Abstract
The modulating effect of recombinant human interferon alpha-2a (IFN) on the antitumor activity of UFT, a mixed compound of tegafur and uracil at a molar ratio of 1:4, was investigated against SC-1-NU, a human gastric cancer xenograft serially transplanted in nude mice. IFN was administered subcutaneously at a dose of 60,000 IU/mouse daily for 14 days, and UFT was given at a dose of 15 mg/kg as tegafur daily, except on Sundays, for 3 weeks. The agents were administered either alone or simultaneously. Synergistic antitumor activity on SC-1-NU was produced by the combination of IFN and UFT without any increment of side effects, and the combination therapy also increased intratumoral thymidylate synthetase (TS) inhibition and the amount of 5-fluorouracil (5-FU) in the intratumoral RNA. Thus, IFN seems to modulate the antitumor activity of UFT against SC-1-NU through an inhibition of DNA synthesis and RNA distortion, and therefore this combination could be useful for clinical application.
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Wadler S, Schwartz EL, Goldman L, Lyver A, Rader M, Zimmermann M, Itri L, Weinberg V, Wiernik PH (1989) Fluorouracil and recombinant alpha-2a-interferon: An active regimen against advanced colorectal carcinoma. J Clin Oncol 7:1769–1775
Geran RL, Greenberg NH, Schumacher A, Abott BJ (1973) Protocols for screening chemical agents and natural products against animal tumors and other biological systems, 3rd edn. Cancer Chemother Rep 3:51–61
Spears CP, Shahinian AM, Moran RG, Heidelberger C, Corbett TH (1982) In vivo kinetics of thymidylate synthetase inhibition on 5-fluorouracil-sensitive and -resistant murine colon adenocarcinomas. Cancer Res 42:450–456
Kubota T, Fujita S, Kodaira S, Yamamoto T, Josui K, Arisawa Y, Suto A, Ishibiki K, Abe O, Mabuchi K, Fuse M (1991) Antitumor activity of fluoropyrimidines and thymidylate synthetase inhibition. Jpn J Cancer Res 82:476–482
Uchida J, Umeno Y, Takeda S (1992) Significance of measuring 5-fluorouracil incorporated into RNA of tumor tissue as a parameter for the antitumor activity of 5-fluorouracil and its analogs (in Japanese). Jpn J Cancer Chemother 19:677–683
Danenberg PV (1977) Thymidylate synthetase—a target enzyme in cancer chemotherapy. Biochim Biophys Acta 473:73–92
Strander HA (1990) Clinical effects of interferon therapy with special emphasis on antitumor efficacy. Acta Oncol 28:355–362
Wadler S, Schwartz EL (1990) Antineoplastic activity of the combination of interferon and cytotoxic agents against experimental and human malignancies: A review. Cancer Res 50:3473–3486
Chu E, Zinn S, Boarmann D, Allegra CJ (1990) Interaction of gamma interferon and 5-fluorouracil in the H630 human colon carcinoma cell line. Cancer Res 50:5834–5840
Schwartz EL, Hoffman M, O'Connor CJ (1992) Stimulation of 5-fluorouracil metabolic activation by interferon-alpha in human colon carcinoma cells. Biochem Biophys Res Commun 182:1232–1239
Kase S, Kubota T, Watanabe M, Furukawa T, Tanino H, Ishibiki K, Teramoto T, Kitajima M (1993) Interferon beta increases antitumor activity of 5-fluorouracil against human colon carcinoma cells in vitro and in vivo. Anticancer Res 13:369–374
Kase S, Kubota T, Watanabe M, Teramoto T, Kitajima M, Hoffman RM (1994) Recombinant human interferon alpha-2a increases 5-fluorouracil efficacy by elevating fluorouridine concentration in tumor tissue. Anticancer Res 14:1155–1160
Glazer RI, Hartman KD, (1979) The effect of 5-fluorouracil on the synthesis and methylation of high-molecular-weight nuclear RNA in L1210 cells. Mol Pharmacol 17:245–249
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Kubota, T., Kurihara, N., Kase, S. et al. The modulating effect of interferon alpha-2a on the antitumor activity of UFT against a human gastric carcinoma xenograft, SC-1-NU, in nude mice. Surg Today 26, 12–14 (1996). https://doi.org/10.1007/BF00311985
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DOI: https://doi.org/10.1007/BF00311985