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1. 发明申请

US20080107637A1 Use of an agent that restores tissue perfusion and oxygenation 有权
公开(公告)号：US20080107637A1
公开(公告)日：2008-05-08
申请号：US12006842
申请日：2008-01-07
申请人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
发明人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
IPC分类号： A61K35/18 , A61K38/16 , A61K33/00 , A61P43/00 , A61K31/04
CPC分类号： A61K38/1709 , A61K31/21 , A61K33/00 , A61K35/18 , A61K38/00 , A61K38/42 , A61K45/06 , A61K47/08 , A61K47/16 , A61K47/6445 , A61K2300/00
摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.

2. 发明申请

US20080113901A1 Use of an agent that restores tissue perfusion and oxygenation 有权
标题翻译：使用恢复组织灌注和氧合的药物
公开(公告)号：US20080113901A1
公开(公告)日：2008-05-15
申请号：US12006849
申请日：2008-01-07
申请人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
发明人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
IPC分类号： A61K38/42 , A61P35/00
CPC分类号： A61K38/1709 , A61K31/21 , A61K33/00 , A61K35/18 , A61K38/00 , A61K38/42 , A61K45/06 , A61K47/08 , A61K47/16 , A61K47/6445 , A61K2300/00
摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.
摘要翻译：目前公开的主题提供了在受试者的组织的缺氧区域中增加灌注的方法。还提供了用于治疗受试者与缺氧相关的疾病和/或病症的方法，用于增加肿瘤对放射和/或化疗治疗的敏感性的方法，用于延迟受试者的肿瘤生长的方法，以及用于抑制受试者的肿瘤血管生长的方法。在一些实施方案中，本发明公开的方法包括向有需要的受试者施用选自亚硝基化血红蛋白和诱导受试者内源性血红蛋白亚硝基化的试剂的第一组合物和包含高氧气体的第二组合物。在一些实施方案中，本发明公开的方法还包括用放射治疗，化疗，光动力疗法，免疫治疗或其组合治疗肿瘤。还提供了可在本公开的方法中使用的可吸入气体。

3. 发明申请

US20060276374A1 Use of an agent that restores tissue perfusion and oxygenation 有权
公开(公告)号：US20060276374A1
公开(公告)日：2006-12-07
申请号：US11404494
申请日：2006-04-13
申请人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
发明人： Mark Dewhirst , Jonathan Stamler , Timothy McMahon , Pierre Sonveaux
IPC分类号： A61K38/42 , A61K31/21
CPC分类号： A61K38/1709 , A61K31/21 , A61K33/00 , A61K35/18 , A61K38/00 , A61K38/42 , A61K45/06 , A61K47/08 , A61K47/16 , A61K47/6445 , A61K2300/00
摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.

4. 发明申请

US20070297984A1 Inhibition of HIF-1 activation for anti-tumor and anti-inflammatory responses 有权
标题翻译：抑制HIF-1激活抗肿瘤和抗炎反应
公开(公告)号：US20070297984A1
公开(公告)日：2007-12-27
申请号：US11731719
申请日：2007-03-30
申请人： Chuan-Yuan Li , Fang Li , Pierre Sonveaux , Mark Dewhirst
发明人： Chuan-Yuan Li , Fang Li , Pierre Sonveaux , Mark Dewhirst
IPC分类号： A61K38/43 , A61K49/00 , A61P43/00 , C12N15/11 , C12N5/06 , C12Q1/68
CPC分类号： A61K41/0038 , A61K45/06 , A61K2300/00
摘要： The presently disclosed subject matter generally relates to methods and compositions for inhibiting the expression and/or activation of hypoxia-inducible factor 1 (HIF-1) genes in a hypoxic cell. More particularly, the methods disclosed herein relate to inhibition of HIF-1 activation in a cell, increasing sensitivity of a tumor cell to radiation and/or chemotherapy, delaying tumor growth, inhibiting tumor blood vessel growth, inhibiting inflammatory responses in a cell through the use of compositions that prevent the nitrosylation of HIF-1, and methods for screening for new inhibitors of HIF-1 activiation. Additionally, the compositions disclosed herein relate to compositions that can be employed in, and are identified by, the disclosed methods.
摘要翻译：目前公开的主题通常涉及用于在缺氧细胞中抑制缺氧诱导因子1（HIF-1）基因的表达和/或活化的方法和组合物。更具体地说，本文公开的方法涉及细胞中HIF-1活化的抑制，增加肿瘤细胞对放射和/或化学疗法的敏感性，延缓肿瘤生长，抑制肿瘤血管生长，抑制细胞中炎性反应使用防止HIF-1的亚硝基化的组合物，以及用于筛选新的HIF-1激活抑制剂的方法。另外，本文公开的组合物涉及可以用于所公开的方法并由所公开的方法鉴定的组合物。

