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  • Title: Chimeric DNA vaccine reverses morphine-induced immunosuppression and tumorigenesis.
    Author: Cheng WF, Chen LK, Chen CA, Chang MC, Hsiao PN, Su YN, Lee CN, Jeng HJ, Hsieh CY, Sun WZ.
    Journal: Mol Ther; 2006 Jan; 13(1):203-10. PubMed ID: 16140583.
    Abstract:
    Although long-term use of morphine has been shown to promote tumor growth, the question whether tumorigenesis occurs as a result of an immunosuppressive effect remains to be investigated. In mice rendered tolerant to morphine, the efficacy and mechanism of a vaccination to rescue morphine-induced immunosuppression and prevent tumor growth was assessed both in vitro and in vivo. Herein, we found that morphine-injected mice exhibited higher tumor growth rates and lower percentages of CD8+ T lymphocytes. The mechanism of morphine suppression of immunity might be through the suppression of E7-specific CD8+ T lymphocyte proliferation and the promotion of apoptosis of these cells by the Bcl-2 and Bax pathways. The suppressive effect of E7-specific CD8+ T lymphocytes by morphine could be reversed by naloxone. We have previously shown that calreticulin linked with E7 (CRT/E7) could enhance the CD8+ T cell response and the anti-tumor effects (W. F. Cheng et al. (2001) J. Clin. Invest. 108, 669-678). CRT/E7 DNA vaccine could overcome the immunosuppressive effect of morphine and suppress tumor growth. Our findings reveal that long-term morphine treatment dose-dependently promotes tumor growth and a DNA vaccine may serve as a useful approach to treat the profound immunosuppressive function and prevent tumorigenesis after long-term morphine treatment.
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