Changes in thymidylate synthase mRNA in blood leukocytes from patients with colorectal cancer after bolus administration of 5-fluorouracil
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Changes in thymidylate synthase mRNA in blood leukocytes from patients with colorectal cancer after bolus administration of 5-fluorouracil. / Ehrnrooth, E; Sørensen, B; Poulsen, J H; Sørensen, B S; von der Maase, H.
I: Acta Oncologica, Bind 39, Nr. 1, 2000, s. 53-7.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Changes in thymidylate synthase mRNA in blood leukocytes from patients with colorectal cancer after bolus administration of 5-fluorouracil
AU - Ehrnrooth, E
AU - Sørensen, B
AU - Poulsen, J H
AU - Sørensen, B S
AU - von der Maase, H
N1 - Keywords: Adult; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Female; Fluorouracil; Humans; Injections, Intravenous; Leukocytes; Male; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Thymidylate Synthase
PY - 2000
Y1 - 2000
N2 - 5-fluorouracil (5-FU) is considered the standard antineoplastic drug of choice for metastatic colorectal cancer. It has been suggested that 5-FU administered as bolus infusion is cytotoxic mainly through an RNA damaging effect. We investigated the effect of i.v. bolus 5-FU 500-600 mg/m2 on the 5-FU target enzyme, thymidylate synthase (TS) mRNA, in blood leukocytes before and after courses 1 and 3 in 21 patients with colorectal cancer. TS mRNA expression was quantified using an RT-PCR assay with an internal RNA standard. Median TS mRNA expression decreased significantly 30 min after course no. 1 (p = 0.004), and both 15 min and 30 min after course 3 (p = 0.01). After course 1, the median TS mRNA expression decreased by 31% and after course 3 by 24%. Pharmacokinetic parameters were similar for individual patients during the two courses but did not correlate with the degree of TS mRNA inhibition. The present results indicate that TS mRNA in blood leukocytes may be an early indicator of an RNA damaging effect after i.v. bolus infusion of 5-FU.
AB - 5-fluorouracil (5-FU) is considered the standard antineoplastic drug of choice for metastatic colorectal cancer. It has been suggested that 5-FU administered as bolus infusion is cytotoxic mainly through an RNA damaging effect. We investigated the effect of i.v. bolus 5-FU 500-600 mg/m2 on the 5-FU target enzyme, thymidylate synthase (TS) mRNA, in blood leukocytes before and after courses 1 and 3 in 21 patients with colorectal cancer. TS mRNA expression was quantified using an RT-PCR assay with an internal RNA standard. Median TS mRNA expression decreased significantly 30 min after course no. 1 (p = 0.004), and both 15 min and 30 min after course 3 (p = 0.01). After course 1, the median TS mRNA expression decreased by 31% and after course 3 by 24%. Pharmacokinetic parameters were similar for individual patients during the two courses but did not correlate with the degree of TS mRNA inhibition. The present results indicate that TS mRNA in blood leukocytes may be an early indicator of an RNA damaging effect after i.v. bolus infusion of 5-FU.
M3 - Journal article
C2 - 10752654
VL - 39
SP - 53
EP - 57
JO - Acta Oncologica
JF - Acta Oncologica
SN - 1100-1704
IS - 1
ER -
ID: 19368857