JP2010500867A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2010500867A5 JP2010500867A5 JP2009517484A JP2009517484A JP2010500867A5 JP 2010500867 A5 JP2010500867 A5 JP 2010500867A5 JP 2009517484 A JP2009517484 A JP 2009517484A JP 2009517484 A JP2009517484 A JP 2009517484A JP 2010500867 A5 JP2010500867 A5 JP 2010500867A5
- Authority
- JP
- Japan
- Prior art keywords
- nucleic acid
- target nucleic
- sample
- secretion
- probe
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000523 sample Substances 0.000 claims description 35
- 108020004707 nucleic acids Proteins 0.000 claims description 31
- 150000007523 nucleic acids Chemical class 0.000 claims description 31
- 102000039446 nucleic acids Human genes 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 29
- 230000028327 secretion Effects 0.000 claims description 20
- 238000001514 detection method Methods 0.000 claims description 7
- 239000002679 microRNA Substances 0.000 claims description 7
- 108700011259 MicroRNAs Proteins 0.000 claims description 6
- 208000002151 Pleural effusion Diseases 0.000 claims description 6
- 210000003296 saliva Anatomy 0.000 claims description 6
- 210000000115 thoracic cavity Anatomy 0.000 claims description 4
- 239000002299 complementary DNA Substances 0.000 claims description 2
- 108091070501 miRNA Proteins 0.000 claims description 2
- 230000000295 complement effect Effects 0.000 claims 7
- 210000004369 blood Anatomy 0.000 claims 5
- 239000008280 blood Substances 0.000 claims 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 4
- 239000012472 biological sample Substances 0.000 claims 4
- 206010003445 Ascites Diseases 0.000 claims 3
- 206010036790 Productive cough Diseases 0.000 claims 3
- 210000004381 amniotic fluid Anatomy 0.000 claims 3
- 210000003756 cervix mucus Anatomy 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 230000002357 endometrial effect Effects 0.000 claims 3
- 230000002496 gastric effect Effects 0.000 claims 3
- 210000003802 sputum Anatomy 0.000 claims 3
- 208000024794 sputum Diseases 0.000 claims 3
- 210000002700 urine Anatomy 0.000 claims 3
- 210000001124 body fluid Anatomy 0.000 claims 2
- 239000010839 body fluid Substances 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims 2
- 208000025661 ovarian cyst Diseases 0.000 claims 2
- 238000003752 polymerase chain reaction Methods 0.000 claims 2
- 210000000582 semen Anatomy 0.000 claims 2
- 210000001519 tissue Anatomy 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 230000003321 amplification Effects 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 210000000038 chest Anatomy 0.000 claims 1
- 210000000416 exudates and transudate Anatomy 0.000 claims 1
- 238000003199 nucleic acid amplification method Methods 0.000 claims 1
- 210000002966 serum Anatomy 0.000 claims 1
- 108091007773 MIR100 Proteins 0.000 description 3
- 108091068853 Homo sapiens miR-100 stem-loop Proteins 0.000 description 1
- 108091053410 let-7 family Proteins 0.000 description 1
- 108091039882 miR-99 stem-loop Proteins 0.000 description 1
- 108091045637 miR-99-1 stem-loop Proteins 0.000 description 1
- 108091051043 miR-99-2 stem-loop Proteins 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80640406P | 2006-06-30 | 2006-06-30 | |
| US82237106P | 2006-08-14 | 2006-08-14 | |
| US85045506P | 2006-10-10 | 2006-10-10 | |
| US87109506P | 2006-12-20 | 2006-12-20 | |
| PCT/IB2007/003732 WO2008029295A2 (en) | 2006-06-30 | 2007-06-29 | A method for detecting nucleic acids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010500867A JP2010500867A (ja) | 2010-01-14 |
| JP2010500867A5 true JP2010500867A5 (enExample) | 2010-07-29 |
