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1. 发明申请

WO2004083399A3 ABERRANTLY METHYLATED GENES IN PANCREATIC CANCER 审中-公开
标题翻译：胰腺癌中的亚甲基化基因
公开(公告)号：WO2004083399A3
公开(公告)日：2007-10-25
申请号：PCT/US2004008061
申请日：2004-03-17
申请人： UNIV JOHNS HOPKINS , GOGGINS MICHAEL G , SATO NORIHIRO
发明人： GOGGINS MICHAEL G , SATO NORIHIRO
IPC分类号： C12Q1/68 , C07H21/00 , C12N20060101 , C12N1/00 , C12N9/00 , C12P19/34
CPC分类号： C12Q1/6827 , C12Q1/6886 , C12Q2600/112 , C12Q2600/154 , C12Q2600/16 , C12Q2523/125 , C12Q2565/501 , C12Q2525/117
摘要： The present invention provides a method for detecting pancreatic carcinoma in a subject. The method includes contacting a nucleic acid-containing specimen from the subject with an agent that provides a determination of the methylation state of at least one gene or associated regulatory region of the gene and identifying aberrant methylation of regions of the gene or regulatory region, wherein aberrant methylation is identified as being different when compared to the same regions of the gene or associated regulatory region in a subject not having the pancreatic carcinoma, thereby detecting pancreatic carcinoma in the subject.
摘要翻译：本发明提供了一种用于检测受试者中胰腺癌的方法。该方法包括使来自受试者的含有核酸的样品与提供基因的至少一个基因或相关调节区的甲基化状态的测定并鉴定基因或调节区的区域的异常甲基化的试剂接触，其中当与不具有胰腺癌的受试者的基因或相关调节区的相同区域相比较时，异常甲基化被鉴定为不同，从而检测受试者中的胰腺癌。

2. 发明申请

WO2010028098A4 PATHWAYS UNDERLYING PANCREATIC TUMORIGENESIS AND AN HEREDITARY PANCREATIC CANCER GENE 审中-公开
标题翻译：胰岛素瘤和遗传性胰腺癌基因途径
公开(公告)号：WO2010028098A4
公开(公告)日：2010-08-19
申请号：PCT/US2009055802
申请日：2009-09-03
申请人： UNIV JOHNS HOPKINS , VOGELSTEIN BERT , KINZLER KENNETH W , PARSONS D WILLIAMS , JONES SIAN , ZHANG XIAOSONG , LIN JIMMY CHANG-HO , LEARY REBECCA J , ANGENENDT PHILIPP , PAPADOPOULOS NICKOLAS , VELCULESCU VICTOR , PARMIGIANI GIOVANNI , KARCHIN RACHEL , KERN SCOTT , HRUBAN RALPH , ESHLEMAN JAMES R , GOGGINS MICHAEL , KLEIN ALISON
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , PARSONS D WILLIAMS , JONES SIAN , ZHANG XIAOSONG , LIN JIMMY CHANG-HO , LEARY REBECCA J , ANGENENDT PHILIPP , PAPADOPOULOS NICKOLAS , VELCULESCU VICTOR , PARMIGIANI GIOVANNI , KARCHIN RACHEL , KERN SCOTT , HRUBAN RALPH , ESHLEMAN JAMES R , GOGGINS MICHAEL , KLEIN ALISON
IPC分类号： C12Q1/68
CPC分类号： G01N33/57438 , C12Q1/6886 , C12Q2600/156 , G01N2800/50
摘要： This invention relates to new insights into the pathogenesis of pancreatic cancers by analyzing the genes altered in 24 pancreatic tumors. First, we determined the sequences of 23,781 transcripts, representing 20,583 protein-encoding genes, in DNA from these tumors. Second, we searched for homozygous deletions and amplifications using microarrays querying one million single nucleotide polymorphisms in each sample. Third, we analyzed the transcriptomes of the same samples using SAGE and next-generation sequencing-by-synthesis technologies We found that pancreatic cancers contain an average of 63 genetic alterations, of which 49 are point mutations, 8 are homozygous deletions, and 6 are amplifications. Further analyses revealed a core set of 12 regulatory processes or pathways that were each genetically altered in 70 % to 100 % of the samples. The data suggest that dysregulation of this core set of pathways is responsible for the major features of pancreatic tumorigenesis.
摘要翻译：本发明涉及通过分析在24个胰腺肿瘤中改变的基因而对胰腺癌的发病机理的新见解。首先，我们确定了来自这些肿瘤的DNA中23,781个转录物的序列，代表20,583个蛋白质编码基因。其次，我们使用微阵列查询每个样本中一百万个单核苷酸多态性来寻找纯合子缺失和扩增。第三，我们使用SAGE和下一代合成测序技术分析了相同样品的转录组我们发现胰腺癌平均含有63个基因改变，其中49个是点突变，8个是纯合子缺失，6个是扩增。进一步的分析揭示了12个监管程序或途径的核心组合，每个过程或途径在70％到100％的样本中均被遗传改变。数据表明这种核心途径的失调调节是胰腺肿瘤发生的主要特征的原因。

