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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

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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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References

  1. 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

    Google Scholar 

  2. 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

  3. 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

    Google Scholar 

  4. 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

    Google Scholar 

  5. 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

    Google Scholar 

  6. Danenberg PV (1977) Thymidylate synthetase—a target enzyme in cancer chemotherapy. Biochim Biophys Acta 473:73–92

    Google Scholar 

  7. Strander HA (1990) Clinical effects of interferon therapy with special emphasis on antitumor efficacy. Acta Oncol 28:355–362

    Google Scholar 

  8. 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

    Google Scholar 

  9. 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

    Google Scholar 

  10. 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

    Google Scholar 

  11. 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

    Google Scholar 

  12. 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

    Google Scholar 

  13. 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

    Google Scholar 

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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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