Antitumor activity of cyclophosphamide and lipopolysaccharide in tumor-bearing mice pretreated with BCG.

Abstract

of Cyclophosphamide and Lipopolysaccharide in TumorBearing Mice Pretreated with BOG. Tohoku J. exp. Med., 1987, 153 (2), [151][152][153][154][155][156][157][158][159][160] Antitumor effects of cyclophosphamide (CY) and lipopolysaccharide (LPS) were investigated in BCG-treated mice. C3H/He mice and CDF1 mice were injected with BCG and were inoculated subcutaneously with syngeneic mouse hepatoma and mastocytoma P815 respectively. A subsequent injection of LPS caused hemorrhagic necrosis and retarded growth of tumor. When mice were treated with LPS plus suboptimal dose of CY, tumor growth was retarded and survival time was prolonged. The antitumor effects were more remarkable when mice were treated with CY prior to the injection of LPS. Without BCG pretreatment, LPS showed no antitumor activity in mice. Sera from mice treated with BCG plus PLS was cytotoxic for cultured tumor cells. However treatment of mice with CY did not increase the in vitro cytotoxicity. In this experimental condition, CY had no effect on delayed type hypersensitivity when evaluated by the footpad reaction to purified protein derivative (PPD). These results seem to indicate that the antitumor effects of the treatment with CY and LPS in BCGtreated mice are mediated by the reduction of tumor burden by CY and a serum factor induced by LPS. Antitumor activity ; cyclophosphamide ; LPS ; BCG ; serum factorWe have observed that an injection of bacterial lipopolysaccharide retarded the growth of tumors inoculated subcutaneously in mice pretreated with BCG (Sato et al. 1986). The antitumor activity of LPS seemed to be mediated by a serum factor. However prolongation of survival time was not significant statistically. Because of toxicity and tolerance (Madonna and Vogel 1985), repeated injections of LPS are not feasible. There have been a number of reports dealing with the antitumor effect of chemotherapeutic agents in BOG-treated animals. However no publication is available concerning the antitumor activity of LPS in combination with anticancer drugs in mice pretreated with BOG. In this study,

Effects of the combination of a monoclonal agonistic mouse anti-OX40 antibody and toll-like receptor agonists: Unmethylated CpG and LPS on an MB49 bladder cancer cell line in a mouse model

“…In the case of the combination of anti-OX40 and the TLR4 ligand lipopolysaccharide treatment, the addition of LPS did not increase the efficacy of anti-OX40 and did not cause a significant increase in lifespan. On the contrary, pathological changes observed with the LPS + anti-OX40 treatment follow those described by Sato et al [19]. Hemorrhagic necrosis has spread to surrounding healthy tissues, breaking down the physical barrier between the tumor and the body, thereby facilitating the spread of tumor cells.…”