Strategies for manipulating apoptosis for cancer therapy with tumor necrosis factor and lymphotoxin

Abstract

Tumor necrosis factor (TNF) and lymphotoxin (LT), initially described as tumoricidal proteins, may be useful as adjuncts in cancer therapy. Treatment with TNF or LT was found to protect cells and animals against damage mediated by radiation or cytotoxic anticancer drugs. By contrast, tumor cells treated with TNF or LT were sensitized to these insults. We present a model in which TNF or LT induces both the synthesis of "protective" proteins such as manganous superoxide dismutase (MnSOD) and the activation of "killing" proteins, such as proteases, depending on the level of the inducing signal. Although the p55-TNF/LT receptor is structurally related to the Fas receptor, they can each signal apoptosis by distinct pathways. Furthermore, activation of both receptors acts synergistically in stimulating apoptosis.

Evaluation of Eosinophilia in Hospitalized Preterm Infants

“…Eosinophils also contain lipidderived proinflammatory substances (prostaglandin E2, thromboxane A2, leukotriene C4, 15-hydroxyeicosatetraenoic acid and lipoxin A 4) that are likely important in the allergic inflammatory reaction. 3 Immunoregulatory factors include IL-2, IL-4, IL-10, and interferon-g. 27 Finally, eosinophils may also affect tissue remodeling and fibrosis by releasing transforming growth factors (TGF)-a 28,29 and TGF-b1. 5 This ensemble of factors can work in concert to protect the host against infection, but can also produce tissue injury if their synthesis, release, and accumulation are not tightly regulated.…”

Immunometabolic profiling of cervicovaginal lavages identifies key signatures associated with adenomyosis

“… 46 TNFβ also has the ability to induce apoptosis within tumor cells while protecting normal cells. 47 …”

Boldenone-induced apoptotic, structural, and functional alterations in the liver of rabbits

“…One of the signalling pathways by which p53 induce apoptosis is the engagement of particular (death) receptors that belong to the tumour necrosis factor receptor (TNF-R) family (Ashkenazi and Dixit, 1998). Moreover, TNF-α is a cytokine capable of initiating a broad range of biological effects, including apoptosis of some tumour cells (Wong et al, 1997). These effects are mediated through TNF receptor oligomerisation, which activates a caspase cascade through cytoplasmic proteins and TNF-receptor complexes.…”