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    Model for studying the role of genes in chemoresistance
    1.
    发明申请
    Model for studying the role of genes in chemoresistance 审中-公开
    研究基因在化学耐药性中的作用的模型

    公开(公告)号：US20090186839A1

    公开(公告)日：2009-07-23

    申请号：US11893540

    申请日：2007-08-15

    申请人： Scott W. Lowe ,  Hans G. Wendel ,  Jerry Pelletier ,  Marie-Eve Bordeleau ,  Francis Robert

    发明人： Scott W. Lowe ,  Hans G. Wendel ,  Jerry Pelletier ,  Marie-Eve Bordeleau ,  Francis Robert

    IPC分类号： A61K31/704 ,  A61K49/00 ,  C12Q1/02 ,  A61K31/335

    CPC分类号： G01N33/5088 ,  A01K67/0271 ,  A01K2227/105 ,  A01K2267/0331 ,  C12N15/8509 ,  G01N33/5011 ,  G01N33/57426 ,  G01N2800/52

    摘要： The invention provides novel inhibitors of protein translation initiation and inhibitors of eIF4F activity that can increase chemosensitivity or diminish or reverse chemoresistance in growth transformed cells and thereby reduce hyperproliferative conditions, such as cancer progression, in select patient populations having particular tumor genotypes. The invention also provides methods which target translation initiation controls in growth-transformed cells, such as tumor subtypes with altered expression of a gene activity, including the human akt, bcl-2, eIF4E, eIF4A or PTEN activities, to restore drug sensitivity in vivo in a genotype selective manner. In one aspect, the inhibitors of translation initiation of the invention are rocaglates, i.e., cyclopenta[b]benzofurons, which increases chemosensitivity or diminishes or reverses chemoresistance either alone or in combination, additively or synergistically, with other agents that alter growth or death. Preferably, the rocaglate is silvestrol, which is used alone or in combination with doxorubicin to reverses chemoresistance in PTEN-deficient lymphomas or eIF4E-over-expressing lymphomas and to promote cancer remission.

    摘要翻译： 本发明提供蛋白质翻译起始的新型抑制剂和eIF4F活性的抑制剂，其可以在具有特定肿瘤基因型的选定患者群体中增加化学敏感性或降低或逆转生长转化细胞中的化学抗性，从而降低过度增殖状况，例如癌症进展。 本发明还提供了靶向生长转化细胞中的翻译起始对照的方法，例如具有改变的基因活性表达的肿瘤亚型，包括人类akt，bcl-2，eIF4E，eIF4A或PTEN活性，以恢复体内药物敏感性 以基因型选择性方式。 在一个方面，本发明的翻译起始抑制剂是环戊二烯并[b]苯并呋喃，其可以增加化学敏感性，或者单独地或组合地降低或逆转化学抗性，与改变生长或死亡的其它试剂相加或协同地。 优选地，罗卡非特是silvestrol，其单独使用或与多柔比星组合使用以逆转PTEN缺陷型淋巴瘤或eIF4E过表达淋巴瘤中的化学抗性并促进癌症缓解。

    Compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein
    4.
    发明授权
    Compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein 失效
    涉及金黄色葡萄球菌基因及其编码蛋白的组成和方法

    公开(公告)号：US06376652B1

    公开(公告)日：2002-04-23

    申请号：US09470512

    申请日：1999-12-22

    申请人： Jerry Pelletier ,  Philippe Gros ,  Mike DuBow

    发明人： Jerry Pelletier ,  Philippe Gros ,  Mike DuBow

    IPC分类号： C07K1400

    CPC分类号： C07K14/005 ,  A61K38/00 ,  C12N2795/10022 ,  C12N2795/10043 ,  C12Q1/18

    摘要： This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, the invention relates to polynucleotides and polypeptides of a Staphylococcus aureus (S. aureus) DnaI related protein, as well as its variants, hereinafter referred to as “S. aureus DnaI”, “S. aureus DnaI polypeptide(s)”, and “S. aureus dnaI polynucleotides” as the case may be. Also, the invention relates to a specific interaction between the S. aureus DnaI related protein and a growth-inhibitory protein encoded by the S. aureus bacteriophage 77 genome. The phage ORF product interacts with the S. aureus DnaI polypeptide, and the invention contemplates use of this interaction target site for the basis of a drug screening assay. In addition, the invention relates to polynucleotides and polypeptides of a protein complex containing S. aureus DnaI and DnaC related proteins, as well as their variants.

