Search results for "Apoptosis Inhibitor"
showing 6 items of 6 documents
cFLIPoverexpression in T cells in thymoma‐associated myasthenia gravis
2015
OBJECTIVE: The capacity of thymomas to generate mature CD4+ effector T cells from immature precursors inside the tumor and export them to the blood is associated with thymoma-associated myasthenia gravis (TAMG). Why TAMG(+) thymomas generate and export more mature CD4+ T cells than MG(-) thymomas is unknown. METHODS: Unfixed thymoma tissue, thymocytes derived thereof, peripheral blood mononuclear cells (PBMCs), T-cell subsets and B cells were analysed using qRT-PCR and western blotting. Survival of PBMCs was measured by MTT assay. FAS-mediated apoptosis in PBMCs was quantified by flow cytometry. NF-κB in PBMCs was inhibited by the NF-κB-Inhibitor, EF24 prior to FAS-Ligand (FASLG) treatment …
Dynamic survivin in head and neck cancer: Molecular mechanism and therapeutic potential
2007
Although disease management of head and neck squamous cell carcinomas (HNSCC) has improved significantly, therapy resistance leading to tumor recurrence still counteracts improvement of long-term survival. Consequently, identification of molecular markers that signal increased risk of treatment failure or, which can be exploited by targeted therapy, is urgently needed. Survivin is strongly expressed in HNSCC, and its proposed dual role as an apoptosis inhibitor and a mitotic effector positioned survivin in the front line of cancer research. Notably, survivin is detected as a cytoplasmic and as a nuclear protein in HNSCC patients, which stimulated numerous studies to investigate and to specu…
Survivin’s Dual Role: An Export’s View
2007
Survivin is proposed to function as a mitotic regulator and an apoptosis inhibitor during development and pathogenesis. As such, survivin has aroused keen interest in disparate areas of basic and translational research. Survivin acts as a subunit of the chromosomal passenger complex (CPC), composed of the mitotic kinase Aurora-B, Borealin and INCENP, and is essential for proper chromosome segregation and cytokinesis. Our recent findings indicate that the nuclear export receptor Crm1 is critically involved in tethering the CPC to the centromere by interacting with a leucine-rich nuclear export signal (NES), evolutionary conserved in all mammalian survivin proteins. In addition, the survivin/…
Nuclear and Cytoplasmic Survivin: Molecular Mechanism, Prognostic, and Therapeutic Potential.
2007
Abstract Survivin's proposed dual role as an apoptosis inhibitor and a mitotic effector positioned it in the front line of cancer research. Notably, survivin is detected as a cytoplasmic and nuclear protein in cancer patients, which stimulated numerous studies to investigate and to speculate on the functional and prognostic significance of its dynamic localization. Recent evidence shows that the direct interaction of survivin with the nuclear export receptor Crm1 is critically involved in its intracellular localization and cancer-relevant functions. Here, we review our current understanding of the Crm1/survivin interface and discuss its potential prognostic and therapeutic relevance. [Cance…
NAIP-deltaEx10-11: a novel splice variant of the apoptosis inhibitor NAIP differently expressed in drug-sensitive and multidrug-resistant HL60 leukem…
2002
Alterations of neuronal apoptosis inhibitory protein (NAIP), a member of the inhibitory of apoptosis protein (IAP) family of inhibitors of apoptosis, have been previously associated with different neurodegenerative disorders. This study indicated the existence of a novel NAIP splice variant. This isoform, NAIP-deltaEx10-11, was found in tumor cell lines of different origin and in normal adult brain. Analysis of the putative protein predicted that the NAIP variant lacks part of the third BIR domain as well as the COOH-terminal tail of regular NAIP. This might suggest that it is endowed with a reduced antiapoptotic activity. This view is supported by the fact that NAIP-deltaEx10-11 mRNA and p…
Targeting NUPR1 with the Small Compound ZZW-115 Is an Efficient Strategy to Treat Hepatocellular Carcinoma
2020
International audience; HCC is a highly lethal malignancy with Sorafenib as the only molecularly targeted drug. The multifunctional stress-associated protein, NUPR1, plays an essential role in controlling cell growth, migration, invasion and Sorafenib resistance in HCC. We report here that NUPR1 expression is absent in healthy liver and it is progressively upregulated in HCC premalignant lesions such as hepatitis and cirrhosis with a maximum expression in HCC samples, highlighting that NUPR1 is a potential drug target for HCC. We therefore assessed in this work, ZZW-115, a strong inhibitor of NUPR1, as a promising candidate for the treatment of HCC. We validated its extraordinary antitumor …