KINETICS OF FOLATE METABOLISM
KINETICS OF FOLATE METABOLISM
批准号:
3852950
负责人:
P F MORRISON
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
breast neoplasms cell line chemical kinetics colon neoplasms enzyme activity enzyme model folate human tissue liver neoplasms methotrexate neoplasm /cancer chemotherapy neoplastic cell nutrition aspect of cancer nutrition related tag thymidylate synthase tissue /cell culture trimetrexate vitamin metabolism
中文摘要
叶酸处理的细胞中叶酸池动态的最新观察结果
甲氨蝶呤或甲氨蝶呤显示了不同的叶酸消耗
在乳腺癌和结肠癌细胞系中的应答比在肝癌细胞系中的应答更高。
对这种差异的解释是从以下方面寻求的:
叶酸循环的生化动力学。 叶酸循环生化
用网络模型预测酶活性
已知存在于几种结肠癌细胞系中的差异是
足以引起观察到的叶酸消耗的不同模式。
胸苷酸合成酶升高十倍和四十倍的细胞
(TS)预测活性显示几乎完全的叶酸消耗
当暴露于1 μ(M)剂量的甲氨蝶呤(MTX)时。 实验
已在NCI医学分支完成,选择了两个细胞系
对于这些增加的活性水平(加上对照),
暴露于1 μ(M)和10 μ(M)剂量的MTX。 比较
人类结肠线数据的理论估计主要基于
在所有非零剂量和TS下,人乳腺线参数均显示一致性
活动 然而,在细胞系中缺乏与正常细胞的一致性。
暴露于较高MTX剂量的TS活性;理论预测短期
增加10-甲酰四氢叶酸,而实验表明,
快速下降。 可能,这种差异是由于代表性过高
TS对MTX多聚谷氨酸抑制的敏感性,
在较大的药物剂量下明显。
英文摘要
Recent observations of folate pool dynamics in cells treated with
trimetrexate or methotrexate have revealed different folate depletion
responses in breast and colon cancer cell lines than in hepatoma lines.
An explanation of this difference is being sought in terms of the
biochemical kinetics of the folate cycle. A folate cycle biochemical
network model has been employed to predict that the enzyme activity
differences known to exist across several colon cancer lines are
sufficient to cause the diverse patterns of folate depletion observed.
Cells with both ten- and fortyfold elevations in thymidylate synthase
(TS) activity were predicted to exhibit nearly complete folate depletion
when exposed to 1-mu(M) doses of methotrexate (MTX). Experiments have
been completed in the Medicine Branch, NCI, on two cell lines selected
for these increased levels of activity (plus controls) in which the cells
were exposed to both 1-mu(M) and 10-mu(M) doses of MTX. Comparisons of
the human colon line data with theoretical estimates based largely on
human breast line parameters showed agreement at all nonzero doses and TS
activities. Agreement, however, was lacking in the cell line with normal
TS activity exposed to the higher MTX dose; theory predicted a short-term
increase in 10-formyl tetrahydrofolate, while experimentation showed a
rapid decrease. Possibly, this disparity is due to an overrepresentation
of the sensitivity of TS to MTX polyglutamate inhibition, an effect more
noticeable at larger drug doses.
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会议论文
THYMIDYLATE SYNTHASE REGULATION
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批准号:5204103
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
THYMIDYLATE SYNTHASE REGULATION
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批准号:3789467
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
SULFONE STRUCTURE-ACTIVITY ANALYSIS
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批准号:3916238
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
DRUG TRANSPORT IN BRAIN
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批准号:2590318
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
SOURCES OF QUINOLINIC ACID
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批准号:2449928
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
KINETICS OF FOLATE METABOLISM
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批准号:3937317
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
DRUG TRANSPORT IN BRAIN
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批准号:3767454
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
THYMIDYLATE SYNTHASE REGULATION
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批准号:3767486
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
KINETICS OF FOLATE METABOLISM
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批准号:3874202
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
SOURCES OF QUINOLINIC ACID
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批准号:6163213
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
CISPLATIN KINETICS
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批准号:3959966
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
CISPLATIN KINETICS
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批准号:3937314
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
DRUG TRANSPORT IN BRAIN
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批准号:5204074
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
KINETICS OF FOLATE METABOLISM
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批准号:3959969
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
KINETICS OF FOLATE METABOLISM
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批准号:3896223
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
KINETICS OF FOLATE METABOLISM
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批准号:3978353
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
DRUG TRANSPORT IN BRAIN
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批准号:4705614
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
DRUG TRANSPORT IN BRAIN
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批准号:3852956
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
DRUG TRANSPORT IN BRAIN
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批准号:3789420
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
PHARMACOKINETICS OF BETA GLUCOCEREBROSIDASE IN GAUCHER'S DISEASE
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批准号:6163225
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:P F MORRISON
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依托单位:
海外基金