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1. 发明授权

US09907976B2 Phosphors and scintillators for light stimulation within a medium 有权
公开(公告)号：US09907976B2
公开(公告)日：2018-03-06
申请号：US14131564
申请日：2012-07-09
申请人： Frederic A. Bourke, Jr. , Harold Walder , Zakaryae Fathi , Michael J. Therien , Mark W. Dewhirst , Ian N. Stanton , Jennifer Ann Ayres , Diane Renee Fels , Joseph A. Herbert
发明人： Frederic A. Bourke, Jr. , Harold Walder , Zakaryae Fathi , Michael J. Therien , Mark W. Dewhirst , Ian N. Stanton , Jennifer Ann Ayres , Diane Renee Fels , Joseph A. Herbert
IPC分类号： A61N5/06 , C08F2/52 , C08J3/28 , A61K41/00 , A61N5/10
CPC分类号： A61N5/062 , A61K41/0085 , A61N5/0622 , A61N5/1077 , A61N2005/0661 , A61N2005/1091 , A61N2005/1098
摘要： A system and method for light stimulation within a medium. The system has a reduced-voltage x-ray source configured to generate x-rays from a peak applied cathode voltage at or below 105 kVp, and a plurality of energy-emitting particles in the medium which, upon radiation from the x-ray source, radiate at a first lower energy than the x-ray source to interact with at least one photoactivatable agent in the medium. The method introduces the plurality of energy-emitting particles into the medium, radiates the energy-emitting particles in the medium with x-rays generated from a peak applied cathode voltage at or below 105 kVp; and emits a lower energy than the x-ray source to interact with the medium or with at least one photoactivatable agent in the medium.

2. 发明申请

US20140323946A1 PHOSPHORS AND SCINTILLATORS FOR LIGHT STIMULATION WITHIN A MEDIUM 有权
标题翻译：用于中等光刺激的磷光体和扫描仪
公开(公告)号：US20140323946A1
公开(公告)日：2014-10-30
申请号：US14131564
申请日：2012-07-09
申请人： Frederic A. Bourke, JR. , Harold Walder , Zakaryae Fathi , Michael J. Therien , Mark W. Dewhirst , Ian N. Stanton , Jennifer Ann Ayres , Diane Renee Fels , Joseph A. Herbert
发明人： Frederic A. Bourke, JR. , Harold Walder , Zakaryae Fathi , Michael J. Therien , Mark W. Dewhirst , Ian N. Stanton , Jennifer Ann Ayres , Diane Renee Fels , Joseph A. Herbert
IPC分类号： A61N5/06 , A61N5/10
CPC分类号： A61N5/062 , A61K41/0085 , A61N5/0622 , A61N5/1077 , A61N2005/0661 , A61N2005/1091 , A61N2005/1098
摘要： A system and method for light stimulation within a medium. The system has a reduced-voltage x-ray source configured to generate x-rays from a peak applied cathode voltage at or below 105 kVp, and a plurality of energy-emitting particles in the medium which, upon radiation from the x-ray source, radiate at a first lower energy than the x-ray source to interact with at least one photoactivatable agent in the medium. The method introduces the plurality of energy-emitting particles into the medium, radiates the energy-emitting particles in the medium with x-rays generated from a peak applied cathode voltage at or below 105 kVp; and emits a lower energy than the x-ray source to interact with the medium or with at least one photoactivatable agent in the medium.
摘要翻译：介质内光刺激的系统和方法。该系统具有被配置为从等于或低于105kVp的施加阴极施加电压产生X射线的低电压x射线源，以及介质中的多个能量发射粒子，其在来自X射线源的辐射以比x射线源低的能量辐射以与介质中的至少一种可光活化剂相互作用。该方法将多个能量发射粒子引入到介质中，用等于或低于105kVp的施加阴极电压产生的x射线照射介质中的能量发射粒子; 并且发射比x射线源更低的能量以与介质或介质中的至少一种可光活化剂相互作用。

3. 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.

4. 发明申请

US20130023587A1 COMPOSITIONS AND METHODS FOR THE TREATMENT OF CANCER 审中-公开
标题翻译：用于治疗癌症的组合物和方法
公开(公告)号：US20130023587A1
公开(公告)日：2013-01-24
申请号：US13638858
申请日：2011-04-01
申请人： Thies Schroeder , Mark W. Dewhirst
发明人： Thies Schroeder , Mark W. Dewhirst
IPC分类号： C12N5/09 , A61P35/00 , A61K31/277
CPC分类号： A61K31/5415 , A61K31/135 , A61K31/137 , A61K31/195 , A61K31/198 , A61K31/402 , A61K31/42 , A61K31/4706 , A61K31/53 , A61K31/55 , A61K45/06
摘要： Provided are methods for inhibiting survival of a proliferating, quiescent, or hypoxic cancer cell that include administering a compound that inhibits lactate clearance (e.g., lactate catabolism, lactate transport, glutamate release, and/or alanine release) in the proliferating, quiescent, or hypoxic cancer cell. Further provided are methods of reducing the proliferation of a neoplastic cell having increased lactate or decreased glucose concentrations relative to a normal cell. Also provided are methods of treating a subject having cancer, wherein the methods may include administering to the subject an inhibitor of lactate clearance.
摘要翻译：提供了抑制增殖，静止或缺氧癌细胞存活的方法，其包括在增殖，静止或静止期中施用抑制乳酸盐清除的化合物（例如乳酸分解代谢，乳酸转运，谷氨酸释放和/或丙氨酸释放）缺氧癌细胞。进一步提供的是相对于正常细胞减少具有增加的乳酸盐或降低葡萄糖浓度的肿瘤细胞的增殖的方法。还提供了治疗患有癌症的受试者的方法，其中所述方法可以包括向受试者施用乳酸盐清除抑制剂。

5. 发明授权

US06472390B1 Use of therapeutic dosages for nitric oxide donors which do not significantly lower blood pressure or pulmonary artery pressure 有权
标题翻译：使用不显着降低血压或肺动脉压力的一氧化氮供体的治疗剂量
公开(公告)号：US06472390B1
公开(公告)日：2002-10-29
申请号：US09986807
申请日：2001-11-13
申请人： Jonathan S. Stamler , Claude A. Piantadosi , Mark W. Dewhirst
发明人： Jonathan S. Stamler , Claude A. Piantadosi , Mark W. Dewhirst
IPC分类号： A61K31535
CPC分类号： A61K31/21 , A61K31/223 , A61K31/5377
摘要： Patients with pathologic conditions involving constriction or proliferation of smooth muscle or disease associated with cysteine containing proteins, or who are at risk for such, are administered a therapeutically effective amount of a nitric oxide (NO) donor which is insufficient to acutely lower mean arterial blood pressure or pulmonary artery pressure by more than 10%. In one subgenus, NO donor is administered to modify red blood cell membrane receptors to prevent red blood cells from causing vasoconstriction. A related method which allows increased dosage of NO donor without acutely lowering mean arterial blood pressure comprises administering the NO donor into an artery of the patient. In another method, patients having a cardiovascular syndrome, or who are at risk for such, are administered a therapeutically effective amount of thiol which does not acutely affect blood pressure to a significant degree.
摘要翻译：患有与包含半胱氨酸的蛋白质相关的平滑肌或疾病的病变状况或患有这种风险的患者的患者被给予治疗有效量的一氧化氮（NO）供体，其不足以急性降低平均动脉血压力或肺动脉压力超过10％。在一个亚属中，施用NO供体以修饰红细胞膜受体以防止红细胞引起血管收缩。允许NO供体的增加剂量而不急性降低平均动脉血压的相关方法包括将NO供体施用到患者的动脉中。在另一种方法中，具有心血管综合征或有风险的患者给予治疗有效量的硫酸盐，所述硫醇在很大程度上不会急剧影响血压。

6. 发明授权

US6020308A Methods for improving therapeutic effectiveness of treatment of vascularization disorders 失效
标题翻译：改善血管化障碍治疗效果的方法
公开(公告)号：US6020308A
公开(公告)日：2000-02-01
申请号：US126930
申请日：1998-07-31
申请人： Mark W. Dewhirst , Robert E. Meyer , Joseph Bonaventura , Joseph DeAngelo
发明人： Mark W. Dewhirst , Robert E. Meyer , Joseph Bonaventura , Joseph DeAngelo
IPC分类号： A61N5/02 , A61F7/00 , A61K31/00 , A61K31/195 , A61K31/198 , A61K31/4045 , A61K31/42 , A61K38/16 , A61K38/42 , A61K41/00 , A61K45/06 , A61P35/00 , A61P43/00 , A61K35/14
CPC分类号： A61K41/0052 , A61K31/00 , A61K31/195 , A61K31/198 , A61K31/4045 , A61K38/42 , Y10S514/832 , Y10S514/833 , Y10S514/929 , Y10S514/93
摘要： The present invention is directed to the use of an inhibitor of NO activity, such as a nitric oxide scavenger or an NO synthase inhibitor, as as an adjunct to treatment of inappropriate tissue vascularization disorders.
摘要翻译：本发明涉及NO活性抑制剂如一氧化氮清除剂或NO合成酶抑制剂作为治疗不适当组织血管化病症的辅助剂。

