20 results about "P53 protein" patented technology

The invention belongs to the field of biological medicine, and particularly relates to a recombinant adenovirus and application thereof. The technical problem to be solved by the invention is to provide the recombinant adenovirus with good tumor inhibition effect and high efficiency. The technical scheme of the invention is a recombinant adenovirus. The recombinant adenovirus is a replication-defective adenovirus, and an exogenous nucleic acid fragment is operably inserted into a viral genome; the exogenous nucleic acid fragment is a coding gene of human p53 protein, a coding gene of GM-CSF and a coding gene of RGD. The coding gene of the human p53 protein, the coding gene of the GM-CSF and the coding gene of the RGD are jointly constructed into the replication-deficient adenovirus, so that the adenovirus with multiple advantages is obtained, the tumor cell killing efficiency is improved by 2-4 times compared with that before recombination, and a new effective choice is provided for tumor immunotherapy.

The invention provides an application of teconazole (C26H31Cl2N5O3) or a pharmaceutical salt or a derivative thereof in a medicine for treating age-related retinal diseases, and relates to the technical field of biology. The application of the invention comprises the application of the teconazole or the pharmaceutical salt or the derivative thereof to the preparation of the medicine for treating, relieving and / or preventing the age-related retinal diseases. The invention proves that the Terconazole can relieve the senescence of retinal pigment epithelial cells and reduce the p53 protein content of the cells, provides a new candidate drug for the treatment of age-related retinal diseases, and has remarkable medical and clinical values.

The application relates to the field of nanobiomedicine, and particularly relates to an engineered vesicle and a preparation method and application thereof. The engineered vesicle comprises a nano-vesicle and a calcium phosphate mineralized film coated on the surface of the nano-vesicle, and the nano-vesicle contains p53 protein. The p53 protein contained in the engineered vesicle promotes tumor aging to inhibit proliferation and metastasis, and the aged tumor cells can enhance the immune response against tumors at the tumor site, and the outer calcium phosphate mineralized film coating enables the nano-vesicle particles to effectively reduce the risk of severe inflammation in the body, to be gathered at the tumor site by the EPR effect, and under the acidic tumor microenvironment, the pH-sensitive calcium phosphate mineralized film is broken to expose the vesicle with certain immune stimulating capacity, which synergistically activates the immune response against tumors. The engineered vesicle has wide application prospects, and also lays a foundation for the design and development of a corresponding drug delivery system.

The invention relates to a method of detecting cancer in a subject based on the level of p53 protein aggregates in a body fluid sample from the subject. The invention also relates to corresponding methods of determining the risk of cancer in a subject, monitoring the progression or onset of cancer, and / or determining the efficacy of a therapeutic intervention for treating cancer in a subject. The invention further relates to kits for use said methods.

The present application relates to the field of biotechnology, and more particularly to an inhibitory peptide targeting p53 protein and application thereof. The present application uses IDProMat to design and obtain the inhibitory peptide targeting p53 protein according to the core binding site of the binding interface of the p53 protein core domain and ASPP2, TSPYL5, iASPP and the like; the inhibitory peptide can bind to p53 protein, competitively block the interaction between E3 ubiquitin ligase COP1 and p53, inhibit the ubiquitination degradation of p53, restore the anticancer function of p53, and has good biological safety and metabolic stability, and is expected to be used for clinical treatment of ovarian cancer, cervical cancer, endometrial cancer, pancreatic cancer and the like.

The present invention discloses an automatic scoring system for immunohistochemical images of colorectal cancer P53 protein. The system comprises a staining channel separation module, a cell nucleus region extraction module, an effective tissue region extraction module, and an immunohistochemical scoring module. The system separates the colorectal cancer P53 immunohistochemical staining image into hematoxylin, DAB, and residual channels; extracts the cell nucleus region staining image from the colorectal cancer P53 immunohistochemical staining image; obtains a tissue region mask; extracts the first eigenvector of the original colorectal cancer P53 immunohistochemical staining image; uses an attention mechanism to learn the cell nucleus region staining intensity and positive staining percentage based on the cell nucleus region staining image and the tissue region mask to obtain a second eigenvector; and concatenates the first and second eigenvectors and outputs them through a fully connected layer to obtain the immunohistochemical scoring result. The present invention enables automatic inspection of immunohistochemical images.

The present invention relates to a pharmaceutical composition containing HER2-binding lipid nanoparticles loaded with mRNA encoding p53 protein. The so-called "p53 mRNA-loaded HER-binding lipid nanoparticles" developed in the present invention were verified to deliver p53 mRNA, a tumor inhibitor, which targets highly expressed HER2 in a "human epidermal growth factor receptor 2 (HER2)-positive cancer cell" model, and thus can induce cancer cell death without systemic toxicity.

