412 results about "DNA injury" patented technology

Novel substituted azole diones are provided that kill cells, suppress cell proliferation, suppress cell growth, abrogate the cell cycle G2 checkpoint and / or cause adaptation to G2 cell cycle arrest. Methods of making and using the invention compounds are provided. The invention provides substituted azole diones to treat cell proliferation disorders. The invention includes the use of substituted azole diones to selectively kill or suppress cancer cells without additional anti-cancer treatment. The invention includes the use of cell cycle G2-checkpoint-abrogating substituted azole diones to selectively sensitize cancer cells to DNA damaging reagents, treatments and / or other types of anti-cancer reagents.

The invention discloses a method for carrying out in-situ repairing on blood coagulation factor F8 / F9. The method comprises the following steps: in a target genome sequence, selecting the mutation sites of blood coagulation factor as the gene sites for in-situ repairing; designing the binding sites of nuclease of sgRNA sequence of a CRISPR / Cas system; designing a homologous recombinant repairing donor sequence for in-situ repairing; delivering nuclease protein and / or sgRNA and the nucleotide sequence of the homologous recombinant repairing donor to the gene sites of in-situ repairing by a delivering carrier; generating damages to the genome DNA by the nuclease on the gene in-situ repairing sites; and inserting the homologous recombinant repairing donor sequence into the gene in-situ repairing sites so as to repair the gene or supplement the expression of gene. The in-situ repairing of mutation sites of blood coagulation factor can be applied to the clinic, and the method has the advantages of precise induction, safer and controllable process, and definite target.

A skin care composition comprising at least one keratinocyte CLOCK or PER1 gene activator and at least one DNA repair enzyme; a method for inhibiting damage to human keratinocytes due to environmental aggressors by applying a composition comprising at least one keratinocyte CLOCK or PER1 gene activator and at least one DNA repair enzyme; and a method for repairing DNA damage in human keratinocytes.

The present invention relates to pharmaceutically acceptable salts of an amide substituted indazole which are inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), previously known as poly(ADP-ribose)synthase and poly(ADP-ribosyl) transferase. The compounds of the present invention are useful as mono-therapies in tumors with specific defects in DNA-repair pathways and as enhancers of certain DNA-damaging agents such as anticancer agents and radiotherapy. Further, the compounds of the present invention are useful for reducing cell necrosis (in stroke and myocardial infarction), down regulating inflammation and tissue injury, treating retroviral infections and protecting against the toxicity of chemotherapy.

The invention discloses a method for predicating a homologous recombination deficiency (HRD) mechanism and a method for predicating response of patients to cancer therapy and relates to the field of biological information predication. The method comprises the step of judging whether a tumor sample has homologous recombination deficiency or not according to one or more comprehensive values in a large-segment INDEL (Insertion / Deletion) fraction, a copy number variation fraction and a tumor mutation load fraction, wherein the comprehensive values can also comprise a loss of heterozygosity variation fraction. By adopting the method disclosed by the invention, predication of a chromosome large-segment structure, a chromosome gene type number, a chromosome gene copy number, a chromosome variation interval and abnormal loss of heterozygosity and chromosome telomeric imbalance is realized, so that an evaluation range is more complete and HRD can be accurately predicated; the comprehensive values also can be used for determining whether the patients have response to a therapeutic regimen containing one or more of a PARP (Poly Adenosine Diphosphate Ribose Polymerase) inhibitor, an DNA (Deoxyribonucleic Acid) injury inhibitor, a topoisomerase II / II+inhibitor, a topoisomerase I inhibitor and radiotherapy; the method is simple and has wide general applicability.