7. 发明申请

US20140249097A1 Inhibition of HIF-1 activation for Anti-Tumor and Anti-Inflammatory responses 审中-公开
标题翻译：抑制HIF-1激活抗肿瘤和抗炎反应
公开(公告)号：US20140249097A1
公开(公告)日：2014-09-04
申请号：US13200819
申请日：2011-09-30
申请人： Mark W. Dewhirst , Yiting Cao
发明人： Mark W. Dewhirst , Yiting Cao
IPC分类号： A61K31/353 , A61K31/155 , A61K31/704
CPC分类号： A61K31/704 , A61K31/4166 , 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 cancer cell, tissue or tumor. More particularly, the methods disclosed herein relate to inhibition of HIF-1 activation in a tumor, 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 activation. Additionally, the compositions disclosed herein relate to compositions that can be employed in, and are identified by, the disclosed methods.
摘要翻译：目前公开的主题一般涉及用于抑制癌细胞，组织或肿瘤中缺氧诱导因子1（HIF-1）基因的表达和/或活化的方法和组合物。更具体地，本文公开的方法涉及抑制肿瘤中的HIF-1活化，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，抑制细胞中的炎性反应使用防止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。

8. 发明申请

US20100298222A1 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：US20100298222A1
公开(公告)日：2010-11-25
申请号：US12847330
申请日：2010-07-30
申请人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre D. Sonveaux
发明人： Mark W. Dewhirst , Jonathan S. Stamler , Timothy J. McMahon , Pierre D. 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。

9. 发明授权

US5554638A Methods for improving therapeutic effectiveness of agents for the treatment of solid tumors and other disorders 失效
标题翻译：提高治疗实体瘤和其他疾病的药物治疗效果的方法
公开(公告)号：US5554638A
公开(公告)日：1996-09-10
申请号：US246882
申请日：1994-05-20
申请人： Mark W. Dewhirst , Robert E. Meyer , Joseph Bonaventura , Joseph DeAngelo
发明人： Mark W. Dewhirst , Robert E. Meyer , Joseph Bonaventura , Joseph DeAngelo
IPC分类号： A61N5/02 , A61F7/00 , A61K31/00 , A61K31/195 , A61K31/198 , A61K31/4045 , A61K31/42 , A61K38/16 , A61K38/42 , A61K41/00 , A61K45/06 , A61P35/00 , A61P43/00 , A61K31/22 , A61K31/415
CPC分类号： A61K41/0052 , A61K31/00 , A61K31/195 , A61K31/198 , A61K31/4045 , A61K38/42 , Y10S514/832 , Y10S514/833 , Y10S514/929 , Y10S514/93
摘要： The present invention is directed to the use of an inhibitor of NO activity, such as a nitric oxide scavenger or an NO synthase inhibitor, as an antitumor therapy to reduce tumor blood flow and oxygenation. The invention is also directed to administration of a nitric oxide scavenger or a nitric oxide synthase inhibitor to enhance the effectiveness of tumor therapy with hypoxic or acidic chemotherapeutic agents or hyperthermia. The invention is also directed to the administration of a nitric oxide synthase substrate to a subject previously administered a nitric oxide synthase inhibitor, in order to selectively inhibit tumor perfusion. In a specific example, administration of cell free hemoglobin, a nitric oxide scavenger, in conjunction with mitomycin C, a hypoxic cytotoxin, results in a significant delay in tumor growth of a human tumor xenograft in a mouse compared to mitomycin C alone. In another example, the administration of an inhibitor of nitric oxide synthase followed by the administration of a substrate of the enzyme causes a specific irreversible reduction of tumor blood flow, while normal blood flow is restored.
摘要翻译：本发明涉及NO活性抑制剂如一氧化氮清除剂或NO合成酶抑制剂作为抗肿瘤疗法以减少肿瘤血流和氧合的用途。本发明还涉及一氧化氮清除剂或一氧化氮合酶抑制剂的施用，以增强用缺氧或酸性化学治疗剂或热疗的肿瘤治疗的有效性。本发明还涉及向先前施用一氧化氮合酶抑制剂的受试者施用一氧化氮合酶底物，以选择性地抑制肿瘤灌注。在具体实例中，与丝裂霉素C单独相比，将无细胞血红蛋白（一氧化氮清除剂）与丝裂霉素C（缺氧细胞毒素）联合导致小鼠中人肿瘤异种移植物的肿瘤生长显着延迟。在另一个实例中，一氧化氮合酶抑制剂的施用随后施用酶底物导致肿瘤血流的特异性不可逆降低，同时正常血流恢复。

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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