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• W2090843375 abstract "Owing to its impressive ability to kill tumor cells, especially in combination with interferon-γ (IFNγ), tumor necrosis factor (TNF) is widely appreciated as being a potential systemic therapeutic for the treatment of cancer. On the other hand, owing to its proinflammatory activities, administration of TNF leads to many systemic side effects and eventually to a potentially lethal systemic inflammatory response syndrome (SIRS). However, systemic treatment of tumor-bearing mice with TNF/IFNγ in combination with BB-94 (a broad-spectrum metalloproteinase inhibitor) confers protection against TNF/IFNγ-induced mortality, whereas preserving the antitumor activity. In this study, we investigated the effect of the adenoviral delivery of human tissue inhibitors of matrix metalloproteinase (hTIMP)-1 and hTIMP-2 genes on the outcome of TNF/IFNγ antitumor therapy. The dose of adenovirus was limited to 108 PFU per mouse owing to the additive toxicity of combining it with TNF/IFNγ therapy. Nevertheless, this dose was sufficient to achieve highly efficient adenoviral transfer and expression of hTIMP-1 and hTIMP-2 in the liver, but not the tumor. Treatment with this low dose of AdhTIMP-1 or AdhTIMP-2 was not enough to protect the host against the toxic effects of TNF/IFNγ. However, it was sufficient to show a synergistic effect of hTIMPs with TNF/IFNγ such that tumors regressed significantly faster. Interestingly, only AdTIMP-2 was able to prevent relapses after treatment." @default.
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• W2090843375 date "2007-01-12" @default.
• W2090843375 modified "2023-10-06" @default.
• W2090843375 title "The use of tissue inhibitors of matrix metalloproteinases to increase the efficacy of a tumor necrosis factor/interferonγ antitumor therapy" @default.
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• W2090843375 doi "https://doi.org/10.1038/sj.cgt.7701020" @default.
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