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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：US07556935B2
公开(公告)日：2009-07-07
申请号：US11538186
申请日：2006-10-03
IPC分类号： C12Q1/50
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.
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公开(公告)号：US07247297B2
公开(公告)日：2007-07-24
申请号：US10244705
申请日：2002-09-16
CPC分类号： C12N15/86 , A61K38/191 , A61K48/00 , A61K48/0058 , C12N2710/10343 , C12N2830/008 , C12N2830/85
摘要： The present invention provides for improved vectors for use in gene therapy. Utilizing the cancer specific DF3/MUC1 promoter to drive a replication essential gene, vectors are made conditionally replication-competent, permitting wider infection and expression of tumor cells. In addition, therapeutic genes and adjunct therapies further increase anti-tumor efficacy.
摘要翻译： 本发明提供用于基因治疗的改良载体。 利用癌特异性DF3 / MUC1启动子来驱动复制必需基因，使得载体有条件地具有复制能力，允许肿瘤细胞的更广泛的感染和表达。 此外，治疗基因和辅助疗法进一步增加抗肿瘤功效。
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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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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：US06589981B2
公开(公告)日：2003-07-08
申请号：US09794417
申请日：2001-02-27
申请人： Corinne L. Reimer , Naoki Agata , Tomio Takeuchi , Hiroyuki Kumagai , Takeo Yoshioka , Masaaki Ishizuka , Donald W. Kufe , Ralph R. Weichselbaum
发明人： Corinne L. Reimer , Naoki Agata , Tomio Takeuchi , Hiroyuki Kumagai , Takeo Yoshioka , Masaaki Ishizuka , Donald W. Kufe , Ralph R. Weichselbaum
IPC分类号： A61K3135
CPC分类号： A61K41/0038
摘要： A method for enhancing the efficacy of chemotherapy and/or radiation in the treatment of cancer in animals, particularly humans, is provided wherein certain isocoumarin derivatives which exhibit unique radiosensitization activity and/or chemopotentiation properties are employed in a combination treatment with ionizing radiation and/or chemotherapy.
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公开(公告)号：US06420335B1
公开(公告)日：2002-07-16
申请号：US09334084
申请日：1999-06-16
IPC分类号： A01N3718
CPC分类号： A61K38/484 , A61K38/208 , A61K38/363 , A61K38/39 , A61K48/00 , A61K2300/00
摘要： The present invention relates generally to the fields of angiogenesis and cancer therapy. More particularly, it concerns the use of anti-angiogenic factors in cancer therapy. The present invention demonstrates that angiostatin or endostatin can sensitize a cell to radiation therapy. Methods and compositions for inhibiting growth, sensitizing a cell to radiotherapy and treating cancer growth by first inhibiting angiogenesis and then employing radiotherapy are described.
摘要翻译： 本发明一般涉及血管发生和癌症治疗的领域。 更具体地说，它涉及抗癌血管生成因子在癌症治疗中的应用。 本发明证明血管抑素或内皮抑素可使细胞对放射治疗敏感。 描述了抑制生长的方法和组合物，通过首先抑制血管发生然后使用放射治疗使细胞对放射治疗敏感和治疗癌症生长。
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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：US5571797A
公开(公告)日：1996-11-05
申请号：US241863
申请日：1994-05-11
IPC分类号： A61K38/00 , C07K14/21 , C07K14/47 , C07K14/525 , C07K14/82 , C12N9/02 , C12N15/67 , C12N15/85 , A61K48/00 , A61K51/00
CPC分类号： C12N9/0089 , C07K14/21 , C07K14/4705 , C07K14/525 , C07K14/82 , C12N15/67 , C12N15/85 , A61K38/00 , C12N2830/002 , C12N2840/20
摘要： The present invention provides a method for delivering ionizing radiation to specific tissues, resulting in the activation of a DNA molecule comprising a radiation responsive enhancer-promoter operatively linked to an encoding region that encodes at least one polypeptide. The radiation source may be will generally be in the form of a radionuclide, capable of gamma or beta emissions. Processes for regulating polypeptide expression and inhibiting tumor growth using such DNA molecules are also provided.
摘要翻译： 本发明提供了将电离辐射递送到特定组织的方法，导致包含可编码至少一种多肽的编码区的辐射响应增强子启动子的DNA分子的活化。 辐射源通常可以是放射性核素的形式，能够进行γ或β辐射。 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：US08034791B2
公开(公告)日：2011-10-11
申请号：US11467799
申请日：2006-08-28
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）的多核苷酸表达的方法，包括使细胞与包含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的多核苷酸和化学治疗剂可操作地连接的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。
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