Postsurgical oral administration of uracil and tegafur inhibits progression of micrometastasis of human breast cancer cells in nude mice.
We recently established a metastasis model in nude mice using the MKL-4 cell line, a contransfectant of the MCF-7 human breast cancer cell line with fgf-4 and lacZ in which micrometastases in several organs can be quantitatively observed. First, to develop a new postsurgical metastasis model, we investigated the timing of occurrence of micrometastasis and the influence of tumor removal on the progression of micrometastasis in this model. Micrometastases into lymph nodes and lungs were detected 3 weeks after the cell injections. Tumor removal 3 weeks after the injections significantly enhanced the progression of micrometastasis into lymph nodes and bone. Second, to study the effect of a mixed compound, UFT (a molar ratio of uracil:tegafur of 4:1), which has been widely used in the postsurgical adjuvant setting in Japan, 15 or 20 mg/kg UFT were administered p.o. for 4 weeks to tumor-bearing mice or to mice in which transplanted tumors were resected 3 weeks after the injections. Either dose of UFT significantly inhibited the tumor growth as well as the progression of micrometastasis into lymph nodes, lungs, liver, and brain. In addition, enhanced progression of micrometastasis in all explored organs by the tumor removal was significantly inhibited by the administration of either dose of UFT. In conclusion, this new postsurgical metastasis model may be useful for evaluating the efficacy of agents used in the postoperative adjuvant setting. UFT may be an effective drug for inhibiting the progression of micrometastasis after surgery.
Kurebayashi
J
J
Department of Breast and Thyroid Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-01, Japan.
Nukatsuka
M
M
Fujioka
A
A
Saito
H
H
Takeda
S
S
Unemi
N
N
Fukumori
H
H
Kurosumi
M
M
Sonoo
H
H
Dickson
R B
RB
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001859:Bone Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007564:Japan; D008207:Lymphatic Metastasis / Q000517:prevention & control; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D005641:Tegafur / Q000627:therapeutic use*; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014498:Uracil / Q000627:therapeutic use*
D005641:Tegafur; D014498:Uracil