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公开(公告)号:US5641755A
公开(公告)日:1997-06-24
申请号:US278452
申请日:1994-07-20
CPC分类号: A61K31/40 , A61K31/70 , A61K41/0019 , A61K41/0023
摘要: Treatment of cells with ionizing radiation is associated with the production of arachidonic acid. Inhibition of phospholipase A2 abolishes radiation-mediated arachidonate production, protein kinase C induction and tumor necrosis factor gene expression. The addition of inhibitors of lipoxygenase, such as ketoconazole, prior to irradiation reduces the expression of of tumor necrosis factor while maintaining the expression of other radiation inducible genes, such as Egr-1 and c-jun. In contrast, indomethacin, an inhibitor of cyclooxygenase, enhanced the expression of tumor necrosis factor as well as other radiation inducible genes. The results show that lipoxygenase inhibitors are useful in the treatment of radiation-induced mucositis, dermatitis, pneumonitis, proctitis, and esophagitis. which may be due to the production of cytokines such as TNF.
摘要翻译: 用电离辐射处理细胞与花生四烯酸的生产有关。 磷脂酶A2的抑制消除辐射介导的花生四烯酸生成,蛋白激酶C诱导和肿瘤坏死因子基因表达。 在照射之前加入脂氧合酶抑制剂如酮康唑可降低肿瘤坏死因子的表达,同时保持其他放射诱导基因如Egr-1和c-jun的表达。 相比之下,吲哚美辛是环氧合酶抑制剂,增强了肿瘤坏死因子以及其他辐射诱导基因的表达。 结果表明,脂氧合酶抑制剂可用于治疗放射诱导的粘膜炎,皮炎,肺炎,直肠炎和食道炎。 这可能是由于产生诸如TNF的细胞因子。
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公开(公告)号:US07041653B2
公开(公告)日:2006-05-09
申请号:US09730630
申请日:2000-12-05
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.
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公开(公告)号:US5817636A
公开(公告)日:1998-10-06
申请号:US486338
申请日:1995-06-07
IPC分类号: A61K41/00 , A61K48/00 , A61K51/00 , A61P9/08 , A61P9/10 , A61P35/00 , C07K14/52 , C07K14/525 , C12N15/09 , C12N15/63 , C12N15/67 , C12N15/85 , A01N63/00 , C12N5/00 , C12N15/00
CPC分类号: A61K41/0023 , C07K14/52 , C07K14/525 , C12N15/63 , C12N15/67 , C12N15/85
摘要: This invention relates to genetic constructs which comprise an enhancer-promoter region which is responsive to radiation, and at least one structural gene whose expression is controlled by the enhancer-promoter. This invention also relates to methods of destroying, altering, or inactivating cells in target tissue by delivering the genetic constructs to the cells of the tissues and inducing expression of the structural gene or genes in the construct by exposing the tissues to ionizing radiation. This invention is useful for treating patients with cancer, clotting disorders, myocardial infarction, and other diseases for which target tissues can be identified and for which gene expression of the construct within the target tissues can alleviate the disease or disorder.
摘要翻译: 本发明涉及包含对辐射有响应的增强子 - 启动子区的遗传构建体和至少一个其表达受增强子启动子控制的结构基因。 本发明还涉及通过将遗传构建体递送至组织的细胞并通过将组织暴露于电离辐射来诱导构建体中的结构基因或基因的表达来破坏,改变或灭活靶组织中的细胞的方法。 本发明可用于治疗癌症患者,凝血障碍,心肌梗塞以及可识别靶组织的其它疾病,靶组织中构建体的基因表达可以缓解疾病或病症。
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公开(公告)号:US6156736A
公开(公告)日:2000-12-05
申请号:US102997
申请日:1998-06-22
IPC分类号: C12N15/09 , A61K31/70 , A61K38/00 , A61K41/00 , A61K48/00 , A61K51/00 , A61P9/08 , A61P9/10 , A61P35/00 , C07H21/04 , C07K14/52 , C07K14/525 , C07K14/82 , C12N5/10 , C12N15/63 , C12N15/67 , C12N15/85 , G03G15/20 , A01N43/04
CPC分类号: A61K41/0023 , A61K48/00 , C07K14/52 , C07K14/525 , C07K14/82 , C12N15/63 , C12N15/635 , C12N15/67 , C12N15/85 , G03G15/2025 , A61K38/00 , C07K2319/00 , C07K2319/61 , C07K2319/71 , C07K2319/81 , C12N2830/001 , C12N2830/002 , C12N2830/008 , C12N2830/85 , 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.
