Cancer Immunology, Immunotherapy

, Volume 19, Issue 3, pp 198–204 | Cite as

Effect of a thymic factor, thymostimulin, on growth and pulmonary metastases of Lewis lung carcinoma

  • Masato Yagi
  • Takashi Yamashita
  • Eiro Tsubura
Original Articles


The antitumor and antimetastatic activities of a thymic factor, thymostimulin (TP-1), with or without cyclophosphamide (CPA) were examined in C57BL/6 mice inoculated with Lewis lung carcinoma (3LL).

Tumor growth was followed by determining the tumor diameter after tumor implantation. TP-1 given to mice every 2 days after tumor implantation significantly inhibited tumor growth without affecting the survival rate.

For induction of spontaneous pulmonary metastases, 3LL cells were implanted into the footpads of mice, and the implanted tumor was removed on day 9. The antimetastatic effect of TP-1 on pulmonary metastases after removal of the primary tumor was evaluated by counting the number of pulmonary surface nodules. TP-1 showed antimetastatic activity depending on its time of administration and dose. Combined therapy with TP-1 plus CPA significantly prolonged the survival of mice with pulmonary metastases.

The cytolytic activities of spleen cells on 3LL cells were enhanced in mice treated with TP-1 and/or CPA and the cytolytic activity of nonadherent spleen cells, the T-cell population, was enhanced.

The role of cytolytic spleen cells in inhibiting and preventing metastases was discussed.


Primary Tumor Tumor Growth Cyclophosphamide Lung Carcinoma Spleen Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



