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1. 发明申请

US20090047742A1 Inhibition of mRNA Interferase-Induced Apoptosis in BAK-Deficient and BAK- and Bax-Deficient Mammalian Cells 审中-公开
标题翻译：抑制BAK缺陷型和BAK-和Bax-缺陷型哺乳动物细胞中mRNA干扰素诱导的细胞凋亡
公开(公告)号：US20090047742A1
公开(公告)日：2009-02-19
申请号：US12064070
申请日：2006-08-22
申请人： Tsutomu Shimazu , Kurt Degenhardt , Eileen White , Masayori Inouye
发明人： Tsutomu Shimazu , Kurt Degenhardt , Eileen White , Masayori Inouye
IPC分类号： C12N15/87 , C12N5/06
CPC分类号： A61K48/0066 , A61K48/00 , C07K14/4747 , C12N9/22 , C12N2800/40
摘要： Ribonucleases, antibiotics, bacterial toxins and viruses inhibit protein synthesis, which results in apoptosis in mammalian cells. How the BCL-2 family of proteins regulates apoptosis in response to shutoff of protein synthesis is not known. According to the present invention, an Escherichia coli toxin MazF inhibited protein synthesis by cleavage of cellular mRNA, and induced apoptosis in mammalian cells. MazF-induced apoptosis required proapoptotic BAK and its upstream regulator, the proapoptotic BH3-only protein NBK/BIK, but not BIM, PUMA or NOXA. Furthermore, NBK/BIK- or BAK-deficient cells were resistant to cell death induced by pharmacologic inhibition of translation and by virus-mediated shutoff of protein synthesis. Thus, the BH3-only protein NBK/BIK is the apical regulator of a BAK-dependent apoptotic pathway in response to shutoff of protein synthesis. Although NBK/BIK is dispensable for development, it is the BH3-only protein targeted for inactivation by viruses, suggesting that it plays a role in pathogen/toxin response through apoptosis activation.
摘要翻译：核糖核酸酶，抗生素，细菌毒素和病毒抑制蛋白质合成，导致哺乳动物细胞凋亡。 BCL-2家族蛋白质如何调节蛋白质合成关闭反应的凋亡是未知的。根据本发明，大肠杆菌毒素MazF通过切割细胞mRNA抑制蛋白质合成，并诱导哺乳动物细胞的细胞凋亡。 MazF诱导的细胞凋亡需要促凋亡BAK及其上游调节因子，即促凋亡BH3蛋白NBK / BIK，而不是BIM，PUMA或NOXA。此外，NBK / BIK-或BAK缺陷细胞对由翻译的药理学抑制和蛋白质合成的病毒介导的切断引起的细胞死亡具有抗性。因此，仅BH3蛋白NBK / BIK是响应于蛋白质合成关闭的BAK依赖性凋亡途径的顶端调节剂。虽然NBK / BIK是不可开发的，但是仅针对通过病毒灭活的BH3蛋白，这表明它通过凋亡激活在病原体/毒素反应中起作用。

2. 发明申请

US20130178382A1 Identification of Modulators of Autophagy 审中-公开
标题翻译：识别自噬调节剂
公开(公告)号：US20130178382A1
公开(公告)日：2013-07-11
申请号：US13565425
申请日：2012-08-02
申请人： Eileen White , Anne M. Strohecker , Richard Possemato , David M. Sabatini
发明人： Eileen White , Anne M. Strohecker , Richard Possemato , David M. Sabatini
IPC分类号： C12Q1/02 , G01N33/53 , C12Q1/68
CPC分类号： G01N33/5023 , C12Q1/025 , C12Q1/6809 , G01N33/5008 , G01N33/53
摘要： Methods for identifying compounds that inhibit or stimulate the autophagy pathway are described. Devices for detecting the expression of autophagy-related genes and kits for assaying the expression of autophagy-related genes are also described. Also described are methods for identifying individuals susceptible to or afflicted with a disease state associated with an autophagy pathway defect.
摘要翻译：描述了鉴定抑制或刺激自噬途径的化合物的方法。还描述了用于检测自噬相关基因表达的装置和用于测定自噬相关基因表达的试剂盒。还描述了用于鉴定对与自噬途径缺陷相关的疾病状态敏感或折磨的个体的方法。

