Malignancies

Aberrant expression and or activation of c-kit has been implicated in a variety of tumors. Although many tumor cells express SCF, which may indirectly stimulate tumor cell growth by inducing cytokine release from mast cells or other cells that normally respond to SCF, the discussion in this chapter will be limited to c-kit activation that has been directly implicated in tumor cell growth. In this regard, the strongest evidence for a contribution of c-kit to neoplastic pathology is associated...

IL18 Signal Transduction Is Similar to that of IL1

It is clear that IL-1 and IL-18 do share signaling pathways, particularly in activating the processes by which nuclear factor-KB (NF-kB) translocates to the nucleus. In terms of IFN-y production, IL-ta, IL-tp, and IL- each induce IFN-y in the presence of IL-2 or IL- (97,98). IL- is 5-t0 times more potent that either form of IL-t (97), which suggests, expectedly, that signal transduction of IL-t and IL- cannot be identical. However, the recruitment of interleukin-t receptor-associated kinase...

VEGFr Tyrosine Kinase Inhibitors

3-Arylidenyl indolin-2-ones have been described as inhibitors of tyrosine kinases, including VEGFr1 (Flk1), FGF-R, PDGFr, ABL, EGF-R, and Her-2 (Sun et al., 1998, 1999, 2000). In this case, inhibitory activity was measured using cell-based kinase assays following ligand-dependent receptor activation and autophosphorylation (Sun et al., 1998, 1999, 2000 Tang et al., 1998). In these studies, compounds possessing different arylidenyl moieties at the C-3 position of the indolin-2-one core scaffold...

Il2

IL-2 has been used primarily in cancer therapy, but it has also been used in congenital and acquired immune deficiencies, in infections, and as an adjuvant to vaccines (149,150). Success has been obtained in the treatment of metastatic renal cell carcinoma and malignant melanoma, although this is often hampered by dose-dependent severe toxicities. Both native and recombinant IL-2 have been used and both have turned out to be immunogenic, although to a varying extent only a few reports have...

Natural Antibodies To Cytokines

It is unknown why and how Ab are induced to some cytokines and not to others in apparently healthy individuals. However, cytokine-reactive B cells seem to occur frequently. As T-cell help is thought to be essential for the production of high-affinity IgG Ab, termination of T-cell tolerance is likely to be involved in the course of events leading to Ab induction. One possibility is that activation of cross-reactive B and T cells is initiated if a native cytokine as a hapten binds to a carrier...