^C3 is selected from H and optionally substituted C_1-7 alkyl; R^x is selected from H, OH and NH₂; R^C4 is selected from: (i) an optionally substituted C_3-12 N-containing heterocyclyl; (ii) C(═O)NR^N5R^N6, where R^N5 and R^N6 are independently selected from H, optionally substituted C_1-7 alkyl, optionally substituted C_3-20 heterocyclyl and optionally substituted C_5-20 aryl or RN5 and RN6 and the nitrogen atom to which they are attached form an optionally substituted N-containing C_5-7 heterocyclyl group; (iii) C(═O)OR^O1, where R^O1 is selected from H, optionally substituted C_1-7 alkyl, optionally substituted C_3-20 heterocyclyl and optionally substituted C_5-20 aryl; (iv) C(═O)NHNHSO₂R^S1, where R^S1 is selected from H, optionally substituted C_1-7 alkyl, optionally substituted C_3-20 heterocyclyl and optionally substituted C_5-20 aryl; (v) OC(═O)RC8, where RC8 is selected from H, optionally substituted C_1-7 alkyl, optionally substituted C_3-20 heterocyclyl and optionally substituted C_5-20 aryl; (vi) OC(═O)NR^N7R^N8, where R^N7 and R^N8 are independently selected from H, optionally substituted C_1-7 alkyl, optionally substituted C_3-20 heterocyclyl and optionally substituted C_5-20 aryl or R^N7 and R^N8 and the nitrogen atom to which they are attached form an optionally substituted N-containing C_5-7 heterocyclyl group; and (vii) C(═O)CH₂NH C(═O)NHNH₂, CHC(CN)₂, CHC(CN)C(═O)NH₂, and carboxy; R_C5 is selected from H, OH and NH₂; or R^C4 and R^C5 together with the carbon atoms to which they are bound form an optionally substituted aromatic ring containing either 5 or 6 ring atoms, of formula: where Q represents O, N, or CR^Q1═CR^Q2, where R^Q1 and R^Q2 are independently selected from H, OH and NH₂; R^C6 is selected from H, OH and NH₂; and R^C7 is selected from optionally substituted C3_12 N-containing heterocyclyl, NHC(═O)R^C9, CH₂NR^N2R^N3 and NHC(═S)NHR^N4, where R^C9 is selected from optionally substituted C_1-7 alkyl, optionally substituted C_3-20 heterocyclyl and optionally substituted C_5-20 aryl, R^N2 and R^N3 are independently selected from H, optionally substituted C_1-7 alkyl, optionally substituted C_3-20 heterocyclyl and optionally substituted C_5-20 aryl or R^N2 and R^N3 and the nitrogen atom to which they are attached form an optionally substituted N-containing C_5-7 heterocyclyl group, and R^N4 is selected from optionally substituted C_1-7 alkyl, optionally substituted C_3-20 heterocyclyl and optionally substituted C_5-20 aryl, and when R^C4 and R^C5 are not bound together, R^C3 may additionally be selected from OR⁰², where R^O2 is a C_1-4 alkyl group, and C(═O)OR^O3, where R^O3 is a C_1-4 alkyl group and R^C2 may additionally be selected from halo, for use in stabilising a p53 protein carrying a Y220C mutation.

The invention relates to the technical field of medicinal chemistry, particularly discloses a small-molecule inhibitor of Mdm<X>/Mdm<2>, and also relates to a preparation method of the small-molecule inhibitor of Mdm<X>/Mdm<2>. The small-molecule inhibitor compound can inhibit the interaction of Mdm<X> protein and p53 protein and also can inhibit the interaction of Mdm<2> protein and p53 protein, has antiproliferative activity on cancer cells, and cannot generate toxic and side effects on patients. The small-molecule inhibitor compound can be combined with other therapies for use.

Various embodiments of the present invention are directed to the field of Oncology, and in particular, embodiments directed to a method of ameliorating, treating, or preventing a malignancy in a human subject wherein the steps of the method assist or boost the immune system in eradicating cancerous cells. In certain embodiments, administration of beneficial bacteria to an individual's microbiome that have been modified so as to produce effective amounts of desired compositions, compounds, agents, e.g. tomatidine, p53 protein, etc., is employed to address cancerous conditions. In several embodiments, the administration of such beneficial bacteria and microbes to an individual's microbiome invokes either an active (or a passive) immune response to destroy, weaken or render less invasive certain cancerous cells, and preferably maintains muscle tissue to combat cancer cachexia.

