52 results about "P53 Mutation" patented technology

The present invention provides peptides and peptidomimetics corresponding to part or to the entirety of the region encompassed by residues 360-386 of human p53, said peptides and peptidomimetics characterized by the ability to activate DNA binding of wild-type p53 and to select tumor-derived p53 mutants. Pharmaceutical compositions of the compounds of the invention and methods of using these compositions therapeutically are also provided.

The present invention provides a method, a system and the composition for forecasting the susceptibility of the patient to the disease, which is based on executing relevancy of p53 mutation state and gene expression profile to a set of predefined gene. The methods for specification, prognosis and diagnosis to the cancer are provided in some execution modes. In other execution modes the present invention provides the statistical method for constructing the categorizer base on gene expression, and the categorizer can be used for forecasting the susceptibility of the patient to the disease, classifying the tumour and doing prognosis to the clinical result.

The present invention provides a human triple-negative breast cancer cell line designated DKAT. The DKAT cell line has a marker profile of high expression of Snail-1 and Snail-2 (Slug); and a p53 mutation in exon 8 at codon 273 (CGT>CAT). The present invention further provides methods of using the DKAT cell line.

The invention relates to methods and compositions for treatment of cancer. In one embodiment the method involves the use of a c-FLIP inhibitor as the sole active agent. In another embodiment the invention relates to the treatment of p53 mutant cancers using combinations of c-FLIP inhibitors and chemotherapeutic agents.

Fatostatin, a recently described inhibitor of SREBP activation, significantly reduces the level of mutant p53 binding to the HMG-CoA reductase gene promoter. Further, fatostatin treatment had a dramatic effect on normalizing the abnormal 3D morphology of 3 strains of breast cancer cells: MDA-468 cells, MDA-231 cells, and SKBR3 cells. The results show a functional interaction with SREBPs as being critical for mutant p53-mediated upregulation of the mevalonate pathway genes. At a clinical level, inhibition of the mevalonate pathway, either alone or in combination with other therapies, offers a novel, safe and much needed therapeutic option for tumors bearing mutant p53.

The invention provides the application of iridoid compound to the preparation of ovarian cancer resistance medicament. The iridoid compound is isovaleric acid base dihydro valerian element or isovaleric acid base dihydro valepotriate J which has the following structural formula. The experiments on the toxic and killing effect of the isovaleric acid base dihydro valerian element or the isovaleric acid base dihydro valepotriate J on the p 53 wild ovarian cancer cells A2780, the p53 mutated OVCAR-3 cells and the normal ovarian cells IOSE144 show that the isovaleric acid base dihydro valerian element or the isovaleric acid base dihydro valepotriate J has the selective toxic and killing effect on the ovarian cancer cells and can inhibit the proliferation of ovarian cancer cells and kill the ovarian cancer cells. The iridoid compound can be used as the active component to prepare the ovarian cancer resistance medicament. The invention provides the novel ovarian cancer treatment medicament for the clinical treatment of the ovarian cancer and brings the joyous news to the patients with the ovarian cancer. The iridoid compound has higher application value.

A method for determining if a subject with cancer or precancerous lesions or a benign tumor, will respond to treatment with an inhibitor selected from the group comprising an inhibitor of one or more enzymes in the mevalonate pathway, an inhibitor of geranylgeranyl transferase, an inhibitor of farnesyl transferase or an inhibitor of squalene synthase, by (i) obtaining a sample of the cancer cells, precancerous cells or benign tumor cells from the subject, (ii) assaying the cells in the sample for the presence of a mutated p53 gene or a mutant form of p53 protein or a biologically active fragment thereof, and (iii) if the cells have the mutated p53 gene or mutant form of the p53 protein, then determining that the subject will respond to treatment with the inhibitor or combinations thereof. Some embodiments are directed to treatment with the inhibitors.

The present invention provides compounds of Formula (I) (wherein R<1>, R<2>, R<3>, L, and X are as defined herein), or a pharmaceutically acceptable salt, solvate or ester thereof. The present invention also provides compositions comprising these compounds that are useful for treating cellular proliferative diseases, disorders associated with activity of mutants of p53, or in causing apoptosis of cancer cells.

The invention discloses a method for quantified detection of mutation DNA through combination of a resonant light scattering probe with a CHA technique based on GQDs. The method comprises the following steps of firstly, synthesizing graphene quantum dots, designing two harigrip probes H1 and H2 in according to objects, and then preparing two probes GQDs-H1 and GQDs-H2 through a condensation reaction. In a PBS buffer solution reaction system, when p53 mutation DNA is added, aggregation of the GQDs-H1 and GQDs-H2 can be caused, obviously-enhanced resonance light signals are generated, and quantified detection of p53 mutation DNA is realized. The method has high sensitivity and selectivity, the liner scope is 1pM to 50mM, the detection limitation is 0.8pMa, and quantified detection of an object can be realized effectively.

