Source:http://linkedlifedata.com/resource/pubmed/id/12118325
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2002-7-15
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| pubmed:abstractText |
Thymidylate synthase (TS) is the molecular target of fluoropyrimidine (FP) chemotherapy, and novel anticancer drugs effective against TS-overexpressing tumors are required to treat patients with FP-refractory solid tumors. We have evaluated the inhibition of cell proliferation in vitro and antitumor activity in vivo of FdUMP[10], an oligodeoxynucleotide 10mer in which 5-fluorouracil (5-FU) is the only nucleobase. FdUMP[10] is a pro-drug of FdUMP, the TS inhibitory metabolite of FPs. FdUMP[10] was 338-fold more potent than 5-FU at inhibiting cell proliferation in the NCI 60 cell line screen. The antitumor activity of FdUMP[10] was compared to 5-FU using H-T29 xenografts in female CD-1 athymic (nu+/nu+) mice. Treatment with FdUMP[10] as a single agent (40 mg/kg/daily x 5, i.v.) delayed tumor growth and resulted in a smaller mean tumor size (T/C value = 51%, p<0.001 compared with the control group). Treatment with 5-FU (25 mg/kg/daily x 5, i.p.) had similar results as single agent FdUMP[10] (T/C value = 65%, p=0.238 compared with the FdUMP[10] treated group. Simultaneous treatment of tumor-bearing mice with both drugs (FdUMP[10] plus 5-FU) further delayed tumor growth (T/C value = 36%; p=0.003 relative to 5-FU). The results from the combined treatment group were not, however, statistically significant relative to the group receiving single agent FdUMP[10] treatment (p=0.059). Histological examination revealed systemic damage was limited to the colonic epithelium in all treatment groups and was least extensive with single agent FdUMP[10] compared to the other treatment groups. The data support the concept that FdUMP[10] is a useful prototype of a novel type of FP that is likely to be more efficacious than FPs in clinical use.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/FdUMP(10),
http://linkedlifedata.com/resource/pubmed/chemical/Fluorodeoxyuridylate,
http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidylate Synthase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1019-6439
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
21
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
303-8
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| pubmed:dateRevised |
2010-12-3
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| pubmed:meshHeading |
pubmed-meshheading:12118325-Animals,
pubmed-meshheading:12118325-Colon,
pubmed-meshheading:12118325-Colonic Neoplasms,
pubmed-meshheading:12118325-Drug Combinations,
pubmed-meshheading:12118325-Drug Screening Assays, Antitumor,
pubmed-meshheading:12118325-Enzyme Inhibitors,
pubmed-meshheading:12118325-Female,
pubmed-meshheading:12118325-Fluorodeoxyuridylate,
pubmed-meshheading:12118325-Humans,
pubmed-meshheading:12118325-Mice,
pubmed-meshheading:12118325-Mice, Nude,
pubmed-meshheading:12118325-Neoplasm Transplantation,
pubmed-meshheading:12118325-Neoplasms, Experimental,
pubmed-meshheading:12118325-Prodrugs,
pubmed-meshheading:12118325-Safety,
pubmed-meshheading:12118325-Thymidylate Synthase,
pubmed-meshheading:12118325-Transplantation, Heterologous,
pubmed-meshheading:12118325-Tumor Cells, Cultured
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| pubmed:year |
2002
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| pubmed:articleTitle |
Efficacy and safety of FdUMP[10] in treatment of HT-29 human colon cancer xenografts.
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| pubmed:affiliation |
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
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| pubmed:publicationType |
Journal Article
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