LightCycler PCR for the Polymorphisms -308 and -238 in the TNF Alpha Gene and for the TNFB1/B2 Polymorphism in the LT Alpha Gene

Abstract

Tumor necrosis factor alpha (TNF-α), a multifunctional cytokine of ~17 kDa composed of 157 amino acids, was initially identified as a macrophage-derived serum protein mediating necrosis of solid tumors in mice and lysis of several types of transformed cells in vitro. Indeed, recombinant tumor necrosis factor alpha (rTNF-α) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNF-α is hampered by severe systemic side effects, with the maximum tolerated dose being at least tenfold less than the effective dose in animals [14]. Thus, systemic treatment with TNF has not become a viable treatment modality for common human cancers. Isolated perfusion of the limbs allows the delivery of high-dose rTNF-α in a closed system with acceptable side effects, and several studies have shown that TNF-α, in combination with other agents such as melphalan, does possess activity against certain human tumors in vivo [12, 20].