3. 发明申请

WO2004099432A2 IDENTIFICATION OF BIOMARKERS FOR DETECTING PANCREATIC CANCER 审中-公开
标题翻译：用于检测胰腺癌的生物标志物的鉴定
公开(公告)号：WO2004099432A2
公开(公告)日：2004-11-18
申请号：PCT/US2004/013344
申请日：2004-04-30
申请人： THE JOHNS HOPKINS UNIVERSITY , CIPHERGEN BIOSYSTEMS, INC. , CHAN, Daniel, W. , ZHANG, Zhen , KOOPMANN, Jens , GOGGINS, Michael , WHITE, Nicole, C. , FUNG, Eric , MENG, Xiao-Ying
发明人： CHAN, Daniel, W. , ZHANG, Zhen , KOOPMANN, Jens , GOGGINS, Michael , WHITE, Nicole, C. , FUNG, Eric , MENG, Xiao-Ying
IPC分类号： C12Q
CPC分类号： G01N33/57438 , C12Q1/6886 , C12Q2600/158
摘要： The present invention relates to a method of qualifying pancreatic cancer status in a subject comprising: (a) measuring at least one of the disclosed biomarkers in a sample from the subject and (b) correlating the measurement with pancreatic cancer status. The invention further relates to kits for qualifying pancreatic cancer status in a subject.
摘要翻译：本发明涉及一种在受试者中鉴定胰腺癌状态的方法，包括：（a）测量来自受试者的样品中所公开的生物标志物中的至少一种和（b）将测量与胰腺癌状态相关联。本发明还涉及用于在受试者中鉴定胰腺癌状态的试剂盒。

4. 发明申请

WO2010102160A3 DIAGNOSTIC METHOD USING PALB2 审中-公开
标题翻译：诊断方法使用PALB2
公开(公告)号：WO2010102160A3
公开(公告)日：2011-01-13
申请号：PCT/US2010026290
申请日：2010-03-05
申请人： UNIV JOHNS HOPKINS , VOGELSTEIN BERT , KINZLER KENNETH W , PARSONS D WILLIAMS , JONES SIAN , KERN SCOTT , HRUBAN RALPH , ESHLEMAN JAMES R , GOGGINS MICHAEL , KLEIN ALISON , HIDALGO MANUEL , VELCULESCU VICTOR E
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , PARSONS D WILLIAMS , JONES SIAN , KERN SCOTT , HRUBAN RALPH , ESHLEMAN JAMES R , GOGGINS MICHAEL , KLEIN ALISON , HIDALGO MANUEL , VELCULESCU VICTOR E
IPC分类号： C12Q1/68 , G01N33/574 , G01N33/68
CPC分类号： C12Q1/6886 , A61K31/407 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158 , G01N33/57438 , G01N2333/47
摘要： The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.
摘要翻译：本发明提供了一种检测胰腺癌患者和具有胰腺癌家族史的个体中PALB2基因突变的方法。还提供了用于诊断患有胰腺癌的倾向，用于预测患者对胰腺癌治疗的反应以及用于治疗患者胰腺癌的方法，其基于在患者体内PALB2突变或异常PALB2基因表达的存在。

5. 发明申请

WO2008005559A2 A STRATEGY FOR DETECTING LOW ABUNDANCE MUTATIONS 审中-公开
标题翻译：检测低渗透突变的策略
公开(公告)号：WO2008005559A2
公开(公告)日：2008-01-10
申请号：PCT/US2007/015631
申请日：2007-07-09
申请人： JOHNS HOPKINS UNIVERSITY , GOGGINS, Michael
发明人： GOGGINS, Michael
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q2537/113 , C12Q2531/113
摘要： The present invention relates, e.g., to a method for screening for mutations in a DNA sample, comprising (a) diluting and distributing the sample to obtain a plurality of aliquots which, on the average, contain between about 2-10 genome equivalents of the DNA; (b) PCR amplifying the DNA in a sufficient number of aliquots, with at least one set of PCR primers, so as to generate amplicons such that, if mutations are present at a frequency of about 1-10% in a given gene in the sample, the probability of there being a mutation in that gene in at least one of the amplicons is at least about 95%; and (c) screening the amplicons for the presence of mutations, using a method that can detect unspecified mutations at unspecified sites within an amplicon (e.g., temperature gradient capillary electrophoresis (TGCE) or cycle sequencing of the DNA).
摘要翻译：本发明涉及例如筛选DNA样品中的突变的方法，其包括（a）稀释和分布样品以获得多个等分试样，其平均含有约2-10个基因组当量的脱氧核糖核酸; （b）使用至少一组PCR引物以足够数量的等分试样PCR扩增DNA，以便产生扩增子，使得如果在给定基因中以约1-10％的频率存在突变，则样品中，至少一个扩增子中该基因中存在突变的概率为至少约95％; 使用可以在扩增子内的未指定位点（例如温度梯度毛细管电泳（TGCE）或DNA的循环测序）中检测未指定突变的方法，筛选扩增子的突变存在。