    摘要翻译： 本发明涉及新鉴定的多核苷酸和多肽及其生产和用途，以及它们的变体，激动剂和拮抗剂及其用途。 特别地，本发明涉及金黄色葡萄球菌（金黄色葡萄球菌）DnaI相关蛋白的多核苷酸和多肽，以及其变体，以下称为“金黄色葡萄球菌DnaI”，“金黄色葡萄球菌DnaI多肽” 和“金黄色葡萄球菌dnaI多核苷酸”的情况。 此外，本发明涉及金黄色葡萄球菌DnaI相关蛋白与由金黄色葡萄球菌噬菌体77基因组编码的生长抑制性蛋白质之间的特异性相互作用。 噬菌体ORF产物与金黄色葡萄球菌DnaI多肽相互作用，本发明考虑使用该相互作用靶位点进行药物筛选测定。 此外，本发明涉及含有金黄色葡萄球菌DnaI和DnaC相关蛋白质的蛋白质复合物的多核苷酸和多肽，以及它们的变体。

    Fragments and variants of Staphylococcus aureus DNAG primase, and uses thereof
    9.
    发明授权
    Fragments and variants of Staphylococcus aureus DNAG primase, and uses thereof 失效
    金黄色葡萄球菌DNAG primase的片段和变体及其用途

    公开(公告)号：US07326541B2

    公开(公告)日：2008-02-05

    申请号：US10025222

    申请日：2001-12-19

    申请人： Jerry Pelletier ,  Philippe Gros ,  Michael DuBow ,  Dominique Bergeron

    发明人： Jerry Pelletier ,  Philippe Gros ,  Michael DuBow ,  Dominique Bergeron

    IPC分类号： C12Q1/48 ,  C12N9/12 ,  C07K1/00

    CPC分类号： G01N33/6893 ,  A61K38/00 ,  C07K14/31 ,  C12Q1/18 ,  G01N2500/00

    摘要： The invention relates to bacterial genes and proteins that are implicated in the process of DNA replication and also to bacteriophage genes and their protein products that interact with bacterial proteins involved in DNA replication. More particularly, the invention relates to compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein STAAU_R9. In addition, the invention relates to screening assays to identify compounds which modulate the level and/or activity of STAAU_R9 and to such compounds.

    摘要翻译： 本发明涉及涉及DNA复制过程的细菌基因和蛋白质，还涉及与参与DNA复制的细菌蛋白相互作用的噬菌体基因及其蛋白质产物。 更具体地说，本发明涉及涉及必需的金黄色葡萄球菌基因及其编码蛋白质STAAU_R9的组合物和方法。 此外，本发明涉及筛选测定以鉴定调节STAAU_R9和这些化合物的水平和/或活性的化合物。

    Model for studying the role of genes in tumor resistance to chemotherapy
    10.
    发明申请
    Model for studying the role of genes in tumor resistance to chemotherapy 审中-公开
    研究基因在肿瘤抗化疗中的作用模型

    公开(公告)号：US20060294604A1

    公开(公告)日：2006-12-28

    申请号：US10546055

    申请日：2004-02-17

    申请人： Jordan Fridman ,  Scott Lowe ,  Elisa de Stanchina ,  Hans Wendel ,  Jerry Pelletier

    发明人： Jordan Fridman ,  Scott Lowe ,  Elisa de Stanchina ,  Hans Wendel ,  Jerry Pelletier

    IPC分类号： A01K67/027 ,  C12N5/06 ,  C12N5/08 ,  C12N15/86

    CPC分类号： C12N15/86 ,  A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0331 ,  A01K2267/0393 ,  C07K14/82 ,  C12N9/1205 ,  C12N15/8509 ,  C12N2740/14043 ,  G01N33/5011 ,  G01N33/502 ,  G01N33/574 ,  G01N2800/52

    摘要： The invention provides the components of in vivo and in vitro systems and methods which use them to study the effects of altered expression of a gene activity, such as the human akt, bcl-2, eIF4E or PTEN activities, on the descendants of stem cells that have been engineered to give rise to hematopoietic tumorigenic or tumor cells, such as lymphomas, with a high frequency. The present invention provides vectors, cells and mammals, and methods which in part depend on such products, useful for understanding tumorigenesis and its treatments, and in particular, for identifying and studying inhibitors and activators associated with tumor cell growth and growth inhibition, cell death through apoptotic pathways, and changes in apoptotic pathway components that affect drug sensitivity and resistance in tumorigenic cells. Methods for identifying molecular targets for drug screening, identifying interacting gene activities, for identifying therapeutic treatments and for identifying candidates for new therapeutic treatments are provided.

    摘要翻译： 本发明提供体内和体外系统和方法的组分，其使用它们来研究基因活性的表达改变如人类akt，bcl-2，eIF4E或PTEN活性对干细胞后代的影响 已被设计成以高频率引起造血致瘤性或肿瘤细胞如淋巴瘤。 本发明提供载体，细胞和哺乳动物，以及部分依赖于这些产物的方法，其可用于了解肿瘤发生及其治疗，特别是鉴定和研究与肿瘤细胞生长和生长抑制相关的抑制剂和激活剂，细胞死亡 通过细胞凋亡途径以及影响致瘤细胞中药物敏感性和抗性的凋亡途径成分的变化。 提供了用于鉴定用于药物筛选的分子靶标，鉴定相互作用的基因活性，用于鉴定治疗性治疗和鉴定新的治疗性治疗候选物的方法。