42 results about "PDGFRA" patented technology

The present invention relates to an in vitro method for diagnosing and/or monitoring in a subject a gastrointestinal stromal tumor or a predisposition to develop a gastrointestinal stromal tumor, comprising detecting and/or analyzing in a test sample derived from the subject one or more mutations at the DNA level in any one or both of the marker genes cKIT (GenBank acc. no. NM_000222.2) and PDGFRA (GenBank acc. no. NM_006206.4), wherein the DNA is circulating DNA, and wherein the presence of any one of the mutations detected in the test sample is indicative of a gastrointestinal stromal tumor or a predisposition to develop a gastrointestinal stromal tumor in the subject. The present invention is also directed to a corresponding kit-of-parts for diagnosing and/or monitoring a gastrointestinal stromal tumor or a predisposition to develop a gastrointestinal stromal tumor, comprising means for detecting and/or analyzing one or more mutations as defined herein, as well as to the use of one or more mutations as defined herein as a panel of molecular markers for diagnosing and/or monitoring a gastrointestinal stromal tumor or a predisposition to develop a gastrointestinal stromal tumor.

The present invention relates to three gene markers that are useful in classifying tumors. The markers are known herein as DOG1 (GenBank GeneID 55107), KIT (GenBank GeneID 3815) and PDGFRA (GenBank GeneID 5156) and can be used alone or in combination to identify subclasses of tumors. The classification methods are exemplified herein using gastrointestinal stromal tumors (GISTs). It is to be understood and will be appreciated that the same markers may be used in the classification of tumors other than GISTs. The methods may further comprise providing diagnostic, prognostic, or predictive information based on the classifying step. Classifying may include stratifying the tumor (and thus stratifying a subject having the tumor), e.g., for a clinical trial. The methods may further comprise selecting a treatment based on the classifying step.

The invention belongs to the technical field of biological medicines, in particular relates to a multi-target kinase inhibitor and a pharmaceutical composition containing the multi-target kinase inhibitor, and also relates to a preparation method and application of the multi-target kinase inhibitor. The structural general formula of the multi-target kinase inhibitor provided by the invention is shown in a formula (I), wherein the structure of R is selected from a formula (a), a formula (b), a formula (c), a formula (d), a formula (f) and the formula (d); the multi-target kinase inhibitor can effectively inhibit the enzymatic activity of RET, VEGFR3 and PDGFRA, and can effectively treat diseases which are regulated and controlled by multi-target kinase and are related to the abnormal signaltransduction pathway of the multi-target kinase, such as cancers of breast, respiratory tract, brain, reproductive organ, digestive tract, urinary tract, eye, liver, skin, head and/or neck, as well as distal metastatic cancers, such as lymphoma, sarcoma, leukemia and the like. The active ingredient of the pharmaceutical composition comprises the multi-target kinase inhibitor, and the weight percentage of the multi-target kinase inhibitor in the composition is 1-50%. (See the instruction for specific formulas.).

The present application generally to the diagnosis and treatment of diseases resulting from the alteration of chromatin boundaries between topologically-associated domains. In particular, the present application relates to detection of mutations causing DNA hypermethylation phenotypes, CpG methylation within CTCF binding motifs, and aberrant gene expression caused by altered chromatin topology. Applicants show that IDH mutant gliomas exhibit hyper-methylation at CTCF binding sites, compromising binding of this methylation-sensitive insulator protein. Applicants also demonstrate that loss of CTCF at a domain boundary permits a constitutive enhancer to aberrantly interact with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene. Thus, Applicants have uncovered that IDH mutations may promote gliomagenesis by disrupting chromosomal topology and allowing aberrant regulatory interactions that induce oncogene expression.

The invention discloses a marker molecule for predicting the sensitivity of a patient to preoperative chemoradiotherapy and surgical mesorectal resection and a derivative product of the marker molecule. The marker molecule is PDGFRA, CTDP1 and/or AGR2; and verification shows that the marker molecule has good diagnostic efficiency for predicting the sensitivity or reactivity of a rectal cancer patient to surgery treatment, and can be widely applied to prediction of the sensitivity of the rectal cancer patient to surgery treatment. The invention further discloses a pharmaceutical composition for improving the sensitivity of the rectal patient to the preoperative chemoradiotherapy and surgical mesorectal resection.

The invention relates to the technical field of gene detection, and discloses a detection kit for oral squamous cell carcinoma lymph node metastasis prediction. The kit comprises forward primer and reverse primer sequences of 7 kinds of genes including PDGFRA, PLAU, SOX9, SPP1, CDKN2A, CASP1 and MAL. The invention also discloses a method for screening the gene or the gene combination for the oralsquamous cell carcinoma lymph node metastasis prediction. The detection kit can be used for objectively, accurately and sensitively predicting the oral squamous cell carcinoma lymph node metastasis condition, so that the survival rate of the oral squamous cell carcinoma patients can be favorably improved.

