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1. 发明公开

EP1453977A4 MOLECULAR CHARACTERISTICS OF NON-SMALL CELL LUNG CANCER 有权
标题翻译： MOLEKULARE EIGENSCHAFTEN VON NICHTKLEINZELLIGEM LUNGENKREBS
公开(公告)号：EP1453977A4
公开(公告)日：2005-04-20
申请号：EP02794901
申请日：2002-08-16
申请人： US HEALTH , GENZYME CORP , UNIV JOHNS HOPKINS
发明人： NACHT MARIANA , DRACHEVA TATIANA , SIDRANSKY DAVID , MADDEN STEPHEN L , JEN JIN
IPC分类号： G01N33/574 , A61K48/00 , A61P35/00 , C12N15/09 , C12P21/04 , C12Q1/04 , C12Q1/68 , G01N33/68 , G01N37/00 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/158
摘要： We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21 WAF1/CIP1 and 14-3-3σ, were consistently under-expressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression observed by SAGE were consistent with the results obtained by quantitative real-time PCR or cDNA array analyses using 43 additional lung tumor and normal samples. Thus, although derived from only a few tissue libraries, molecular signatures of non-small cell lung cancer derived from SAGE most likely represent an unbiased yet distinctive molecular signature for human lung cancer.
摘要翻译：我们使用分层聚类来检查在总共九个正常肺上皮细胞和非小细胞肺癌（NSCLC）中通过基因表达（SAGE）的连续分析产生的基因表达谱。正常和肿瘤样本的分离以及组织病理学亚型，使用3,921个最丰富的转录标签是明显的。当仅使用115个高度差异表达的转录标记时，这种区别仍然存在。此外，这115个转录标签聚集成组，表明所检测的不同组织的独特的生物学和病理学特征。腺癌的特征在于高水平表达小气道相关或免疫相关的蛋白质，而鳞状细胞癌过度表达参与细胞解毒或抗氧化的基因。两个p53调节基因p21 WAF1 / CIP1和14-3-3sigma的信息在腺癌中一贯低表达，这表明p53途径本身可能在这种癌症类型中受损。通过SAGE观察到的基因表达与通过使用43个额外的肺肿瘤和正常样品的定量实时PCR或cDNA阵列分析获得的结果一致。因此，尽管仅来自少部分组织库，但从SAGE衍生的非小细胞肺癌的分子特征最有可能代表人类肺癌的无偏差但独特的分子特征。

2. 发明专利

DE60234467D1 未知
公开(公告)号：DE60234467D1
公开(公告)日：2009-12-31
申请号：DE60234467
申请日：2002-08-16
申请人： US HEALTH , GENZYME CORP , UNIV JOHNS HOPKINS MED
发明人： NACHT MARIANA , DRACHEVA TATIANA , SIDRANSKY DAVID THE JOHN HOPKI , MADDEN STEPHEN L , JEN JIN
IPC分类号： C12Q1/68 , G01N33/574 , A61K48/00 , A61P35/00 , C07H21/04 , C12N15/09 , C12P19/34 , C12P21/04 , C12Q1/04 , C12Q1/6886 , G01N33/68 , G01N37/00
摘要： We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21WAF1/CIP1 and 14-3-3&sgr;, were consistently under-expressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression observed by SAGE were consistent with the results obtained by quantitative real-time PCR or cDNA array analyses using 43 additional lung tumor and normal samples. Thus, although derived from only a few tissue libraries, molecular signatures of non-small cell lung cancer derived from SAGE most likely represent an unbiased yet distinctive molecular signature for human lung cancer.

3. 发明专利

AT449187T 未知
公开(公告)号：AT449187T
公开(公告)日：2009-12-15
申请号：AT02794901
申请日：2002-08-16
申请人： US HEALTH , GENZYME CORP , UNIV JOHNS HOPKINS
发明人： NACHT MARIANA , DRACHEVA TATIANA , SIDRANSKY DAVID , MADDEN STEPHEN L , JEN JIN
IPC分类号： C12Q1/68 , G01N33/574 , A61K48/00 , A61P35/00 , C07H21/04 , C12N15/09 , C12P19/34 , C12P21/04 , C12Q1/04 , C12Q1/6886 , G01N33/68 , G01N37/00
摘要： We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21WAF1/CIP1 and 14-3-3&sgr;, were consistently under-expressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression observed by SAGE were consistent with the results obtained by quantitative real-time PCR or cDNA array analyses using 43 additional lung tumor and normal samples. Thus, although derived from only a few tissue libraries, molecular signatures of non-small cell lung cancer derived from SAGE most likely represent an unbiased yet distinctive molecular signature for human lung cancer.

