Human colorectal malignancy and oral UFT.
Thymidylate synthase (EC 2.1.1.45) and thymidine kinase (EC 2.71.21) are key enzymes involved in de novo and salvage pathways for pyrimidine nucleotide synthesis. Both enzyme activities are increased in rapidly proliferating normal, fetal and neoplastic tissues. In a previous study, the activities of thymidylate synthase and thymidine kinase were relatively predominant in the poorly-and well-differentiated types of a gastric cancer. In the present study of patients with colorectal cancer, the serum thymidine kinase activities are elevated in cases at a clinically late stage, and in cases with a recurrence and a distant metastasis associated with abundant blood supply, i.e. metastasis to the liver, lung and bone. Well-differentiated colorectal cancer shows higher thymidine kinase activity than moderately-well-differentiated type as was previously shown in gastric cancer patients. Furthermore, neoadjuvant chemotherapy using the 5-fluorouracil derivative UFT demonstrates a stronger suppression of increased activities of thymidylate synthase in the tumorous tissues than in the non-tumorous mucosa.
Sakamoto
Shinobu
S
Medical Research Institute, School of Medicine, Tokyo Medical and Dental University, Japan. motoend@tmd.ac.jp
Tsukada
Kunio
K
Sagara
Tetsuro
T
Kawachi
Yasuyuki
Y
Murakami
Saburo
S
Iwama
Takeo
T
D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D005472:Fluorouracil / Q000493:pharmacokinetics; D006801:Humans; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D005641:Tegafur / Q000008:administration & dosage / Q000493:pharmacokinetics; D013937:Thymidine Kinase / Q000097:blood / Q000378:metabolism; D013940:Thymidylate Synthase / Q000097:blood / Q000378:metabolism; D014498:Uracil / Q000008:administration & dosage / Q000493:pharmacokinetics
D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D013937:Thymidine Kinase; D005472:Fluorouracil