The invention discloses a method for constructing a lung cancer multi-gene mutation library. The method can realize mutation of 1435 somatic cells of human genes EGFR, K-ras, B-raf, N-ras, PIK3CA, c-MET, TP53, c-Kit, PDGFRA, ALK, ROS1, RET, ERBB2, NTRK1 and NTRK3. The method can individually manage multiple target sequences and fast finish library construction. The whole library construction process is finished in 2-3h and the manual operation time is only 45min. The method can be used for Illumina and Ion torrent platforms. Through combination of the method and a high-throughput sequencing platform, the problem that a small amount of paraffin tissue slices and peripheral blood samples of a lung cancer patient need multi-gene and multi-target detection of somatic cells is solved and a costis low.

The invention relates to the field of molecular biology, and particularly relates to an application of miRNA. 15 miRNAs non-odontogenic tissue derived mesenchymal stem cells and odontogenic tissue derived mesenchymal stem cells are differentially expressed, wherein compared with odontogenic tissue derived mesenchymal stem cells, 9 non-odontogenic tissue derived mesenchymal stem cells are highly expressed, while 6 odontogenic tissue derived mesenchymal stem cells are lowly expressed. Inhibition of candidate miRNAs(hsa-miR-615-3p, hsa-miR-196b-5p) can be used for improving the dentin differentiation potential of WJCMSCs. Furthermore, seven key target genes which are highly expressed in dental tissues derived from mesenchymal stem cells can be obtained, including TFAP2C, SEMA6D, PDGFRA, PAX9, NR4A3, SATB2 and ZNF367.

The invention provides a kit for combined detection of chronic myeloid leukemia. The kit comprises a special linker for DNA library construction, a specific composite primer for detecting gene mutation, fusion and deletion, and a composite primer for library amplification. The special linker is eight dimers formed by a linker primer 1 and eight different i5-terminal primers respectively; the typesof gene mutation, fusion and deletion are BCR/ABL fusion, FGFR1 rearrangement, JAK2 gene V617F mutation, JAK2 rearrangement, NUP98 rearrangement, PDGFRA rearrangement and PDGFRB rearrangement; and the library amplification composite primer has different i7 ends, and the sequence of the primer is SEQ ID NO:39-46. The kit can be used for detecting a plurality of common molecular genetic variationsof chronic myeloid leukemia at one time, and is simple to operate, short in time and high in detection efficiency.

The invention provides an Imatinib-drug-resistance KIT and PDGFRA wild type GIST cell strain which is named as GIST-FR and preserved in the China Center for Type Culture Collection with the preservation number being CCTC NO:C2017111. The invention further provides an establishment method of the cell strain and application of the cell strain as a cell model for discussing the human GIST drug resistance mechanism and researching relevant signal channels thereof. A tissue block culture method is adopted to obtain GIST primary cells, immortalization is carried out, and a GIST-F cell line is established; then Imatinib drug resistance induction is carried out on the GIST-F cell line, and the Imatinib-drug-resistance GIST cell strain GIST-FR is established. The GIST-FR cells are subjected to in-vitro passage for more than 40 generations, growth is slow compared with GIST-F cells, IC50 of Imatinib is remarkably increased, and the drug resistance index is 3.52 (P is less than 0.01); and a wholeexon group sequencing result shows that KIT and PDGFRA of the GIST-FR cells are negative. The GIST cell line is successfully built from human GIST primary tissue, and further induction is carried outto obtain the Imatinib-drug-resistance cells thereof, so that a foundation is laid for the GIST pathogenesis and drug resistance related research.

A set of gene groups for predicting or for the auxiliary prediction of the survival time prognosis of patients with neuroglioma consists of a PM gene group and an EM gene group with a total of 68 genes. A subtype marking gene group consisting of two major gene groups co-expressed with PDGFRA and EGFR can stably divide neuroglioma samples from different database sources into three specific subtypes, and can be applied to clinical diagnosis for neuroglioma and judging the survival time prognosis of patients with neuroglioma.

The N-(3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylphenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide derivative exhibits excellent inhibitory activity against at least one kinase selected from the group consisting of ABL1, ABL2, AURKB, BRK, CDK11, CDK8, CDK9, CDKL2, CIT, DDR1, FLT3, HIPK4, HUNK, JAK3, KIT, LOK, LTK, MET, MLK2, MUSK, MYO3A, PAK3, PCTK3, PDGFRA, PDGFRB, RIPK1, TIE1 and ZAK, and thus being useable as a therapeutic agent for kinase-related disease.

