title: Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA levels in thymoma.
abstract: OBJECTIVE
  Thymoma is one of the most common solid tumors in the mediastinum. However, there is no definitive consensus regarding the optimal adjuvant chemotherapy for advanced thymoma.
  
  
  METHODS
  To predict tumor sensitivity to 5-fluorouracil (5-FU) in thymoma, we investigated the mRNA levels of thymidylate synthase (TS), the key enzyme that catalyzes the methylation of deoxyuridine monophosphate, and correlates with the resistance of 5-FU and dihydropyrimidine dehydrogenase (DPD), which degrades 5-FU in thymoma. We used real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using the LightCycler to monitor the TS and DPD gene expression levels in thymoma tissue specimens from patients, coamplified with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard.
  
  
  RESULTS
  In the resected tumor specimens, TS and DPD mRNA levels were 3.876 and 14.651, respectively. Both the TS and DPD mRNA levels were significantly higher in the tumor tissue specimens than in the normal adjacent thymus tissue specimens. No significant correlations were observed between the TS or DPD levels and other clinicopathological factors.
  
  
  CONCLUSIONS
  The combined use of measurements of TS and DPD mRNA levels using real-time RT-PCR analyses may provide an indication of the selective cytoxicity of 5-FU on thymoma. In general, 5-FU itself is not considered to be a useful treatment for thymoma. The usufulness of DPD-inhibiting fluoropyrimidine (DIF) drugs for thymoma should therefore be further considered.
authors.affiliation: Department of Surgery II, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Fukai
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kiriyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kaji
authors.forename: Motoki
authors.initials: M
authors.lastname: Yano
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamakawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D042943:Dihydrouracil Dehydrogenase (NADP); D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000032:analysis* / Q000235:genetics; D013945:Thymoma / Q000188:drug therapy / Q000201:enzymology*; D013953:Thymus Neoplasms / Q000188:drug therapy / Q000201:enzymology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil