DEVELOPMENT OF NEW CANCER THERAPY USING HISTONE DEACETHYLASE INHIBITORS

使用组蛋白脱乙酰酶抑制剂开发新的癌症疗法

基本信息

  • 批准号:
    13670465
  • 负责人:
  • 金额:
    $ 2.3万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2002
  • 项目状态:
    已结题

项目摘要

1. Biological effects of aceylated peptidesHDAC inhibitors have a core domain which mimicks acetylated lysines, and bind to HDAC directly. We thus explored whether peptides carrying acetylated lysines can inhibit HDAC and introduce apoptosis in cancer cells. So far, our several peptides cannot have sufficient effects on HDAC. We are now frying other peptides.2. HDAC inhibitor-mediated cancer therapyHDAC inhibitors alone introduce apoptosis in a variety of carcinoma cells. These drugs are promising anticancer agents. However, phase I clinical trial revealed that there are some adverse effects and thus we should consider how their administration doses are reduced. In this regard, we are now investigating their combination therapy. To date, we found that HDAC inhibitors can be strongly effective with some technique. We are now preparing a new manuscript and have already submitted this patent. Our data strongly suggest that our technique can reduce required doses for their anticancer activity.3. Biological effect of HAT overexpressoin using reporter assaysWe transfected p300 or CBP-expression vectors into several cancer cells. Using a luciferase-reporter assay, we found that there are some difference in their transcriptional activation. Especially, both genes strongly activate AP-1 transcription. This strongly suggest that p300 and CBP are tightly linked to MEK/ERK pathway. We thus investigating this mechanism.
1.乙酰化肽的生物学效应HDAC抑制剂具有模拟乙酰化赖氨酸的核心结构域,并直接与HDAC结合。因此,我们探索了携带乙酰化赖氨酸的肽是否可以抑制HDAC并在癌细胞中引入凋亡。到目前为止,我们的几种肽不能对HDAC具有足够的作用。我们现在正在炒其他肽。2. HDAC抑制剂单独在多种癌细胞中引入凋亡。这些药物是很有前途的抗癌药物。但是,I期临床试验显示有一些不良反应,因此我们应该考虑如何减少其给药剂量。在这方面,我们现在正在研究他们的联合治疗。迄今为止,我们发现HDAC抑制剂可以通过一些技术强烈有效。我们现在正在准备一份新的手稿,并已经提交了这项专利。我们的数据强烈表明,我们的技术可以减少抗癌活性所需的剂量。用报告基因分析法研究HAT过表达的生物学效应我们将p300或CBP表达载体转染到几种癌细胞中。通过酶-报告基因分析,我们发现它们的转录激活有一定的差异。特别是,这两个基因强烈激活AP-1转录。这强烈表明p300和CBP与MEK/ERK通路紧密相连。因此,我们正在研究这种机制。

项目成果

期刊论文数量(24)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hiroshi Yasui: "Combination of tumor necrosis factor-α with sulindac augments its apoptotic potential and suppresses tumor growth of human carcinoma cells in nude mice"Cancer. 97. 1412-1420 (2003)
Hiroshi Yasui:“肿瘤坏死因子-α 与舒林酸的组合可增强其凋亡潜力并抑制裸鼠中人类癌细胞的肿瘤生长”癌症。 97. 1412-1420 (2003)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Masaaki Adachi: "The proapoptotic BH3-only protein BAD transduces cell death signals independently of its interaction with Bcl-2"Cell Death and Diff.. 9. 1240-1247 (2002)
Masaaki Adachi:“仅促凋亡 BH3 蛋白 BAD 转导细胞死亡信号,独立于其与 Bcl-2 的相互作用”Cell Death and Diff.. 9. 1240-1247 (2002)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Hiroshi Yasui: "Combination of tumor necrosis factor-a with sulindac augments its apoptotic potential and suppresses tumor growth of human carcinoma cells in nude mice"Cancer. 98. 1412-1420 (2003)
Hiroshi Yasui:“肿瘤坏死因子-a 与舒林酸的组合可增强其凋亡潜力并抑制裸鼠体内人类癌细胞的肿瘤生长”癌症。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
Yoshihiko Satoh: "Expression of CD66a in multiple myeloma"J Clini.Lab.Anal.. 16. 79-85 (2002)
Yoshihiko Satoh:“多发性骨髓瘤中 CD66a 的表达”J Clini.Lab.Anal.. 16. 79-85 (2002)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Shonai T: "NEK/ERK pathway protects ionizing radiation-induced loss of mitochondrial membrane potential and cell death in lymphocytic leukemia cells"Cell Death Diff.. (in press). (2002)
Shonai T:“NEK/ERK 通路可保护淋巴细胞白血病细胞中电离辐射引起的线粒体膜电位损失和细胞死亡”细胞死亡差异(正在出版)。
  • DOI:
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  • 影响因子:
    0
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ADACHI Masaaki其他文献

ADACHI Masaaki的其他文献

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{{ truncateString('ADACHI Masaaki', 18)}}的其他基金

Ultrahigh-precision 3D-shape measurement technique usable under vertical vibration
可在垂直振动下使用的超高精度3D形状测量技术
  • 批准号:
    21360115
  • 财政年份:
    2009
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular diagnosis by evaluating histone methylation
通过评估组蛋白甲基化进行分子诊断
  • 批准号:
    19590566
  • 财政年份:
    2007
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
3D-shape measurement method of a small object vibrating vertically
小物体垂直振动的三维形状测量方法
  • 批准号:
    18560247
  • 财政年份:
    2006
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of a new anticancer therapy by reguration of machinery for epigenetics
通过表观遗传学机制的调节开发新的抗癌疗法
  • 批准号:
    17590273
  • 财政年份:
    2005
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Analysis of proapoptotic functions of BH3-only protein BAD
BH3-only蛋白BAD的促凋亡功能分析
  • 批准号:
    15603004
  • 财政年份:
    2003
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Vertical-scanning profilometry having nanometric height resolution and high scanning speed using two short-coherent-light sources of different wavelengths
使用两个不同波长的短相干光源,具有纳米级高度分辨率和高扫描速度的垂直扫描轮廓测定法
  • 批准号:
    14350129
  • 财政年份:
    2002
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Study of real-time and precision measurement for 2-D deformation amounts of machine tool
机床二维变形量实时精密测量研究
  • 批准号:
    11650120
  • 财政年份:
    1999
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Suppression of tumor metastasis through anti-apoptotic molecules BCL-2/BAG-1
通过抗凋亡分子BCL-2/BAG-1抑制肿瘤转移
  • 批准号:
    09670484
  • 财政年份:
    1997
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Significance and functional analysis of protein-tyrosine phosphatases expressed in hematopoietic disorders.
造血障碍中表达的蛋白酪氨酸磷酸酶的意义和功能分析。
  • 批准号:
    05807096
  • 财政年份:
    1993
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Waveness Profilometer of Large Optical Parts Insensitive to the Waveness and Roughness of Reference Mirror
对参考镜的波度和粗糙度不敏感的大型光学零件的波度轮廓仪
  • 批准号:
    02650028
  • 财政年份:
    1990
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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EBV潜伏期主要抗氧化剂NRF2对p62的转录激活
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定义控制转录激活域功能的蛋白质序列特征
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