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公开(公告)号:US5612318A
公开(公告)日:1997-03-18
申请号:US212308
申请日:1994-03-14
IPC分类号: A61K41/00 , A61K48/00 , A61K51/00 , A61P9/08 , A61P9/10 , A61P35/00 , C07K14/52 , C07K14/525 , C12N15/09 , C12N15/63 , C12N15/67 , C12N15/85
CPC分类号: A61K41/0023 , C07K14/52 , C07K14/525 , C12N15/63 , C12N15/67 , C12N15/85
摘要: This invention relates to genetic constructs which comprise an enhancer-promoter region which is responsive to radiation, and at least one structural gene whose expression is controlled by the enhancer-promoter. This invention also relates to methods of destroying, altering, or inactivating cells in target tissue by delivering the genetic constructs to the cells of the tissues and inducing expression of the structural gene or genes in the construct by exposing the tissues to ionizing radiation. This invention is useful for treating patients with cancer, clotting disorders, myocardial infarction, and other diseases for which target tissues can be identified and for which gene expression of the construct within the target tissues can alleviate the disease or disorder.
摘要翻译: 本发明涉及包含对辐射有响应的增强子 - 启动子区的遗传构建体和至少一个其表达受增强子启动子控制的结构基因。 本发明还涉及通过将遗传构建体递送至组织的细胞并通过将组织暴露于电离辐射来诱导构建体中的结构基因或基因的表达来破坏,改变或灭活靶组织中的细胞的方法。 本发明可用于治疗癌症患者,凝血障碍,心肌梗塞以及可识别靶组织的其它疾病,靶组织中构建体的基因表达可以缓解疾病或病症。
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公开(公告)号:US5770581A
公开(公告)日:1998-06-23
申请号:US474445
申请日:1995-06-07
IPC分类号: C12N15/09 , A61K31/70 , A61K38/00 , A61K41/00 , A61K48/00 , A61K51/00 , A61P9/08 , A61P9/10 , A61P35/00 , C07H21/04 , C07K14/52 , C07K14/525 , C07K14/82 , C12N5/10 , C12N15/63 , C12N15/67 , C12N15/85 , G03G15/20
CPC分类号: A61K41/0023 , A61K48/00 , C07K14/52 , C07K14/525 , C07K14/82 , C12N15/63 , C12N15/635 , C12N15/67 , C12N15/85 , G03G15/2025 , A61K38/00 , C07K2319/00 , C07K2319/61 , C07K2319/71 , C07K2319/81 , C12N2830/001 , C12N2830/002 , C12N2830/008 , C12N2830/85 , 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.
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7.
公开(公告)号:US07919310B2
公开(公告)日:2011-04-05
申请号:US12019428
申请日:2008-01-24
IPC分类号: C12N15/74
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。
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8.
公开(公告)号:US06605712B1
公开(公告)日:2003-08-12
申请号:US07943812
申请日:1992-09-11
IPC分类号: C12N1511
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.
摘要翻译: 本发明提供了包含可编码至少一种多肽的编码区可操作地连接的辐射响应增强子 - 启动子的DNA分子。 编码区可以包含多肽的单个编码序列或编码转录因子的DNA结合,激活或抑制结构域的两个或多个编码序列。 还提供了使用这样的DNA分子调节多肽表达和抑制肿瘤生长的方法。
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公开(公告)号:US06486170B1
公开(公告)日:2002-11-26
申请号:US08248058
申请日:1994-05-24
IPC分类号: A61K3144
CPC分类号: A61K31/40 , A61K31/70 , A61K41/0019 , A61K41/0023 , A61K31/495 , A61K31/41 , A61K31/38 , A61K2300/00
摘要: A signaling pathway is identified that involves the activation of phospholipase A2 and protein kinase C in human cells, which in turn confers x-ray induction of the tumor necrosis factor &agr; (TNF) gene. Inhibition of phospholipase A2 abolishes radiation-mediated arachidonate production, as well as the subsequent activation of protein kinase C and TNF gene expression. These phospholipase A2 inhibitors may be used to ameliorate the adverse-effects of radiotherapy associated with TNF production.
摘要翻译: 识别出涉及人细胞中磷脂酶A2和蛋白激酶C的活化的信号通路,其进而赋予肿瘤坏死因子α(TNF)基因的x射线诱导。 磷脂酶A2的抑制消除辐射介导的花生四烯酸生产,以及随后激活蛋白激酶C和TNF基因表达。 这些磷脂酶A2抑制剂可用于改善与TNF产生相关的放射治疗的不良反应。
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10.
公开(公告)号:US07592317B1
公开(公告)日:2009-09-22
申请号:US08289290
申请日:1994-08-11
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。
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