TW202012638A - 用於癌症及贅瘤之評估的組合物及方法 - Google Patents
用於癌症及贅瘤之評估的組合物及方法 Download PDFInfo
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| US11702704B2 (en) | 2019-10-31 | 2023-07-18 | Mayo Foundation For Medical Education And Research | Detecting ovarian cancer |
| CN111833965B (zh) * | 2019-11-08 | 2024-06-04 | 中国科学院北京基因组研究所(国家生物信息中心) | 一种尿沉渣基因组dna的分类方法、装置和用途 |
| US20230002832A1 (en) * | 2019-11-27 | 2023-01-05 | Keio University | Upper urinary tract urothelial carcinoma identification method |
| JP7801235B2 (ja) * | 2020-03-20 | 2026-01-16 | シングレラ・ヘルス・テクノロジーズ（シャンハイ）・リミテッド | 結腸直腸新生物をスクリーニングするための方法およびキット |
| EP4419714A4 (en) * | 2021-11-23 | 2025-02-26 | Pleno, Inc. | CODED DOSAGES |
| TW202328459A (zh) * | 2021-12-20 | 2023-07-16 | 大陸商江蘇鵾遠生物技術有限公司 | 一種腫瘤檢測方法及應用 |
| CN114959038B (zh) * | 2022-06-13 | 2024-12-17 | 湖南宏雅基因技术有限公司 | 一种hoxa9基因甲基化检测试剂及其应用 |
| CN117766028B (zh) * | 2022-09-16 | 2025-03-11 | 深圳吉因加医学检验实验室 | 一种基于甲基化差异预测样本来源的方法及装置 |
| WO2024117791A1 (ko) | 2022-11-29 | 2024-06-06 | 주식회사 지씨지놈 | 식도암 및 위암 진단용 dna 메틸화 마커 및 이의 용도 |
| WO2024137858A2 (en) * | 2022-12-22 | 2024-06-27 | Singlera Genomics Inc. | Methods and compositions for assessing colorectal cancer |
| WO2024178248A1 (en) * | 2023-02-22 | 2024-08-29 | University Of Southern California | Pan-cancer early detection and mrd cfdna methylation |
| WO2025203031A2 (en) * | 2024-03-26 | 2025-10-02 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Methods of cancer detection by discordant methylation in cfdna |
Family Cites Families (14)
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|---|---|---|---|---|
| IL154663A0 (en) * | 2000-09-01 | 2003-09-17 | Epigenomics Ag | Method for determining the degree of methylation of defined cytosines in genomic dna in the sequence context 5'-cpg-3' |
| EP2129796B1 (en) * | 2007-02-21 | 2013-10-23 | Oslo Universitetssykehus HF | New markers for cancer |
| US20100297067A1 (en) * | 2007-05-14 | 2010-11-25 | The Johns Hopkins University | Methylation markers for prostate cancer and methods of use |
| US7843254B2 (en) * | 2007-10-31 | 2010-11-30 | Texas Instruments Incorporated | Methods and apparatus to produce fully isolated NPN-based bandgap reference |
| WO2009108917A2 (en) * | 2008-02-29 | 2009-09-03 | Oncomethylome Sciences, S.A. | Markers for improved detection of breast cancer |
| WO2011112845A2 (en) * | 2010-03-11 | 2011-09-15 | Board Of Regents, The University Of Texas System | Methods and compositions related to a multi-methylation assay to predict patient outcome |
| DK2850212T3 (da) * | 2012-05-18 | 2020-03-23 | Clinical Genomics Pty Ltd | Fremgangsmåde til screening for colorektal cancer |
| EP2959016A4 (en) * | 2013-02-21 | 2016-10-12 | Toma Biosciences Inc | METHOD, COMPOSITIONS AND NUCLEIC ACID ANALYSIS KITS |
| EP2886659A1 (en) * | 2013-12-20 | 2015-06-24 | AIT Austrian Institute of Technology GmbH | Gene methylation based colorectal cancer diagnosis |
| EP3224377B1 (en) * | 2014-11-25 | 2020-01-01 | AIT Austrian Institute of Technology GmbH | Diagnosis of lung cancer |
| US9984201B2 (en) * | 2015-01-18 | 2018-05-29 | Youhealth Biotech, Limited | Method and system for determining cancer status |
| EP3640341B1 (en) * | 2015-02-24 | 2022-07-27 | Zymo Research Corporation | Assays to determine dna methylation and dna methylation markers of cancer |
| WO2017048932A1 (en) * | 2015-09-17 | 2017-03-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cancer detection methods |
| CN109563546B (zh) * | 2016-05-05 | 2022-09-09 | 精密科学发展有限责任公司 | 通过分析甲基化dna来检测肺肿瘤 |
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| EP3775290A1 (en) | 2021-02-17 |
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