MOLECULAR MECHANISM IN RESISTANCE TO FOLATE ANALOGUES
抵抗叶酸类似物的分子机制
基本信息
- 批准号:3164383
- 负责人:
- 金额:$ 33.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1977
- 资助国家:美国
- 起止时间:1977-05-01 至 1990-04-30
- 项目状态:已结题
- 来源:
- 关键词:dihydrofolate reductase drug resistance extrachromosomal DNA fibroblasts folate folate antagonist gene expression genetic manipulation genome immunologic techniques messenger RNA methotrexate molecular oncology neoplasm /cancer chemotherapy neoplasm /cancer genetics neoplastic cell nucleic acid metabolism nucleic acid sequence nutrition related tag tissue /cell culture virus RNA
项目摘要
The long-term objectives of this grant are to increase understanding of the
mechanisms whereby cultured cells and tumors change genetic properties by
the process of gene amplification, predominately with studies on resistance
to methotrexate. The studies to be undertaken include: 1) an analysis of
the nucleotide sequences constituting promoter regions of the dihydrofolate
reductase gene, and studies on the synthesis and metabolism of the
dihydrofolate reductase mRNA in the cell cycle; 2) an analysis of the
propensity of normal, malignant, and metastatic breast epithelium to
undergo spontaneous or induced amplification of the dihydrofolate reductase
gene as detected by use of the fluorescence activated cell sorter and
molecular biology technology; 3) an analysis of resistance to methotrexate
that is associated with an unstable phenotype and increased ability to bind
methotrexate at 4 degrees, and which has the properties of an altered
transport of methotrexate, employing a combination of techniques to
characterize the putative overproduced protein and its gene; 4) an attempt
to generate resistance to radiomimetic drugs in such a fashion as to select
for cells in which there is an increased capability for DNA recombination
which results in the resistance phenotype by a gene amplification mechanism.
这笔赠款的长期目标是增进对
培养细胞和肿瘤通过以下方式改变遗传特性的机制
基因扩增过程,主要是耐药性研究
甲氨蝶呤。 需要进行的研究包括: 1) 分析
构成二氢叶酸启动子区的核苷酸序列
还原酶基因及其合成与代谢研究
细胞周期中的二氢叶酸还原酶 mRNA; 2)分析
正常、恶性和转移性乳腺上皮的倾向
经历二氢叶酸还原酶的自发或诱导扩增
使用荧光激活细胞分选仪检测到的基因
分子生物学技术; 3)甲氨蝶呤耐药性分析
这与不稳定的表型和增强的结合能力有关
甲氨蝶呤在 4 度时具有改变的特性
甲氨蝶呤的运输,采用多种技术的组合
描述假定的过量产生的蛋白质及其基因的特征; 4)尝试
以这样的方式产生对拟放射药物的抗性,以便选择
对于 DNA 重组能力增强的细胞
这通过基因扩增机制导致抗性表型。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ROBERT T SCHIMKE其他文献
ROBERT T SCHIMKE的其他文献
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{{ truncateString('ROBERT T SCHIMKE', 18)}}的其他基金
GENOME EVOLUTION/REGULATION OF PROTEIN LEVELS IN AGING
衰老过程中蛋白质水平的基因组进化/调节
- 批准号:
3091022 - 财政年份:1985
- 资助金额:
$ 33.01万 - 项目类别:
GENOME EVOLUTION/REGULATION OF PROTEIN LEVELS IN AGING
衰老过程中蛋白质水平的基因组进化/调节
- 批准号:
3091019 - 财政年份:1985
- 资助金额:
$ 33.01万 - 项目类别:
GENOME EVOLUTION/REGULATION OF PROTEIN LEVELS IN AGING
衰老过程中蛋白质水平的基因组进化/调节
- 批准号:
3091024 - 财政年份:1985
- 资助金额:
$ 33.01万 - 项目类别:
GENOME EVOLUTION/REGULATION OF PROTEIN LEVELS IN AGING
衰老过程中蛋白质水平的基因组进化/调节
- 批准号:
3091023 - 财政年份:1985
- 资助金额:
$ 33.01万 - 项目类别:
GENOME EVOLUTION/REGULATION OF PROTEIN LEVELS IN AGING
衰老过程中蛋白质水平的基因组进化/调节
- 批准号:
3091021 - 财政年份:1985
- 资助金额:
$ 33.01万 - 项目类别:
MOLECULAR MECHANISM IN RESISTANCE TO FOLATE ANALOGUES
抵抗叶酸类似物的分子机制
- 批准号:
3164386 - 财政年份:1977
- 资助金额:
$ 33.01万 - 项目类别:
MOLECULAR MECHANISM IN RESISTANCE TO FOLATE ANALOGUES
抵抗叶酸类似物的分子机制
- 批准号:
3164385 - 财政年份:1977
- 资助金额:
$ 33.01万 - 项目类别:
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