CA2467455C - Method of detection of prostate cancer - Google Patents
Method of detection of prostate cancer Download PDFInfo
- Publication number
- CA2467455C CA2467455C CA 2467455 CA2467455A CA2467455C CA 2467455 C CA2467455 C CA 2467455C CA 2467455 CA2467455 CA 2467455 CA 2467455 A CA2467455 A CA 2467455A CA 2467455 C CA2467455 C CA 2467455C
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- methylation
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Classifications
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- C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
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- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/6851—Quantitative amplification
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- C12Q2523/00—Reactions characterised by treatment of reaction samples
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Families Citing this family (72)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090226915A1 (en) | 2001-01-24 | 2009-09-10 | Health Discovery Corporation | Methods for Screening, Predicting and Monitoring Prostate Cancer |
| US20090215058A1 (en) * | 2001-01-24 | 2009-08-27 | Health Discovery Corporation | Methods for screening, predicting and monitoring prostate cancer |
| US20090215024A1 (en) * | 2001-01-24 | 2009-08-27 | Health Discovery Corporation | Biomarkers upregulated in prostate cancer |
| US8008012B2 (en) * | 2002-01-24 | 2011-08-30 | Health Discovery Corporation | Biomarkers downregulated in prostate cancer |
| US7718364B2 (en) * | 2003-03-25 | 2010-05-18 | John Wayne Cancer Institute | DNA markers for management of cancer |
| GB0307428D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Compartmentalised combinatorial chemistry |
| GB0307403D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Selection by compartmentalised screening |
| US20060078893A1 (en) | 2004-10-12 | 2006-04-13 | Medical Research Council | Compartmentalised combinatorial chemistry by microfluidic control |
| WO2005024068A2 (en) | 2003-09-05 | 2005-03-17 | Sequenom, Inc. | Allele-specific sequence variation analysis |
| EP1689885B1 (en) * | 2003-10-20 | 2012-10-17 | St Vincent's Hospital Sydney Limited | Assessment of predisposition to cancer by quantitative determination of methylation in normal cells of healthy persons. |
| ES2801379T3 (es) | 2003-12-01 | 2021-01-11 | Epigenomics Ag | Métodos y ácidos nucleicos para el análisis de la expresión génica asociada con el desarrollo de trastornos proliferativos de células de próstata |
| JP4537050B2 (ja) * | 2003-12-25 | 2010-09-01 | 国立大学法人三重大学 | 前立腺癌、そのリスク又はその初期罹患の判定方法 |
| WO2005089414A2 (en) * | 2004-03-17 | 2005-09-29 | The Johns Hopkins University | Neoplasia diagnostic compositions and methods of use |
| AU2005230936B2 (en) | 2004-03-26 | 2010-08-05 | Agena Bioscience, Inc. | Base specific cleavage of methylation-specific amplification products in combination with mass analysis |
| US7608394B2 (en) * | 2004-03-26 | 2009-10-27 | Sequenom, Inc. | Methods and compositions for phenotype identification based on nucleic acid methylation |
| US20050221339A1 (en) | 2004-03-31 | 2005-10-06 | Medical Research Council Harvard University | Compartmentalised screening by microfluidic control |
| WO2005111232A2 (en) * | 2004-05-17 | 2005-11-24 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Silencing of tumor-suppressive genes by cpg-methylation in prostate cancer |
| US7968287B2 (en) | 2004-10-08 | 2011-06-28 | Medical Research Council Harvard University | In vitro evolution in microfluidic systems |
| US11105808B2 (en) | 2004-11-12 | 2021-08-31 | Health Discovery Corporation | Methods for screening, predicting and monitoring prostate cancer |
| US8268549B2 (en) * | 2005-04-15 | 2012-09-18 | University Of Maryland, Baltimore | Method and assay for determining methylation of GAL3 promoter for early diagnosis of prostate cancer |
| US7632634B2 (en) * | 2005-04-15 | 2009-12-15 | University Of Maryland Biotechnology Institute | Method and assay for early diagnosis of prostate cancer |