6. 发明申请

WO2005017183A2 METHYLATED GENE BIOMARKERS FOR DETECTING CANCER 审中-公开
标题翻译：用于检测癌症的甲基化基因生物标志物
公开(公告)号：WO2005017183A2
公开(公告)日：2005-02-24
申请号：PCT/US2004020535
申请日：2004-06-24
申请人： UNIV JOHNS HOPKINS , GOGGINS MICHAEL G , NORIHIRO SATO
发明人： GOGGINS MICHAEL G , NORIHIRO SATO
IPC分类号： C07H21/02 , C07H21/04 , C12Q20060101 , C12Q1/68 , C12Q
CPC分类号： C12Q1/6886 , C12Q2523/125 , C12Q2600/154 , C12Q2600/156 , C12Q2600/16
摘要： The present invention includes methods diagnosising of cancer by analysis of a patient sample, particularly for the presence of a methylated SPARC nucleic acid molecule, and particularly for the diagnosis of pancreatic cancer. The invention also includes therapeutic methods for treating cancers by administering to cancers patients therapeutically effective amounts of demethylating agents.
摘要翻译：本发明包括通过分析患者样品，特别是甲基化SPARC核酸分子的存在，特别是诊断胰腺癌来诊断癌症的方法。本发明还包括通过向癌症患者施用治疗有效量的去甲基化剂来治疗癌症的治疗方法。

7. 发明申请

WO2010102160A2 DIAGNOSTIC METHOD USING PALB2 审中-公开
标题翻译：诊断方法使用PALB2
公开(公告)号：WO2010102160A2
公开(公告)日：2010-09-10
申请号：PCT/US2010/026290
申请日：2010-03-05
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth W. , PARSONS, D. Williams , JONES, Sian , KERN, Scott , HRUBAN, Ralph , ESHLEMAN, James R. , GOGGINS, Michael , KLEIN, Alison , HIDALGO, Manuel , VELCULESCU, Victor E.
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth W. , PARSONS, D. Williams , JONES, Sian , KERN, Scott , HRUBAN, Ralph , ESHLEMAN, James R. , GOGGINS, Michael , KLEIN, Alison , HIDALGO, Manuel , VELCULESCU, Victor E.
IPC分类号： C12Q1/68 , G01N33/68 , G01N33/574
CPC分类号： C12Q1/6886 , A61K31/407 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158 , G01N33/57438 , G01N2333/47
摘要： The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.
摘要翻译：本发明提供了一种检测胰腺癌患者和具有胰腺癌家族史的个体中PALB2基因突变的方法。还提供了用于诊断患有胰腺癌的倾向，用于预测患者对胰腺癌治疗的反应以及用于治疗患者胰腺癌的方法，其基于在患者体内PALB2突变或异常PALB2基因表达的存在。