The application discloses an antibody against P53 protein, a tumor diagnosis product and application thereof, and relates to the technical field of antibodies. The antibody comprises a heavy chain complementarity determining region in a heavy chain variable region shown in SEQ ID NO: 14 and a light chain complementarity determining region in a light chain variable region shown in SEQ ID NO: 15. The antibody can be used for diagnosing diseases with P53 as a marker. The application provides more protein options for the detection of P53 and the diagnosis of diseases with P53 as a marker, and enriches the types of monoclonal antibodies against P53 protein. In addition, the antibody provided by the application can be used for preparing a tumor efficacy evaluation product, a prognosis evaluation product or a recurrence and metastasis monitoring product.

The invention discloses a coumarin compound as well as a preparation method and a medicinal composition thereof. Compared with the prior art, the coumarin compound shown in the formula (I) can inhibit the interaction of lncRNA-PSF and increase the expression of p53 protein so as to change the cell cycle, has a sensitization effect on an immune checkpoint inhibitor, improves the treatment effect of the immune checkpoint inhibitor on tolerant tumors, and has very good popularization and application values.

The invention relates to the technical field of biology, in particular to a p53 protein targeting inhibitor and a design method thereof. The molecular mechanism and microscopic details of interaction of azurin-p53 protein complexes are analyzed through an MD simulation technology and an MM-PBSA free energy decomposition method, key binding sites between the complexes and spatial distribution of the key binding sites are determined, and an affinity model is established, so that a candidate affinity ligand peptide library is constructed. Then, screening and verifying the affinity ligand library through methods of molecular docking, conformation analysis, binding site comparison, hydrophobicity analysis, MD simulation and the like to obtain a high-affinity ligand aiming at a p53 protein target spot, and verifying the binding performance of the affinity peptide ligand and the p53 protein through a double-antibody sandwich ELISA (Enzyme-Linked Immunosorbent Assay) experiment. And screening to obtain the p53 protein inhibitory peptide with high affinity with the p53 protein.

This invention discloses an epigenetic drug targeting lncRNA-PSF interaction, its composition, and its application. First, this invention synthesizes an epigenetic drug targeting lncRNA-PSF interaction as shown in formula (I) or formula (II). Compared with existing technologies, the epigenetic drugs shown in formulas (I) and (II) can inhibit lncRNA-PSF interaction, alter the cell cycle by increasing the expression of p27 and p53 proteins, arrest cancer cells in the G2 / M phase, and thus exert an anti-cancer effect. When the epigenetic drugs shown in formulas (I) and (II) are used in combination with immunosuppressants, they can enhance the effect of immunosuppressants, increase antigen presentation by cancer cells, and reduce their immune escape, thus becoming a novel anti-cancer sensitization strategy.

The invention discloses an antisense oligonucleotide medicine for treating pituitary tumor. According to evidence of molecular biology experiments and the like and verification in human primary pituitary tumor cells, the designed specific ASO medicine is applied to treatment of pituitary tumors for the first time. The ASO drug inhibits the expression of MDM2, recovers the activity of P53 protein, inhibits the proliferation of pituitary tumors and promotes apoptosis by inhibiting the splicing process mediated by a splicing factor FUS, and provides a new direction for a potential medication scheme for pituitary tumor treatment.

In fibrotic lung fibroblasts, basal levels of p53 protein (and miR-34a) are markedly suppressed, leading to reduced p53-mediated inhibition of uPA and uPAR, or concurrent induction of PAI-1. These changes contribute to excessive FL-fibroblast proliferation and production of extracellular matrix (ECM), and, therefore, pulmonary fibrosis. These processes are reversed by treating the cells, and treating subjects suffering from idiopathic pulmonary fibrosis (IPF) with the small organic molecule nutlin-3a (NTL) or with a peptide, CSP-4 (SEQ ID NO:1), or variants or derivatives or multimers of this peptide, which increase p53 levels by inhibiting MDM2-mediated degradation of p53 protein. Use of these compounds serves as a new approach to the treatment of IPF, as they restore p53 expression and p53-mediated changes in the uPA-fibrinolytic system in FL-fibroblasts and restrict production and deposition of ECM.

Provided herein are methods of treating or preventing cancer in a subject in need thereof, the methods comprise administering to the subject in need thereof (a) one or more nucleic acids encoding an elephant p53 protein, an elephant LIF protein, and / or combinations thereof, or (b) one or more elephant p53 proteins, elephant LIF proteins, and / or combinations thereof. Also provided are pharmaceutical compositions comprising a pharmaceutically acceptable carrier and (a) one or more nucleic acids encoding an elephant p53 protein, an elephant LIF protein, and / or combinations thereof, or (b) one or more elephant p53 proteins, elephant LIF proteins, and / or combinations thereof.

