Popis: |
Tumor necrosis factor (TNF), a macrophage-derived polypeptide, was initially described by Carswell and coworkers at Sloan-Kettering as the agent that produced hemorrhagic necrosis of certain transplanted sarcomas in mice presensitized with bacille Calmette-Guerin (BCG) and challenged with bacterial endotoxin [1], As a result, investigators at our institution have had a long-standing interest in TNF as an antitumor agent, and a number of phase I trials as well as a phase II study in patients with colon cancer have been undertaken. In addition, the discovery by Beutler and coworkers [2] that the amino acid sequence of TNF was homologous with that of cachectin, and the suggestion that TNF might be an important mediator of endotoxic shock, were the basis for an evaluation of its metabolic effects in patients participating in the initial studies [3]. |