The invention provides a rapid detection method for p53 gene mutation. The rapid detection method comprises the steps of designing wild type primers and mutant type primers of exon 6 (p53-E6) of p53 and exon 8 (p53-E8) of p53; amplifying a corresponding wild type target segment and mutant type target segment respectively; mixing the above two segments according to different proportions so as to make the content of the mutant type target segments being 1/10, 1/100, 1/1,000 and 0; and finally distinguishing by an HRM method. Compared with other methods, the method provided by the invention has the advantages of high specificity and high sensitivity, is convenient and efficient, and has higher throughput and lower cost for single detection.

A method of enhancing p53 activity of a p53 mutant polypeptide is provided. The method includes interacting a compound to an open L1/S3 binding site of the p53 mutant polypeptide, where the p53 activity of the p53 mutant polypeptide is enhanced in the presence of the compound. Compounds were identified from databases of compounds for virtual drug screening. Methods of screening for compounds that enhance p53 activity by binding to the open L1/S3 binding site, and methods of treatment using the identified compounds, are also provided.

Disclosed are methods of isolating T cells having antigenic specificity for a mutated p53 amino acid sequence encoded by a cancer-specific p53 mutation, the method comprising: inducing autologous APCs of the patient to present the mutated p53 amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated p53 amino acid sequence; and selecting the autologous T cells. Also disclosed are related methods of preparing a population of cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

The invention discloses new application of P53 gene mutation and telomere dysfunction, namely, application of a reagent for detecting cancer suppressor gene P53 gene mutation and telomere dysfunction in preparing a reagent for clinical diagnosis of polycystic kidney disease, or the application of P53 gene mutation and telomere dysfunction in screening the therapeutics for the polycystic kidney disease. An experimental result shows that the hybrid descendant of the mice with p53N236S gene mutation and the mice suffering from Werner syndrome (WS) suffers from the polycystic kidney disease so that a novel PKD disease model is acquired. According to the application, the condition that the happening of the polycystic kidney disease possibly is a new phenomenon of abnormal proliferation of kidney cells caused by the combined action of mutation p53 and aging signal is discovered for the first time. Through the discovery, the pathogenesis of the polycystic kidney disease is enriched, and a new biomarker for the clinical diagnosis of the polycystic kidney disease is provided.

The invention features methods for identifying compounds that modulate the activity of phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) Inhibitors of PI5P4K can be used in, for example, the treatment or prevention of cell proliferation dis orders (e.g., the prevention of tumor cell growth in p53 mutated cancers).

The invention provides combination therapies and methods for the treatment of cancers associates with p53 mutations. The method comprises the separate, sequential or simultaneous administration of a therapeutically effective amount of a) a specific binding member, for example CH-11, which binds to a cell death receptor, for example Fas, or a nucleic acid encoding said binding member and b) a chemotherapeutic agent, wherein the chemotherapeutic agent is a topoisomerase inhibitor, for example CPT-1 or a thymidylate synthase inhibitor, for example TDX. Synergistic cytotoxic effects have been demonstrated using such combinations.

The invention provides an in-vitro detection method for quickly screening the exon 5-8 mutation of a P53 gene. The method comprises the following steps: (1) extracting the genome DNA of a peripheral blood sample; (2) designing and synthesizing 4 pairs of specific primers for amplifying exon 5-8 of the P53 gene; (3) performing high resolution melting curve analysis and grounding PCR on the genome DNA of the sample by using the primers; and (4) obtaining the sample with a positive result in the curve analysis, meaning occurrence of P53 gene mutation. The detection method is not limited by site or type of mutated base, does not need a sequence specific probe, and can directly run high resolution melting after PCR is completed to complete analysis on the sample mutation. The method is simple, convenient and quick in operation, is low in use cost and accurate in result, can realize truly closed pipe operation. Furthermore, the method has the characteristics of high through-put, high speed, kit availability, low detection cost and the like for quick screening of population.

The invention discloses a drug T-VISA-miR34a liposome capable of efficient and highly specific killing of P53 gene mutation type of breast cancer cells. A T-VISA-miR34a treatment carrier capable of efficient and highly specific killing of P53 gene mutation type of breast cancer cells has a nucleotide sequence shown as a SEQ ID NO.1. The drug T-VISA-miR34a liposome capable of efficient and highly specific killing of P53 gene mutation type of breast cancer cells includes a liposome and a T-VISA-miR34a treatment carrier encapsulated by the liposome; and the T-VISA-miR34a treatment carrier has a nucleotide sequence shown as a SEQ ID NO.1. Encapsulated and delivered by the liposome, the T-VISA-miR34a treatment carriers of the invention enrich in the breast cancer site, and can efficiently target breast cancer BCL-2 and CD44 targets, completely or incompletely pair with 3 ' UTR, degrade mRNA of the target gene or inhibit its translation and lead to apoptosis of breast cancer cells without killing the normal cells. The drug can be delivered systemically, has advantages of high gene expression amount, long time, high efficiency, exact efficacy, low toxicity and side effect, no toxicity on kidney or liver, and has broad prospects in the treatment of P53 mutation type breast cancer.