Family
ID=39157641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009517484A Pending JP2010500867A (ja) | 2006-06-30 | 2007-06-29 | 核酸の検出方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9115389B2 (enExample) |
| EP (1) | EP2038432B1 (enExample) |
| JP (1) | JP2010500867A (enExample) |
| AU (1) | AU2007293187A1 (enExample) |
| CA (1) | CA2672246A1 (enExample) |
| DK (1) | DK2038432T3 (enExample) |
| IL (1) | IL196241A0 (enExample) |
| WO (1) | WO2008029295A2 (enExample) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2487261B1 (en) | 2006-01-05 | 2015-07-01 | The Ohio State University Research Foundation | MicroRNA-based methods and compositions for the diagnosis and treatment of solid cancers |
| CA2646051A1 (en) | 2006-03-20 | 2007-09-27 | Carlo M. Croce | Microrna fingerprints during human megakaryocytopoiesis |
| US9096906B2 (en) * | 2007-03-27 | 2015-08-04 | Rosetta Genomics Ltd. | Gene expression signature for classification of tissue of origin of tumor samples |
| US8802599B2 (en) * | 2007-03-27 | 2014-08-12 | Rosetta Genomics, Ltd. | Gene expression signature for classification of tissue of origin of tumor samples |
| US20100273172A1 (en) | 2007-03-27 | 2010-10-28 | Rosetta Genomics Ltd. | Micrornas expression signature for determination of tumors origin |
| CA2695184A1 (en) | 2007-07-31 | 2009-02-05 | The Ohio State University Research Foundation | Methods for reverting methylation by targeting dnmt3a and dnmt3b |
| ES2570359T3 (es) | 2007-08-03 | 2016-05-18 | Univ Ohio State Res Found | Regiones ultraconservadas que codifican ARNnc |
| EP3028708A1 (en) | 2007-08-22 | 2016-06-08 | The Ohio State University Research Foundation | Methods and compositions for inducing deregulation of epha7 and erk phosphorylation in human acute leukemias |
| ES2595489T3 (es) | 2008-07-18 | 2016-12-30 | Trovagene, Inc. | Métodos para la detección de secuencias de ácidos nucleicos "ultracortos" basados en PCR |
| US8936909B2 (en) | 2008-07-18 | 2015-01-20 | Qiagen Gmbh | Method for determining the origin of a sample |
| WO2010018564A1 (en) * | 2008-08-13 | 2010-02-18 | Rosetta Genomics Ltd. | Compositions and methods for determining the prognosis of bladder urothelial cancer |
| WO2010058393A2 (en) * | 2008-11-20 | 2010-05-27 | Rosetta Genomics Ltd. | Compositions and methods for the prognosis of colon cancer |
| US20110275534A1 (en) * | 2008-12-05 | 2011-11-10 | The Ohio State University | MicroRNA-Based Methods and Compositions for the Diagnosis, Prognosis and Treatment of Ovarian Cancer Using a Real-Time PCR Platform |
| WO2010103522A1 (en) * | 2009-03-10 | 2010-09-16 | Rosetta Genomics Ltd. | Method for detection of nucleic acid sequences |
| EP2432896A1 (en) * | 2009-05-18 | 2012-03-28 | INSERM - Institut National de la Santé et de la Recherche Médicale | A method for predicting the responsiveness of a patient to a treatment with an anti-cd20 antibody and a method for diagnosing rheumatoid arthritis |
| JP5960060B2 (ja) | 2009-11-23 | 2016-08-02 | ジ・オハイオ・ステート・ユニバーシティ | 腫瘍細胞の増殖、遊走および浸潤に影響を与えるために有用な物質および方法 |
| CA2802049C (en) * | 2010-06-07 | 2018-07-10 | Firefly Bioworks, Inc. | Scanning multifunctional particles |
| CA2816603A1 (en) | 2010-11-12 | 2012-05-18 | The Ohio State University Research Foundation | Materials and methods related to microrna-21, mismatch repair, and colorectal cancer |
| US9163329B2 (en) | 2010-11-12 | 2015-10-20 | Agilent Technologies, Inc. | RNA labeling method |
| EP2640368B1 (en) | 2010-11-15 | 2020-12-30 | The Ohio State University Research Foundation | Controlled release mucoadhesive systems |
