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1. 发明申请

US20060058258A1 Gene transcription and ionizing radiation: methods and compositions 审中-公开
公开(公告)号：US20060058258A1
公开(公告)日：2006-03-16
申请号：US11257553
申请日：2005-10-25
申请人： Ralph Weichselbaum , Dennis Hallahan , Vikas Sukhatme , Donald Kufe
发明人： Ralph Weichselbaum , Dennis Hallahan , Vikas Sukhatme , Donald Kufe
IPC分类号： A61K48/00 , C07H21/04
CPC分类号： A61K41/0023 , A61K38/00 , A61K48/00 , C07K14/52 , C07K14/525 , C07K14/82 , C07K2319/00 , C07K2319/61 , C07K2319/71 , C07K2319/81 , C12N15/63 , C12N15/635 , C12N15/67 , C12N15/85 , C12N2830/001 , C12N2830/002 , C12N2830/008 , C12N2830/85 , G03G15/2025 , G03G2215/2083
摘要： The present invention provides a DNA molecule comprising a radiation responsive enhancer-promoter operatively linked to an encoding region that encodes at least one polypeptide. An encoding region can comprise a single encoding sequence for a polypeptide or two or more encoding sequences encoding DNA binding, activation or repression domains of a transcription factor. Processes for regulating polypeptide expression and inhibiting tumor growth using such DNA molecules are also provided.

2. 发明申请

US20080118471A1 CONSTITUTIVE GENE EXPRESSION IN CONJUNCTION WITH IONIZING RADIATION 有权
标题翻译：与辐射相关的组成型基因表达
公开(公告)号：US20080118471A1
公开(公告)日：2008-05-22
申请号：US12019428
申请日：2008-01-24
申请人： Ralph Weichselbaum , Dennis Hallahan , Donald Kufe , Vikas Sukhatme
发明人： Ralph Weichselbaum , Dennis Hallahan , Donald Kufe , Vikas Sukhatme
IPC分类号： A61K48/00
CPC分类号： A61K48/005 , C12N2799/022
摘要： The present disclosure demonstrates the successful use of constitutive promoters operatively linked to genes encoding radiosensitizing or radioprotecting factors, administered to cells, tissues, or patients in conjunction with radiation exposure. Also disclosed are pharmacological preparations to be used to increase the levels of radiosensitizing compounds such as TNF-α, or radioprotective compounds such as MnSOD, in specified tissues or tumors of a subject.
摘要翻译：本公开内容显示了与辐射照射联合施用于细胞，组织或患者的与编码放射增敏剂或放射防护因子的基因有效连接的组成型启动子的成功应用。还公开了用于在受试者的特定组织或肿瘤中增加放射增敏化合物如TNF-α或放射防护化合物如MnSOD的药理学制剂。

3. 发明申请

US20050147591A1 Methods and compositions for viral enhancement of cell killing 审中-公开
标题翻译：病毒增强细胞杀伤的方法和组合物
公开(公告)号：US20050147591A1
公开(公告)日：2005-07-07
申请号：US10946365
申请日：2004-09-21
申请人： Dennis Hallahan , Ralph Weichselbaum , Donald Kufe , Gregory Sibley , Bernard Roizman
发明人： Dennis Hallahan , Ralph Weichselbaum , Donald Kufe , Gregory Sibley , Bernard Roizman
IPC分类号： A61K51/00 , A61K31/00 , A61K31/40 , A61K31/70 , A61K35/761 , A61K35/763 , A61K45/00 , A61K48/00 , A61N5/10 , A61P35/00 , C12Q1/70 , C12N15/869
CPC分类号： A61K48/00 , A61K35/761 , A61K35/763 , A61K38/191 , A61K45/06 , A61N2005/1098 , C12N2710/10032 , C12N2710/10332 , A61K2300/00
摘要： The present invention is directed to novel methods of enhancing the effectiveness of DNA damaging agents by exposing cells to viruses prior to or during exposure to the damaging agent. In certain embodiments of the invention, the DNA damaging agent is ionizing radiation, the virus is an adenovirus, and the increase in cell killing is synergistic when compared to radiation alone.
摘要翻译：本发明涉及通过在暴露于损伤剂之前或期间将细胞暴露于病毒来增强DNA损伤剂的有效性的新方法。在本发明的某些实施方案中，DNA损伤剂是电离辐射，病毒是腺病毒，与单独的辐射相比，细胞杀伤的增加是协同的。

4. 发明申请

US20080014175A1 Methods and Compositions for Viral Enhancement of Cell Killing 审中-公开
标题翻译：病毒增强细胞杀伤的方法和组合
公开(公告)号：US20080014175A1
公开(公告)日：2008-01-17
申请号：US11863173
申请日：2007-09-27
申请人： Dennis Hallahan , Ralph Weichselbaum , Donald Kufe , Gregory Sibley , Bernard Roizman
发明人： Dennis Hallahan , Ralph Weichselbaum , Donald Kufe , Gregory Sibley , Bernard Roizman
IPC分类号： A61K48/00 , A61N5/00 , A61K31/407
CPC分类号： A61K48/00 , A61K35/761 , A61K35/763 , A61K38/191 , A61K45/06 , A61N2005/1098 , C12N2710/10032 , C12N2710/10332 , A61K2300/00
摘要： The present invention is directed to novel methods of enhancing the effectiveness of DNA damaging agents by exposing cells to viruses prior to or during exposure to the damaging agent. In certain embodiments of the invention, the DNA damaging agent is ionizing radiation, the virus is an adenovirus, and the increase in cell killing is synergistic when compared to radiation alone.
摘要翻译：本发明涉及通过在暴露于损伤剂之前或期间将细胞暴露于病毒来增强DNA损伤剂的有效性的新方法。在本发明的某些实施方案中，DNA损伤剂是电离辐射，病毒是腺病毒，与单独的辐射相比，细胞杀伤的增加是协同的。

5. 发明申请

US20070212298A1 USE OF THE COMBINATION COMPRISING TEMOZOLOMIDE AND TNF-ALPHA FOR TREATING GLIOBLASTOMA 审中-公开
标题翻译：包含TEMOZOLOMIDE和TNF-ALPHA联合治疗GLIOBLASTOMA的应用
公开(公告)号：US20070212298A1
公开(公告)日：2007-09-13
申请号：US11574108
申请日：2005-08-25
申请人： Ralph Weichselbaum , Donald Kufe
发明人： Ralph Weichselbaum , Donald Kufe
IPC分类号： A61K38/19 , A61K51/00 , C07K14/52 , C12N5/08
CPC分类号： A01K67/0271 , A01K2227/105 , A01K2267/0331 , A61K31/41 , A61K38/191 , A61K41/0038 , A61K2300/00
摘要： Disclosed are methods of synergistically inhibiting growth of a glioma cell comprising contacting the cell with temozolomide and TNFα, or with temozolomide, TNFα, and radiation. Also disclosed are methods of synergistically inhibiting growth of a glioma in a human cancer patient comprising administering temozolomide and TNFα, or with temozolomide, TNFα, and radiation. Pharmaceutical combinations and therapeutic combinations suitable for use in the methods of the invention are also disclosed.
摘要翻译：公开了协同抑制神经胶质瘤细胞生长的方法，包括使细胞与替莫唑胺和TNFα或与替莫唑胺，TNFα和辐射接触。还公开了协同抑制人类癌症患者中神经胶质瘤生长的方法，包括给予替莫唑胺和TNFα，或与替莫唑胺，TNFα和辐射。还公开了适用于本发明方法的药物组合和治疗组合。

6. 发明申请

US20070105772A1 Induction of Apoptosis by Cellular Stress 失效
标题翻译：诱导细胞凋亡的细胞应激
公开(公告)号：US20070105772A1
公开(公告)日：2007-05-10
申请号：US11538186
申请日：2006-10-03
申请人： Donald Kufe , Rima Kaddurah-Daouk , Ralph Weichselbaum
发明人： Donald Kufe , Rima Kaddurah-Daouk , Ralph Weichselbaum
IPC分类号： A61K38/55 , C12Q1/30
CPC分类号： G01N33/5011 , C12Q1/30 , G01N33/5079 , G01N2510/00
摘要： The invention provides methods of screening to identify compounds that modulate the ability of a protein to translocate to the mitochondria when a cell is subjected to cellular stress. Such compounds can be useful to modulate the level of apoptosis in a cell. For example, compounds identified according to the methods described herein can be used to treat disorders characterized by excessive apoptosis, e.g., a neurological disorder, or insufficient apoptosis, e.g., cancer.
摘要翻译：本发明提供筛选方法，以鉴定当细胞经受细胞应激时调节蛋白质转移至线粒体的能力的化合物。这样的化合物可用于调节细胞凋亡的水平。例如，根据本文描述的方法鉴定的化合物可用于治疗以过度凋亡为特征的疾病，例如神经障碍或细胞凋亡不足，例如癌症。

