共 24 条
The novel DNA methylation inhibitor zebularine is effective against the development of murine T-cell lymphoma
被引:50
作者:

Herranz, M
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机构: Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain

Martín-Caballero, J
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机构: Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain

Fraga, MF
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机构: Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain

Ruiz-Cabello, J
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机构: Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain

Flores, JM
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机构: Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain

Desco, M
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机构: Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain

Marquez, V
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h-index: 0
机构: Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain

Esteller, M
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h-index: 0
机构: Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain
机构:
[1] Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain
[2] Spanish Natl Canc Ctr, Anim Facil Unit, Madrid 28029, Spain
[3] Univ Complutense Madrid, Sch Vet, Inst Estudios Biofuncionales, Madrid, Spain
[4] Univ Complutense Madrid, Sch Vet, Dept Pathol, Madrid, Spain
[5] Univ Hosp Gregorio Maranon, Dept Expt Surg, Med Image Lab, Madrid, Spain
[6] NCI, Med Chem Lab, NIH, Frederick, MD 21701 USA
来源:
关键词:
D O I:
10.1182/blood-2005-05-2033
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Gene silencing by CpG island promoter hypermethylation has awakened the interest for DNA demethylating agents as chemotherapy drugs. Zebularine (1-[beta-D-ribofuranosil]-1,2-dihydropyrimidin-2-1) has been recently described as a new DNA methylation inhibitor. Here we have studied its effects in a mouse model of radiation-induced lymphomagenesis using nuclear magnetic resonance (NMR) and positron emission tomography (PET). All control animals presented large thymic T lymphomas and died between 4 and 5.5 months. In contrast, 40% (12 of 30) of zebularine-treated animals were still alive after 1 year (Kaplan-Meier P < .001). NMR and PET imaging showed that surviving animals presented a thymus structure/volume similar to normal mice of the same age. Most important, zebularine demonstrated a complete lack of toxicity in nonirradiated control mice. DNA hypomethylation induced by zebularine occurred in association with depletion in extractable DNA methyltransferase 1 protein. Thus, our data support the role of zebularine as a DNA demethylating agent with antitumor activity and little toxicity.
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页码:1174 / 1177
页数:4
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机构: Spanish Natl Canc Ctr, CNIO, Mol Pathol Programme, Canc Epigenet Lab, Madrid 28029, Spain

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机构: Spanish Natl Canc Ctr, CNIO, Mol Pathol Programme, Canc Epigenet Lab, Madrid 28029, Spain

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机构: Spanish Natl Canc Ctr, CNIO, Mol Pathol Programme, Canc Epigenet Lab, Madrid 28029, Spain

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机构: Spanish Natl Canc Ctr, CNIO, Mol Pathol Programme, Canc Epigenet Lab, Madrid 28029, Spain

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