| US8703653B2 (en) | 2011-02-18 | 2014-04-22 | NVS Technologies, Inc. | Quantitative, highly multiplexed detection of nucleic acids |
| ES2703133T3 (es) * | 2011-05-24 | 2019-03-07 | Rosetta Genomics Ltd | Métodos y composiciones para determinar insuficiencia cardiaca o un riesgo de insuficiencia cardiaca |
| CN104364390B (zh) | 2011-10-14 | 2016-08-24 | 俄亥俄州立大学 | 与卵巢癌相关的方法和材料 |
| SG11201402341QA (en) * | 2011-11-17 | 2014-06-27 | Nvs Technologies Inc | Quantitative, highly multiplexed detection of nucleic acids |
| EP2790735A4 (en) | 2011-12-13 | 2015-12-09 | Ohio State Innovation Foundation | METHODS AND COMPOSITIONS RELATING TO MIR-21 AND MIR-29A, EXOSOME INHIBITION, AND CANCER METASTASIS |
| CN104685065B (zh) | 2012-01-20 | 2017-02-22 | 俄亥俄州立大学 | 浸润性和预后的乳腺癌生物标志物标签 |
| CA2867144C (en) | 2012-03-27 | 2019-07-02 | Ventana Medical Systems, Inc. | Signaling conjugates and methods of use |
| CA2886605A1 (en) | 2012-09-28 | 2014-04-03 | Cepheid | Two-primer pcr for microrna multiplex assay |
| ES3049590T3 (en) | 2012-11-02 | 2025-12-17 | Life Technologies Corp | Small rna capture, detection and quantification |
| KR101922125B1 (ko) | 2012-11-29 | 2018-11-26 | 삼성전자주식회사 | 표적 핵산을 표지하는 방법 |
| US10799584B2 (en) | 2014-06-09 | 2020-10-13 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services National Institutes Of Health | Combination therapies using agents that target tumor-associated stroma or tumor cells and alkylating agents |
| WO2015191610A2 (en) | 2014-06-09 | 2015-12-17 | Biomed Valley Discoveries, Inc. | Combination therapies using agents that target tumor-associated stroma or tumor cells and other pathways |
| WO2015191590A2 (en) | 2014-06-09 | 2015-12-17 | Biomed Valley Discoveries, Inc. | Combination therapies targeting tumor-associated stroma or tumor cells and microtubules |
| US11034757B2 (en) | 2014-06-09 | 2021-06-15 | Biomed Valley Discoveries, Inc. | Combination therapies using agents that target tumor-associated stroma or tumor cells and tumor vasculature |
| US10758614B2 (en) | 2014-06-09 | 2020-09-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services National Institutes Of Health | Combination therapies targeting tumor-associated stroma or tumor cells and topoisomerase |
| WO2015191617A2 (en) | 2014-06-09 | 2015-12-17 | Biomed Valley Discoveries, Inc. | Combination therapies using anti-metabolites and agents that target tumor-associated stroma or tumor cells |
| WO2015191596A1 (en) | 2014-06-09 | 2015-12-17 | Biomed Valley Discoveries, Inc. | Combination therapies using platinum agents and agents that target tumor-associated stroma or tumor cells |
| EP3486329A1 (en) * | 2015-02-17 | 2019-05-22 | Bio-Rad Laboratories, Inc. | Method of generating and amplifying cdna |
| CN114250278B (zh) | 2015-03-13 | 2024-08-06 | 生命技术公司 | 捕获、检测和定量小rna的方法、组合物与试剂盒 |
| EP3070178B1 (en) | 2015-03-20 | 2020-02-12 | Albert-Ludwigs-Universität Freiburg | Method for diagnosing breast cancer |
| CN113005181B (zh) * | 2020-12-22 | 2022-01-18 | 广州血康陆道培生物技术有限公司 | 一种基于茎环法的多重荧光定量pcr检测非编码小rna的引物组 |
| JP7743246B2 (ja) * | 2021-09-29 | 2025-09-24 | 栄研化学株式会社 | 標的ｒｎａ検出方法及びプローブキット |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4766064A (en) * | 1984-05-07 | 1988-08-23 | Allied Corporation | Displacement polynucleotide assay employing polyether and diagnostic kit |
| US5430136A (en) * | 1984-10-16 | 1995-07-04 | Chiron Corporation | Oligonucleotides having selectably cleavable and/or abasic sites |
| US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
| US5235033A (en) * | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
| EP0232967B1 (en) | 1986-01-10 | 1993-04-28 | Amoco Corporation | Competitive homogeneous assay |