This invention concerns the use of cyclopamine in vivo on basal cell carcinomas (BCC's) to achieve therapeutic effect by causing differentiation of the tumor cells and, at the same time, apoptotic death and removal of these tumor cells while preserving the normal tissue cells, including the undifferentiated cells of the normal epidermal basal layer and hair follicles. Causation of apoptosis by cyclopamine is by a non-genotoxic mechanism and thus unlike the radiation therapy and most of the currently used cancer chemotherapeutics which act by causing DNA-damage. These novel effects, previously unachieved by a cancer chemotherapeutic, make the use of cyclopamine highly desirable in cancer therapy, in the treatment of BCC's and other tumors that use the hedgehog / smoothened signal transduction pathway for proliferation and prevention of apoptosis.

A method of prevention / treatment of pathological consequences of DNA damage triggered by incorporation of circulating apoptotic chromatin fragments into healthy cells of individuals / patients in need therefore, said method comprising ex vivo or extra corporeal treatment of blood / plasma for removal of circulating chromatin fragments released from apoptotic cells which apoptotic chromatin fragments are capable of triggering DNA damage leading to genomic instability, senescence, apoptosis and cancerous transformation of healthy cells on being integrated into their genomes

The invention provides a method for improving the gene targeting efficiency and a method for carrying out in-situ repair on the base on a beta-globulin gene locus. The method for improving the gene targeting efficiency comprises the following steps of: S10, determining a gene locus to undergo in-situ repair; and S20, introducing a CRISPR / Ca system to cleave editing lotus DNA to cause DNA damage and simultaneously providing a repair template segment. Based on the deficiency of existing gene modification, the gene modification efficiency, the timeliness and the modification quality are improved after single-stranded oligonucleotides (ss ODNs) and a small molecule compound participate in a CRISPR / Cas9 gene modification system.

The present invention relates to the signalling pathways connecting DNA damage, such as that induced by ionizing radiation or alkylating agents, and phosphorylation by tyrosine kinases.

Aryl- and heteroaryl-substituted urea compounds useful in the treatment of diseases and conditions related to DNA damage or lesions in DNA replication are disclosed. Methods of making the compounds, and their use as therapeutic agents, for example, in treating cancer and other diseases characterized by defects in DNA replication, chromosome segregation, or cell division also are disclosed.

Compositions comprising hydroxytyrosol-containing formulations and treatment regiments comprising hydroxytyrosol and / or oleuropein and chemotherapeutic agents are disclosed. Compositions and / or regiments may optionally include the administration of vitamins, minerals, and anti-oxidants. Methods for using these compositions and treatment regimens for treating subjects for diseases, such as a malignancy, and for inducing or enhancing angiogenesis, treating or preventing oxidative stress, for treating or preventing high glucose-induced dysfunction, treating or preventing chemotherapy-induced dysfunction, and for improving cell viability are provided. Various methods for use of the hydroxytyrosol compositions for inhibition of lysine specific demethylase 1 (LSD1) in various cancers are also provided.

The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

This invention is in the area of tricyclic lactam compounds, compositions and methods of protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, protection of healthy cells is disclosed using compounds that act as cyclin-dependent kinase 4 / 6 (CDK 4 / 6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

The present invention relates to methods and compositions for the modulation of bacterial topoisomerase enzymes within bacterial cells. More specifically, the present invention relates to bacterial assays wherein the levels of bacterial topoisomerase enzymes or the levels of target sites within the enzymes are varied within bacterial test strains in order to screen for compounds that target, i.e., interact with the topoisomerase enzymes, causing DNA damage and hence, bacterial growth inhibition and / or cell death. The present methods and compositions are useful for the identification and characterization of novel therapeutic antibacterial compounds.

