Journal of the Chinese Medical Association
Volume 70, Issue 3 , Pages 94-102, March 2007

Effect of Age on Pulmonary Metastases and Immunotherapy in Young and Middle-aged Mice

  • Yuh-Min Chen

      Affiliations

    • Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • Institute of Cancer Research, National Health Research Institutes, Taipei, Taiwan, R.O.C.
    • Corresponding Author InformationCorrespondence to: Dr Yuh-Min Chen, Chest Department, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C.
    • ,
  • Pi-Sheng Wang

      Affiliations

    • Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Jacqueline Ming Liu

      Affiliations

    • Institute of Cancer Research, National Health Research Institutes, Taipei, Taiwan, R.O.C.
    • ,
  • Yi-Lin Hsieh

      Affiliations

    • Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Chun-Ming Tsai

      Affiliations

    • Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Reury-Perng Perng

      Affiliations

    • Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Jacqueline Whang-Peng

      Affiliations

    • Institute of Cancer Research, National Health Research Institutes, Taipei, Taiwan, R.O.C.

Received 21 September 2006; accepted 30 January 2007.

Article Outline

Background

We used B16-F10 (B16) melanoma tumor cells and syngeneic C57BL/6 (B6) mice as a study model for pulmonary metastases, to better understand whether or not there exist differences in tumorigenicity and in the effectiveness of immunotherapy as a function of host age (1-, 3-, 12- and 24-month-old).

Methods

Intravenous injection of B16 melanoma cells were administered to B6 mice of different ages with/without interleukin (IL)-2 and IL-12 daily treatment. Tumor growth, splenocyte function, serum cytokines (IL-10, interferon-γ, vascular endothelial growth factor) and survival were compared.

Results

The study showed that, without IL-2 and IL-12 treatment, middle-aged mice suffering from pulmonary metas-tases had fewer pulmonary metastases and better survival than younger mice suffering from pulmonary metastases. Three days' IL-2 plus IL-12 treatment could not prolong mice survival, but prolonged treatment significantly improved the survival of both the younger and older tumor-bearing mice, especially the older mice, despite the fact that the younger mice had a better serum cytokine and splenocyte cellular immune response to cytokine treatment.

Conclusion

The young B6 mice that suffered from B16 pulmonary metastases had a poorer prognosis than the middle-aged mice. Short-term IL-2 plus IL-12 treatment is ineffective in prolonging survival, and a longer duration of treatment is needed. This kind of immunotherapy was effective in both the young and middle-aged mice, but it was more effective in the middle-aged mice.

Key Words:  age , immunotherapy , pulmonary metastases

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Neuman HW , Ellis FH , McDonald JR . Bronchogenic carcinoma in persons under forty years of age . N Engl J Med . 1956;254:502–507
  2. DeCaro L , Benfield JR . Lung cancer in young persons . J Thorac Cardiovasc Surg . 1982;83:372–376
  3. Bourke W, Milstein D, Guira R, Donghi M, Luisetti M, Rubin AH, et al. Lung cancer in young adults . Chest . 1992;102:1723–1729
  4. Green LS , Fortoul TI , Ponciano G , Robles C , Rivero O . Bronchogenic cancer in patients under 40 years old: the experience of a Latin American country . Chest . 1993;104:1477–1481
  5. Kuo CW , Chen YM , Chao JY , Tsai CM , Perng RP . Non-small cell lung cancer in very young and very old patients . Chest . 2000;117:354–357
  6. Chen YM , Tsai CM , Perng RP . Differential effects of different cytokines on the tumorigenicity and immunogenicity of murine tumors . J Chin Med Assoc . 1999;62:807–816
  7. Ershler WB , Stewart JA , Hacker MP , Moore AL , Tindle BH . B16 murine melanoma and aging: slower growth and longer survival in old mice . J Natl Cancer Inst . 1984;72:161–164
  8. Nishimura T, Watanabe K, Yahata T, Ushaku L, Ando K, Kimura M, et al  Application of interleukin 12 to anti-tumor cytokine and gene therapy . Cancer Chemother Pharmacol . 1996;38:27–34
  9. Trinchieri G . Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes . Blood . 1994;84:4008–4027
  10. Chen YM, Yang WK, Ting CC, Tsai WY, Yang DM, Whang-Peng J, et al. Cross regulation by IL-10 and IL-2/IL-12 of the cytolytic activity of lymphocytes from malignant effusion of lung cancer patients . Chest . 1997;112:960–966
  11. Chen YM , Hsieh YL , Tsai CM , Perng RP . Interleukin-2 stimulation activates mesothelial cellular functioning against autologous tumor cells . J Chin Med Assoc . 2004;67:323–330
  12. Chen YM , Yang WK , Ting CC , Yang DM , Whang-Peng J , Perng RP . Depressed cytolytic activity of peripheral blood mononuclear cells in unusually high paclitaxel concentrations: reversal by IL-2 and IL-12 . J Chin Med Assoc . 1999;62:867–874
  13. Pili R , Guo Y , Chang J , Nakanishi H , Martin GR , Passaniti A . Altered angiogenesis underlying age-dependent changes in tumor growth . J Natl Cancer Inst . 1994;86:1303–1314
  14. Kreisle RA , Stebler BA , Ershler WB . Effect of host age on tumor-associated angiogenesis in mice . J Natl Cancer Inst . 1990;82:44–47
  15. Silagi S , Dutkowski R , Schaefer A . Eradication of mouse melanoma by combined treatment with recombinant human interleukin 2 and recombinant murine interferon-gamma . Internat J Cancer . 1988;41:315–322

PII: S1726-4901(09)70338-7

doi:10.1016/S1726-4901(09)70338-7

Journal of the Chinese Medical Association
Volume 70, Issue 3 , Pages 94-102, March 2007

Article Tools