5. 发明授权

US08466110B2 Use of an agent that restores tissue perfusion and oxygenation 有权
公开(公告)号：US08466110B2
公开(公告)日：2013-06-18
申请号：US13449932
申请日：2012-04-18
申请人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
发明人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
IPC分类号： A61K38/00
CPC分类号： A61K38/1709 , A61K31/21 , A61K33/00 , A61K35/18 , A61K38/00 , A61K38/42 , A61K45/06 , A61K47/08 , A61K47/16 , A61K47/6445 , A61K2300/00
摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.

6. 发明授权

US07790204B2 Use of an agent that restores tissue perfusion and oxygenation 有权
标题翻译：使用恢复组织灌注和氧合的药物
公开(公告)号：US07790204B2
公开(公告)日：2010-09-07
申请号：US12006842
申请日：2008-01-07
申请人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
发明人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
IPC分类号： A61K9/00 , A61K38/00
CPC分类号： A61K38/1709 , A61K31/21 , A61K33/00 , A61K35/18 , A61K38/00 , A61K38/42 , A61K45/06 , A61K47/08 , A61K47/16 , A61K47/6445 , A61K2300/00
摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.
摘要翻译：目前公开的主题提供了在受试者的组织的缺氧区域中增加灌注的方法。还提供了用于治疗受试者与缺氧相关的疾病和/或病症的方法，用于增加肿瘤对放射和/或化疗治疗的敏感性的方法，用于延迟受试者的肿瘤生长的方法，以及用于抑制受试者的肿瘤血管生长的方法。在一些实施方案中，本发明公开的方法包括向有需要的受试者施用选自亚硝基化血红蛋白和诱导受试者内源性血红蛋白亚硝基化的试剂的第一组合物和包含高氧气体的第二组合物。在一些实施方案中，本发明公开的方法还包括用放射治疗，化疗，光动力疗法，免疫治疗或其组合治疗肿瘤。还提供了可在本公开的方法中使用的可吸入气体。

7. 发明申请

US20120225133A1 USE OF AN AGENT THAT RESTORES TISSUE PERFUSION AND OXYGENATION 有权
标题翻译：使用恢复组织灌注和氧化的药剂
公开(公告)号：US20120225133A1
公开(公告)日：2012-09-06
申请号：US13449932
申请日：2012-04-18
申请人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
发明人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
IPC分类号： A61K33/00 , A61P3/10 , A61P9/10 , A61P29/00 , A61P25/00 , A61P35/00 , A61P1/16
CPC分类号： A61K38/1709 , A61K31/21 , A61K33/00 , A61K35/18 , A61K38/00 , A61K38/42 , A61K45/06 , A61K47/08 , A61K47/16 , A61K47/6445 , A61K2300/00
摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.
摘要翻译：目前公开的主题提供了在受试者的组织的缺氧区域中增加灌注的方法。还提供了用于治疗受试者与缺氧相关的疾病和/或病症的方法，用于增加肿瘤对放射和/或化疗治疗的敏感性的方法，用于延迟受试者的肿瘤生长的方法，以及用于抑制受试者的肿瘤血管生长的方法。在一些实施方案中，本发明公开的方法包括向有需要的受试者施用选自亚硝基化血红蛋白和诱导受试者内源性血红蛋白亚硝基化的试剂的第一组合物和包含高氧气体的第二组合物。在一些实施方案中，本发明公开的方法还包括用放射治疗，化疗，光动力疗法，免疫治疗或其组合治疗肿瘤。还提供了可在本公开的方法中使用的可吸入气体。