4. 发明专利

AU2002355963A1 Molecular characteristics of non-small cell lung cancer 未知
公开(公告)号：AU2002355963A1
公开(公告)日：2003-03-03
申请号：AU2002355963
申请日：2002-08-16
申请人： US HEALTH , GENZYME CORP , UNIV JOHNS HOPKINS
发明人： JEN JIN , MADDEN STEPHEN L , NACHT MARIANA , SIDRANSKY DAVID , DRACHEVA TATIANA
IPC分类号： G01N33/574 , A61K48/00 , A61P35/00 , C12N15/09 , C12P21/04 , C12Q1/04 , C12Q1/68 , C12Q1/6886 , G01N33/68 , G01N37/00 , C12P19/34 , C07H21/04
摘要： We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21WAF1/CIP1 and 14-3-3&sgr;, were consistently under-expressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression observed by SAGE were consistent with the results obtained by quantitative real-time PCR or cDNA array analyses using 43 additional lung tumor and normal samples. Thus, although derived from only a few tissue libraries, molecular signatures of non-small cell lung cancer derived from SAGE most likely represent an unbiased yet distinctive molecular signature for human lung cancer.

5. 发明专利

CA2456334A1 MOLECULAR CHARACTERISTICS OF NON-SMALL CELL LUNG CANCER 未知
公开(公告)号：CA2456334A1
公开(公告)日：2003-02-27
申请号：CA2456334
申请日：2002-08-16
申请人： US HEALTH , GENZYME CORP , UNIV JOHNS HOPKINS
发明人： NACHT MARIANA , DRACHEVA TATIANA , SIDRANSKY DAVID , MADDEN STEPHEN L , JEN JIN
IPC分类号： G01N33/574 , A61K48/00 , A61P35/00 , C12N15/09 , C12P21/04 , C12Q1/04 , C12Q1/68 , C12Q1/6886 , G01N33/68 , G01N37/00 , C12Q1/00 , C12Q1/02 , G01N33/53
摘要： We used hierarchical clustering to examine gene expression profiles generate d by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of norm al and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examine d. Adenocarcinomas were characterized by high-level expression of small airway- associated or immunologically related proteins, while squamous cell carcinom as overexpressed genes involved in cellular detoxification or antioxidation. Th e messages of two p53-regulated genes, p21 WAF I ICIPI and 14-3-3.sigma., were consistently under-expressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression observed by SAGE were consistent with the results obtained by quantitative real-time PCR or cDNA array analyses using 43 additional lung tumor and norm al samples. Thus, although derived from only a few tissue libraries, molecular signatures of non-small cell lung cancer derived from SAGE most likely represent an unbiased yet distinctive molecular signature for human lung cancer.

6. 发明申请

WO9949774A9 METHODS FOR THE DIAGNOSIS AND TREATMENT OF LUNG CANCER 审中-公开
标题翻译：肺癌诊断和治疗方法
公开(公告)号：WO9949774A9
公开(公告)日：2000-02-24
申请号：PCT/US9906947
申请日：1999-03-30
申请人： GENZYME CORP , UNIV JOHNS HOPKINS , JEN JIN , BEAUDRY GARY A , MADDEN STEPHEN L , BERTELSEN ARTHUR H
发明人： JEN JIN , BEAUDRY GARY A , MADDEN STEPHEN L , BERTELSEN ARTHUR H
IPC分类号： G01N33/50 , A61K45/00 , A61K48/00 , A61P35/00 , C12N15/09 , C12Q1/68 , G01N33/574 , D21C1/00 , A01N43/04
CPC分类号： C12Q1/6886 , C12Q2600/136
摘要： The present invention provides methods for aiding in the diagnoses of the neoplastic condition of a lung cell, and methods of screening for a potential therapeutic agent for the reversal of the neoplastic condition.
摘要翻译：本发明提供了有助于诊断肺细胞肿瘤状况的方法，以及筛选用于逆转肿瘤病症的潜在治疗剂的方法。

