Linked Life Data

7872962

Source:http://linkedlifedata.com/resource/pubmed/id/7872962

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1995-3-30
pubmed:abstractText
Two human colon cell lines, HCT-8 and HT-29, were exposed to 5-fluorouracil (FUra) under conditions similar to the human plasma pharmacokinetic profile achieved by a single bolus dose or a sustained i.v. infusion. The bolus treatment for 5 days caused a substantial cell kill; however, only a moderate inhibition in cell growth was obtained with sustained exposure to the clinically relevant level of 2 microM. To achieve a cell kill equivalent to the bolus method, a sustained concentration of 10 microM was required. This would constitute a 60% increase in the total area under the curve (AUC) compared with the bolus treatment. After three courses of therapy with each of the schedules, emerging cell lines displayed a similar degree of resistance. HT-29 resistant cell lines returned to the original sensitivity within a few weeks, and most of the enzymes involved in the metabolic activation of FUra returned to their pretreatment activities. However, resistance and enzymatic modifications remained in the HCT-8 line for at least 3 months. In the HCT-8 cell line derived from bolus treatment, resistance was associated with a 50-60% reduction in uridine kinase activity. In the line derived from continuous exposure, there was a 35-40% reduction in uridine kinase in addition to a greater reduction in the activity of orotate phosphoribosyltransferase. These changes in both resistant cell lines resulted in a decreased incorporation of [3H]FUra into nucleic acids and a reduced formation of di- and triphosphate nucleotides of FUra.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
559-65
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Effect of clinically modeled regimens on the growth response and development of resistance in human colon carcinoma cell lines.
pubmed:affiliation
Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't