Nitro Oxide And Ovarian Cancer

Abstract

The precise mechanisms by which the host defense to malignant tumors is mediated in vivo is not known. It is now believed that cancer cells themselves may trigger an immune response and this may limit the progression of the tumor. It is also possible to induce non specific resistance to cancer cells therapeutically. Intraperitoneal (i.p.) inoculation of Cornebacterium parvum, which increases nonspecific resistance to murine ovarian teratocarcinoma (MOT) cells can cure mice bearing these tumor cells [1]. Similarly, i.p. administration of Cornebacterium parvum to women [2] was at least partially effective in the treatment of minimal residual ovarian cancer in women. However, the mechanism by which this occurs is not known. Similarly, bacillus Calmette-Guerin (BCG) also appears to be an immununostimulant. When cultured in vitro, peritoneal macrophages obtained from mice previously inoculated with BCG release NO, which is cytostatic or cytolytic for tumor cells [3],[4]. This in vitro cytostatic and/or cytolytic activity is also observed after activation of the macrophages by cytokines [5],[6]. Interferon γ (INFγ) is important for the priming of macrophages, and tumor necrosis factor α (TNFα) or some other cytokine or bacterial lipopolysaccharide (LPS) is necessary for full induction of activated macrophage cytotoxicity [7],[8]. However, the role of NO in mediating tumoricidal activity in vivo and the mechanism by which this occurs is not exactly known. We therefore evaluated the role of NO in mediating both tumoricidal activity in vivo and the mechanism by which this occurs.