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1. 发明申请

US20070293453A1 Combinatorial Methods For Inducing Cancer Cell Death 审中-公开
标题翻译：用于诱导癌细胞死亡的组合方法
公开(公告)号：US20070293453A1
公开(公告)日：2007-12-20
申请号：US11839314
申请日：2007-08-15
申请人： Paul Fisher , Zao-Zhong Su
发明人： Paul Fisher , Zao-Zhong Su
IPC分类号： A61K48/00 , A61P43/00 , C12N15/00 , C12N15/86 , C12Q1/02
CPC分类号： C12N15/1135 , A61K38/1709 , A61K48/00 , A61K48/0083 , C07K14/4703 , C12N15/86 , C12N2310/111 , C12N2710/10343 , C12N2799/021 , G01N33/5011 , G01N2510/00
摘要： The present invention relates to methods and compositions for inhibiting proliferation and inducing cell death in a population of cancer cells by (i) increasing the amount of the differentiation associated protein MDA-7, and (ii) decreasing RAS activity within the population. It is based, at least in part, on the discovery that decreasing expression of a mutated, activated K-ras gene, together with introducing an expressible mda-7 gene, in pancreatic cells had a synergistic growth-inhibitory and anti-survival effect, and abolished tumorigenicity of the cells in athymic nude mice. The methods of the invention may be directed to the therapy of pancreatic cancer and other malignancies.
摘要翻译：本发明涉及通过（i）增加分化相关蛋白MDA-7的量和（ii）降低群体内的RAS活性来抑制癌细胞群体增殖和诱导细胞死亡的方法和组合物。至少部分地基于以下发现：突变的活化的K-ras基因的表达与在胰腺细胞中引入可表达的mda-7基因一起具有协同生长抑制和抗生存作用，并消除无胸腺裸鼠中细胞的致瘤性。本发明的方法可以涉及胰腺癌和其他恶性肿瘤的治疗。

2. 发明授权

US07329649B2 Combinatorial methods for inducing cancer cell death 失效
标题翻译：诱导癌细胞死亡的组合方法
公开(公告)号：US07329649B2
公开(公告)日：2008-02-12
申请号：US10783571
申请日：2004-02-20
申请人： Paul B. Fisher , Zao-Zhong Su
发明人： Paul B. Fisher , Zao-Zhong Su
IPC分类号： A61K48/00
CPC分类号： C12N15/1135 , A61K38/1709 , A61K48/00 , A61K48/0083 , C07K14/4703 , C12N15/86 , C12N2310/111 , C12N2710/10343 , C12N2799/021 , G01N33/5011 , G01N2510/00
摘要： The present invention relates to methods and compositions for inhibiting proliferation and inducing cell death in a population of cancer cells by (i) increasing the amount of the differentiation associated protein MDA-7, and (ii) decreasing RAS activity within the population. It is based, at least in part, on the discovery that decreasing expression of a mutated, activated K-ras gene, together with introducing an expressible mda-7 gene, in pancreatic cells had a synergistic growth-inhibitory and anti-survival effect, and abolished tumorigenicity of the cells in athymic nude mice. The methods of the invention may be directed to the therapy of pancreatic cancer and other malignancies.
摘要翻译：本发明涉及通过（i）增加分化相关蛋白MDA-7的量和（ii）降低群体内的RAS活性来抑制癌细胞群体增殖和诱导细胞死亡的方法和组合物。至少部分地基于以下发现：突变的活化的K-ras基因的表达与在胰腺细胞中引入可表达的mda-7基因一起具有协同生长抑制和抗生存作用，并消除无胸腺裸鼠中细胞的致瘤性。本发明的方法可以涉及胰腺癌和其他恶性肿瘤的治疗。

3. 发明授权

US06982148B2 Progressive elevated gene-3 (PEG-3) induces aggressive cancer phenotype and regulates angiogenesis 失效
公开(公告)号：US06982148B2
公开(公告)日：2006-01-03
申请号：US10177811
申请日：2002-06-20
申请人： Paul B. Fisher , Zao-Zhong Su
发明人： Paul B. Fisher , Zao-Zhong Su
IPC分类号： C12Q1/68
CPC分类号： C12N15/85 , A61K48/00 , C07K14/4748 , C12N2799/022 , C12N2830/008 , C12N2830/85 , C12Q1/6883 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158
摘要： The present invention provides a method for identifying a gene which is expressed at a modulated level in an aggressive cancer by: (a) measuring baseline expression levels of genes in cancer cells; (b) introducing into the cancer cells an expression vector which directs expression of rat PEG-3; (c) measuring the expression levels of genes in the cells from step (b); and (d) identifying genes, the expression of which is modulated in an aggressive cancer. In another aspect of this invention, the measurement of expression levels of genes in step (a) and/or step (c) comprises measuring mRNA levels. In yet another aspect of the invention, the measurement of expression levels of genes in step (a) and/or step (c) comprises measuring RNA levels. In another aspect of the invention, the genes identified in step (d) are used for diagnosing whether a subject suffers from an aggressive form of cancer.