Inositol hexaphosphate (IP-6) is a polyphosphorylated carbohydrate with potent antioxidant activity to prevent active oxygen species-mediated mutagenesis, cell injury and carcinogenesis. IP-6 also activates DNA repair mechanisms. Sublethal radiation causes DNA damage through the formation of free radicals, reactive oxygen species, and pyrimidine crosslinks leading to cellular proliferation, cell cycle arrest and apoptosis. In the skin it results in the induction of skin cancer, premature skin aging, immuno-suppression, inflammation, and cell death. Likewise sublethal exposure to ionizing radiation as in nuclear blasts (war-time, accidental, terrorist-induced etc), cosmic radiation, etc. also causes the same spectrum of damage to the cells and the organisms with acute symptoms and eventual high risk of many cancers. IP-6 and / or inositol and their pharmaceutically acceptable salts and derivatives, including pyrophosphates and citrate derivatives, significantly counteract the harmful effects of radiation, affecting cell cycle progression in a protective manner (more cells in the protective GI phase) as well as decreasing apoptosis and caspase-3 activation. Various salts of IP-6 are used with comparable efficacy and the combination of IP-6+inositol affords the best protection against radiation-induced cell injury. Thus IP-6 and inositol are effective agents for protection against nuclear, solar and other radiation injuries.

The present invention provides methods for modulating cell death in a eukaryotic cell, and methods for reducing DNA damage in a eukaryotic cell. The methods generally comprise modulating a biological activity of DNA-PK in a cell. The invention further provides methods of treating a condition related to cell death in an individual. The invention further provides methods of identifying agents which modulate a biological activity of DNA-PK, as well as agents identified by the methods. Methods of modulating an immune response using an identified agent are also provided.

The present technology relates to a method of treating cancer by sensitizing human tumours to DNA damaging therapies through activating FBXO32 expression. Transactivation of FBXO32 through the inhibition of EZH2, a histone methyltransferase, decreases p21 protein induction which results in the sensitization of human tumours to chemotherapy. The method further provides a prognostic method to determine if a combination treatment would be effective.

The invention provides compositions and methods used to inhibit USP1 deubiquitinase activity and to identify new inhibitors of USP1 deubiquitinase. The inhibitors can be used to treat or prevent cancer, bone marrow failure, and damage to cells or DNA resulting from genotoxic agents such as antineoplasic agents, including chemotherapeutic agents and radiation. The inhibitors include siRNA directed at inhibiting the expression of USP1 or UAF1, a protein which forms a heterodimeric complex with USP1. The inhibitors can be used to enhance cell survival if administered either before or after radiation exposure. Methods are also provided to enhance chemotherapy or radiotherapy of cancer and to enhance DNA repair. Transgenic knockout animals and knockdown cells are provided, whose USP1 expression is impaired.

The present invention relates a method for the enumeration of mammalian cell micronuclei, while distinguishing micronuclei from the chromatin of dead and dying cells. The method utilizes differential staining of chromatin from dead and dying cells, to distinguish the chromatin from micronuclei and nuclei that can be detected based upon fluorescent emission and light scatter following exposure to an excitatory light source. Counting of micronuclei events relative to the number of nuclei can be used to assess the DNA-damaging potential of a chemical agent, the DNA-damaging potential of a physical agent, the effects of an agent which can modify endogenously-induced DNA damage, and the effects of an agent which can modify exogenously-induced DNA damage. Kits for practicing the invention are also disclosed.

The invention provides an enzyme-linked immunoassay method for determining the content of a cell DNA (Deoxyribonucleic Acid) injury marker H2AX. The enzyme-linked immunoassay method is characterized by comprising the steps that sandwich recognition on the specificity of a target protein H2AX is carried out by using a specific H2AX antibody and an enzyme-linked second antibody, a substrate after enzyme reaction is added, then the substrate is subjected to enzyme catalysis to be changed into a fluorescence product, wherein quantitative determination for the H2AX content can be realized according to a fluorescence value of the substrate. According to the method, the content change of the H2AX in the cells, caused by the fact that cigarette smoke is exposed, is quantitatively determined so that the aim of evaluating the virulence of cigarette smoke genes is realized. Compared with a traditional organic dye, the enzyme-linked antibody has the advantages that the catalyzing frequency of an enzyme is high, an amplification reaction effect is amplified and the detection sensitivity is improved; the enzyme has a stable property at a room temperature, is low in price, and is suitable for a lot of analysis. An enzyme-linked immunosorbent assay has the advantages of rapidness, accuracy, high throughput, high sensitivity and the like.

