ANTITUMOR THERAPIES BASED ON INHIBITION OF SUPEROXIDE DISMUTASE

基于抑制超氧化物歧化酶的抗肿瘤疗法

基本信息

  • 批准号:
    6203295
  • 负责人:
  • 金额:
    $ 11.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1999
  • 资助国家:
    美国
  • 起止时间:
    1999-08-31 至 2001-06-30
  • 项目状态:
    已结题

项目摘要

The purpose of this proposal is to study the role of active oxygen species in cancer cell cytotoxicity and to determine if lipids are a major target of these species. In order to study the role of active oxygen, superoxide dismutase (SOD) levels of parental and doxorubicin- resistant human breast carcinoma MCF-7 cells will be modulated and the effect on cell killing by selected antitumor agents (doxorubicin, bleomycin, ionizing radiation, tumor necrosis factor) determined. Modulation of superoxide dismutase will be accomplished by transfection of sense and anti-sense SOD cDNA. After transfection, clones with lower and higher than control levels of SOD activity will be isolated. These clones will then be tested for sensitivity to the selected antitumor agents. Both CuZnSOD and MnSOD will be transfected. Verification that superoxide dismutase modulation has occurred will be accomplished using enzyme activity, immunoreactive protein, Northern and Southern blot assays. Catalase, glutathione peroxidase, glutathione reductase, and glutathione levels will also be measured in the stable clones to determine if any of the other common antioxidants have been altered. Similar studies will be performed after glutathione peroxidase (GPX) transfection. GPX will be transferred into wild type MCF-7 cells as well as an SOD-overexpressing clone. The role of oxygen and lipid radicals will also be tested directly by measuring qualitatively and quantitatively the radicals present after treatment of control and SOD-and/or GPX-modified cells with the selected antitumor agents. Measurement of radicals will be accompanied by using the electron paramagnetic resonance technique of spin trapping. Last, the role of lipids in the antitumor effect will be studied. This will be done in two different ways: 1) measuring the amount of lipid peroxidation that occurs during tumor cell killing by the above agents; and 2) modifying the lipids of the cell and determining the effect on tumor cell killing by selected antitumor combinations in control and SOD- and/or GPX-transfected cell lines. This research should provide valuable new information on the mechanisms and targets of antitumor agents. It is hoped this knowledge will eventually lead to more powerful antitumor protocols.
本提案的目的是研究活性氧的作用

项目成果

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专利数量(0)

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LARRY OBERLEY其他文献

LARRY OBERLEY的其他文献

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{{ truncateString('LARRY OBERLEY', 18)}}的其他基金

Oxidative Stress and Metabolism Research Cluster
氧化应激和代谢研究集群
  • 批准号:
    7359471
  • 财政年份:
    2007
  • 资助金额:
    $ 11.34万
  • 项目类别:
Molecular Species Responsible for Tumor Suppressive Effect of MnSOD
负责 MnSOD 肿瘤抑制作用的分子种类
  • 批准号:
    7261605
  • 财政年份:
    2007
  • 资助金额:
    $ 11.34万
  • 项目类别:
FREE READICAL CANCER BIOLOGY PROGRAM
免费的癌症生物学课程
  • 批准号:
    7127074
  • 财政年份:
    2005
  • 资助金额:
    $ 11.34万
  • 项目类别:
CORE--ANTIOXIDANT ENZYME
核心--抗氧化酶
  • 批准号:
    6616896
  • 财政年份:
    2002
  • 资助金额:
    $ 11.34万
  • 项目类别:
THERAPIES BASED ON ANTIOXIDANT ENZYME MODULATION
基于抗氧化酶调节的疗法
  • 批准号:
    6616893
  • 财政年份:
    2002
  • 资助金额:
    $ 11.34万
  • 项目类别:
TRAINING PROGRAM IN FREE RADICAL AND RADIATION BIOLOGY
自由基和辐射生物学培训计划
  • 批准号:
    6376872
  • 财政年份:
    1999
  • 资助金额:
    $ 11.34万
  • 项目类别:
Training Program in Free Radical and Radiation Biology
自由基和放射生物学培训计划
  • 批准号:
    7194150
  • 财政年份:
    1999
  • 资助金额:
    $ 11.34万
  • 项目类别:
Training Program in Free Radical and Radiation Biology
自由基和放射生物学培训计划
  • 批准号:
    7119831
  • 财政年份:
    1999
  • 资助金额:
    $ 11.34万
  • 项目类别:
Training Program in Free Radical and Radiation Biology
自由基和放射生物学培训计划
  • 批准号:
    7012855
  • 财政年份:
    1999
  • 资助金额:
    $ 11.34万
  • 项目类别:
Training Program in Free Radical and Radiation Biology
自由基和放射生物学培训计划
  • 批准号:
    7197193
  • 财政年份:
    1999
  • 资助金额:
    $ 11.34万
  • 项目类别:

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