4. 发明授权

US06737523B1 Nucleic acids comprising regions of the rat PEG-3 promoter that display elevated expression in human cancer cells and uses thereof 有权
标题翻译：包含显示人癌细胞中升高的表达的大鼠PEG-3启动子区域的核酸及其用途
公开(公告)号：US06737523B1
公开(公告)日：2004-05-18
申请号：US09621781
申请日：2000-07-21
申请人： Paul B. Fisher , Zao-Zhong Su
发明人： Paul B. Fisher , Zao-Zhong Su
IPC分类号： C07H2104
CPC分类号： G01N33/57496 , A01K2217/05 , A61K38/00 , A61K39/00 , A61K48/00 , A61K48/0058 , A61K2035/126 , A61K2035/128 , C07K14/47 , C12N15/85 , C12N2799/022 , C12N2830/002 , C12N2830/008 , C12N2830/85 , C40B30/04 , G01N33/68
摘要： This invention provides an isolated nucleic acid comprising a PEG-3 promoter comprising the nucleotide sequence of −270 to +194 of FIG. 2. The invention also provides a method for identifying an agent that modulates PEG-3 promoter activity using a cell which comprises a PEG-3 promoter operatively linked to a reporter gene, wherein reduced reporter gene expression in the presence of the agent is indicative of an agent that inhibits PEG-3 promoter activity and wherein increased reporter gene expression in the presence of the agent is indicative of an agent that enhances PEG-3 promoter activity. The invention provides a method for treating cancer in a subject which comprises administering a nucleic acid comprising a PEG-3 promoter operatively linked to a gene-of-interest, wherein the gene-of-interest is selectively expressed in cancerous cells in the subject and such expression results in growth suppression or death of the cancerous cells.
摘要翻译：本发明提供了包含PEG-3启动子的分离的核酸，其包含图17的-270至+ 194的核苷酸序列。本发明还提供了一种用于鉴定使用包含与报道基因可操作地连接的PEG-3启动子的细胞来调节PEG-3启动子活性的试剂的方法，其中在试剂存在下，报告基因表达降低表明抑制PEG-3启动子活性的试剂，并且其中在试剂存在下增加的报告基因表达指示增强PEG-3启动子活性的试剂。本发明提供了一种用于治疗受试者的癌症的方法，其包括施用包含可操作地连接到感兴趣的基因的PEG-3启动子的核酸，其中感兴趣的基因在受试者的癌细胞中选择性表达，这种表达导致癌细胞的生长抑制或死亡。

5. 发明授权

US06204001B1 Methods for determining compounds capable of inhibiting the activities of the Ha-Ras oncongene 失效
标题翻译：用于测定能够抑制Ha-Ras oncongene活性的化合物的方法
公开(公告)号：US06204001B1
公开(公告)日：2001-03-20
申请号：US08749737
申请日：1996-11-15
申请人： Paul B. Fisher , Zao-Zhong Su
发明人： Paul B. Fisher , Zao-Zhong Su
IPC分类号： G01N33574
CPC分类号： C07K14/82 , A61K38/00 , C07K14/4703
摘要： This invention provides a method for determining whether a compound is capable of suppressing ras functions comprising: (a) contacting an effective amount of the compound with Ha-ras transformed cloned rat embryo fibroblast cells under conditions permitting the compound to suppress ras functions in the cells; and (b) determining the expression or inhibition of certain indicator gene or genes, thereby determining whether the compound is capable of suppressing ras function. This invention further provides the determined compound and a pharmaceutical composition comprising the compound and a pharmaceutically acceptable carrier. This invention also provides methods for generating transcriptional switched Ha-ras transformed cloned rat embryo fibroblast cells. This invention also provides the generated cells and different uses of the cells.
摘要翻译：本发明提供了一种用于确定化合物是否能够抑制ras功能的方法，包括：（a）在允许化合物抑制细胞中的ras功能的条件下，使有效量的化合物与Ha-ras转化的克隆的大鼠胚胎成纤维细胞接触 ; 和（b）确定某些指示基因或基因的表达或抑制，从而确定该化合物是否能够抑制ras功能。本发明进一步提供所确定的化合物和包含该化合物和药学上可接受的载体的药物组合物。本发明还提供用于产生转录转录的Ha-ras转化的克隆的大鼠胚胎成纤维细胞的方法。本发明还提供所生成的细胞和细胞的不同用途。

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