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- W2069812515 abstract "Systemically administered tumour necrosis factor (TNF) has anti-tumour effects in animal tumour models but its clinical application is limited by severe toxicity. Interferon-γ(IFN-γ) has been shown to augment the anti-tumour effect of TNF. We evaluated the effect of paralesional (p.l.) injections of TNF plus IFN-γ in a murine tumour model and compared the toxicity and anti-tumour effect with that seen with systemic administration. C57BL6 mice with 10-day subcutaneous MCA sarcomas were treated with daily p.l. injections of recombinant huTNF ± IFN-γ for 5 days. Optimal mean survival and 30-day cure rate was seen with doses of 5 μg TNF-α + 5000 U IFN-γ (P < 0.05 vs. control or IFN-γ alone). Tumour response after a single i.v. injection of 0–15 μg TNF + 5000 U IFN-γ was then compared with five daily p.l. injections of the same dose of TNF-α and IFN-γ. All animals with p.l. injections of > 5 μg TNF had initial complete necrosis of tumour with a variable degree of surrounding tissue necrosis, with rapid regrowth of tumour seen in some animals. Although treatment-related mortality was similar between i.v. and p.l. therapy, there was a higher percentage of animals cured with p.l. injections with overall cure rates in treated animals at 30 days of 17% vs. 72% (i.v. vs. p.l., P < 0.01) and 13% vs. 67% (P < 0.04) in a repeat study. Paralesional administration of TNF-α and IFN-γ results in a dose-dependent improvement in antitumour effect and cure rate that is significantly greater than that of systemic injection. This improvement in therapeutic efficacy that is obtainable with regional administration of cytokines may have clinical applications." @default.
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- W2069812515 date "1992-08-01" @default.
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- W2069812515 title "Effective regional therapy of experimental cancer with paralesional administration of tumour necrosis factor-α + interferon-γ" @default.
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- W2069812515 doi "https://doi.org/10.1016/0960-7404(92)90090-8" @default.
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