The invention discloses a nucleic acid aptamer specifically binding to a p53 mutant protein p53R175H, wherein the nucleic acid aptamer comprises a sequence shown in SEQ ID NO.1. The invention also discloses a derivative of the nucleic acid aptamer, a screening method of the nucleic acid aptamer and a use of the nucleic acid aptamer in treating tumor.

Methods of treating certain types of cancer with ganetespib are disclosed. Also provided are methods of treating certain types of cancer with ganetespib in combination with a taxane derivative, and a platinum-containing anticancer agent. Also provided are methods of treating certain types of cancer with p53 mutation by a combination of ganetespib with a taxane derivative, and a platinum-containing anticancer agent. Also provided are methods of treating certain types of cancer with ganetespib in combination with a platinum-containing anticancer agent, and an antimetabolite. Also provided are methods of treating certain types of cancer with ganetespib in combination with a taxane derivative, an anthracycline derivative, and an alkylating antineoplastic agent. Also provided is a pharmaceutical composition comprising ganetespib and one or more other anticancer agents as described above.

The invention discloses a compound having a radiosensitization function and an application of the compound. The compound has an anti-proliferation effect on p53 wild tumor cells and p53 mutant tumor cells and can reduce TG2 gene expression of two kinds of cells while no remarkable change occurs to p53 gene expression. The compound and IR are subjected to combined treatment, two kinds of cells have remarkable cell apoptosis increasing and remarkable cell cycle arresting, the radiosensitivity is remarkably improved, and the TG2 gene expression is remarkably reduced. Therefore, the compound has a remarkable radiosensitization function on the p53 wild tumor cells and the p53 mutant tumor cells and is expected to substantially improve the tumor radiotherapy effect after being applied to tumor radiotherapy as an active ingredient of a radiosensitizer and particularly applied to p53 signal path activation enhanced tumor radiotherapy after excessive activation of a p53 signal path and ionizing radiation induction.

The invention relates to application of B7H4 in preparation of an endometrial cancer molecular typing reagent and system. The method comprises the following steps: firstly, screening out a POLE mutant by a sequencing method; detecting four kinds of mismatch repair proteins on a specimen without pathogenic mutation, and screening out a dMMR type; screening out a p53 mutant from a sample without dMMR by means of immunohistochemical detection of p53 protein; if the p53 mutation does not exist, determining that the p53 mutation is an NSMP type; and for specimens for interpreting the dMMR type and the NSMP type, detecting expression of protein B7H4 through immunohistochemistry, wherein B7H4 coloring in more than 1% of tumor cells is judged as a B7H4 expression type, and B7H4 non-expression types are judged in the rest. According to the invention, endometrial cancer is divided into a POLE mutant type, a B7H4 expression type, a B7H4 non-expression type and a p53 mutant type; and the improved molecular typing is still based on molecular pathology, has the characteristics of relative objectiveness, high repeatability and clinical feasibility of the existing molecular typing, but has higher predictive ability than the existing model, and is beneficial to avoiding excessive treatment and insufficient treatment.

The invention relates to the field of natural medicaments, in particular to the application of tanshinone IIA in preparation of a medicament for treating p53 mutational or deficient tumor. The tanshinone IIA can induce cellular poison and apoptosis of p53 mutational H596-NQO1 non-small cell lung cancer cells; and simultaneously, in wild A549 cells of p53, when P53 small interfere ribose nucleic acid (siRNA) silences endogenous P53 genes, the tanshinone IIA can still induce the cellular poison and apoptosis of the A549 cells, reduction in the mitochondrial membrane potential of the A549 cells induced by the tanshinone IIA is not influenced in the process of treating the P53siRNA, the ratio of BAX/Bcl-x1 is increased, cytochrome C is released, and Caspase is activated, so that an anti-tumor effect which does not depend on the p53 is generated.

The invention relates to the technical field of organoid culture, and particularly discloses a culture method for screening tumor organoids based on P53 mutation. The culture method comprises the following steps: S1, unfreezing untreated tumor organoid to generate a cell suspension, adding the cell suspension into a basic culture medium, uniformly conducting mixing and centrifuging, and removing supernate to obtain a tumor organoid mixture; S2, adding matrigel to resuspend the tumor organoid mixture, and after resuspending, inoculating the organoid mixture into an organoid culture medium containing y27632 for culturing; and S3, after the liquid of the tumor organoid mixture is changed for the first time, absorbing and removing the organoid culture medium, and then adding a culture medium containing Nutlin3A for continuous culture. The culture method is low in cost and price, sequencing is not needed, the detection cost is saved in the early stage of culture of the tumor organoids, and accurate and simplified culture of the tumor organoids is achieved.