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  • 1
    Abstract: Constitutively active NFkappaB promotes survival of many cancers, especially T-cell lymphomas and leukemias by upregulating antiapoptotic proteins such as inhibitors of apoptosis (IAPs) and FLICE-like inhibitory proteins (cFLIPs). IAPs and cFLIPs negatively regulate the ripoptosome, which mediates cell death in an apoptotic or necroptotic manner. Here, we demonstrate for the first time, that DMF antagonizes NFkappaB by suppressing Thioredoxin-1 (Trx1), a major regulator of NFkappaB transcriptional activity. DMF-mediated inhibition of NFkappaB causes ripoptosome formation via downregulation of IAPs and cFLIPs. In addition, DMF promotes mitochondrial Smac release and subsequent degradation of IAPs, further enhancing cell death in tumor cells displaying constitutive NFkappaB activity. Significantly, CTCL patients treated with DMF display substantial ripoptosome formation and caspase-3 cleavage in T-cells. DMF induces cell death predominantly in malignant or activated T-cells. Further, we show that malignant T-cells can die by both apoptosis and necroptosis, in contrast to resting T-cells, which are restricted to apoptosis upon DMF administration. In summary, our data provide new mechanistic insight in the regulation of cell death by targeting NFkappaB via Trx1 in cancer. Thus, interference with Trx1 activity is a novel approach for treatment of NFkappaB-dependent tumors.
    Type of Publication: Journal article published
    PubMed ID: 28233787
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  • 2
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The luminescence properties of lead ions and their sensitizing effect on cerium activators in strontium sulfide thin-film electroluminescence (TFEL) devices have been investigated. Polycrystalline SrS:Pb and SrS:Ce,Pb thin active layers for such TFEL devices have been prepared by multi-source deposition. Emission spectroscopy under application of a high electric field (EL), under e-beam excitation [cathodoluminescence (CL)], and under CL conditions with additional EL drive has been carried out. It has been found that the luminescence of SrS:Pb under EL drive is very weak, while the CL signal is considerably higher. This CL signal has shown strong quenching effects upon application of an additional ac voltage. The Pb2+ emission dropped to some 5% at an applied voltage of 100 V0p, being roughly 40 V below EL threshold. More than half of this drop occurred between 0 and 30 V0p. A remarkably lower quenching effect on the Ce3+ activator luminescence has been observed. Such luminescence quenching is attributed to the field induced ionization of the luminescent ions. From the obtained results it is concluded that the optical energy transfer from Pb2+ sensitizers to Ce2+ activators in SrS TFEL devices is low. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
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