| US7851154B2 (en) * | 2005-07-22 | 2010-12-14 | Simon Daniel Spivack | GC tag-modified bisulfite genomic DNA sequencing for continuous methylation spectra |
| US20070059753A1 (en) * | 2005-09-15 | 2007-03-15 | Tatiana Vener | Detecting gene methylation |
| AU2006339538A1 (en) * | 2005-11-08 | 2007-09-13 | Euclid Diagnostics Llc | Materials and methods for assaying for methylation of CpG islands associated with genes in the evaluation of cancer |
| WO2007081791A2 (en) * | 2006-01-04 | 2007-07-19 | The Johns Hopkins University | Compare-ms:method rapid, sensitive and accurate detection of dna methylation |
| EP1984738A2 (en) | 2006-01-11 | 2008-10-29 | Raindance Technologies, Inc. | Microfluidic devices and methods of use in the formation and control of nanoreactors |
| US9562837B2 (en) | 2006-05-11 | 2017-02-07 | Raindance Technologies, Inc. | Systems for handling microfludic droplets |
| WO2007133710A2 (en) | 2006-05-11 | 2007-11-22 | Raindance Technologies, Inc. | Microfluidic devices and methods of use thereof |
| EP2077912B1 (en) | 2006-08-07 | 2019-03-27 | The President and Fellows of Harvard College | Fluorocarbon emulsion stabilizing surfactants |
| IL186935A0 (en) * | 2006-10-31 | 2008-02-09 | Veridex Llc | Prostate cancer field effect analysis methods and kits |
| US8772046B2 (en) | 2007-02-06 | 2014-07-08 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
| US20080213781A1 (en) * | 2007-02-15 | 2008-09-04 | Baden Jonathan F | Methods of detecting methylation patterns within a CpG island |
| JP2008202978A (ja) * | 2007-02-16 | 2008-09-04 | Hirosaki Univ | 前立腺癌の診断方法 |
| US20080254455A1 (en) * | 2007-04-12 | 2008-10-16 | Haiying Wang | Detecting prostate cancer |
| WO2008130623A1 (en) | 2007-04-19 | 2008-10-30 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
| CN102016067A (zh) * | 2008-01-22 | 2011-04-13 | 维里德克斯有限责任公司 | 前列腺癌中gstp1高甲基化的检测 |
| WO2010009365A1 (en) | 2008-07-18 | 2010-01-21 | Raindance Technologies, Inc. | Droplet libraries |
| US12038438B2 (en) | 2008-07-18 | 2024-07-16 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
| US8968210B2 (en) | 2008-10-01 | 2015-03-03 | Covidien LLP | Device for needle biopsy with integrated needle protection |
| US9186128B2 (en) | 2008-10-01 | 2015-11-17 | Covidien Lp | Needle biopsy device |
| US9332973B2 (en) | 2008-10-01 | 2016-05-10 | Covidien Lp | Needle biopsy device with exchangeable needle and integrated needle protection |
| US11298113B2 (en) | 2008-10-01 | 2022-04-12 | Covidien Lp | Device for needle biopsy with integrated needle protection |
| US9782565B2 (en) | 2008-10-01 | 2017-10-10 | Covidien Lp | Endoscopic ultrasound-guided biliary access system |
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| US8528589B2 (en) | 2009-03-23 | 2013-09-10 | Raindance Technologies, Inc. | Manipulation of microfluidic droplets |
| EP2486409A1 (en) | 2009-10-09 | 2012-08-15 | Universite De Strasbourg | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
| WO2011079176A2 (en) | 2009-12-23 | 2011-06-30 | Raindance Technologies, Inc. | Microfluidic systems and methods for reducing the exchange of molecules between droplets |
| US9399797B2 (en) | 2010-02-12 | 2016-07-26 | Raindance Technologies, Inc. | Digital analyte analysis |
| EP4484577A3 (en) | 2010-02-12 | 2025-03-26 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
| US9366632B2 (en) | 2010-02-12 | 2016-06-14 | Raindance Technologies, Inc. | Digital analyte analysis |
| US10351905B2 (en) | 2010-02-12 | 2019-07-16 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
| WO2012045012A2 (en) | 2010-09-30 | 2012-04-05 | Raindance Technologies, Inc. | Sandwich assays in droplets |
| JP2014519310A (ja) | 2011-02-02 | 2014-08-14 | エクザクト サイエンシーズ コーポレイション | Dnaメチル化のデジタル配列分析 |
| WO2012109600A2 (en) | 2011-02-11 | 2012-08-16 | Raindance Technologies, Inc. | Methods for forming mixed droplets |
| US9150852B2 (en) | 2011-02-18 | 2015-10-06 | Raindance Technologies, Inc. | Compositions and methods for molecular labeling |
