Dihydropyrimidine dehydrogenase mRNA level correlates with the response to 5-fluorouracil-based chemo-immuno-radiation therapy in human oral squamous cell cancer.
The measurement of the intra-tumoral level of thymidylate synthetase (TS), and dihydropyrimidine dehydrogenase (DPD), may be useful in predicting tumor sensitivity to 5-fluorouracil (5-FU). In this study, we examined the mRNA levels of DPD and TS in 28 oral squamous cell carcinomas (SCC), and 22 salivary gland tumors by semi-quantitative reverse transcription polymerase chain reaction. Then we examined the correlation of the responsiveness of the patients with oral SCC to 5-FU with the intra-tumoral levels of DPD and TS mRNA. All specimens were obtained at the biopsy before treatment, and then the patients were treated by oral administration of a 5-FU compound (UFT), the irradiation of cobalt-60 (upto 60 Gy) and injection of an immuno-potentiator (OK-432). Intra-tumoral levels of DPD mRNA in the patients who showed CR (complete response) and PR (partial response) were significantly lower than those in the patients who showed NC (no change). However, intra-tumoral levels of DPD mRNA did not correlate with the local recurrence of the tumor during the observation period after initial treatment with or without surgical resection of the residual tumors. On the other hand, TS mRNA levels in the tumors did not correlate with any clinico-pathological parameters. These observations suggest that intra-tumoral levels of DPD mRNA may predict the tumor response to 5-FU-based chemo-immuno-radiation therapy in the patients with oral SCC.
Hoque
M O
MO
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima 770-8504, Japan.
Kawamata
H
H
Nakashiro
K I
KI
Omotehara
F
F
Shinagawa
Y
Y
Hino
S
S
Begum
N M
NM
Uchida
D
D
Yoshida
H
H
Sato
M
M
Fujimori
T
T
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000628:therapy*; D003037:Cobalt Radioisotopes / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D017931:DNA Primers / Q000737:chemistry; D042943:Dihydrouracil Dehydrogenase (NADP); D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D010844:Picibanil / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000201:enzymology / Q000628:therapy*; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D003037:Cobalt Radioisotopes; D017931:DNA Primers; D012333:RNA, Messenger; D010844:Picibanil; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil