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ANTICANCER DRUG RESISTANCE BY BCL-2 ONCOGENE EXPRESSION

ANTICANCER DRUG RESISTANCE BY BCL-2 ONCOGENE EXPRESSION
BCL-2 癌基因表达的抗癌药物耐药性
批准号：
2429875
负责人：
RAYMOND E MEYN
金额：
$19.75万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
项目状态：
已结题
起止时间：
1996-06-01 至 1999-05-31
来源：
https://reporter.nih.gov/project-details/2429875
关键词：
animal genetic material tag antineoplastics antioxidants antisense nucleic acid apoptosis biological signal transduction buthionine sulfoximine drug resistance free radical oxygen gene expression glutathione human genetic material tag ionizing radiation mitochondria oligonucleotides oncogenes polymerase chain reaction protein structure function thiols tissue /cell culture transfection /expression vector

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DESCRIPTION: This proposal is aimed at evaluating the hypothesis that bcl-2 inhibition of apoptosis is mediated by increased levels of glutathione (GSH). The LY-as lymphoma cell line, which readily undergoes apoptosis in response to chemotherapeutic agents and ionizing radiation, will be transfected with bcl-2 under control of the inducible lac promoter. Antisense phosphorothioate oligonucleotides will be used to reduce bcl-2 expression in the LY-ar cell line which expresses high levels of bcl-2 and is resistant to induction of apoptosis. The relationship between GSH levels and apoptosis will be characterized in both systems. The mechanisms responsible for higher levels of GSH in cells resistant to apoptosis will be delineated and the role of reactive oxygen species (ROS) as mediators of apoptosis and GSH scavenging will be further defined. Animal models using the LY-as and LY-ar cell lines will be used to evaluate strategies with buthionine sulfoximine (BSO) to lower GSH to increase sensitivity to apoptosis.
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Extension of Radiotherapy Research
Extension of Radiotherapy Research
GENE THERAPY STRATEGIES TO RADIOSENSITIZE HUMAN TUMOR CELLS
TUMOR CELL RADIOSENSITIZATION BY ADENOVIRAL-MEDIATED P16
  • 批准号：
    6205352
  • 项目类别：
  • 资助金额：
    $17.49万
  • 财政年份：
    2000
  • 负责人：
    RAYMOND E MEYN
  • 依托单位：
    INTROGEN THERAPEUTICS, INC.
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