8. 发明申请

WO2010028098A2 PATHWAYS UNDERLYING PANCREATIC TUMORIGENESIS AND AN HEREDITARY PANCREATIC CANCER GENE 审中-公开
标题翻译：基于胰腺癌和胰腺癌基因的途径
公开(公告)号：WO2010028098A2
公开(公告)日：2010-03-11
申请号：PCT/US2009/055802
申请日：2009-09-03
申请人： THE JOHNS HOPKINS UNIVERSITY , VOGELSTEIN, Bert , KINZLER, Kenneth, W. , PARSONS, D., Williams , JONES, Sian , ZHANG, Xiaosong , LIN, Jimmy Chang-Ho , LEARY, Rebecca J. , ANGENENDT, Philipp , PAPADOPOULOS, Nickolas , VELCULESCU, Victor , PARMIGIANI, Giovanni , KARCHIN, Rachel , KERN, Scott , HRUBAN, Ralph , ESHLEMAN, James R. , GOGGINS, Michael , KLEIN, Alison
发明人： VOGELSTEIN, Bert , KINZLER, Kenneth, W. , PARSONS, D., Williams , JONES, Sian , ZHANG, Xiaosong , LIN, Jimmy Chang-Ho , LEARY, Rebecca J. , ANGENENDT, Philipp , PAPADOPOULOS, Nickolas , VELCULESCU, Victor , PARMIGIANI, Giovanni , KARCHIN, Rachel , KERN, Scott , HRUBAN, Ralph , ESHLEMAN, James R. , GOGGINS, Michael , KLEIN, Alison
IPC分类号： C12Q1/68
CPC分类号： G01N33/57438 , C12Q1/6886 , C12Q2600/156 , G01N2800/50
摘要： There are currently few therapeutic options for patients with pancreatic cancers and new insights into the pathogenesis of this lethal disease are urgently needed. To this end, we performed a comprehensive analysis of the genes altered in 24 pancreatic tumors. First, we determined the sequences of 23,781 transcripts, representing 20,583 protein-encoding genes, in DNA from these tumors. Second, we searched for homozygous deletions and amplifications using microarrays querying ~one million single nucleotide polymorphisms in each sample. Third, we analyzed the transcriptomes of the same samples using SAGE and next-generation sequencing-by-synthesis technologies. We found that pancreatic cancers contain an average of 63 genetic alterations, of which 49 are point mutations, 8 are homozygous deletions, and 6 are amplifications. Further analyses revealed a core set of 12 regulatory processes or pathways that were each genetically altered in 70 % to 100 % of the samples. The data suggest that dysregulation of this core set of pathways is responsible for the major features of pancreatic tumorigenesis.
摘要翻译：目前对胰腺癌患者几乎没有治疗方案，迫切需要对这种致死性疾病的发病机制的新见解。为此，我们对24个胰腺肿瘤中改变的基因进行了综合分析。首先，我们从这些肿瘤的DNA中确定了23,781个转录本，代表20,583个蛋白质编码基因的序列。其次，我们使用微阵列查询了每个样本中一百万个单核苷酸多态性的纯合缺失和扩增。第三，我们使用SAGE和下一代按序合成技术分析了相同样品的转录组。我们发现胰腺癌平均存在63个遗传改变，其中49个是点突变，8个是纯合缺失，6个是扩增。进一步的分析揭示了一组核心的12个调节过程或途径，在70％至100％的样品中进行了遗传改变。数据表明，这种核心途径的失调导致了胰腺肿瘤发生的主要特征。

9. 发明申请

WO2008005559A3 A STRATEGY FOR DETECTING LOW ABUNDANCE MUTATIONS 审中-公开
标题翻译：检测低渗透突变的策略
公开(公告)号：WO2008005559A3
公开(公告)日：2009-02-19
申请号：PCT/US2007015631
申请日：2007-07-09
申请人： UNIV JOHNS HOPKINS , GOGGINS MICHAEL
发明人： GOGGINS MICHAEL
IPC分类号： C12P19/34
CPC分类号： C12Q1/6827 , C12Q2537/113 , C12Q2531/113
摘要： The present invention relates, e.g., to a method for screening for mutations in a DNA sample, comprising (a) diluting and distributing the sample to obtain a plurality of aliquots which, on the average, contain between about 2-10 genome equivalents of the DNA; (b) PCR amplifying the DNA in a sufficient number of aliquots, with at least one set of PCR primers, so as to generate amplicons such that, if mutations are present at a frequency of about 1-10% in a given gene in the sample, the probability of there being a mutation in that gene in at least one of the amplicons is at least about 95%; and (c) screening the amplicons for the presence of mutations, using a method that can detect unspecified mutations at unspecified sites within an amplicon (e.g., temperature gradient capillary electrophoresis (TGCE) or cycle sequencing of the DNA).
摘要翻译：本发明涉及例如筛选DNA样品中的突变的方法，其包括（a）稀释和分布样品以获得多个等分试样，其平均含有约2-10个基因组当量的脱氧核糖核酸; （b）使用至少一组PCR引物以足够数量的等分试样PCR扩增DNA，以便产生扩增子，使得如果在给定基因中以约1-10％的频率存在突变，样品中，至少一个扩增子中该基因中存在突变的概率为至少约95％; 使用可以在扩增子内的未指定位点（例如温度梯度毛细管电泳（TGCE）或DNA的循环测序）中检测未指定突变的方法，筛选扩增子的突变存在。

10. 发明申请

WO2005017183A3 METHYLATED GENE BIOMARKERS FOR DETECTING CANCER 审中-公开
公开(公告)号：WO2005017183A3
公开(公告)日：2005-02-24
申请号：PCT/US2004/020535
申请日：2004-06-24
申请人： JOHNS HOPKINS UNIVERSITY , GOGGINS, Michael, G. , NORIHIRO, Sato
发明人： GOGGINS, Michael, G. , NORIHIRO, Sato
IPC分类号： C12Q1/68
摘要： The present invention includes methods diagnosising of cancer by analysis of a patient sample, particularly for the presence of a methylated SPARC nucleic acid molecule, and particularly for the diagnosis of pancreatic cancer. The invention also includes therapeutic methods for treating cancers by administering to cancers patients therapeutically effective amounts of demethylating agents.

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