1998
DOI: 10.1038/bjc.1998.443
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Thymidylate synthase expression and activity: relation to S-phase parameters and 5-fluorouracil sensitivity

Abstract: Summary Six human cancer cell lines exhibiting a large range of sensitivity to 5-fluorouracil (5-FU) were evaluated for thymidylate synthase (TS) and p53 gene expression, TS and dihydropyrimidine dehydrogenase (DPD) activity, as well as cell cycle parameters, S-phase fraction (SPF), bromodeoxyuridine labelling index (LI) and S-phase duration (SPD). All None of the cell lines had previously been exposed to 5-FU. and thus exhibited spontaneous difference in sensitivity to 5-FU. MtATERIALS AND METHODS Material… Show more

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Cited by 41 publications
(32 citation statements)
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References 20 publications
(8 reference statements)
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“…TS protein or gene expression has been reported to be strongly associated with response to 5-FU treatment and patient survival after chemotherapy, 11,12,20,31,32) but the correlation between sensitivity to 5-FU and TS activity has been reported to be relatively poor in panels of human tumor cell lines, 9,10) and the absence of any correlation between TS activity and sensitivity to 5-FU has been documented in several recent reports. 16,18,33) The inconsistent results concerning the association between TS expression and response to 5-FU may in part be attributable to the different measurement procedures. The role of TS in sensitivity to 5-FU may be more accurately demonstrated by real-time RT-PCR than by enzyme activity, because it provides a very broad dynamic range.…”
Section: Discussionmentioning
confidence: 99%
“…TS protein or gene expression has been reported to be strongly associated with response to 5-FU treatment and patient survival after chemotherapy, 11,12,20,31,32) but the correlation between sensitivity to 5-FU and TS activity has been reported to be relatively poor in panels of human tumor cell lines, 9,10) and the absence of any correlation between TS activity and sensitivity to 5-FU has been documented in several recent reports. 16,18,33) The inconsistent results concerning the association between TS expression and response to 5-FU may in part be attributable to the different measurement procedures. The role of TS in sensitivity to 5-FU may be more accurately demonstrated by real-time RT-PCR than by enzyme activity, because it provides a very broad dynamic range.…”
Section: Discussionmentioning
confidence: 99%
“…Because this is the only pathway that provides the essential thymidylate precursor for DNA synthesis, and because TS is highly expressed in oral cancer cells (48) and in patients diagnosed with oral cancer (49), TS represents an important and critical target in oral cancer chemotherapy. 5-FU, the most common drug used to treat oral cancer, arrests different types of cancer cells in the S phase of the cell cycle (42,44).…”
Section: Discussionmentioning
confidence: 99%
“…Tumor cells were incubated (+10 µL of drug in 190 µL of culture medium) with a range of equivalent DTX concentrations from 0.5 to 500 nM (100 nM of DTX corresponds to 0.35 µg of TiONts from TGA). After 96 h of incubation, cell viability was evaluated using MTS assay (Promega Corporation, Fitchburg, WI, USA) according to Mirjolet et al 15 …”
Section: In Vitro Evaluation Of Nanohybrid Cytotoxicitymentioning
confidence: 99%