Dihydropyrimidine dehydrogenase activity and mRNA expression in advanced gastric cancer analyzed in relation to effectiveness of preoperative 5-fluorouracil-based chemotherapy.
Dihydroxypyrimidine dehydrogenase (DPD) is an enzyme involved in degradation and inactivation of 5-fluorouracil (5-FU). The amount of its expression in a tumor is thought to be a factor determining the response of the tumor to 5-FU therapy. We compared DPD activity and DPD mRNA expression in resected tumors between two groups of patients, i.e., a group of 14 patients with advanced gastric cancer who received preoperative chemotherapy (neoadjuvant chemotherapy; NAC) and surgery and a group of 24 patients with advanced gastric cancer who underwent surgery without preoperative chemotherapy. Tumor DPD activity was found to correlate well with tumor DPD mRNA expression. In the surgery alone group, DPD activity decreased significantly as the tumor stage advanced. This change was not observed in the NAC plus surgery group. Neither tumor depth (T factor) nor lymph node metastasis was found to correlate with DPD activity. Patients who responded to preoperative chemotherapy had lower DPD mRNA levels. Based on these results, we anticipate that measurement of DPD expression in clinical specimens may be clinically useful in managing advanced gastric cancer.
Takabayashi
A
A
Department of Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Kita-ku, Osaka 530-8480, Japan. atakaba@kitano-hp.or.jp
Iwata
S
S
Kawai
Y
Y
Kanai
M
M
Taki
Y
Y
Takechi
T
T
Fukushima
M
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D042943:Dihydrouracil Dehydrogenase (NADP); D019008:Drug Resistance, Neoplasm; D004790:Enzyme Induction; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005743:Gastrectomy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D010088:Oxidoreductases / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D011292:Premedication; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000032:analysis* / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil