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1. 发明申请

WO2008100913A3 EARLY DETECTION AND PROGNOSIS OF COLON CANCERS 审中-公开
标题翻译：早期检测和预防结肠癌
公开(公告)号：WO2008100913A3
公开(公告)日：2008-12-18
申请号：PCT/US2008053689
申请日：2008-02-12
申请人： UNIV JOHNS HOPKINS , ONCOMETHYLOME SCIENCES SA , BAYLIN STEPHEN B , SCHUEBEL KORNEL E , CRIEKINGE WIM VAN
发明人： BAYLIN STEPHEN B , SCHUEBEL KORNEL E , CRIEKINGE WIM VAN
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2523/125 , C12Q2600/106 , C12Q2600/154
摘要： We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island hypermethylation and transcriptional silencing in colorectal cancer (CRC). By screening cell lines and validating tumor specific hypermethylation in a panel of primary human CRC samples, we estimate that nearly 5% of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find a much larger number of genes hypermethylated in individual tumors, and much higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken. The genes we identified can be used inter alia diagnostically to detect cancer, pre-cancer, and likelihood of developing cancer.
摘要翻译：我们已经开发了一种转录组范围的方法来鉴定受启动子CpG岛高甲基化和转录沉默在结肠直肠癌（CRC）中影响的基因。通过筛选细胞系并验证一组原代人CRC样品中的肿瘤特异性高甲基化，我们估计所有已知基因中的近5％可能是单个肿瘤中的启动子甲基化。当与基因突变直接比较时，我们发现在个体肿瘤中超甲基化的基因数量更多，并且在具有遗传或表观遗传变化的个体基因内的高甲基化频率高得多。因此，为了列举人类癌症基因组中的全部变化，并促进最有效的肿瘤分组以鉴定癌症生物标志物并定制治疗方法，应进行遗传和表观遗传筛选。我们确定的基因可以用于诊断上检测癌症，癌前病症和发展癌症的可能性。

2. 发明申请

WO2003076594A3 GENOMIC SCREEN FOR EPIGENETICALLY SILENCED TUMOR SUPPRESSOR GENES 审中-公开
公开(公告)号：WO2003076594A3
公开(公告)日：2003-09-18
申请号：PCT/US2003/007245
申请日：2003-03-07
申请人： THE JOHNS HOPKINS UNIVERSITY , SIDRANSKY, David , BAYLIN, Stephen, B. , HERMAN, James , SUZUKI, Hiromu
发明人： SIDRANSKY, David , BAYLIN, Stephen, B. , HERMAN, James , SUZUKI, Hiromu
IPC分类号： C12Q1/68 , C07H21/02 , C07H21/04
摘要： Methods of genomic screening to identify epigenetically silenced genes, including epigenetically silenced tumor suppressor genes are provided. Also provided are methods of detecting a cancer, for example, an esophageal squamous cell carcinoma or a head and neck squamous cell carcinoma, as are methods of treating a subject having such a cancer.

3. 发明申请

WO2005042700A2 USE OF HEDGEHOG PATHWAY INHIBITORS IN SMALL-CELL LUNG CANCER 审中-公开
标题翻译： HEDGEHOG路径抑制剂在小细胞肺癌中的应用
公开(公告)号：WO2005042700A2
公开(公告)日：2005-05-12
申请号：PCT/US2004/034534
申请日：2004-10-20
申请人： THE JOHNS HOPKINS UNIVERSITY , WATKINS, David, N. , BERMAN, David, M. , BAYLIN, Stephen, B. , BEACHY, Philip, A.
发明人： WATKINS, David, N. , BERMAN, David, M. , BAYLIN, Stephen, B. , BEACHY, Philip, A.
IPC分类号： C12N
CPC分类号： G01N33/57423 , G01N33/5011 , G01N2800/52
摘要： Elevated Hedgehog (Hh) pathway activity, including ligand stimulated Hh pathway activity, was detected in small-cell lung cancer (SCLQ cells, and determined to be associated with growth and proliferation of the cancer cells. Accordingly, methods are provided for treating SCLC associated with elevated Hh pathway activity by reducing or inhibiting the Hh pathway activity. Also provided are methods of determining the responsiveness of SCLC to treatment with a Hh pathway antagonist.
摘要翻译：在小细胞肺癌（SCLQ细胞）中检测到高刺猬（Hh）通路活性，包括配体刺激的Hh通路活性，并确定与癌细胞的生长和增殖相关，因此提供了用于治疗SCLC相关的方法通过降低或抑制Hh通路活性，具有升高的Hh通路活性。还提供了确定SCLC对用Hh途径拮抗剂治疗的反应性的方法。

4. 发明申请

WO2008010975A3 EARLY DETECTION AND PROGNOSIS OF COLON CANCERS 审中-公开
标题翻译：早期检测和预防结肠癌
公开(公告)号：WO2008010975A3
公开(公告)日：2008-12-31
申请号：PCT/US2007016104
申请日：2007-07-16
申请人： UNIV JOHNS HOPKINS , ONCOMETHYLOME SCIENCES S A , BAYLIN STEPHEN B , CRIEKINGE WIM VAN , SCHUEBEL KORNEL E , COPE LESLIE , SUZUKI HIROMI , HERMAN JIM
发明人： BAYLIN STEPHEN B , CRIEKINGE WIM VAN , SCHUEBEL KORNEL E , COPE LESLIE , SUZUKI HIROMI , HERMAN JIM
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6827 , C12Q1/6886 , C12Q2600/106 , C12Q2600/154 , C12Q2523/125
摘要： A genome wide microarray gene expression approach for human colorectal cancer cells was used to identify hundreds of hypermethylated genes for colon cancer. We compared isogenic cells altered pharmacologically versus genetically to induce genomic demethylation, to pinpoint genes activated by DNA demethylation, but not by inhibition of class I and II histone deacetylases (HDACs). We achieve an 82% success rate in predicting genes with densely hypermethylated CpG islands and complete gene silencing. The genes are similarly hypermethylated in primary tumors and have previously undetected tumor suppressor functions. The genes can be used diagnostically to detect cancer, pre-cancer, and likelihood of developing cancer.
摘要翻译：用于人结肠直肠癌细胞的全基因组微阵列基因表达方法用于鉴定数百个结肠癌的高甲基化基因。我们比较了等位基因细胞在药理学上与遗传学上的改变，以诱导基因组去甲基化，以确定通过DNA去甲基化激活的基因，但不能抑制I类和II类组蛋白脱乙酰酶（HDAC）。我们在预测密度高的甲基化CpG岛的基因和完整的基因沉默中达到82％的成功率。这些基因在原发性肿瘤中类似地是高甲基化的，并且以前未检测到肿瘤抑制功能。这些基因可以在诊断上用于检测癌症，癌前病症和发展癌症的可能性。

5. 发明申请

WO2008010975A2 EARLY DETECTION AND PROGNOSIS OF COLON CANCERS 审中-公开
标题翻译：结肠癌的早期发现和预后
公开(公告)号：WO2008010975A2
公开(公告)日：2008-01-24
申请号：PCT/US2007/016104
申请日：2007-07-16
申请人： THE JOHNS HOPKINS UNIVERSITY , ONCOMETHYLOME SCIENCES, S .A. , BAYLIN, Stephen, B. , CRIEKINGE, Wim, Van , SCHUEBEL, Kornel, E. , COPE, Leslie , SUZUKI, Hiromi , HERMAN, Jim
发明人： BAYLIN, Stephen, B. , CRIEKINGE, Wim, Van , SCHUEBEL, Kornel, E. , COPE, Leslie , SUZUKI, Hiromi , HERMAN, Jim
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6886 , C12Q2600/106 , C12Q2600/154 , C12Q2523/125
摘要： A genome wide microarray gene expression approach for human colorectal cancer cells was used to identify hundreds of hypermethylated genes for colon cancer. We compared isogenic cells altered pharmacologically versus genetically to induce genomic demethylation, to pinpoint genes activated by DNA demethylation, but not by inhibition of class I and II histone deacetylases (HDACs). We achieve an 82% success rate in predicting genes with densely hypermethylated CpG islands and complete gene silencing. The genes are similarly hypermethylated in primary tumors and have previously undetected tumor suppressor functions. The genes can be used diagnostically to detect cancer, pre-cancer, and likelihood of developing cancer.
摘要翻译：使用人类结肠直肠癌细胞的全基因组微阵列基因表达方法来鉴定数百个用于结肠癌的高甲基化基因。我们比较了药理学和遗传学改变的等基因细胞诱导基因组去甲基化，以查明由DNA去甲基化激活的基因，但不是通过抑制I类和II类组蛋白脱乙酰酶（HDACs）。我们在预测具有密集超甲基化CpG岛和完全基因沉默的基因方面实现了82％的成功率。这些基因在原发性肿瘤中类似地高甲基化，并且以前未检测到肿瘤抑制剂功能。这些基因可以用于诊断癌症，癌症前期和发展癌症的可能性。

