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公开(公告)号:US08748445B2
公开(公告)日:2014-06-10
申请号:US11791588
申请日:2005-10-27
申请人: W. Joon Chung , Harald Sontheimer
发明人: W. Joon Chung , Harald Sontheimer
IPC分类号: A01N43/54 , A61K31/505 , A01N43/40 , A61K31/44 , A01N41/10 , A61K31/10 , C07D239/02 , C07D213/72 , C07D211/72 , C07D211/84 , C07C315/00 , C07C317/00
CPC分类号: G01N33/566 , A61K31/00 , A61K31/63
摘要: The present disclosure provides for method of treatment and/or prevention of disease states that require cystine for maintenance or progression of the disease state. In addition, methods for screening and identifying novel therapeutic agents useful in the treatment of such disease states are described. In one embodiment, the disease state is a cancer, such as, but not limited to, glioma. In this embodiment, methods for the treatment and prevention of glioma by inhibiting cystine uptake or decreasing intracellular cystine concentrations are provided. The present disclosure teaches that glioma cells are dependent on system Xc for cystine uptake. Pharmacological inhibition of system Xc causes a rapid depletion of intracellular glutathione, resulting in decreased cell growth. In contrast, non-malignant astrocytes and cortical neurons remain viable in the presence of Xc inhibitors and continue to take up cystine via alternate amino acid transporters.
摘要翻译: 本公开提供了治疗和/或预防需要胱氨酸以维持或发展疾病状态的疾病状态的方法。 此外,描述了筛选和鉴定用于治疗这种疾病状态的新型治疗剂的方法。 在一个实施方案中,疾病状态是癌症,例如但不限于神经胶质瘤。 在该实施方案中,提供了通过抑制胱氨酸摄取或减少细胞内胱氨酸浓度来治疗和预防神经胶质瘤的方法。 本公开内容教导了神经胶质瘤细胞依赖于系统Xc用于胱氨酸摄取。 系统Xc的药理学抑制导致细胞内谷胱甘肽的快速消耗,导致细胞生长减少。 相比之下,非恶性星形胶质细胞和皮层神经元在Xc抑制剂存在下保持存活,并通过替代氨基酸转运体继续摄取胱氨酸。
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公开(公告)号:US20090117031A1
公开(公告)日:2009-05-07
申请号:US11791588
申请日:2005-10-27
申请人: W. Joon Chung , Harald Sontheimer
发明人: W. Joon Chung , Harald Sontheimer
IPC分类号: A61K51/00 , A61K31/198 , A61K31/4402 , G01N33/574 , C12Q1/00 , C12N5/06 , G01N33/68 , G01N33/536 , A61K33/24
CPC分类号: G01N33/566 , A61K31/00 , A61K31/63
摘要: The present disclosure provides for method of treatment and/or prevention of disease states that require cystine for maintenance or progression of the disease state. In addition, methods for screening and identifying novel therapeutic agents useful in the treatment of such disease states are described. In one embodiment, the disease state is a cancer, such as, but not limited to, glioma. In this embodiment, methods for the treatment and prevention of glioma by inhibiting cystine uptake or decreasing intracellular cystine concentrations are provided. The present disclosure teaches that glioma cells are dependent on system Xc for cystine uptake. Pharmacological inhibition of system Xc causes a rapid depletion of intracellular glutathione, resulting in decreased cell growth. In contrast, non-malignant astrocytes and cortical neurons remain viable in the presence of Xc inhibitors and continue to take up cystine via alternate amino acid transporters.
摘要翻译: 本公开提供了治疗和/或预防需要胱氨酸以维持或发展疾病状态的疾病状态的方法。 此外,描述了筛选和鉴定用于治疗这种疾病状态的新型治疗剂的方法。 在一个实施方案中,疾病状态是癌症,例如但不限于神经胶质瘤。 在该实施方案中,提供了通过抑制胱氨酸摄取或减少细胞内胱氨酸浓度来治疗和预防神经胶质瘤的方法。 本公开内容教导了神经胶质瘤细胞依赖于系统Xc用于胱氨酸摄取。 系统Xc的药理学抑制导致细胞内谷胱甘肽的快速消耗,导致细胞生长减少。 相比之下,非恶性星形胶质细胞和皮层神经元在Xc抑制剂存在下保持存活,并通过替代氨基酸转运体继续摄取胱氨酸。
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公开(公告)号:US20050142062A1
公开(公告)日:2005-06-30
申请号:US11057602
申请日:2005-02-15
申请人: Harald Sontheimer , Nicole Ullrich
发明人: Harald Sontheimer , Nicole Ullrich
IPC分类号: A61K38/00 , A61K47/48 , C07K14/435 , C07K16/28 , C07K16/30 , G01N33/574 , A61K39/395 , A61K51/00
CPC分类号: G01N33/57492 , A61K38/00 , A61K47/6415 , A61K2039/505 , C07K14/43522 , C07K16/28 , C07K16/3053 , C07K2319/23 , C07K2319/55 , G01N33/57407 , G01N2333/705 , Y10S436/813
摘要: The present invention provides a recombinant toxin and monoclonal antibody which specifically binds to glial-derived or meningioma-derived tumor cells. Also provided are various methods of screening for malignant gliomas and meningiomas. Further provided are methods of treating malignant gliomas, including glioblastoma multiforme and astrocytomas.
摘要翻译: 本发明提供了特异性结合胶质衍生或脑膜瘤来源的肿瘤细胞的重组毒素和单克隆抗体。 还提供了筛选恶性胶质瘤和脑膜瘤的各种方法。 还提供了治疗恶性胶质瘤的方法,包括多形性成胶质细胞瘤和星形细胞瘤。
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