PMID- 10744051
OWN - NLM
STAT- MEDLINE
DCOM- 20000419
LR  - 20190513
IS  - 0910-5050 (Print)
IS  - 1876-4673 (Electronic)
IS  - 0910-5050 (Linking)
VI  - 91
IP  - 1
DP  - 2000 Jan
TI  - Dihydropyrimidine dehydrogenase and messenger RNA levels in gastric cancer: 
      possible predictor for sensitivity to 5-fluorouracil.
PG  - 105-12
AB  - We investigated the correlation between tumor sensitivity to 5-fluorouracil 
      (5-FU) and enzymatic activities of thymidylate synthetase (TS) and 
      dihydropyrimidine dehydrogenase (DPD) in human gastric cancer specimens. 
      Forty-one patients with advanced gastric cancer gave informed consent and were 
      enrolled in the study. Biopsy specimens of gastric cancer were obtained 
      preoperatively through gastrofiberscopy and used to determine TS and DPD 
      messenger RNA (mRNA) levels. TS and DPD enzyme activity and mRNA levels were also 
      measured in resected tumor tissue samples obtained after surgical resection. TS 
      and DPD activity were measured using the TS-binding assay and a radioenzymatic 
      assay, respectively, while mRNA levels were measured by semi-quantitative reverse 
      transcription-polymerase chain reaction (RT-PCR), with co-amplification of 
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. 5-FU 
      sensitivity of resected tumor specimens was measured by the tetrazolium-based 
      colorimetric assay (MTT assay). Both TS and DPD mRNA levels correlated well 
      between biopsied and resected tumor specimens. A statistically significant 
      correlation was also observed between mRNA levels in biopsied specimens and 
      enzymatic activities in resected specimens. DPD levels significantly correlated 
      with 5-FU sensitivity, such that high DPD activity and high DPD mRNA levels 
      resulted in low sensitivity to 5-FU. In contrast, no correlation was observed 
      between TS activity or TS mRNA levels and 5-FU sensitivity. We conclude that 
      tumor DPD mRNA level, as assessed from biopsy specimens obtained by 
      gastrofiberscopy, may be a useful indicator in predicting tumor sensitivity to 
      5-FU in patients with gastric cancer.
FAU - Ishikawa, Y
AU  - Ishikawa Y
AD  - Department of Surgery, School of Medicine, Keio University, Tokyo.
FAU - Kubota, T
AU  - Kubota T
FAU - Otani, Y
AU  - Otani Y
FAU - Watanabe, M
AU  - Watanabe M
FAU - Teramoto, T
AU  - Teramoto T
FAU - Kumai, K
AU  - Kumai K
FAU - Takechi, T
AU  - Takechi T
FAU - Okabe, H
AU  - Okabe H
FAU - Fukushima, M
AU  - Fukushima M
FAU - Kitajima, M
AU  - Kitajima M
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Jpn J Cancer Res
JT  - Japanese journal of cancer research : Gann
JID - 8509412
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Coloring Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.3.1.2 (Dihydrouracil Dehydrogenase (NADP))
RN  - EC 2.1.1.45 (Thymidylate Synthase)
RN  - EUY85H477I (thiazolyl blue)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Antimetabolites, Antineoplastic/*therapeutic use
MH  - Biopsy
MH  - Coloring Agents/metabolism
MH  - Dihydrouracil Dehydrogenase (NADP)
MH  - Drug Resistance, Neoplasm
MH  - Fluorouracil/*therapeutic use
MH  - Humans
MH  - Oxidoreductases/genetics/*metabolism
MH  - RNA, Messenger/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stomach Neoplasms/*drug therapy/*enzymology/genetics
MH  - Tetrazolium Salts/metabolism
MH  - Thiazoles/metabolism
MH  - Thymidylate Synthase/metabolism
PMC - PMC5926227
EDAT- 2000/04/01 09:00
MHDA- 2000/04/25 09:00
PMCR- 2000/01/01
CRDT- 2000/04/01 09:00
PHST- 2000/04/01 09:00 [pubmed]
PHST- 2000/04/25 09:00 [medline]
PHST- 2000/04/01 09:00 [entrez]
PHST- 2000/01/01 00:00 [pmc-release]
AID - CAE105 [pii]
AID - 10.1111/j.1349-7006.2000.tb00866.x [doi]
PST - ppublish
SO  - Jpn J Cancer Res. 2000 Jan;91(1):105-12. doi: 10.1111/j.1349-7006.2000.tb00866.x.