6. 发明申请

WO2003076593A3 GENOMIC SCREEN FOR EPIGENETICALLY SILENCED GENES ASSOCIATED WITH CANCER 审中-公开
公开(公告)号：WO2003076593A3
公开(公告)日：2003-09-18
申请号：PCT/US2003/007244
申请日：2003-03-07
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , BAYLIN, Stephen, B. , HERMAN, James, G. , SUZUKI, Hiromu , SIDRANSKY, David
发明人： BAYLIN, Stephen, B. , HERMAN, James, G. , SUZUKI, Hiromu , SIDRANSKY, David
IPC分类号： C12Q1/68
摘要： A method of identifying epigenetically silenced genes, e.g., methylation silenced genes,in cancer cells is provided. In addition, methods of identifying a cancer by detecting epigenetic silencing of gene expression are provided, as are methods of treating a subject having such a cancer, for example, a colorectal cancer and/or gastric cancer. Reagents for practicing such methods also are provided.

7. 发明申请

WO0227019A8 METHOD OF PREDICTING THE CLINICAL RESPONSE TO CHEMOTHERAPEUTIC TREATMENT WITH ALKYLATING AGENTS 审中-公开
标题翻译：用碱性药物预防化疗治疗的临床应答方法
公开(公告)号：WO0227019A8
公开(公告)日：2002-07-11
申请号：PCT/US0130881
申请日：2001-10-01
申请人： UNIV JOHNS HOPKINS MED , BAYLIN STEPHEN B , HERMAN JAMES G , ESTELLER MANEL
发明人： BAYLIN STEPHEN B , HERMAN JAMES G , ESTELLER MANEL
IPC分类号： C12N15/09 , A61K38/51 , C07K16/40 , C12P19/34 , C12Q1/37 , C12Q1/48 , C12Q1/68 , G01N33/50 , G01N33/53
CPC分类号： C07K16/40 , C12Q1/683 , C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/154 , Y10S435/975 , C12Q2523/125
摘要： The present invention provides methods relating to chemotherapeutic treatment of a cell proliferative disorder. In particular, a method is provided for predicting the clinical response to certain types of chemotherapeutic agents. Aklylating agents, used for the treatment of certain types of tumors including tumors of the nervous system and lymph system, are efficacious agents when the damage they do to tumor cell DNA is not repaired by cellular DNA repair mechanisms. The present invention provides a method for determining the activity of a gene encoding a DNA repair enzyme, thus providing a prediction of the clinical response to alkylating agents. Figure (1) shows the overall survival among subjects with gliomas treated carmustine, and the time of progression of disease according to the methylation status of the MGMT promoter.
摘要翻译：本发明提供了与细胞增殖性疾病的化学治疗有关的方法。特别地，提供了一种用于预测对某些类型的化学治疗剂的临床反应的方法。用于治疗某些类型的肿瘤（包括神经系统和淋巴系统的肿瘤）的Aklylating剂是当它们对肿瘤细胞DNA的损伤不被细胞DNA修复机制修复时是有效的试剂。本发明提供了确定编码DNA修复酶的基因的活性的方法，从而提供了对烷化剂的临床应答的预测。图（1）显示根据MGMT启动子的甲基化状态，治疗卡莫司汀的神经胶质瘤受试者和疾病进展时间的总生存期。

