1991
DOI: 10.1097/00002371-199112000-00006
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Phase II Studies of Recombinant Human Tumor Necrosis Factor Alpha in Patients with Malignant Disease: A Summary of the Southwest Oncology Group Experience

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Cited by 62 publications
(24 citation statements)
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“…Despite the ability of TNF and FasL to induce apoptosis in cancer cells, severe toxic side effects preclude both ligands from use in systemic anticancer therapy. Systemic administration of TNF caused an inflammatory response resembling septic shock in humans [107]. FasL or agonistic anti-Fas antibody caused lethal liver injuries in preclinical models [108].…”
Section: Tnfmentioning
confidence: 99%
“…Despite the ability of TNF and FasL to induce apoptosis in cancer cells, severe toxic side effects preclude both ligands from use in systemic anticancer therapy. Systemic administration of TNF caused an inflammatory response resembling septic shock in humans [107]. FasL or agonistic anti-Fas antibody caused lethal liver injuries in preclinical models [108].…”
Section: Tnfmentioning
confidence: 99%
“…CD95, so-called Fas or Apo1, is the best-known death receptor belonging to the TNF receptor superfamily (Schmitz et al, 2000;Timmer et al, 2002); however, before long it was appreciated that systemic treatment with Fas-targeting therapy causes severe liver damage (Ogasawara et al, 1993;Galle et al, 1995). The therapeutic potential of TNFa was also tempered by the demonstration that the systemic administration of recombinant TNFa resulted in a significant systemic toxicity associated with its strong pro-inflammatory activity, including fever, lung or liver failure, increased blood clotting and hypotension (Creaven et al, 1987;Creagen et al, 1988;Hersh et al, 1991;Vassalli, 1992). Thus, the use of Fas or TNFa receptors as cancer targets appeared fruitless, and more recently efforts have been made to focus on minimizing unfavorable side effects by using local administration, inducible FasL-or TNF-expressing vectors, and tumor targeting gene delivery methods (Kircheis et al, 2002).…”
Section: Targeting the Tnf Receptor Superfamily In Cancermentioning
confidence: 99%
“…However, several studies have found that treatment with either TNF or anti-Fas antibodies was toxic to normal tissues 27,28) . Intravenous TNF administration caused hypotension and a systemic inflammatory syndrome similar to septic shock.…”
Section: Therapeutic Approaches Using Trailmentioning
confidence: 99%