3. 发明申请

US20120202707A1 CELL LINES USEFUL FOR ASSESSING MODULATION OF AUTOPHAGY 审中-公开
标题翻译：用于评估自动调节的细胞线
公开(公告)号：US20120202707A1
公开(公告)日：2012-08-09
申请号：US13440596
申请日：2012-04-05
申请人： Eileen White , Anne Marie Strohecker , Robin Mathew , Cristina Karp
发明人： Eileen White , Anne Marie Strohecker , Robin Mathew , Cristina Karp
IPC分类号： C40B30/06 , C12Q1/02
CPC分类号： G01N33/5023 , C12Q1/025 , C12Q1/6809 , G01N33/5008 , G01N33/53
摘要： Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.
摘要翻译：公开了筛选自噬调节剂的方法。公开了用于鉴定表达抑制自噬的基因的方法，以及表达促进自噬的基因。还公开了用于鉴定刺激自噬的化合物的方法以及抑制自噬的化合物。还可以公开可用于鉴定方法的细胞系。

4. 发明申请

US20140134661A1 THERAPEUTIC MODULATION OF AUTOPHAGY 审中-公开
标题翻译：自动化的治疗方法
公开(公告)号：US20140134661A1
公开(公告)日：2014-05-15
申请号：US13895497
申请日：2013-05-16
申请人： Eileen White , Anne Marie Storhecker , Robin Mathew , Cristina Karp
发明人： Eileen White , Anne Marie Storhecker , Robin Mathew , Cristina Karp
IPC分类号： G01N33/50
CPC分类号： G01N33/5023 , C12Q1/025 , C12Q1/6809 , G01N33/5008 , G01N33/53
摘要： Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.
摘要翻译：公开了筛选自噬调节剂的方法。公开了用于鉴定表达抑制自噬的基因的方法，以及表达促进自噬的基因。还公开了用于鉴定刺激自噬的化合物的方法以及抑制自噬的化合物。还可以公开可用于鉴定方法的细胞系。

5. 发明授权

US08187802B2 Cell lines useful for assessing modulation of autophagy 有权
标题翻译：可用于评估自噬调节的细胞系
公开(公告)号：US08187802B2
公开(公告)日：2012-05-29
申请号：US12622410
申请日：2009-11-19
申请人： Eileen White , Anne Marie Strohecker , Robin Mathew , Cristina Karp
发明人： Eileen White , Anne Marie Strohecker , Robin Mathew , Cristina Karp
IPC分类号： C12Q1/00 , C12N5/00 , C12N5/07
CPC分类号： G01N33/5023 , C12Q1/025 , C12Q1/6809 , G01N33/5008 , G01N33/53
摘要： Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.
摘要翻译：公开了筛选自噬调节剂的方法。公开了用于鉴定表达抑制自噬的基因的方法，以及表达促进自噬的基因。还公开了用于鉴定刺激自噬的化合物的方法以及抑制自噬的化合物。还可以公开可用于鉴定方法的细胞系。

6. 发明授权

US5604113A Cells having oncogene-suppressed p53-mediated apoptosis and methods of use to identify anti-oncogenic compounds 失效
标题翻译：具有致癌基因抑制p53介导的凋亡的细胞和用于鉴定抗致癌化合物的方法
公开(公告)号：US5604113A
公开(公告)日：1997-02-18
申请号：US224209
申请日：1994-04-07
申请人： Eileen White , Shuin-Kwei Chiou , Huey-Jen L. Lin
发明人： Eileen White , Shuin-Kwei Chiou , Huey-Jen L. Lin
IPC分类号： G01N33/50 , C12Q1/02 , C12N5/06
CPC分类号： G01N33/5011
摘要： The present invention is a method for determining if a compound potentially modulates the ability of a putative oncogene to suppress p53-mediated effects, comprising (A) adding an amount of said compound to genetically engineered cells that express (i) a gene product that induces p53 mediated apoptosis; (ii) a gene product for a p53 gene, wherein either the gene or the gene product are externally controllable; and (iii) a putative oncogene that inhibits the effect of the gene product that induces p53 mediated apoptosis, and (B) examining said cells to determine whether apoptosis has occurred. In particular, the invention provides a method wherein said gene product that induces p53 mediated apoptosis is adenovirus gene E1A, wherein said externally controllable p53 gene product is a temperature-sensitive mutant of p53, and wherein the putative oncogene is selected from the group bcl-2, ras, or the adenovirus E1B(19K) gene. In addition, the invention provides genetically engineered cell lines that can be used to carry out the methods described.
摘要翻译：本发明是一种用于确定化合物是否潜在地调节推定的癌基因抑制p53介导的作用的能力的方法，其包括（A）向转基因工程细胞中加入一定量的所述化合物，所述细胞表达（i）诱导的基因产物 p53介导凋亡; （ii）p53基因的基因产物，其中所述基因或基因产物可外部控制; 和（iii）抑制诱导p53介导的凋亡的基因产物的作用的推定的癌基因，和（B）检查所述细胞以确定是否发生细胞凋亡。特别地，本发明提供了一种方法，其中所述诱导p53介导的细胞凋亡的基因产物是腺病毒基因E1A，其中所述外部可控的p53基因产物是p53的温度敏感突变体，其中推定的致癌基因选自bcl- 2，ras或腺病毒E1B（19K）基因。此外，本发明提供可用于实施所述方法的基因工程细胞系。