8. 发明申请

WO2008100913A2 EARLY DETECTION AND PROGNOSIS OF COLON CANCERS 审中-公开
标题翻译：结肠癌的早期发现和预后
公开(公告)号：WO2008100913A2
公开(公告)日：2008-08-21
申请号：PCT/US2008/053689
申请日：2008-02-12
申请人： THE JOHNS HOPKINS UNIVERSITY , ONCOMETHYLOME SCIENCES SA , BAYLIN, Stephen, B. , SCHUEBEL, Kornel, E. , CRIEKINGE, Wim, Van
发明人： BAYLIN, Stephen, B. , SCHUEBEL, Kornel, E. , CRIEKINGE, Wim, Van
IPC分类号： C12Q1/68 , A61K31/7088 , A61P35/00
CPC分类号： C12Q1/6886 , C12Q2523/125 , C12Q2600/106 , C12Q2600/154
摘要： We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island hypermethylation and transcriptional silencing in colorectal cancer (CRC). By screening cell lines and validating tumor specific hypermethylation in a panel of primary human CRC samples, we estimate that nearly 5% of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find a much larger number of genes hypermethylated in individual tumors, and much higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken. The genes we identified can be used inter alia diagnostically to detect cancer, pre-cancer, and likelihood of developing cancer.
摘要翻译：我们开发了转录组范围的方法来鉴定受启动子CpG岛超甲基化和转录沉默影响的结肠直肠癌（CRC）中的基因。通过筛选细胞系并验证一组原发性人类CRC样品中的肿瘤特异性超甲基化，我们估计所有已知基因中接近5％可能是在个体肿瘤中甲基化的启动子。当直接与基因突变相比时，我们发现个体肿瘤中超甲基化的基因数量大得多，并且在个体基因内高甲基化的频率高出遗传或表观遗传变化。因此，为了列举人类癌症基因组的全部改变，并促进最有效的肿瘤分组来鉴定癌症生物标志物和定制治疗方法，应进行遗传和表观遗传学筛选。我们确定的基因可以用于诊断癌症，癌症前期和发展癌症的可能性等。

9. 发明申请

WO2005042700A3 USE OF HEDGEHOG PATHWAY INHIBITORS IN SMALL-CELL LUNG CANCER 审中-公开
标题翻译： HEDGEHOG路径抑制剂在小细胞肺癌中的应用
公开(公告)号：WO2005042700A3
公开(公告)日：2006-02-23
申请号：PCT/US2004034534
申请日：2004-10-20
申请人： UNIV JOHNS HOPKINS , WATKINS DAVID N , BERMAN DAVID M , BAYLIN STEPHEN B , BEACHY PHILIP A
发明人： WATKINS DAVID N , BERMAN DAVID M , BAYLIN STEPHEN B , BEACHY PHILIP A
IPC分类号： C12N20060101 , A61K38/00
CPC分类号： G01N33/57423 , G01N33/5011 , G01N2800/52
摘要： Elevated Hedgehog (Hh) pathway activity, including ligand stimulated Hh pathway activity, was detected in small-cell lung cancer (SCLQ cells, and determined to be associated with growth and proliferation of the cancer cells. Accordingly, methods are provided for treating SCLC associated with elevated Hh pathway activity by reducing or inhibiting the Hh pathway activity. Also provided are methods of determining the responsiveness of SCLC to treatment with a Hh pathway antagonist.
摘要翻译：在小细胞肺癌（SCLQ细胞）中检测到高刺猬（Hh）通路活性，包括配体刺激的Hh通路活性，并确定与癌细胞的生长和增殖相关，因此提供了用于治疗SCLC相关的方法通过降低或抑制Hh通路活性，具有升高的Hh通路活性。还提供了确定SCLC对用Hh途径拮抗剂治疗的反应性的方法。

10. 发明申请

WO2003076593A2 GENOMIC SCREEN FOR EPIGENETICALLY SILENCED GENES ASSOCIATED WITH CANCER 审中-公开
标题翻译：用于与癌症相关的特异性沉默基因的基因组筛选
公开(公告)号：WO2003076593A2
公开(公告)日：2003-09-18
申请号：PCT/US2003/007244
申请日：2003-03-07
申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE , BAYLIN, Stephen, B. , HERMAN, James, G. , SUZUKI, Hiromu
发明人： BAYLIN, Stephen, B. , HERMAN, James, G. , SUZUKI, Hiromu
IPC分类号： C12N
CPC分类号： C12Q1/6886 , C12Q1/6809 , C12Q2600/154 , C12Q2537/164
摘要： A method of identifying epigenetically silenced genes, e.g., methylation silenced genes,in cancer cells is provided. In addition, methods of identifying a cancer by detecting epigenetic silencing of gene expression are provided, as are methods of treating a subject having such a cancer, for example, a colorectal cancer and/or gastric cancer. Reagents for practicing such methods also are provided.
摘要翻译：提供了一种在癌细胞中鉴定表观基因沉默基因，例如甲基化沉默基因的方法。此外，提供了通过检测基因表达的表观遗传学沉默来鉴定癌症的方法，以及治疗患有这种癌症的受试者例如结肠直肠癌和/或胃癌的方法。也提供了实施这种方法的试剂。

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