Linked Life Data

12477049

Source:http://linkedlifedata.com/resource/pubmed/id/12477049

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-12-12
pubmed:abstractText
Deoxycytidine kinase (dCK) is essential for the phosphorylation of gemcitabine (2',2'-difluorodeoxycytidine), a deoxycytidine analogue active against various solid tumors. Cytidine deaminase (CDA) catalyzes the degradation of gemcitabine. We determined whether dCK and/or CDA levels would predict response to gemcitabine. Activities of dCK and CDA were measured in a panel of eight gemcitabine-sensitive and -resistant tumors of a different origin (pancreas, lung, colon, ovary, and head and neck) grown as s.c. tumors in mice. Sensitivity to gemcitabine was expressed as treated versus control (tumor volume treated mice/control mice). Gemcitabine was given on days 0, 3, 6, and 9 (q3dx4) at its maximum tolerated dose. In addition, we measured the mRNA expression and protein levels of dCK in seven human tumor xenografts. dCK activity (mean +/- SE) ranged from 3.3+/-0.3 to 18.4+/-1.2 nmol/h/mg protein. Sensitivity to gemcitabine, expressed as treated versus control, ranged from 0.98 to 0.02, and the activity of CDA varied from 2+/-2 to 411+/-4 nmol/h/mg protein. In contrast to CDA, dCK activity was clearly related to gemcitabine sensitivity (p = -0.93; P < 0.001). This indicates that dCK might be an important prognostic marker for gemcitabine sensitivity. Protein levels were significantly related to both dCK activity (r = 0.96; P < 0.001) and gemcitabine sensitivity (rho = -0.96; P < 0.001). dCK expression as determined by competitive template reverse transcriptase PCR was significantly related with the dCK activity (r = 0.88; P = 0.025) and protein levels (p = 0.80; P = 0.052) but not with gemcitabine sensitivity, suggesting a post-translational regulation of dCK. In conclusion, the clear correlation between dCK levels and gemcitabine sensitivity in various murine tumors and human tumor xenografts may be a prognostic parameter when considering gemcitabine therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
371-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12477049-Animals, pubmed-meshheading:12477049-Antimetabolites, Antineoplastic, pubmed-meshheading:12477049-Blotting, Western, pubmed-meshheading:12477049-Cytidine Deaminase, pubmed-meshheading:12477049-DNA Primers, pubmed-meshheading:12477049-Deoxycytidine, pubmed-meshheading:12477049-Deoxycytidine Kinase, pubmed-meshheading:12477049-Female, pubmed-meshheading:12477049-Humans, pubmed-meshheading:12477049-Mice, pubmed-meshheading:12477049-Mice, Inbred C57BL, pubmed-meshheading:12477049-Mice, Nude, pubmed-meshheading:12477049-Neoplasm Transplantation, pubmed-meshheading:12477049-Neoplasms, Experimental, pubmed-meshheading:12477049-RNA, Messenger, pubmed-meshheading:12477049-RNA, Neoplasm, pubmed-meshheading:12477049-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12477049-Skin Neoplasms
pubmed:year
2002
pubmed:articleTitle
Pretreatment deoxycytidine kinase levels predict in vivo gemcitabine sensitivity.
pubmed:affiliation
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't