| EP3709018A1 (en) | 2011-06-02 | 2020-09-16 | Bio-Rad Laboratories, Inc. | Microfluidic apparatus for identifying components of a chemical reaction |
| US8841071B2 (en) | 2011-06-02 | 2014-09-23 | Raindance Technologies, Inc. | Sample multiplexing |
| US8658430B2 (en) | 2011-07-20 | 2014-02-25 | Raindance Technologies, Inc. | Manipulating droplet size |
| EP3495817B1 (en) | 2012-02-10 | 2024-10-16 | Bio-Rad Laboratories, Inc. | Molecular diagnostic screening assay |
| WO2013165748A1 (en) | 2012-04-30 | 2013-11-07 | Raindance Technologies, Inc | Digital analyte analysis |
| US20140274767A1 (en) | 2013-01-23 | 2014-09-18 | The Johns Hopkins University | Dna methylation markers for metastatic prostate cancer |
| US20140274757A1 (en) | 2013-03-14 | 2014-09-18 | Marie K. Kirby | Differential Methylation Level of CpG Loci That Are Determinative of a Biochemical Reoccurrence of Prostate Cancer |
| WO2014172288A2 (en) | 2013-04-19 | 2014-10-23 | Raindance Technologies, Inc. | Digital analyte analysis |
| US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
| US9944977B2 (en) | 2013-12-12 | 2018-04-17 | Raindance Technologies, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
| WO2015103367A1 (en) | 2013-12-31 | 2015-07-09 | Raindance Technologies, Inc. | System and method for detection of rna species |
| US10647981B1 (en) | 2015-09-08 | 2020-05-12 | Bio-Rad Laboratories, Inc. | Nucleic acid library generation methods and compositions |
| US10998178B2 (en) | 2017-08-28 | 2021-05-04 | Purdue Research Foundation | Systems and methods for sample analysis using swabs |
| US11427874B1 (en) | 2019-08-26 | 2022-08-30 | Epi One Inc. | Methods and systems for detection of prostate cancer by DNA methylation analysis |
| CN110951871B (zh) * | 2019-11-21 | 2024-01-05 | 瑞博奥(广州)生物科技股份有限公司 | Pca3和psa rna检测试剂盒和扩增体系 |
| CN116179694B (zh) * | 2022-11-02 | 2024-11-05 | 武汉艾米森生命科技有限公司 | 检测甲基化水平的试剂在制备前列腺癌诊断产品中的应用以及前列腺癌诊断试剂盒 |
| CN119391860B (zh) * | 2024-12-25 | 2025-03-21 | 慧算基因科技(上海)有限公司 | 一种用于胰腺癌术后mrd检测及动态监测的引物探针组合物、试剂盒及应用 |
Family Cites Families (6)
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| US6017704A (en) * | 1996-06-03 | 2000-01-25 | The Johns Hopkins University School Of Medicine | Method of detection of methylated nucleic acid using agents which modify unmethylated cytosine and distinguishing modified methylated and non-methylated nucleic acids |
| AUPP312998A0 (en) * | 1998-04-23 | 1998-05-14 | Commonwealth Scientific And Industrial Research Organisation | Diagnostic assay |
| US6331393B1 (en) * | 1999-05-14 | 2001-12-18 | University Of Southern California | Process for high-throughput DNA methylation analysis |
| JP2004505612A (ja) * | 2000-03-31 | 2004-02-26 | ユニバーシティ・オブ・サザン・カリフォルニア | 食道腺ガンに関する後成的配列 |
| US20050021240A1 (en) * | 2000-11-02 | 2005-01-27 | Epigenomics Ag | Systems, methods and computer program products for guiding selection of a therapeutic treatment regimen based on the methylation status of the DNA |
| DE10112515B4 (de) * | 2001-03-09 | 2004-02-12 | Epigenomics Ag | Verfahren zum Nachweis von Cytosin-Methylierungsmustern mit hoher Sensitivität |
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- 2002-11-15 CA CA 2467455 patent/CA2467455C/en not_active Expired - Lifetime
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- 2002-11-15 ES ES02789696T patent/ES2304462T3/es not_active Expired - Lifetime
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| DE60226271T2 (de) | 2009-07-16 |
| EP1456413A4 (en) | 2005-05-18 |
| US20090181400A1 (en) | 2009-07-16 |
| AU2002352745A1 (en) | 2003-06-10 |
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| JP4381142B2 (ja) | 2009-12-09 |
| ATE393240T1 (de) | 2008-05-15 |
| DE60226271D1 (de) | 2008-06-05 |
| EP1456413A1 (en) | 2004-09-15 |
| US20080026395A1 (en) | 2008-01-31 |
| CA2467455A1 (en) | 2003-05-30 |
| US7252935B2 (en) | 2007-08-07 |
| EP1456413B1 (en) | 2008-04-23 |
| US20030124600A1 (en) | 2003-07-03 |
| JP2005509445A (ja) | 2005-04-14 |
| WO2003044232A1 (en) | 2003-05-30 |
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