| US5359100A (en) * | 1987-10-15 | 1994-10-25 | Chiron Corporation | Bifunctional blocked phosphoramidites useful in making nucleic acid mutimers |
| US5124246A (en) * | 1987-10-15 | 1992-06-23 | Chiron Corporation | Nucleic acid multimers and amplified nucleic acid hybridization assays using same |
| US5681697A (en) | 1993-12-08 | 1997-10-28 | Chiron Corporation | Solution phase nucleic acid sandwich assays having reduced background noise and kits therefor |
| US5580731A (en) * | 1994-08-25 | 1996-12-03 | Chiron Corporation | N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith |
| US5597909A (en) * | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US5681702A (en) | 1994-08-30 | 1997-10-28 | Chiron Corporation | Reduction of nonspecific hybridization by using novel base-pairing schemes |
| US5780233A (en) * | 1996-06-06 | 1998-07-14 | Wisconsin Alumni Research Foundation | Artificial mismatch hybridization |
| US6506559B1 (en) | 1997-12-23 | 2003-01-14 | Carnegie Institute Of Washington | Genetic inhibition by double-stranded RNA |
| US6080868A (en) | 1998-01-23 | 2000-06-27 | The Perkin-Elmer Corporation | Nitro-substituted non-fluorescent asymmetric cyanine dye compounds |
| US6270973B1 (en) * | 1998-03-13 | 2001-08-07 | Promega Corporation | Multiplex method for nucleic acid detection |
| US6235480B1 (en) * | 1998-03-13 | 2001-05-22 | Promega Corporation | Detection of nucleic acid hybrids |
| AUPP249298A0 (en) | 1998-03-20 | 1998-04-23 | Ag-Gene Australia Limited | Synthetic genes and genetic constructs comprising same I |
| GB9817078D0 (en) * | 1998-08-05 | 1998-10-07 | Habib Nagy A | Device for liver surgery |
| AU3274500A (en) | 1999-03-18 | 2000-10-09 | Exiqon A/S | Detection of mutations in genes by specific lna primers |
| EP1130113A1 (en) * | 2000-02-15 | 2001-09-05 | Johannes Petrus Schouten | Multiplex ligation dependent amplification assay |
| EP1130119A1 (en) * | 2000-02-17 | 2001-09-05 | Amsterdam Support Diagnostics B.V. | Reducing background in hybridisation reactions |
| US6653081B2 (en) * | 2000-06-12 | 2003-11-25 | Virologic, Inc. | Methods for monitoring antiretroviral therapy and guiding therapeutic decision in the treatment of HIV/AIDS |
| US20020102557A1 (en) * | 2001-01-31 | 2002-08-01 | Gentile-Davey Maria C. | Self -complementary molecular probe |
| EP1280090A1 (de) * | 2001-07-27 | 2003-01-29 | iSenseIt AG | Verfahren zur Konfiguration paralleler Nukleinsäureanalyseverfahren |
| ES2282460T3 (es) * | 2001-09-27 | 2007-10-16 | Gangagen, Inc. | Composciones bacterianas inmunogenicas de celulas completas incapacitadas. |
| KR20030042581A (ko) * | 2001-11-23 | 2003-06-02 | 삼성전자주식회사 | 대립유전자－특이적 프라이머 연장반응에서 프라이머간의 식별을 증가시키는 방법 |
| US7582739B2 (en) | 2002-03-11 | 2009-09-01 | Epoch Biosciences, Inc. | Negatively charged minor groove binders |
| JP2004024247A (ja) * | 2002-04-30 | 2004-01-29 | Internatl Reagents Corp | 遺伝子変異検出用プローブ及び遺伝子変異検出方法 |
| US6797464B2 (en) * | 2002-07-10 | 2004-09-28 | University Of Massachusetts | Detection of drug-resistant human immunodeficiency virus |
| EP2669377A3 (en) * | 2003-04-17 | 2015-10-14 | Alnylam Pharmaceuticals Inc. | Modified iRNA agents |
| US7745117B2 (en) * | 2003-06-06 | 2010-06-29 | The Regents Of The University Of Michigan | Methods for incorporating non-perfectly matched oligonucleotides into target-specific hybridization sequences |
| CA2532196A1 (en) | 2003-06-18 | 2005-01-20 | Chinese National Human Genome Center At Shanghai | Characterization of the earliest stages of the severe acute respiratory syndrome (sars) virus and uses thereof |
