Linked Life Data

12168813

Source:http://linkedlifedata.com/resource/pubmed/id/12168813

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-8-9
pubmed:abstractText
Gemcitabine (Gem) is a deoxycytidine analogue whose active metabolite, dFdCTP, blocks DNA elongation and has a cytotoxic effect. Hydroxyurea (HU) is an S-phase specific inhibitor of ribonucleotide reductase (RR) with a broad spectrum of antitumor effects. We report here that low-dose HU enhanced the activity of Gem in a time- and sequence-dependent manner. Exposure of human oropharyngeal carcinoma KB cells to HU followed by the addition of Gem at various times significantly enhanced cytotoxicity when compared to controls. The greatest enhancement of cytotoxicity occurred when Gem was added 8 hours after HU. By treating KB cells with radiolabeled-Gem following HU treatment, we further confirmed that the incorporation of dFdCTP into DNA increased 6-fold over control reactions under these conditions. The mechanism of the time- and sequence-dependent enhancement is associated with a decrease in hRRM2 RNA, protein, and activity between 4 and 8 hours. The subsequent depletion of dNTP pools allows for increased incorporation of dFdCTP into cells arrested in S-phase, resulting in higher levels of cytotoxicity than either treatment alone.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0250-7005
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1369-77
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
Time and sequence dependence of hydroxyurea in combination with gemcitabine in human KB cells.
pubmed:affiliation
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA 91010, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.