The invention discloses a nanometer vesica capable of detecting wild type p53 protein and variant p53 protein in cells simultaneously. Nanogold capable of specifically recognizing wild type p53 protein wraps inside the vesica, and an antibody resisting variant p53 protein marked by fluorescein isothiocyanate decorates the surface of the vesica. The nanometer vesica has the advantages that (1) the nanometer vesica recognizes different types of tumor suppressor proteins p53 with high specificity, and the detection specificity and the sensitivity are improved; (2) plasma resonance imaging and fluorescence imaging technologies are adopted, after the vesica enters the cell, the cell is subjected to in-situ imaging by adopting a microscope, and wild type p53 protein and variant p53 protein on the single-cell layers are detected simultaneously; (3) the nanometer vesica designed according to the technical scheme is capable of carrying out in-situ monitoring on variation of expression of p53 protein in the cell under the action of medicine, and a novel method is provided for researching physiological process in the cell participated by the vesica.

Provided are a method of ex-vivo culture of natural killer (NK) cells by treating the cells with a reactive oxygen species (ROS) inhibitor and/or a p53 protein inhibitor; and a composition comprising the cultured NK cells. By reducing the activity of ROS and p53 proteins during ex-vivo culture, NK cells may have achieved greater expansion efficiency without altering their anti-tumor cytotoxicity.

The invention belongs to the technical field of medicines, in particular relates to a physalin A extracting process and medical application thereof, in particular relates to a novel application of physalin A in preparation of an anti-tumor dug and in particular relates to the use of physalin A in treatment of human fibrosarcoma and human malignant melanoma. After process optimization, the extracting rate of physalin A is 0.2133%. Physalin A can be used for inhibiting the growth of various tumor cells, particularly has obvious inhibiting action on the growth of the human fibrosarcoma and human malignant melanoma, but does not inhibit the activities of the human normal cells obviously. The mechanism is that the downstream caspase family-associated protein is activated by activating Fas death receptors, so that the tumor cells are induced to generate apoptosis. Meanwhile, the physalin A can be used for inducing the tumor cells to generate autophagy for achieving autophagy antagonism apoptosis in the HT1080 and the A375-S2 cells; and the p53 protein and the MAPK (Mitogen-Activated Protein Kinase)-familty p38 protein have a key regulation effect. The physalin A can be used for preparing a digestive tract dosage form or a non-digestive tract dosage form, which can be used for treating tumors including the human fibrosarcoma and human malignant melanoma.

The invention relates to a p53 fusion protein and an application thereof. The invention provides the p53 protein and the p53 fusion protein in the tetrameric shape having the bioactivity. In the invention, the p53 protein and the p53 fusion protein inclusion body is produced by using the recombination expression by escherichia coli, and the inactivated p53 protein and the p53 fusion protein in the tetrameric shape and having the bioactivity are prepared by the renaturation and other steps. The invention also provides the medical application of the p53 protein and the p53 fusion protein.

The invention belongs to the field of biotechnology, and in particular relates to a method for regulating expression, quantity and activity of a heat shock protein 70 and application thereof. The method provided by the invention can also regulate tumor tissue, activity of a transcription factor NF-kB, expression and activity of a death receptor DR4 and DR5, phosphorylation and activity of JNK and c-Jun, expression and activity of a p53 protein, expression and proapoptotic activity of proapoptotic molecules Bax, Bid, t-Bid, capsase 3, capsase 8 and capsase 9, and expression and activity of c-FLIP and Bcl-2, and promote apoptosis of tumor tissues and cells. The invention also relates to application of the above method to preparation of drugs cooperatively applied with cell apoptosis induced drug.

The invention provides a recombination BCG viable bacterium strain capable of expressing and secreting human p53 protein, a viable bacterium vaccine and a construction method and application thereof, and relates to the technical field of biology, in particular to the technical field of genetic engineering. The novel viable bacterium vaccine capable of being used for prevention and treatment of human tumor diseases is provided. The recombination BCG viable bacterium strain is provided first, and the recombination BCG viable bacterium strain is a recombination strain which is obtained after a human p53 optimization gene sequence obtained after the preference of a codon is modified by a human p53 gene sequence for coding the human p53 protein referring to a BCG genome is led into the BCG viable bacterium strain. The invention further provides the construction method of the recombination strain and the viable bacterium vaccine obtained through the construction method. The viable bacterium strain can express and secrete the human p53 protein in cells, and zoology experiments show that the function for prevention and treatment of cancers can be achieved after the viable bacterium strain is used as a vaccination organism.

The invention provides a stable polypeptide protein targeted inhibitor, the amino acid sequence of the stable polypeptide protein targeted inhibitor is as shown in the specification: Ac-Q-S-Q-Q-F-K-N-Mq-W-R-L-L-D-Q-N-NH2, and Mq is as shown in the specification. The invention also provides application of the stable polypeptide protein targeted inhibitor in preparation of drugs for inhibiting MDM4 protein. Nuclear magnetism, secondary mass spectrometry and the like prove that polypeptide disclosed by the invention can be covalently bound with lysine on the MDM4 protein, so that the binding activity of the MDM4 protein and the p53 protein is influenced. Meanwhile, cell proliferation experiments also prove that the polypeptide can inhibit proliferation of breast cancer cells.