thymic factor, thymostimulin


Lewis lung carcinoma




1- (2-chloroethyl)-3-cyclohexyl-1-nitrosourea


1,3-bis (2-chloroethyl)-1-nitrosourea


fetal calf serum


standard deviation


standard error


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Allison AC, Tayler RB (1967) Observations on thymectomy and carcinogenesis. Cancer Res 27:703Google Scholar
  2. 2.
    Bernengo MG, Capella G, DeMatteis A, Tovo PAG, Zina G (1979) The in vitro effect of a calf thymus extract on the peripheral blood lymphocytes of 66 melanoma patients. Clin Exp Immunol 36:279Google Scholar
  3. 3.
    Bernengo MG, Fra P, Lisa F, Meregalli M, Zina G (1983) Thymostimulin therapy in melanoma patients: Correlation of immunologic effects with clinical course Clin Immunol Immunopathol 28:311Google Scholar
  4. 4.
    Carnaud C, Hoch B, Trainin N (1974) Influence of immunologic competence of the host on metastases induced by the 3LL Lewis tumor in mice. J Natl Cancer Inst 52:395Google Scholar
  5. 5.
    Chirigos MA (1978) In vitro and in vivo studies with thymosin. In: Chirigos MA (ed) Immune modulation and control of neoplasia by adjuvant therapy. p 305 (Progress in cancer research and therapy, vol 7)Google Scholar
  6. 6.
    Chretien PB, Lipson SD, Makuch R, Kenady DE, Cohen MH, Minna JD (1978) Thymosin in cancer patients: In vitro effects and correlations with clinical response to thymosin immunotherapy. Cancer Treat Rep 62:1787Google Scholar
  7. 7.
    Cohen MH, Chretien PB, Ihde DC, Fossieck BE, Makuch R, Bunn PA, Johnston AV, Shackney SE, Matthews MJ, Lipson SD, Kenady DE, Minna JD (1979) Thymosin fraction V and intensive combination chemotherapy prolonging the survival of patients with small-cell lung cancer. JAMA 241:1813Google Scholar
  8. 8.
    Costanzi JJ, Gagliano RG, Delaney F, Harris N, Thurman GB, Sakai H, Goldstein AL, Loukas D, Cohen GB, Thomson PD (1977) The effect of thymosin on patients with disseminated malignancies. A phase 1 study. Cancer 40:14Google Scholar
  9. 9.
    Cupissol D, Touraine JL, Serrou B (1981) Ability of lymphocytes treated with thymic factor to decrease lung metastasis in tumor-bearing mice. Thymus 3:9Google Scholar
  10. 10.
    Falchetti R, Bergesi G, Caprino L (1976) Isolation, partial characterization and biological effects of a thymus factor. Third European Immunology Meeting, Copenhagen, August 25–27Google Scholar
  11. 11.
    Falchetti R, Bergesi G, Eshkol A, Cafiero C, Adorini L, Caprino L (1977) Pharmacological and biological properties of a calf thymus extract (TP-1). Drugs Exp Clin Res 3:39Google Scholar
  12. 12.
    Gabizon A, Trainin N (1981) Effect of a thymic hormone, THF, on tumor-bearing mice and tumor-resected mice. Cancer Immunol Immunother 10:105Google Scholar
  13. 13.
    Grant GA, Miller JFAP (1965) Effect of neonatal thymectomy on the induction of sarcomata in C57BL mice. Nature 205:1124Google Scholar
  14. 14.
    Havas HF, Schiffman G (1981) Effect of cyclophosphamide on the immune response of BALB/c mice bearing an immunoglobulin M plasmacytoma (TEPC-183). Cancer Res 41:801Google Scholar
  15. 15.
    Hengst JCD, Mokyr MB, Dray S (1980) Importance of timing in cyclophosphamide therapy of MOPC-315 tumor-bearing mice. Cancer Res 40:2135Google Scholar
  16. 16.
    Kagawa K, Yamashita T, Tsubura E, Yamamura Y (1984) Inhibition of pulmonary metastases by Nocardia rubra cell wall skeleton, with special reference to macrophage activation. Cancer Res 44:665Google Scholar
  17. 17.
    Klein AS, Shoham J (1981) Effect of the thymus factor, thymostinulin (TP-1), on the survival rate of tumor-bearing mice. Cancer Res 41:3217Google Scholar
  18. 18.
    Klimpel GR, Henney CS (1978) BCG-induced suppressor cells. 1: Demonstration of a macrophage-like suppressor cell that inhibits cytotoxic T cell generation in vitro. J. Immunol 120:563Google Scholar
  19. 19.
    Lau CY, Goldstein G (1980) Functional effects of thymopoietin (TP5) on cytotoxic lymphocyte precursor units (CLP-U). 1: Enhancement of splenic CLP-U in vitro and in vivo after suboptimal antigenic stimulation. J Immunol 124:1861Google Scholar
  20. 20.
    Law LW (1966) Immunologic responsiveness and the induction of experimental neoplasms. Cancer Res 26:1121Google Scholar
  21. 21.
    Lipson SD, Chretien PB, Makuch R, Kenady DE, Cohen MH (1979) Thymosin immunotherapy in patients with small cell carcinoma of the lung. Cancer 43:863Google Scholar
  22. 22.
    Martelli MF, Velardi A, Rambotti P, Cernetti C, Bertotto A, Spinozzi F, Bracaglis AM, Falini B, Davis S (1982) The in vitro effect of thymic factor (thymostimulin) on immunologic parameters of patients with untreated Hodgkin's disease. Cancer 50:490Google Scholar
  23. 23.
    Martinez C (1964) Effect of early thymectomy on development of mammary tumor in mice. Nature (Lond) 203:1188Google Scholar
  24. 24.
    Rinehart JJ, Lange P, Gormus BJ, Kaplan M (1978) Human monocyte-induced tumor cell cytotoxicity. Blood 52:211Google Scholar
  25. 25.
    Sanford BH, Kohn HI, Daly JJ, Soo SF (1973) Long-term spontaneous tumor incidence in neonatally thymectomized mice. J Immunol 110:1437Google Scholar
  26. 26.
    Shoham J, Theoder E, Brenner HJ, Goldman B, Lusky A, Chaitchick S (1980) Enhancement of the immune system of chemotherapy-treated cancer patients by simultaneous treatment with thymic extract, TP-1. Cancer Immunol Immunother 9:173Google Scholar
  27. 27.
    Yamamoto T, Yamashita T, Tsubura E (1981) Inhibition of pulmonary metastasis of Lewis lung carcinoma by a glucan, schizophyllan. Invasion and Metastasis 1:71Google Scholar
  28. 28.
    Zaizov R, Vogel R, Wolach B, Cohen IJ, Varsano I, Shohat B (1979) The effect of THF in lymphoproliferative and myeloproliferative diseases in children. Ann NY Acad Sci 332:172Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Masato Yagi
    • 1
  • Takashi Yamashita
    • 1
  • Eiro Tsubura
    • 1
  1. 1.Third Department of Internal MedicineThe University of Tokushima, School of MedicineTokushimaJapan

Personalised recommendations