TRAIL enhances efficacy of radiotherapy in a p53 mutant, Bcl-2 overexpressing lymphoid malignancy.

Background And Purpose: Resistance to apoptosis is a contributing factor in the response to radiotherapy. Aim of this study was to evaluate whether TRAIL--in a soluble isoleucine zippered form--enhances the cytotoxic effect of irradiation on tumour cells with a blockade in the mitochondrial apoptosis route and/or a dysfunctional p53 pathway.

Materials And Methods: The p53 mutant human T acute lymphoblastic leukemia line Jurkat transduced with the Bcl-2 gene was used as model system in vitro and in a subcutaneous transplant setting in immunodeficient mice.

Preclinical differentiation between apparently safe and potentially hepatotoxic applications of TRAIL either alone or in combination with chemotherapeutic drugs.

Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) exhibits potent antitumor activity on systemic administration in nonhuman primates without deleterious side effects for normal tissue. However, there is a controversy about the potential toxicity of TRAIL on human hepatocytes. The use of different recombinant TRAIL forms only partially explains the contradicting reports on TRAIL sensitivity in primary human hepatocytes (PHH).