The invention provides a kit for detecting the prognosis of patients with esophageal squamous cell carcinoma in the Xinjiang region. The kit comprises a phospholipase epsilon 1 protein, an IKB alpha protein and a mutant P53 protein. The kit also comprises a citrate buffer solution with the content of 0.01M, an ethylenediaminetetraacetic acid repair solution with the content of 10mM, a H2O2 solution with the mass concentration of 3%, a phosphate buffer solution with the content of 0.01M, a BSA blocking solution with the mass concentration of 5%, an immunohistochemical Envision kit and a DAB developing reagent. The kit can forecast the prognosis of patients through detecting the expression case of the paraffin-embedded surgical specimen of the patients with esophageal squamous cell carcinomathrough PLCE1, IKB alpha and P53 proteins. Compared with the existing kit realizing single index detection, the kit has higher prediction effects and has the prediction ability similar to the TNM staged prediction ability. The two-step immunohistochemical method using the kit is a mature and reliable method that can be widely used in primary hospitals.

The invention belongs to the field of analysis and relates to breast cancer cell endogenous biological macromolecule acetylation p53 protein isotope quantitative analysis. The acetylation p53 protein in a complex cell matrix sample is extracted, separated and purified by utilizing the technical means such as co-immunoprecipitation and gel electrophoresis. The method comprises the following steps: by utilizing a strategy for performing qualitative and quantitative analysis on specific peptide fragments generated by performing trypsin hydrolysis on recombinant human p53 proteins and p53 proteins in breast cancer cells, by taking synthetic peptide fragments generated by performing stable carbon 13 and nitrogen 15 isotope labeling on amino acids in the specific peptide fragment sequence as interior labels, realizing quantitative analysis of acetylation p53 proteins on specific sites in a DNA binding domain in a breast cancer cell sample. The method mainly comprises a sample extraction and gel electrophoresis method, an Obitrap measurement method, preparation of a standard curve and measurement of precision and density. The method is good in linear relationship, high in accuracy and high in reproducibility and can be used for quantitative analysis of acetylation p53 proteins in cells.

The invention discloses an electronic mediator type enzymatic electrochemical immunodetection method of p53 protein. The electronic mediator type enzymatic electrochemical immunodetection method specifically comprises the following steps: preparing an immune molecule immobilized active interface; constructing and optimizing an electronic mediator type enzymatic electrochemical immunoassay system; and performing quantitative detection on p53 protein. The method specifically comprises the following steps: performing electrostatic spinning and performing electropolymerization on thionine to obtain a PA6-MWCNTs-PTH immune molecule immobilized active interface, constructing the electronic mediator type enzymatic electrochemical immunoassay system on the PA6-MWCNTs-PTH interface by virtue of sandwich immunoreaction, performing relevant parameter optimization, and performing quantitative detection on p53 protein by using the constructed immunoassay system. The detection method disclosed by the invention has the characteristics of high sensitivity, high selectivity, high stability, regeneration performance, wide linear range, low detection limit and the like.

Biologically active tetrameric p53 proteins and p53 fusion proteins are provided. These proteins may be generated and refolded into tetrameric form using denatured proteins produced from E. coli. Therapeutic uses of p53 proteins and p53 fusion proteins are also provided.

The invention discloses a medicine for treating or preventing human cervical cancer as well as a preparation method and application thereof, belongs to the technical field of medicines, and particularly relates to a medicine for treating or preventing human cervical cancer based on an MDM2-p53 protein and protein interaction signal channel and a target mechanism as well as a preparation method and application thereof. The invention finds that the action mechanism of the compound 1, 5, 6-trimethoxy-2, 7-dihydroxyphenanthrene is a new mechanism based on an MDM2-p53 protein and protein interaction signal pathway and a target spot. The medicine disclosed by the invention has the characteristics of novel action mechanism, no addiction and small dosage, and has the effect of inhibiting the growth of Hela cells. The IC50 on Hela cells for 48 hours is 0.42 [mu]M. And cell apoptosis can be caused by acting on an MDM2-p53 pathway, and meanwhile, mitochondrial apoptosis is caused.

The invention relates to an AMPK activator (such as for instance metformin) for use in preventing metastasis in a patient suffering from a cancer, wherein said patient has a non-mutated p53 gene or lacks a mutant form of the p53 protein. The invention also relates to an AMPK activator for use in improving the survival time of a patient suffering from a cancer, wherein said patient has a non-mutated p53 gene or lacks a mutant form of the p53 protein.