7. 发明授权

US08183395B2 Compositions and methods for treating cancer 有权
标题翻译：用于治疗癌症的组合物和方法
公开(公告)号：US08183395B2
公开(公告)日：2012-05-22
申请号：US12530415
申请日：2008-03-05
申请人： Paul Falkowski , Eric H. Andrianasolo , Liti Haramaty , Eileen White , Richard Lutz
发明人： Paul Falkowski , Eric H. Andrianasolo , Liti Haramaty , Eileen White , Richard Lutz
IPC分类号： C07D407/06 , C07C69/74 , C07C69/035 , A61K31/352 , A61K31/215 , A61K31/22
CPC分类号： C07D407/06 , C07C69/007
摘要： Compounds of formulas I-IV: (I), (II), (III) (IV), wherein: R1 and R4-R23 are independently selected from H and 1-3 carbon lower alkyl; and R2 and R3 are independently selected from H, 1-3 carbon lower O II alkyl, and —C—Ra, wherein Ra is 1-3 carbon lower alkyl. Pharmaceutical compositions, which include any of Compounds I-IV and a pharmaceutically acceptable carrier, methods of inducing tumor cell apoptosis by administering to a patient in need thereof an effective amount of any of Compounds I-IV, and methods for obtaining any of Compounds I-IV by extracting the compound from coral are also provided.
摘要翻译：式I-IV化合物：（I），（II），（III）（Ⅳ），其中：R 1和R 4 -R 23独立地选自H和1-3碳低级烷基; 并且R 2和R 3独立地选自H，1-3碳低级O II烷基和-C-R a，其中R a是1-3碳低级烷基。药物组合物，其包括任何化合物I-IV和药学上可接受的载体，通过向有需要的患者施用有效量的任何化合物I-IV诱导肿瘤细胞凋亡的方法，以及获得化合物I 还提供了从珊瑚中提取化合物的方法。

8. 发明申请

US20100233730A1 THERAPEUTIC MODULATION OF AUTOPHAGY 有权
标题翻译：自动化的治疗方法
公开(公告)号：US20100233730A1
公开(公告)日：2010-09-16
申请号：US12622410
申请日：2009-11-19
申请人： Eileen White , Anne Marie Strohecker , Robin Mathew , Cristina Karp
发明人： Eileen White , Anne Marie Strohecker , Robin Mathew , Cristina Karp
IPC分类号： G01N33/53 , C12N5/07
CPC分类号： G01N33/5023 , C12Q1/025 , C12Q1/6809 , G01N33/5008 , G01N33/53
摘要： Methods for screening for modulators of autophagy are disclosed. Methods for identifying genes whose expression inhibits autophagy, as well as genes whose expression promotes autophagy, are disclosed. Also disclosed are methods for identifying compounds that stimulate autophagy, as well as compounds that inhibit autophagy. Cell lines that may be used in the methods of identification are also disclosed.
摘要翻译：公开了筛选自噬调节剂的方法。公开了用于鉴定表达抑制自噬的基因的方法，以及表达促进自噬的基因。还公开了用于鉴定刺激自噬的化合物的方法以及抑制自噬的化合物。还可以公开可用于鉴定方法的细胞系。

9. 发明授权

US06890716B1 Recombinant cell line and screening method for identifying agents which regulate apoptosis and tumor suppression 有权
标题翻译：重组细胞系和筛选方法，用于鉴定调节细胞凋亡和肿瘤抑制的药物
公开(公告)号：US06890716B1
公开(公告)日：2005-05-10
申请号：US09674876
申请日：1999-05-06
申请人： Eileen White , Anju Thomas , Gary Kasof , Lakshmi Goyal
发明人： Eileen White , Anju Thomas , Gary Kasof , Lakshmi Goyal
IPC分类号： C12Q1/68 , G01N33/50 , C12N5/00
CPC分类号： C12Q1/6897 , G01N33/5014 , G01N2510/00
摘要： This invention provides recombinant cell lines and screening methods useful for identifying agents that induce apoptosis in target cells and therefore may be used to advantage in the treatment of neoplastic disorders.
摘要翻译：本发明提供了重组细胞系和筛选方法，其用于鉴定诱导靶细胞凋亡的试剂，因此可用于治疗肿瘤性疾病。

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