Ciba Foundation Symposium 131 - Tumour Necrosis Factor and

The variety of components implicated within the rules of phone proliferation and differentiation is already huge and extra are consistently being pointed out. This booklet concentrates on tumor necrosis issue (cachectin) and lymphotoxin, yet comprises observations in their interactions with different cytokines, specially the interferons and interleukins. TNF might be both cytostatic or cytotoxic to cultured telephone strains, and quite a few mechanisms are proposed, starting from DNA fragmentation to activation of phospholiopases. TNF is additionally said to stimulate the expansion of standard fibroblasts in vivo. The in vivo activities of TNF defined right here comprise haemorrhagic necrosis of tumors, cachexia, results at the vasculature, and antiparasitic and antiviral actions. additionally offered is a few fascinating facts from the 1st phases of scientific trials of TNF as an anticancer agent.

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Relationship to other cytotoxic factors Several cytotoxic activities have been identified from macrophages, T lymphocytes, natural killer cells and other cell sources (see review by Aiyer & Aggarwal 1987). The relationship of these factors to TNF-a and TNF-b, described here, is not yet fully understood. This is primarily due to the lack of sufficient physicochemical characterization of activities other than TNF-a and TNF-P. It is uncertain at present whether cytokines named by various workers as cytotoxin, necrosin, halotoxin, monocyte cytotoxic factor (MCF), cachectin, monocyte cytotoxin (MCT) and tumour necrosis factor (TNF) are identical to TNF-a as described here.

If you withdraw the growth factor, the cultures senesce rapidly. The key point is that in these non-transformed cultures we see a process that looks very much like tumour killing: within 24-48 hours of adding TNF plus IFN-y, endothelial cells shed massively from the dish and fail to exclude Trypan blue. 38 Discussion References Balkwill FR, Lee A, Aldam G, Moodie E, Thomas A, Tavernier J, Fiers W 1986 Human tumor xenografts treated with recombinant human tumor necrosis factor alone or in combination with interferons.

RHuTNF-a and rHuTNF-p treatment (intraperitoneal) at the doses indicated was on a QD1-7 schedule after tumour implantation. contained a factor which induced the haemorrhagic necrosis of a panel of murine tumours, including S-180 sarcoma in CD-1 Swiss mice, BP8 leukaemia in C3H mice, P815 mastocytoma in DBA mice, several BALB/c leukaemias, and Meth A sarcoma, also of BALB/c origin. The tumours were injected subcutaneously into mice and after approximately seven days the mice were injected intravenously with serum containing a TNF-like activity.

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