According to the treatment method, a drug containing a DNA alkylating agent prodrug compound and salts, esters, solvates and isotope isomers of the DNA alkylating agent prodrug compound is combined with a drug for up-regulating p53 protein expression or activating p53 functions to treat cancer and tumor patients. The DNA alkylating agent prodrug compound, a drug of salt, ester, solvate and isotope isomer of the DNA alkylating agent prodrug compound and a drug for up-regulating p53 protein expression or activating a p53 function are combined to be applied to preparation of drugs for treating cancers and tumors. Methods for inhibiting the growth of cells detached from organisms using DNA alkylating agent prodrug compounds and salts, esters, solvates, isotopic isomers thereof in combination with drugs that up-regulate p53 protein expression or activate p53 function. The invention relates to a pharmaceutical composition containing a DNA alkylating agent prodrug compound, a salt, an ester, a solvate and an isotope isomer of the DNA alkylating agent prodrug compound, and a drug for up-regulating p53 protein expression or activating a p53 function. The drug containing the DNA alkylating agent prodrug compound and salts, esters, solvates and isotope isomers of the DNA alkylating agent prodrug compound is combined with a drug containing a p53-MDM2 inhibitor to treat cancer and tumor patients.

This invention relates to the field of medicinal chemistry, disclosing a compound that targets and degrades CK1α protein and activates P53 protein, and its applications. Specifically, it relates to a compound that can target ubiquitination and degrade CK1α protein and activate P53 protein, its pharmaceutically acceptable salts and hydrates, and pharmaceutical combinations with the compound as the active ingredient, as well as its use in the preparation of CK1α protein degraders and P53 protein agonists and their use in the treatment and / or prevention of cancer. The structures of the compound and its pharmaceutically acceptable salts and hydrates described in this invention are as follows: their variables are as described in the claims and specification.

Provided are a signaling ribonucleic acid (mRNA) comprising a 5'non-translated region (5 'UTR), a sequence encoding a p53 protein, and a 3' non-translated region (3 'UTR), a composition comprising the signaling ribonucleic acid for delivering the signaling ribonucleic acid or p53 to a subject, and a composition and method for preventing or treating cancer.

The application discloses application of a substance for inhibiting expression of ZNF8 protein in preparation of a product for preventing and treating cancer. Experiments prove that the ZNF8 protein can be combined with p53 protein; the expression of the ZNF8 protein can increase transcriptional activity of the p53 protein, down-regulate expression of VEGF gene and ANGPLT4 gene, inhibit proliferation of tumor cells, inhibit migration of tumor cells, inhibit transfer of tumor cells, inhibit invasion and transfer of tumor cells, inhibit formation of blood vessels, inhibit growth of tumors, inhibit transfer of tumors, inhibit lung transfer of tumors and improve survival rate of tumor-bearing animals, so that the expression of the ZNF8 protein has important application value in inhibition of growth and invasion and transfer of tumors; the expression of the ZNF8 protein can prevent and treat cancer.

The invention is based on designed ankyrin repeat proteins (DARPins) specifically binding to a DNA binding domain of human p53. The DARPins of the invention are capable of forming a binding interface with the DNA binding domain of p53, and upon binding facilitate p53 protein stability. The DARPins of the invention are for use in the treatment of p53 related diseases such as cancer. Further, the invention pertains to nucleic acid constructs encoding the DARPin of the invention, methods for their production and cells comprising the DARPins or nucleic acid constructs of the invention.

The invention discloses a p53 protein liquid-liquid phase separation enhanced improved p53, namely an application of LLPSEp53 in inhibition of tumor cell proliferation. The invention firstly discloses a mechanism for enhancing the function of a wild type p53 tumor inhibition factor through p53 liquid-liquid phase separation, and finds that LLPSEp53 can obviously improve the transcriptional level of downstream target genes (such as CDKN1A, MDM2, PUMA, NOXA, BAF, DDB2 and RRM2B) in cells; the recombinant protein has a remarkable killing effect on various human tumor cell lines; in addition, knock-down of the DEF6 gene can further promote the anti-cancer activity of the LLPSEp53, which indicates that the LLPSEp53 can be used in combination with a DEF6 inhibitor to enhance the anti-cancer effect. Meanwhile, the LLPSEp53 protein is respectively combined with the FGFR inhibitor TAS-120 and the Wnt signal channel inhibitor IWR-1 for use, so that the tumor killing effect is obviously improved. The invention proves that liquid-liquid phase separation can enhance the transcriptional activity of p53 and inhibit the proliferation of tumor cells, and the tumor inhibition effect can be improved when the liquid-liquid phase separation is combined with drugs. The discovery shows that the LLPSEp53 has high clinical transformation potential, and meanwhile, a new thought is provided for application of the LLPSEp53 to clinical tumor treatment when the LLPSEp53 is used in cooperation with drugs.