Hemorrhagic necrosis, antitumor

As is implied by its name, the first TNF-a-dependent mechanism described was the induction of tumor necrosis in vivo through its role in tumor vasculature. However the mechanisms of the in vitro toxicity of TNF-a to tumor cells imply apoptosis rather than necrosis [97], Tumor necrosis in SCID (severe combined immuno-deficiency) mice treated with LPS does not lead to the rejection of tumors [98], Furthermore, necrosis and tumor regression must be dissociated since anti-IFN-y antibodies inhibit LPS-induced regression of Meth A sarcoma in mice, but not the necrotic hemorrhage attributed to TNF-a. It is now accepted that the antitumoral effect of TNF-a is indirect and dependent on acquired immune response. Matsumoto et al. [99] reported that, while TNF-a itself has no effect on hepatoma KDH-8 tumor cells in vitro, the antitumoral effect of the lipid A ONO-4007 against KDH-8 tumors in vivo is inhibited by anti-TNF-a antibodies in WKAH rat, showing an indirect effect of TNF-a. 

The nature of the antitumor action of a polysaccharide is not entirely clear, but certain bacterial polysaccharides may directly attack tumors, as evidenced by the resulting intratumoral hemorrhage and necrosis. On the other hand, most of the polysaccharides from other botanical sources cannot be shown to exert any direct action on tumor cells. Their antitumor action must, therefore, be considered to be dependent upon the reaction of the host that is, their effect is host-mediated. It is possible that, in some instances, these two types of action may be interwoven. The discussion in this Section covers only those polysaccharides that effect a host-mediated reaction. 

Several workers have reported that bacterial, antitumor agents cannot have a direct effect on tumor cells, as the bacterial polysaccharide-preparations that produced hemorrhage and necrosis in solid tumors had no effect on tumor cells in vitro208 or in tissue culture.209,210 Seligman and coworkers211 found that only a small propor-... 

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