7. 发明申请

US20070036748A1 COMBINATION THERAPIES FOR CANCER 有权
标题翻译：癌症联合治疗
公开(公告)号：US20070036748A1
公开(公告)日：2007-02-15
申请号：US11467799
申请日：2006-08-28
申请人： Ralph Weichselbaum , Donald Kufe , Mitchell Posner , Helena Mauceri , James Park
发明人： Ralph Weichselbaum , Donald Kufe , Mitchell Posner , Helena Mauceri , James Park
IPC分类号： A61K48/00 , A61K38/19 , A61K31/7072 , A61K31/704 , A61K31/66 , A61K33/24
CPC分类号： A61K45/06 , A61K31/66 , A61K31/704 , A61K31/7072 , A61K33/24 , A61K38/191 , A61K2300/00
摘要： The present invention relates to methods of inducing expression of a polynucleotide encoding a therapeutic polypeptide, e.g., TNF-α, in a cell comprising contacting the cell with a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding the polypeptide, and at least one chemotherapeutic agent, wherein the chemotherapeutic agent induces expression of the polypeptide. The invention also relates to methods of inhibiting a neoplastic cell, comprising contacting the cell with a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding TNF-α and a chemotherapeutic agent. The present invention further relates to methods of inhibiting or reducing the growth of a tumor in a subject, comprising co-administering to the subject a construct comprising an Egr-1 promoter operably linked to a polynucleotide encoding TNF-α and a chemotherapeutic agent, wherein the co-administration inhibits or reduces the ability of the tumor to grow.
摘要翻译：本发明涉及在细胞中诱导编码治疗性多肽例如TNF-α的多核苷酸的表达的方法，包括使细胞与包含与编码多肽的多核苷酸可操作地连接的Egr-1启动子的构建体接触，至少一种化学治疗剂，其中所述化学治疗剂诱导所述多肽的表达。本发明还涉及抑制肿瘤细胞的方法，包括使细胞与包含与编码TNF-α和化学治疗剂的多核苷酸可操作地连接的Egr-1启动子的构建体接触。本发明还涉及抑制或减少受试者中肿瘤生长的方法，包括向受试者共同施用包含与编码TNF-α的多核苷酸和化学治疗剂可操作连接的Egr-1启动子的构建体，其中共同给药抑制或降低肿瘤生长的能力。

8. 发明申请

US20100221228A1 y134.5 Deficient HSV and the MAPK Pathway 审中-公开
标题翻译： y134.5缺血性HSV和MAPK通路
公开(公告)号：US20100221228A1
公开(公告)日：2010-09-02
申请号：US12161763
申请日：2007-01-24
申请人： Kerrington D. Smith , James J. Mezhir , Ralph Weichselbaum , Bernard Roizman
发明人： Kerrington D. Smith , James J. Mezhir , Ralph Weichselbaum , Bernard Roizman
IPC分类号： A61K35/76 , A61P35/00 , C12N7/00
CPC分类号： C12N9/1205 , A61K35/763 , A61K38/00 , C07K2319/43 , C12N15/86 , C12N2710/16632 , C12N2710/16643 , A61K2300/00
摘要： The invention provides materials and methods for the identification of cells exhibiting a cell proliferative disorder that are amenable to treatment with a herpes simplex virus that does not express an approximately wild-type level of ICP34.5. Also provided are methods of treating cell proliferative diseases, disorders or conditions, such as cancers, rheumatoid arthritis and macular degeneration, using these HSVs. Further provided are methods for preventing such cell proliferative disorders by administering the HSVs as well as methods for ameliorating a symptom associated with a cell proliferative disorder by administering such HSVs.
摘要翻译：本发明提供用于鉴定表现出细胞增殖性病症的细胞的材料和方法，其适于用不表达近似野生型水平的ICP34.5的单纯疱疹病毒处理。还提供了使用这些HSV来治疗细胞增殖性疾病，病症或病症如癌症，类风湿性关节炎和黄斑变性的方法。还提供了通过施用HSV来预防这种细胞增殖性疾病的方法以及通过施用这种HSV来改善与细胞增殖性病症相关的症状的方法。