Compositions comprising a water soluble spinach extract, compositions comprising a water soluble spinach extract, a liposome, a cardiolipin, and at least one antioxidant, compositions comprising a water soluble spinach extract, an extract of Arabidopsis thaliana or of the mustard (Brassica) plant, a liposome, a cardiolipin, and at least one antioxidant, processes for obtaining such compositions, and methods of using such compositions to repair damage to nuclear DNA, mitochondrial DNA, or both, prevent or decrease damage to such DNA from, for example, reactive oxygen species or 8-hydroxydeoxyguanosine and / or to repair or prevent mitochondrial damage and loss of membrane fluidity are disclosed. Compositions of the present invention may be topically administered, orally administered or parenterally, such as administration by injection. When topically administered, additives such as penetration enhancers, fragrances, preservatives, moisturizers and cosmetic adjuvants may be included in compositions of the present invention.

This invention provides novel methods of detecting or treating aberrant cell cycle regulation associated with expression of a nuclear protein encoded by a gene that is linked to map position 8q22.3 of the human genome, and to novel reagents that are useful therefor. More particularly, the invention provides novel nucleic acid and proteinaceous probes, for detecting a gene that is linked to map position 8q22.3 of the human genome or the expression products thereof, wherein expression or elevated expression of said gene is associated with the appearance or occurrence of tumors associated with cancer, DNA damage and progesterone-receptor-mediated effects on cells. The invention also provides reagents and methods for detecting or modulating the expression products of the gene, such as, for example, in the diagnosis or treatment of cancer, cellular proliferation, DNA damage or progesterone receptor-mediated effects on cells.

The health condition of a living organism is detected by electrochemically analyzing samples from selected areas of the body of said living organism for elevated free levels of nucleotide excision products resulting from DNA or RNA damage.

Disclosed are combination therapies and related compositions that may contain one or more of a p53 potentiating agent, a DNA-damaging agent, an agent that inhibits cell cycle check point, and a pharmaceutically acceptable carrier. Also disclosed are methods of using such compositions for the treatment of conditions related to T cell and / or B cell activation in subjects in need of such treatment.

Ulcer is a serious oxidative stress induced disease with complex pathologic events including upregulation of H+K+ ATPase of parietal cell (PC) membrane, damage of mucin layer around PC, PC-DNA damage etc. The polysaccharide (GRPP) fraction and antioxidant extract (GRAOX) of ginger was examined for their ability to inhibit H+ K+ ATPase. Results indicated that the inhibition of H+ K+ ATPase activity which causes acidity in the lumen of the stomach, also exhibited better H+K+ ATPase inhibition (PPI) at the IC50 of 27.2 μg (GRPP) and 16.5 μg GAE (AOX) respectively than the known antiulcer proton pump blocker Lansoprazole (19.3 μg). Further the antioxidant activity in antioxidant extract (GRAOX) by various assay systems was examined such as Reducing power, Free radical scavenging (FRS), DNA and cytoprotection systems etc. GRAOX exhibited concentration dependent reducing power ability at 5-25 g equivalent of phenol. FRS activity with IC50 of 6.8 μg equivalent of phenol etc. At 0.3 μg level GRAOX offered >80% protection to DNA and against FeSO4-Asc'orbate induced oxidation. The major active phenolic components were identified as Gallic acid / Tannic acid (46%), and Cinnamic acid (51%).

The invention relates to gene regulation in ageing, and age-related cognitive decline. The invention, in particular relates to methods for screening a subject for a propensity to develop diseases associated with oxidative stress, and for age-related conditions, by examining the up-regulation and / or down-regulation of at least one gene associated within the central nervous system.