Role of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine against non-small cell lung cancer--in correlation with the tumoral expression of thymidylate synthase and dihydropyrimidine dehydrogenase.
5-Fluorouracil (5-FU) and its derivatives have been used worldwide for the treatment of several malignancies in solid organs. The effectiveness of these drugs is well proven in gastrointestinal malignancy, and has been reported upon the inverse correlation with the tumoral expression of dihydropyrimidine dehydrogenase (DPD). However, the significance of DPD expression in 5-FU based chemotherapy has not been well investigated in non-small cell lung cancer (NSCLC). We examined enzymatic activities and immunohistochemical expression of thymidylate synthase (TS) and DPD in 84 cases of NSCLC. In vitro sensitivity for 5-FU was tested in 53 cases of them to evaluate these predictive values for effectiveness of 5-FU. Efficacy of 5-chloro-2,4-dihydroxypyridine (CDHP), potent DPD inhibitor, was also examined in 27 cases of them. There was a reversal correlation between protein expression of DPD and sensitivity to 5-FU (r = -0.65; p < 0.001). Six (33.3%) of 18 cases with strong expression of DPD showed 10% or more increment of the anti-tumor effect by adding CDHP to 5-FU. DPD inhibitory fluoropyrimidine and examination of the tumoral expression of DPD might be a promising chemotherapeutic strategy in NSCLC.
Inoue
Kentarou
K
Depatment of Thoracic Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Takao
Motoshi
M
Watanabe
Fumiaki
F
Tarukawa
Tomohito
T
Shimamoto
Akira
A
Kaneda
Masanori
M
Sakai
Takashi
T
Fukushima
Masakazu
M
Shimpo
Hideto
H
Yada
Isao
I
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology*; D013940:Thymidylate Synthase / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
C417063:5-chlorodihydroxypyridine; D000964:Antimetabolites, Antineoplastic; D011725:Pyridines; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil