42 results about "IDH1" patented technology

Methods of treating and evaluating subjects having neoactive mutants of IDH (e.g., IDH1 or IDH2).

The invention relates to an isolated genetically modified microorganism in which the gene IDH1 and at least one of the genes SDH2 and DIC1 are under the control of a first promoter that is repressed to a growth culture medium by means of a cultivation additive and is active in the absence of the cultivation additive. The genes that are part of the group comprising “PYC1, ACS1, CIT1, ACO1, ICL1, MSL1, and CIT2, optionally also MDH3” are constitutively active. The invention further relates to uses of such a microorganism, especially for producing succinic acid.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of IDH1 and mutant IDH1 gene expression and/or activity, and/or modulate an IDH1 or mutant IDH1 gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules, including small nucleic acid molecules such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules, that are capable of mediating or that mediate RNA interference (RNAi) against IDH1 or mutant IDH1 gene expression.

The invention discloses a test kit of auxiliary diagnosis of non-small cell lung cancer patients. The test kit comprises a product used for detecting protein landmark isocitrate dehydrogenase 1(IDH1), a product used for detecting protein landmark carbonic anhydrase 125 (CA125), a product used for detecting protein landmark CYFRA21-1 and a carrier on which a functional expression p=1/(1+(20.186*0.406<x1>*0.923<x2>*0.656<x3>)<-1>) is recorded, wherein x1 represents the concentration of IDH1, x2 represents the concentration of CA125, and x3 represents the concentration of CYFRA21-1. The test kit is adopted and the non-small cell lung cancer patients are diagnosed in an auxiliary mode according to corresponding diagnosis standards, the test kit has the advantages of being high in sensitivity and strong in specificity, reliability of the diagnosis is far higher than that of diagnosis which is carried out with each single protein landmark, and the test kit has great value and application prospects for diagnosis and treatment of non-small cell lung cancer.

The invention relates to an isolated, genetically modified microorganism, wherein compared to the wild type a) the idh1 and idp1 genes have been deleted or inactivated, and/or b) the sdh2 and sdh1 genes have been deleted or inactivated, and/or c) the PDC2 gene has been deleted or inactivated or is under the control of a promoter which can be suppressed or induced by exposure of the microorganism using an inductor substance, and/or d) one or more genes from the group consisting of ICL1, MLS1, ACS1 and MDH3 has been replaced or supplemented by a corresponding foreign gene or corresponding foreign genes from Crabtree-negative organisms, and to the uses thereof.

The invention discloses a reagent kit for an auxiliary diagnosis of a lung adenocarcinoma patient. The reagent kit comprises a first product, a second product, a third product and a carrier. The first product is used for detecting protein markers IDH1, the second product is used for detecting protein markers CA125, the third product is used for detecting protein markers CYFRA21-1, and the carrier records the following functional expression: x1 represents the concentration of the IDH1, x2 represents the concentration of the CA125, and x3 represents the concentration of the CYFRA21-1. By means of the reagent kit for the auxiliary diagnosis of the lung adenocarcinoma patient, the lung adenocarcinoma patient is diagnosed in an auxiliary mode according to corresponding diagnostic criteria. Furthermore, the reagent kit for the auxiliary diagnosis of the lung adenocarcinoma patient has the advantages of high sensitivity and strong specificity. In addition, the reliability of the diagnosis is far higher than that of the diagnosis of adopting each individual protein marker, so that the reagent kit for the auxiliary diagnosis of the lung adenocarcinoma patient has a significant value and an application prospect for the diagnosis and treatment of lung adenocarcinoma.

Methods that rapidly, sensitively, and specifically detect mutations in IDH1/2 and the TERT promoter employ amplification of particular portions of the genes that experience frequent and exquisitely localized mutations. The ability to distinguish between sequences that differ only by one nucleotide and which may be present in very low ratios is essential for such an assay.

Genetic signatures capable of distinguishing among several types of gliomas provide clinically relevant information that can serve as an adjunct to histopathological diagnosis. For example, mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. The genetic signatures permit the stratification of the glioma patients into distinct cohorts.