7. 发明申请

WO0205857A3 PHOSPHATONIN-RELATED GENE AND METHODS OF USE THEREOF 审中-公开
标题翻译：磷脂相关基因及其使用方法
公开(公告)号：WO0205857A3
公开(公告)日：2003-03-27
申请号：PCT/US0123014
申请日：2001-07-19
申请人： GENZYME CORP , SCHIAVI SUSAN , MADDEN STEPHEN L , MANAVALAN PARTHASARATHY , LEVINE MICHAEL , DE BEUR SUZANNE JAN , UNIV JOHNS HOPKINS
发明人： SCHIAVI SUSAN , MADDEN STEPHEN L , MANAVALAN PARTHASARATHY , LEVINE MICHAEL , DE BEUR SUZANNE JAN
IPC分类号： G01N33/50 , A61K38/00 , A61K45/00 , A61K48/00 , A61P3/12 , A61P7/08 , A61P19/00 , A61P19/08 , A61P35/00 , C07K14/575 , C12N5/06 , C12N5/10 , C12N15/09 , C12Q1/02 , C12Q1/68 , G01N33/15 , G01N33/53 , G01N33/566 , G01N33/68 , G01N33/74
CPC分类号： A61K48/00 , A61K38/00 , C07K14/575 , C12Q1/6886 , C12Q2600/136 , G01N33/68 , G01N33/6872 , G01N33/6893 , G01N33/74
摘要： This invention provides methods for modulating phosphate homeostasis and renal phosphate transport ba delivering agents that alter the expression of the FRP-4 gene of alter the activity of the FRP-4 protein. The methods of the invention are useful for modulating bone mineralization, renal phosphate transport, alleviating oncogenic osteomalacia-associated symptoms and treating phosphate homeostasis-related disease. The invention further provides methods for reducing phosphate re-absorption by delivering to a subject FRP-4 protein or polynucleotides that encode this protein. In addition, the invention provides methods for detecting and monitoring expression of the FRP-4 gene and modulating the phenotype of a neoplastic cell associated with oncogenic osteomalacia. Finally, the invention provides methods for screening candidate agents to identify compositions that modify the activity of the FRP-4 gene and protein.
摘要翻译：本发明提供了调节磷酸酶稳态的方法以及改变FRP-4基因表达改变FRP-4蛋白活性的磷酸盐转运的递送剂。本发明的方法可用于调节骨矿化，肾磷酸盐转运，减轻致癌性骨软化症相关症状和治疗磷酸酶体内平衡相关疾病。本发明还提供了通过递送到受试者FRP-4蛋白或编码该蛋白质的多核苷酸来减少磷酸盐再吸收的方法。此外，本发明提供了用于检测和监测FRP-4基因表达并调节与致癌性骨软化相关的肿瘤细胞表型的方法。最后，本发明提供筛选候选试剂以鉴定修饰FRP-4基因和蛋白质活性的组合物的方法。

8. 发明申请

WO9949774A2 METHODS FOR THE DIAGNOSIS AND TREATMENT OF LUNG CANCER 审中-公开
标题翻译：方法诊断和治疗肺癌
公开(公告)号：WO9949774A2
公开(公告)日：1999-10-07
申请号：PCT/US9906947
申请日：1999-03-30
申请人： GENZYME CORP , UNIV JOHNS HOPKINS , JEN JIN , BEAUDRY GARY A , MADDEN STEPHEN L , BERTELSEN ARTHUR H
发明人： JEN JIN , BEAUDRY GARY A , MADDEN STEPHEN L , BERTELSEN ARTHUR H
IPC分类号： G01N33/50 , A61K45/00 , A61K48/00 , A61P35/00 , C12N15/09 , C12Q1/68 , G01N33/574 , A61B
CPC分类号： C12Q1/6886 , C12Q2600/136
摘要： The present invention provides methods for aiding in the diagnoses of the neoplastic condition of a lung cell, and methods of screening for a potential therapeutic agent for the reversal of the neoplastic condition.
摘要翻译：本发明提供了帮助诊断肺细胞肿瘤状况的方法，以及筛选用于逆转肿瘤病症的潜在治疗剂的方法。

9. 发明公开

EP1095183A4 METHODS FOR THE DIAGNOSIS AND TREATMENT OF LUNG CANCER 有权
标题翻译：方法进行诊断和治疗肺癌
公开(公告)号：EP1095183A4
公开(公告)日：2004-09-15
申请号：EP99914292
申请日：1999-03-30
申请人： GENZYME CORP , UNIV JOHNS HOPKINS
发明人： JEN JIN , BEAUDRY GARY A , MADDEN STEPHEN L , BERTELSEN ARTHUR H
IPC分类号： G01N33/50 , A61K45/00 , A61K48/00 , A61P35/00 , C12N15/09 , C12Q1/68 , G01N33/574
CPC分类号： C12Q1/6886 , C12Q2600/136

10. 发明专利

CA2323058C METHODS FOR THE DIAGNOSIS AND TREATMENT OF LUNG CANCER BY DETECTION OF PROTO-ONCOGENE OVEREXPRESSION 未知
公开(公告)号：CA2323058C
公开(公告)日：2011-03-29
申请号：CA2323058
申请日：1999-03-30
申请人： GENZYME CORP , UNIV JOHNS HOPKINS
发明人： JEN JIN , BEAUDRY GARY A , MADDEN STEPHEN L , BERTELSEN ARTHUR H , SIDRANSKY DAVID
IPC分类号： C12Q1/68 , G01N33/50 , A01N43/04 , A61K45/00 , A61K48/00 , A61P35/00 , C07H21/00 , C12N15/09 , C12Q1/6886 , D21C1/00 , G01N33/574
摘要： The present invention provides methods for aiding in the diagnosis of the neoplastic condition of a lung cell comprising detecting the presence of an overexpressed proto-oncogene selected from the group consisting of b-myb, p67, PGP9.5 and 8-oxo-dGTPase, in a lung cell sample, wherein said presence is indicative of the neoplastic condition of the lung cell. Also provided are methods to identify potential therapeutic agents for reversal of a neoplastic condition of a lung cell where the cell is characterized by overexpression of such a proto-oncogene. Also provided are probes or primers suitable for detection of the proto-oncogene and kits for use in the diagnostic method.

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