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Hyperthermia enhances the inhibition of tumor growth by 1‐(2‐tetrahydrofuryl)‐5‐fluorouracil/uracil (1:4) in tumors in mice and humans
Author(s) -
Emi Yasunori,
Kohnoe Shunji,
Yoshida Motofumi,
Takahashi Ikuo,
Maehara Yoshihiko,
Sugimachi Keizo
Publication year - 1992
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19920901)70:5<1177::aid-cncr2820700525>3.0.co;2-g
Subject(s) - uracil , hyperthermia , metabolism , fluorouracil , cytotoxicity , intracellular , sarcoma , cancer research , cell culture , biochemistry , medicine , chemistry , pharmacology , microbiology and biotechnology , chemotherapy , biology , pathology , in vitro , dna , genetics
The cytotoxicity of several antitumor drugs is enhanced by hyperthermia (HT). Using mouse Sarcoma‐180 (S‐180) tumors, the authors examined the effects of 5‐fluoroura‐cil (5‐FU) and a combined oral preparation of l‐(Gtetra‐hydrofuryl)‐5‐fluorouracil (FT) and uracil in a molar ratio of 1:4 (UFT), in combination with HT. The antitumor effect of 5‐FU was not enhanced significantly by HT. Growth inhibition by UFT plus HT was significantly greater than that by UFT alone, whereas inhibition by UFT alone was significantly greater than that by 5‐FU. The intracellular metabolism of 5‐FU and FT in whole homogenates of S‐180 cells, human tumor cell lines (SC‐2 and Lu‐99), and five fresh human tumor tissues also was investigated. Conversion of FT to 5‐FU, phosphorylation, and degradation of 5‐FU were assayed with [ 3 H]FT or [ 3 H]5‐FU, and the products were separated by thin‐layer chromatography. The conversion of FT to 5‐FU and the phosphorylation of 5‐FU were more rapid at 43°C than at 37°C, whereas the degradation of 5‐FU to 2‐fluoro‐β‐alanine remained unchanged. This acceleration of the active metabolism of FT and 5‐FU may be one explanation for the enhanced effect of UFT by HT. Cancer 1992; 70:1177–1182.