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The key events implicated in ceramide-triggered apoptosis remain unknown. In this study we show that 25 microM C6-ceramide induced significant H2O2 production within 60 min, which increased up to 180 min in human myeloid leukemia U937 cells. Inactive analogue dihydro-C6-ceramide had no effect. Furthermore, no H2O2 production was observed in(More)
The proteasome inhibitor bortezomib is currently an important drug for treatment of relapsed and refractory multiple myeloma (MM) and for elderly patients. However, cells from some patients show resistance to bortezomib. We have evaluated the possibility of improving bortezomib therapy with Apo2L/TRAIL, a death ligand that induces apoptosis in MM but not in(More)
Preformed Fas ligand (FasL) and APO2 ligand (APO2L)/TNF-related apoptosis-inducing ligand (TRAIL) are stored in the cytoplasm of the human Jurkat T cell line and of normal human T cell blasts. The rapid release of these molecules in their bioactive form is involved in activation-induced cell death. In this study, we show by confocal microscopy that FasL and(More)
Cancer cells usually display higher proliferation rates than normal cells. Some currently used antitumor drugs, such as vinca alkaloids and taxanes, act by targeting microtubules and inhibiting mitosis. In the last years, different mitotic regulators have been proposed as drug target candidates for antitumor therapies. In particular, inhibitors of Cdks,(More)
UNLABELLED The smoking habit is a key factor in the development of inflammatory bowel disease (IBD), but little information exists as to the relationship between smoking habit, the need of surgery and its complications. OBJECTIVES To investigate the relationship between smoking habit, the need of surgery, their complications and clinical recurrence after(More)
The mechanisms responsible for the down-modulation of the activation of separated CD4(+) or CD8(+) human T cell blasts were studied using cells obtained from healthy donors. In the absence of IL-2, human CD4(+) T cell blasts were sensitive to both FasL and Apo2L/TRAIL, but human CD8(+) T cell blasts died, with no additional effect of death receptor(More)
Activation-induced cell death is a process by which overactivated T cells are eliminated, thus preventing potential autoimmune attacks. Two known mediators of activation-induced cell death are Fas(CD95) ligand (FasL) and APO2 ligand (APO2L)/TNF-related apoptosis-inducing ligand (TRAIL). We show here that upon mitogenic stimulation, bioactive FasL and APO2L(More)
alpha-Fetoprotein and albumin, two members of a multigene family, reversibly bind fatty acids with high affinity. The origin of alpha-fetoprotein (AFP) and albumin present in fetal tissues other than the liver and yolk sac is a subject of controversy. In this work, we have searched for the presence of the albumin and AFP mRNA molecules in different fetal(More)
Purified cytolytic T lymphocyte (CTL) proteases granzyme (gzm)A and gzmB with sublytic dose of perforin (perf) initiate distinct proapoptotic pathways. Their physiological relevance in CTL-mediated target cell apoptosis is elusive. Using ex vivo virus-immune CD8(+) T cells from mice deficient in perf, gzmA and/or gzmB, and the Fas-resistant EL4.F15 tumor(More)
BACKGROUND AND AIMS Tumour necrosis factor alpha (TNF-alpha) plays a key role in the pathogenesis of intestinal inflammation in Crohn's disease. The effect of bacteria on TNF-alpha release by intestinal mucosa was investigated. METHODS Ileal specimens were obtained at surgery from 10 patients with Crohn's disease (ileal stricture) and five disease(More)