公开(公告)号：US20070082339A1

公开(公告)日：2007-04-12

申请号：US11246802

申请日：2005-10-07

申请人： Dalia Cohen ,  Shaowen Wang

发明人： Dalia Cohen ,  Shaowen Wang

IPC分类号： C12Q1/68 ,  G01N33/567

CPC分类号： C12Q1/48 ,  C12Q1/6876 ,  C12Q2600/158

摘要： The invention relates to the use of gene and protein expression levels as a marker for HDAC inhibition. Also disclosed are in vivo and in vitro methods for screening a compound for HDAC inhibitory activity, as well as methods for monitoring the therapeutic efficacy of an HDAC inhibitor in a subject in vivo and for determining resistance to an HDAC inhibitor in vitro or in vivo.

摘要翻译： 本发明涉及使用基因和蛋白质表达水平作为HDAC抑制的标志物。 还公开了用于筛选化合物用于HDAC抑制活性的体内和体外方法，以及用于监测体内受试者体内HDAC抑制剂的治疗功效以及用于在体外或体内测定对HDAC抑制剂的抗性的方法。

公开(公告)号：US20060040884A1

公开(公告)日：2006-02-23

申请号：US11191875

申请日：2005-07-28

申请人： Francis Buxton ,  Dalia Cohen ,  Denise Fischer ,  Shaowen Wang

发明人： Francis Buxton ,  Dalia Cohen ,  Denise Fischer ,  Shaowen Wang

IPC分类号： A61K48/00 ,  C07H21/04

CPC分类号： C12N15/1137 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3341 ,  C12N2310/341 ,  C12N2310/346 ,  C12Y203/01048 ,  G01N2333/91057 ,  C12N2310/3525

摘要： Antisense compounds, compositions and methods are provided for modulating the expression of trapoxin A regulated genes, including but not limited to those genes induced by ectopic expression of p21waf1 that are disclosed herein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding these genes. Methods of using these compounds for modulation of expression of these genes and for treatment of diseases associated with these genes, as well as those associated with abnormal HDAC activity, particularly cancer or others characterized by abnormal cell proliferation, are provided. Furthermore, the invention relates to the use of RhoB as a biomarker to evaluate the efficacy of treatment of humans with abnormal HDAC activity including proliferative diseases such as cancer. Also disclosed is a method for identifying HDAC inhibitors and trapoxin analogs based on the surprising discovery that up regulation or RhoB and increased RhoB protein levels are associated with HDAC inhibition.

摘要翻译： 提供反义化合物，组合物和方法用于调节调节蛋白A调节的基因的表达，包括但不限于本文公开的由p21 的异位表达诱导的那些基因。 组合物包含靶向编码这些基因的核酸的反义化合物，特别是反义寡核苷酸。 提供了使用这些化合物调节这些基因的表达和治疗与这些基因有关的疾病的方法，以及与异常HDAC活性相关的疾病，特别是癌症或以异常细胞增殖为特征的其他方法。 此外，本发明涉及RhoB作为生物标志物的用途，以评估治疗具有异常HDAC活性的人的功效，包括增殖性疾病如癌症。 还公开了基于令人惊讶的发现，鉴定HDAC抑制剂和诱导蛋白类似物的方法，即上调或RhoB和增加的RhoB蛋白水平与HDAC抑制相关。