The invention discloses a kit for detecting the mutation of gastrointestinal stromal tumor-related genes and application thereof. The invention provides application of a primer pair group (as shown in sequence 1 to sequence 40) and a readable vector recording a method for detecting the mutation of the gastrointestinal stromal tumor-related genes of a to-be-detected person to preparation of the kit used for detecting the mutation of the gastrointestinal stromal tumor-related genes. According to the invention, instead of traditional tumor tissue or section, blood plasma is use as a detection sample in the invention; 20 specific primer pairs are designed directed at the gastrointestinal stromal tumor-related genes, i.e., a KIT gene and a PDGFRA gene; a high-flux sequencing detection method is employed; so the data volume of detection is increased, the accuracy of experimental results is improved, and the mutation of the gastrointestinal stromal tumor-related genes can be accurately and effectively monitored.

The invention provides a clonal eosinophilia fusion gene detection probe composition, a kit and application thereof. According to the invention, firstly, related fusion genes are classified, wherein core genes FGFR1, PDGFRA and PDGFRB for clonal eosinophilia fusion detection are I-type genes, so that full-length transcripts of the genes are used as target regions; and other genes are II-type genes, so that only fragments near the fusion breakpoint are used as target regions. According to a base complementary pairing principle, complementary sequences of target regions are designed as probes to form a 'liquid phase chip', the probes relate to 39 target genes, eosinophilia fusion genes are detected by capturing corresponding target sequences in a transcriptome library and combining high-throughput sequencing, multiple fusion can be detected at a time, new fusion can be discovered, the detection cost is reduced, and the accuracy of a detection result is improved.

The invention discloses lung cancer targeted drug and chemotherapy drug genomes and an application thereof in lung cancer clinical drug treatment. The targeted drug genome comprises AKT1, ALK, BRAF, CCND1, CDKN2A, DDR2, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, HRAS, IGF1R, KDR, KIT, KRAS, MAP2K1, MET, NF1, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RET, ROS1, STK11 and TP53; and the chemotherapy drug genome comprises ABCB1, CDA, CEP72, CYP1B1, CYP2C8, DPYD, ERCC1, ERCC2, GSTM, GSTP1, MTHFR, RRM1, SLCO1B1, TEKT4, TPMT, TYMS, UMPS, XPC and XRCC1. The lung cancer targeted drug and chemotherapy drug genomes disclosed by the invention are applied to guidance of clinical precise chemotherapy of the lung cancer or auxiliary diagnosis of the lung cancer and curative effect and after-healingmonitoring, can provide the most effective drug selection for lung cancer patients with drug resistance or toxic and side effect intolerance caused by conventional drugs and targeted and chemotherapydrug requirements, improve the drug treatment effect, and reduce the toxic and side effects of the drugs.

The invention discloses a primer and a kit for detecting PDGFRA (platelet-derived growth factor receptor alpha) gene D842V polymorphic sites and a PCR (polymerase chain reaction) method of the primer and the kit. The primer comprises a wild specific sense primer, a mutant type specific sense primer, and a reverse primer shared by the wild specific sense primer and the mutant type specific sense primer. The wild specific sense primer has an SEQ No.17 sequence, the mutant type specific sense primer has an SEQ No.14 sequence, and the shared reverse primer has an SEQ No.16 sequence. The kit has the advantages of simplicity in detection, quickness, accuracy, low cost and the like, and powerful tools are provided for scientific research and clinic analysis of the PDGFRA gene D842V polymorphic sites.

The invention provides a pharmaceutical composition for treating glioblastoma. The pharmaceutical composition comprises an expression inhibitor of hepatic ligand protein type A receptor 2 (EPHA2) and an expression inhibitor of platelet-derived growth factor receptor (PDGFRA). The invention also provides a diagnostic reagent for monitoring glioblastoma prognosis, which comprises a first composition for detecting the expression quantity of the EPHA2 gene and a second composition for detecting the expression quantity of the PDGFRA coding gene. The invention provides a scheme for treating GBM by jointly inhibiting PDGFRA and EPHA2 for the first time, and solves the problem that the anti-tumor effect cannot be achieved in clinical application by only using a single PDGFRA inhibitor.

The invention relates to an application of famitinib or a pharmaceutically acceptable salt thereof in preparation of a medicine for treating tumors with c-KIT or PDGFRA mutation. Specifically, the invention relates to application of famitinib or a pharmaceutically acceptable salt thereof in preparation of medicines for treating gastrointestinal stromal tumor, testicular spermatogonoma, mastocyte diseases, melanoma or acute myeloid leukemia with c-KIT or PDGFRA mutation.