作者：Remco van Horssen, Timo L. M. ten Hagen, Alexander M. M. Eggermont
【关键词】 Cancer,•,TNF-,•,TNFR-1,•,Tumor,vasculature,•,Isolated,limb,perfusion
LEARNING OBJECTIVES
After completing this course, the reader will be able to:
Discuss the role of TNF-a in cancer survival and apoptosis.
Describe the mechanism of chemotherapy potentiation by TNF-a.
Explain the selective targeting of tumor vasculature by TNF-a.
Discuss TNFR-1 and TNFR-2 signaling.
ABSTRACT
Tumor necrosis factor alpha (TNF-), isolated 30 years ago, is a multifunctional cytokine playing a key role in apoptosis and cell survival as well as in inflammation and immunity. Although named for its antitumor properties, TNF has been implicated in a wide spectrum of other diseases. The current use of TNF in cancer is in the regional treatment of locally advanced soft tissue sarcomas and metastatic melanomas and other irresectable tumors of any histology to avoid amputation of the limb. It has been demonstrated in the isolated limb perfusion setting that TNF- acts synergistically with cytostatic drugs. The interaction of TNF- with TNF receptor 1 and receptor 2 (TNFR-1, TNFR-2) activates several signal transduction pathways, leading to the diverse functions of TNF-. The signaling molecules of TNFR-1 have been elucidated quite well, b……
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