| CA2528577C (en) * | 2003-06-20 | 2012-08-07 | Illumina, Inc. | Methods and compositions for whole genome amplification and genotyping |
| KR100936908B1 (ko) | 2003-07-18 | 2010-01-18 | 삼성전자주식회사 | 전계발광 디바이스의 박막 트랜지스터, 이를 이용한전계발광 디바이스 및 이의 제조 방법 |
| US7888497B2 (en) * | 2003-08-13 | 2011-02-15 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof |
| US20050123959A1 (en) * | 2003-09-30 | 2005-06-09 | Brett Williams | Methods and kits for hybridizing multiple probe panels to nucleic acid samples |
| US20050182005A1 (en) * | 2004-02-13 | 2005-08-18 | Tuschl Thomas H. | Anti-microRNA oligonucleotide molecules |
| US7127355B2 (en) | 2004-03-05 | 2006-10-24 | Perlegen Sciences, Inc. | Methods for genetic analysis |
| US8192937B2 (en) * | 2004-04-07 | 2012-06-05 | Exiqon A/S | Methods for quantification of microRNAs and small interfering RNAs |
| CN101031658A (zh) * | 2004-05-26 | 2007-09-05 | 罗塞塔金诺米克斯有限公司 | 病毒和病毒相关mirna及其用途 |
| US7642348B2 (en) * | 2004-10-04 | 2010-01-05 | Rosetta Genomics Ltd | Prostate cancer-related nucleic acids |
| US7825229B2 (en) * | 2005-03-25 | 2010-11-02 | Rosetta Genomics Ltd. | Lung cancer-related nucleic acids |
| KR100682923B1 (ko) * | 2005-01-22 | 2007-02-15 | 삼성전자주식회사 | 허들 ｄｎａ와 인공적인 미스매치가 도입된 프로브를이용한 단일 염기 미스매치에 대한 구별 향상 방법 |
| WO2006126040A1 (en) | 2005-05-25 | 2006-11-30 | Rosetta Genomics Ltd. | Bacterial and bacterial associated mirnas and uses thereof |
| CN100510105C (zh) * | 2006-02-08 | 2009-07-08 | 博奥生物有限公司 | 一种序列特异性寡核苷酸探针及其应用 |
| KR100813263B1 (ko) * | 2006-08-17 | 2008-03-13 | 삼성전자주식회사 | 표적 서열 검출용 프로브 설계 방법 및 상기 프로브를이용한 표적 서열 검출 방법 |
-
2007
- 2007-06-29 CA CA002672246A patent/CA2672246A1/en not_active Abandoned
- 2007-06-29 WO PCT/IB2007/003732 patent/WO2008029295A2/en not_active Ceased
- 2007-06-29 DK DK07848974.7T patent/DK2038432T3/en active
- 2007-06-29 AU AU2007293187A patent/AU2007293187A1/en not_active Abandoned
- 2007-06-29 US US12/308,954 patent/US9115389B2/en not_active Expired - Fee Related
- 2007-06-29 JP JP2009517484A patent/JP2010500867A/ja active Pending
- 2007-06-29 EP EP07848974.7A patent/EP2038432B1/en not_active Not-in-force
-
2008
- 2008-12-28 IL IL196241A patent/IL196241A0/en unknown
-
2015
- 2015-06-11 US US14/736,521 patent/US20150376695A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2010500867A5 (enExample) | ||
| CN107365852B (zh) | 血清外泌体中肺癌相关microRNA分子标记的应用及其检测试剂盒 | |
| ES2788737T3 (es) | Conjunto de sondas para analizar una muestra de ADN y método para usar el mismo | |
| JP6092655B2 (ja) | テスト体液サンプルの分類方法 | |
| HRP20140692T1 (hr) | Postupci i nukleinske kiseline za analizu poremeä†aja proliferacije stanica | |
| CN111004862B (zh) | 用于快速检测并鉴定隐球菌的引物和探针及其应用 | |
| CN117529560A (zh) | 检测微小rna的方法和试剂盒 | |
| CN116356075A (zh) | 一种用于检测的引物探针、引物探针组及其应用 | |
| CN105793438A (zh) | 未知序列的双股线性核酸的全长扩增方法 | |
| JP2023547498A (ja) | マルチプレックス核酸検出のためのジェネリックカートリッジおよび方法 | |
| CN102251061A (zh) | 甲型/乙型流感病毒核酸双重荧光pcr检测试剂盒 | |
| CN107012241B (zh) | 一种U6、miR 92a及miR 21的三重RT-qPCR检测方法及试剂盒 | |
| WO2013179672A1 (ja) | 子宮内膜症の判定方法 | |
| CN110511984A (zh) | Egfr基因19号外显子缺失突变的快速荧光检测方法及应用 | |
| CN108728532A (zh) | 一种微小rna标志物及其应用 | |
| CN116121439B (zh) | 一种多重定量pcr检测真菌的方法以及试剂盒 | |
| CN104450702B (zh) | 一种血清miRNA生物标志物组合物与应用 | |
| JP2024086170A (ja) | 分析方法、キット及び検出用デバイス | |
| CN102534045A (zh) | 一种丙型肝炎病毒基因分型荧光pcr检测试剂盒 | |
| CN103409541B (zh) | 一种试剂盒在检测多种生物pcr反应假阴性中的用途 | |
| JP7297902B2 (ja) | 分析方法及びキット | |
| US9528163B2 (en) | Reagents and methods for detecting HCV | |
| KR20100120760A (ko) | 인체유두종바이러스 검출용 프라이머, 프로브 및 이를 이용한 인체유두종바이러스의 검출방법 | |
| CN106811549B (zh) | 禽流感病毒na亚型多重探针组合荧光定量rt-pcr分型方法 | |
| CN108384848A (zh) | 血清中circ_0021132作为深静脉血栓形成诊断标志物的应用 |