9. 发明申请

US20070281040A1 COMBINATION THERAPY OF HEDGEHOG INHIBITORS, RADIATION AND CHEMOTHERAPEUTIC AGENTS 审中-公开
标题翻译： HEDGEHOG抑制剂，辐射和化学治疗剂的联合治疗
公开(公告)号：US20070281040A1
公开(公告)日：2007-12-06
申请号：US11576310
申请日：2005-09-30
申请人： Ralph Weichselbaum , Zahra Shafaee , Wei Du
发明人： Ralph Weichselbaum , Zahra Shafaee , Wei Du
IPC分类号： A61K31/4355 , A61K31/337 , A61K31/56 , A61K31/70 , A61K33/24 , A61N5/10 , A61P35/00
CPC分类号： A61K31/56 , A61K31/337 , A61K31/4355 , A61K31/7068 , A61K33/24 , A61K45/06 , A61K2300/00
摘要： The present invention relates to therapeutic combinations and methods of inhibiting the proliferation of cancerous cells, the abnormal growth of cells, and tumor cell growth using the combination of a hedgehog inhibitor with chemotherapy and/or radiation therapy. The present invention also relates to methods of enhancing the antiproliferative effect of chemotherapy and/or radiation therapy in a mammalian cancer patient undergoing either chemotherapy or radiation or a combination of radiation and chemotherapy by co-administering a therapeutically amount of a hedgehog inhibitor, concurrently or sequentially, with the chemotherapy and/or radiation therapy.
摘要翻译：本发明涉及使用刺猬蛋白抑制剂与化疗和/或放射治疗的组合来抑制癌细胞增殖，细胞异常生长和肿瘤细胞生长的治疗组合和方法。本发明还涉及通过共同施用治疗量的刺猬蛋白抑制剂同时或同时施用化学疗法和/或放射治疗在化疗或放射的哺乳动物癌症患者或辐射和化学疗法的组合中增强抗增殖作用的方法依次进行化疗和/或放射治疗。

10. 发明申请

US20060113482A1 Image-guided medical intervention apparatus and method 有权
标题翻译：图像引导医疗介入装置及方法
公开(公告)号：US20060113482A1
公开(公告)日：2006-06-01
申请号：US10998509
申请日：2004-11-29
申请人： Charles Pelizzari , Chin-Tu Chen , Ralph Weichselbaum , Samuel Hellman
发明人： Charles Pelizzari , Chin-Tu Chen , Ralph Weichselbaum , Samuel Hellman
IPC分类号： G01T1/24
CPC分类号： G01T1/1641 , A61N5/1049 , A61N5/1065 , A61N2005/1052 , A61N2005/1061 , G01T1/166
摘要： In some embodiments, an image-guided radiotherapy apparatus and method is provided in which a radiotherapy radiation source and a gamma ray photon imaging device are positioned with respect to a patient area so that a patient can be treated by a beam emitted from the radiotherapy apparatus and can have images taken by the gamma ray photon imaging device. Radiotherapy treatment and imaging can be performed substantially simultaneously and/or can be performed without moving the patient in some embodiments. The gamma ray photon imaging device can be coupled and movable with respect to any part of a building structure, can be located on a portable frame movable to and from the radiotherapy radiation source and patient, or can take other forms. In some embodiments, the gamma ray photon imaging device can be used for imaging in connection with other types of medical interventions.
摘要翻译：在一些实施例中，提供了一种图像引导放射治疗装置和方法，其中放射治疗辐射源和伽马射线光子成像装置相对于患者区域定位，使得可以通过从放射治疗装置发射的束来对患者进行治疗并且可以具有由伽马射线光子成像装置拍摄的图像。在一些实施例中，放射治疗和成像可以基本上同时进行和/或执行而不移动患者。伽马射线光子成像装置可以相对于建筑结构的任何部分联接和移动，可以位于可移动到放射治疗辐射源和患者的便携式框架上，或者可以采取其他形式。在一些实施例中，伽马射线光子成像装置可用于与其他类型的医疗干预相结合的成像。

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