公开(公告)号：US20110142827A1

公开(公告)日：2011-06-16

申请号：US12886027

申请日：2010-09-20

申请人： Martin Gleave ,  Gabriella Zupi

发明人： Martin Gleave ,  Gabriella Zupi

IPC分类号： A61K39/395 ,  A61P35/00

CPC分类号： C07K16/32 ,  A61K39/39558 ,  A61K2039/505 ,  C07K2317/24 ,  A61K2300/00

摘要： Agents that perturb the EGF signaling pathway and that are known to be useful in the treatment of cancer are found also to result in increased expression of the protein clusterin. Since clusterin can provide protection against apoptosis, this secondary effect detracts from the efficacy of the therapeutic agent. This is overcome using a combination of an agent that has known therapeutic efficacy against the cancer to be treated by perturbation of the EGF signaling pathway and that stimulates expression of clusterin as a secondary effect, and an oligonucleotide that is effective to reduce the amount of clusterin in cancer cells. For example, the agent may be an antibody specific for HER-2, a small molecule inhibitor of HER-2, an antisense oligonucleotide specific for HER-2, or a peptide agent capable of interfering with HER-2 protein. The oligonucleotide may be an antisense oligonucleotide or an RNAi oligonucleotide.

摘要翻译： 发现干扰EGF信号通路并且已知可用于治疗癌症的试剂也导致蛋白质簇的表达增加。 由于簇蛋白可以提供针对细胞凋亡的保护作用，所以这种二次效应会降低治疗剂的功效。 使用具有已知治疗功效的药剂与通过EGF信号通路的扰动来治疗并刺激簇蛋白表达作为次要作用的药物的组合克服，以及有效降低簇的量的寡核苷酸 在癌细胞中。 例如，该试剂可以是对HER-2特异的抗体，HER-2的小分子抑制剂，对HER-2特异性的反义寡核苷酸，或能够干扰HER-2蛋白质的肽试剂。 寡核苷酸可以是反义寡核苷酸或RNAi寡核苷酸。

公开(公告)号：US20080014198A1

公开(公告)日：2008-01-17

申请号：US11718815

申请日：2005-11-22

申请人： Martin Gleave ,  Gabriella Zupi

发明人： Martin Gleave ,  Gabriella Zupi

IPC分类号： A61K31/7088 ,  A61K39/395 ,  A61P35/00

CPC分类号： C07K16/32 ,  A61K39/39558 ,  A61K2039/505 ,  C07K2317/24 ,  A61K2300/00

摘要： Agents that perturb the EGF signaling pathway and that are known to be useful in the treatment of cancer are found also to result in increased expression of the protein clusterin. Since clusterin can provide protection against apoptosis, this secondary effect detracts from the efficacy of the therapeutic agent. This is overcome using a combination of an agent that has known therapeutic efficacy against the cancer to be treated by perturbation of the EGF signaling pathway and that stimulates expression of clusterin as a secondary effect, and an oligonucleotide that is effective to reduce the amount of clusterin in cancer cells small molecule inhibitor of HER-2, an antisense oligonucleotide specific for HER-2, or a peptide agent capable of interfering with HER-2 protein. The oligonucleotide may be an antisense oligonucleotide or an RNAi oligonucleotide.

摘要翻译： 发现干扰EGF信号通路并且已知可用于治疗癌症的试剂也导致蛋白质簇的表达增加。 由于簇蛋白可以提供针对细胞凋亡的保护作用，所以这种二次效应会降低治疗剂的功效。 使用具有已知治疗功效的药剂与通过EGF信号通路的扰动来治疗并刺激簇蛋白表达作为次要作用的药物的组合克服，以及有效降低簇的量的寡核苷酸 在癌细胞中HER-2的小分子抑制剂，对HER-2特异性的反义寡核苷酸或能干扰HER-2蛋白的肽试剂。 寡核苷酸可以是反义寡核苷酸或RNAi寡核苷酸。

公开(公告)号：US06080727A

公开(公告)日：2000-06-27

申请号：US827036

申请日：1997-03-25

申请人： Gabriella Zupi

发明人： Gabriella Zupi

IPC分类号： A61K38/00 ,  C12N15/113 ,  A61K31/70 ,  C07H21/00

CPC分类号： A61K31/7125 ,  C12N15/1135 ,  A61K38/00 ,  C12N2310/314 ,  C12N2310/3145 ,  C12N2310/315

摘要： The invention generally provides for compositions and methods of inhibiting the proliferation of human melanoma cancer cells. By administering a therapeutically effective amount of a c-myc oligonucleotide to a human melanoma cancer cell, melanoma cancer cell proliferation can be arrested or inhibited, metastases reduced from a tumor, and apoptosis induced in melanoma cancer cells. Oligonucleotides that are complementary to c-myc polynucleotides are referred to herein as "c-myc oligonucleotides." A particularly efficacious embodiment of the invention relates to compositions and methods concerning the co-administration of c-myc oligonucleotides and cisplatin.

摘要翻译： 本发明通常提供抑制人黑素瘤癌细胞增殖的组合物和方法。 通过向人黑素瘤癌细胞施用治疗有效量的c-myc寡核苷酸，可以阻止或抑制黑素瘤癌细胞增殖，从肿瘤中减少转移以及在黑素瘤癌细胞中诱导凋亡。 与c-myc多核苷酸互补的寡核苷酸在本文中称为“c-myc寡核苷酸”。 本发明特别有效的实施方案涉及关于共注射c-myc寡核苷酸和顺铂的组合物和方法。