Full Description
Tumor necrosis factor (TNF)-? is a pleiotropic cytokine involved in a va- ety of physiological and pathological processes. After initial discovery of its ability to induce cell death and animal cachexia, it was soon realized that this cytokine played pivotal roles in the regulation of homeostasis and inflam- tory-immune responses. This led to an explosion of interest in basic and tra- lational research activities on the role of TNF in many diseases, such as cancer, septic shock, rheumatoid arthritis, and infectious diseases of the central n- vous system. Because of its potential therapeutic value, many academic and industrial research groups have worked to discover compounds that can block its activity. These studies have led to the approval of anti-TNF antibodies and soluble TNF receptors for the therapy of rheumatoid arthritis and Crohn's d- ease. TNF also can be an attractive anticancer agent capable of damaging tum- associated vessels and of inducing tumor necrosis in patients.
The unique properties of TNF have led to its registration as a drug for locoregional tre- ment of sarcomas of the extremities, and stimulated many preclinical studies aimed at improving its therapeutic index for systemic use. Tumor Necrosis Factor: Methods and Protocols provides an overview of basic and translational research along with a series of practical procedures on TNF production, characterization, mutagenesis, detection in biological spe- mens, as well as several in vitro assays and animal models for studying the role of TNF in various diseases.
Contents
Tumor Necrosis Factor as a Pharmacological Target.- Production and Characterization of Recombinant Human and Murine TNF.- Purification of TNF Binding Proteins.- Production and Characterization of Receptor-Specific TNF Muteins.- TNF? Promoter Polymorphisms.- Detection of TNF and TNF Receptor mRNA in Cells and Tissues.- Immunohistochemical Localization of TNF? and Its Receptors in the Rodent Central Nervous System.- TNF Signaling.- More Than One Way to Die.- Assessment of TNF?-Induced Endothelial Damage Through the Loss of Its Barrier Function.- Genetic Engineering in the Mouse.- TNF? in Experimental Diseases of the CNS.- In Vivo Vascular Leakage Assay.- Animal Models of Endotoxic Shock.- Collagen-Induced Arthritis as a Model for Rheumatoid Arthritis.- Myocardial Infarction.- Tumor Vascular Therapy With TNF.- Strategies for Improving the Anti-Neoplastic Activity of TNF by Tumor Targeting.
