PMID- 15604991
OWN - NLM
STAT- MEDLINE
DCOM- 20050616
LR  - 20191210
IS  - 1340-6868 (Print)
IS  - 1340-6868 (Linking)
VI  - 11
IP  - 4
DP  - 2004
TI  - Evaluation of sensitivity to 5-FU on the basis of thymidylate synthase 
      (TS)/dihydropyrimidine dehydrogenase (DPD) activity and chromosomal analysis in 
      micro tissue specimens of breast cancer.
PG  - 356-66
AB  - BACKGROUND: Preoperative assessment of the anticancer drug sensitivity of tumors 
      plays an important role in the selection of therapy. If evaluation of the 5-FU 
      sensitivity of microtissue specimens obtained by techniques such as core needle 
      biopsy could be performed, the addition of fluorouracil to adriamycin and 
      cyclophosphamide may further enhance response rates. In order to evaluate a 
      simple sensitivity test for the anti-tumor agent 5-fluorouracil (5-FU), we 
      examined whether an assay of a small sample could measure mRNA to predict the 
      activities of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase 
      (DPD). In addition, gene abnormalities on chromosomes 1 and 18 corresponding to 
      DPD, TS and the relationships between the gene abnormalities and the amount of 
      mRNA and activity were examined. METHOD: TS and DPD activity were measured using 
      the fluorodeoxyuridine monophosphate ligand binding assay and radio enzymatic 
      assay, respectively, while mRNA levels were assayed by real-time polymerase chain 
      reaction. Chromosome 1 and 18 aberrations were investigated by fluorescence in 
      situ hybridization (FISH) with centromere probes. RESULTS: TS mRNA and TS 
      activity showed a positive correlation (r=0.518, p=0.0017). TS activity and TS 
      mRNA were significantly higher in the nuclear grade 3 group than in the other 
      groups (p=0.04, p=0.0072, respectively). TS activity and mRNA in tumor tissue 
      tended to decrease in the progesterone receptor positive groups (p=0.059, 
      p=0.066, respectively). There was no correlation between DPD mRNA and DPD 
      activity in tumor tissue (r=0.139, p=0.4423). DPD mRNA was measured as 
      282.88+/-170.68 copies/cell in tumor tissue and 635.88+/-310.04 copies/cell in 
      normal tissue, and was thus significantly higher in normal tissue (p<0.001). 
      CONCLUSIONS: TS mRNA showed a positive correlation with TS activity, suggesting 
      that this method of using small amounts of tissue can replace anti-cancer drug 
      sensitivity tests.
FAU - Ota, Daisuke
AU  - Ota D
AD  - Third Department of Surgery, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, 
      Shinjuku-ku, Tokyo 160-0023, Japan.
FAU - Kusama, Mikihiro
AU  - Kusama M
FAU - Kaise, Hiroshi
AU  - Kaise H
FAU - Nakayama, Shun
AU  - Nakayama S
FAU - Misaka, Takeharu
AU  - Misaka T
FAU - Tsuchida, Akihiko
AU  - Tsuchida A
FAU - Aoki, Tatsuya
AU  - Aoki T
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PL  - Japan
TA  - Breast Cancer
JT  - Breast cancer (Tokyo, Japan)
JID - 100888201
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (DNA Primers)
RN  - 0 (RNA, Messenger)
RN  - EC 1.3.1.2 (Dihydrouracil Dehydrogenase (NADP))
RN  - EC 2.1.1.45 (Thymidylate Synthase)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antimetabolites, Antineoplastic/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/enzymology/genetics/pathology
MH  - DNA Primers
MH  - Dihydrouracil Dehydrogenase (NADP)/genetics/metabolism
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Fluorouracil/*therapeutic use
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - Predictive Value of Tests
MH  - RNA, Messenger/analysis
MH  - Thymidylate Synthase/genetics/metabolism
EDAT- 2004/12/18 09:00
MHDA- 2005/06/17 09:00
CRDT- 2004/12/18 09:00
PHST- 2004/12/18 09:00 [pubmed]
PHST- 2005/06/17 09:00 [medline]
PHST- 2004/12/18 09:00 [entrez]
AID - 10.1007/BF02968043 [doi]
PST - ppublish
SO  - Breast Cancer. 2004;11(4):356-66. doi: 10.1007/BF02968043.