8. 发明授权

US08198241B2 Use of an agent that restores tissue perfusion and oxygenation 有权
标题翻译：使用恢复组织灌注和氧合的药物
公开(公告)号：US08198241B2
公开(公告)日：2012-06-12
申请号：US12847330
申请日：2010-07-30
申请人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
发明人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
IPC分类号： A61K38/00 , A61K33/00
CPC分类号： A61K38/1709 , A61K31/21 , A61K33/00 , A61K35/18 , A61K38/00 , A61K38/42 , A61K45/06 , A61K47/08 , A61K47/16 , A61K47/6445 , A61K2300/00
摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.
摘要翻译：目前公开的主题提供了在受试者的组织的缺氧区域中增加灌注的方法。还提供了用于治疗受试者与缺氧相关的疾病和/或病症的方法，用于增加肿瘤对放射和/或化疗治疗的敏感性的方法，用于延迟受试者的肿瘤生长的方法，以及用于抑制受试者的肿瘤血管生长的方法。在一些实施方案中，本发明公开的方法包括向有需要的受试者施用选自亚硝基化血红蛋白和诱导受试者内源性血红蛋白亚硝基化的试剂的第一组合物和包含高氧气体的第二组合物。在一些实施方案中，本发明公开的方法还包括用放射治疗，化疗，光动力疗法，免疫治疗或其组合治疗肿瘤。还提供了可在本公开的方法中使用的可吸入气体。

9. 发明授权

US07338670B2 Use of an agent that restores tissue perfusion and oxygenation 有权
公开(公告)号：US07338670B2
公开(公告)日：2008-03-04
申请号：US11404494
申请日：2006-04-13
申请人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
发明人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre Sonveaux
IPC分类号： A61K9/00 , A61K38/00 , C06D3/00
CPC分类号： A61K38/1709 , A61K31/21 , A61K33/00 , A61K35/18 , A61K38/00 , A61K38/42 , A61K45/06 , A61K47/08 , A61K47/16 , A61K47/6445 , A61K2300/00
摘要： The presently disclosed subject matter provides methods for increasing perfusion in hypoxic regions of tissues in subjects. Also provided are methods for treating diseases and/or disorders associated with hypoxia in subjects, methods for increasing sensitivity of tumors to radiation and/or chemotherapy treatments, methods for delaying tumor growth in subjects, and methods for inhibiting tumor blood vessel growth in subjects. In some embodiments, the presently disclosed methods involve administering to subjects in need thereof a first composition selected from the group consisting of a nitrosylated hemoglobin and an agent that induces nitrosylation of endogenous hemoglobin in the subject and a second composition comprising a hyperoxic gas. In some embodiments, the presently disclosed methods also include treating a tumor with radiation therapy, chemotherapy, photodynamic therapy, immunotherapy, or combinations thereof. Also provided are inhalable gases that can be employed in the presently disclosed methods.

10. 发明授权

US08968702B2 Inhibition of HIF-1 activation for anti-tumor and anti-inflammatory responses 有权
标题翻译：抑制HIF-1激活抗肿瘤和抗炎反应
公开(公告)号：US08968702B2
公开(公告)日：2015-03-03
申请号：US11731719
申请日：2007-03-30
申请人： Chuan-Yuan Li , Fang Li , Pierre Sonveaux , Mark W. Dewhirst
发明人： Chuan-Yuan Li , Fang Li , Pierre Sonveaux , Mark W. Dewhirst
IPC分类号： A61K49/00 , C12N5/00 , C12N5/02 , A61K41/00 , A61K45/06
CPC分类号： A61K41/0038 , A61K45/06 , A61K2300/00
摘要： The presently disclosed subject matter generally relates to methods and compositions for inhibiting the expression and/or activation of hypoxia-inducible factor 1 (HIF-1) genes in a hypoxic cell. More particularly, the methods disclosed herein relate to inhibition of HIF-1 activation in a cell, increasing sensitivity of a tumor cell to radiation and/or chemotherapy, delaying tumor growth, inhibiting tumor blood vessel growth, inhibiting inflammatory responses in a cell through the use of compositions that prevent the nitrosylation of HIF-1, and methods for screening for new inhibitors of HIF-1 activiation. Additionally, the compositions disclosed herein relate to compositions that can be employed in, and are identified by, the disclosed methods.
摘要翻译：目前公开的主题通常涉及用于在缺氧细胞中抑制缺氧诱导因子1（HIF-1）基因的表达和/或活化的方法和组合物。更具体地说，本文公开的方法涉及细胞中HIF-1活化的抑制，增加肿瘤细胞对放射和/或化学疗法的敏感性，延缓肿瘤生长，抑制肿瘤血管生长，抑制细胞中炎性反应使用防止HIF-1的亚硝基化的组合物，以及用于筛选新的HIF-1激活抑制剂的方法。另外，本文公开的组合物涉及可以用于所公开的方法并由所公开的方法鉴定的组合物。

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