The invention discloses primers, a reagent kit and a method for detecting IDH1 (isocitrate dehydrogenase 1) R132H gene variation by the aid of ddPCR (droplet digital polymerase chain reaction) technologies. The method includes extracting cfDNA (cell-free deoxyribonucleic acid) in peripheral blood; designing two probes and a pair of primers for IDH1R132H mutant types and wild types; carrying out ddPCR amplification by the aid of the cfDNA used as a template; carrying out data analysis on obtained amplification products to obtain absolute quantities and proportions of IDH1R132H mutant genes. Thereagent kit for detecting the IDH1R132H gene variation is based on the method. The primers, the reagent kit and the method have the advantages that provided primer amplification fragments 83bp are particularly applicable to amplifying small-fragment DNA samples such as plasma free DNA and can be combined with the detection probes, accordingly, the IDH1R132H gene variation with extremely low abundance can be detected from the cfDNA, the primers, the reagent kit and the method are good in specificity and high in sensitivity, human IDH1R132H gene variation can be absolutely quantitatively detected by the aid of the primers, the reagent kit and the method, and important effects can be realized by the primers, the reagent kit and the method for guiding clinical treatment and improving patientprognosis; the IDH1R132H gene variation can be detected only by the aid of the peripheral blood without tissue specimen collection, and accordingly the method is particularly suitable for patients intolerant to tissue sampling.

The invention discloses an establishing method of a sgRNA expression component driven by a gene editing U6 promoter, and belongs to biogenetic engineering. By using an IDH1 gene of a human genome as atarget gene for CRISPR/Cas9 gene editing and designing the specific sequence of the gene in sgRNA, the complete sequence of the sgRNA expression component with the U6 promoter is obtained, the U6-sgRNA expression component is amplified, a PCR primer of the U6-sgRNA expression component is synthesized, PAGE purification is conducted, and finally the step of overlapping PCR to obtain a complete double-chain DNA fragment of the U6-sgRNA expression component is conducted for completing establishment; the whole establishing method is high in gene editing success rate, convenient to use and low incost.

IDH1-mutant cell lines and xenografts (e.g., IDH1R132H heterozygous and IDH1R132H homozygous) are derived from human glioblastoma multiforme (GBM) samples. Methods use said cells and xenografts as tools for determining the impact of IDH1R132H on cancer properties including cellular morphology, tumorigenesis, DNA, apoptosis, and metabolic profiles. Methods also use these cell lines for the screening and identification of candidate therapeutic targets.

It was discovered that a compound of general formula (I) that has an isoxazole skeleton has an excellent inhibitory activity on a mutated IDH1 protein, inhibits 2-HG production by the aforesaid protein and can effectively inhibit the proliferation of various tumors expressing the aforesaid protein. In general formula (I), R1, R2, R3, Y and Z are each as defined in claim 1.

The present invention relates to a detection system of IDH1/2 gene mutation and its kit. The kit includes a PCR detection solution and a SYBR GreenI mixed solution; the PCR detection solution A includes a C394T site and a Upstream and downstream primers A and peptide nucleic acid A of the 395th codon G395A site, PCR detection solution B includes upstream and downstream primers B and peptide nucleic acid B for detecting IDH1/2 gene 419th codon G419A site, PCR detection solution C Including upstream and downstream primers C and peptide nucleic acid C for detecting the 515th codon G515A site of IDH1/2 gene. The IDH1/2 gene mutation detection system and the kit thereof of the present invention have high sensitivity and specificity, less sample demand, and can quickly, conveniently and accurately detect the IDH1/2 gene mutation.

This disclosure relates to the production and use of an isolated, purified and/or recombinant T cell receptor (TCR) that specifically binds to a mutant IDH1 protein, or a fragment thereof, wherein the mutant IDH1 protein or fragment thereof comprises an R132H mutation.

We provide IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous and IDH1R132H homozygous) derived from dissociated human astrocytoma samples. The cells can be used alone or in combination with each other or other cell types as a tool for determining the impact of IDH1R132H on cellular biology, tumorigenesis, and metabolic profiles. The cell lines may be used to test and identify therapeutic targets and to screen for molecular therapeutic agents.