Search results for "Inhibitor of apoptosis"
showing 10 items of 61 documents
Addition of AEG35156 XIAP antisense oligonucleotide in reinduction chemotherapy does not improve remission rates in patients with primary refractory …
2011
Background XIAP (X-linked inhibitor of apoptosis protein) is an inhibitor of caspases 3 and 9 that is overexpressed in acute myeloid leukemia (AML) and may contribute to chemoresistance. We report an open-label randomized phase II trial of reinduction chemotherapy with and without the XIAP antisense oligonucleotide AEG35156 in patients with AML who did not achieve remission with initial induction chemotherapy. Methods Twenty-seven patients with AML who were refractory to initial induction chemotherapy were randomized and treated with AEG35156 (650 mg) in combination with high-dose cytarabine and idarubicin. Thirteen patients were randomized and treated with high-dose cytarabine and idarubic…
Dysregulated Survivin Expression in Nasal Polyps of Individuals with Aspirin Exacerbated Respiratory Disease
2012
Background A derailed balance of cell proliferation and apoptosis is presumed to result in cell hyperplasia as a typical feature of nasal polyps. Survivin, a protein of the inhibitors of the apoptosis family is proposed to promote polyp formation. However, studies concerning survivin expression in chronic rhinosinusitis (CRS) with nasal polyps are rare and the specificity of the survivin expression in nasal polyps from individuals with aspirin-exacerbated respiratory disease (AERD) has not been investigated. Methods Immunohistochemical survivin expression analysis was performed. Samples were taken from the ethmoid sinus of individuals with CRS with nasal polyps with and without AERD during …
Induction of apoptosis by the adenosine derivative IB-MECA in parental or multidrug-resistant HL-60 leukemia cells: possible relationship to the effe…
2004
<i>Background:</i> The effects of the A<sub>3</sub> adenosine receptor (A<sub>3</sub>AR) agonist IB-MECA were examined in HL-60 leukemia and in its multidrug-resistant variant HL-60R cells. <i>Methods:</i> Cytotoxicity was evaluated by MTS assays and apoptosis by flow cytometry analyses of DNA fragmentation and phosphatidylserine exposure. The mRNAs of A<sub>3</sub>AR and inhibitor of apoptosis proteins (IAPs) were determined by RT-PCR. <i>Results:</i> A<sub>3</sub>AR expression was similar in HL-60 and HL-60R cells. At ≧100 µ<i>M</i>, IB-MECA exhibited strong cytotoxic and apoptotic effects in H…
Expression of the IAPs in multidrug resistant tumor cells
2003
We have investigated the expression of the IAPs (inhibitory of apoptosis proteins) in the human HL-60 leukemia and in its multidrug resistant, P-glycoprotein (P-gp) over-expressing variant, HL-60R. HL-60R exhibits resistance to apoptosis induced from P-gp substrate drugs and also from other triggers (cisplatin, TNF-alpha, Fas ligation, TRAIL, IFN-gamma and serum starvation) not related to the multidrug transporter. Except for c-IAP-1 mRNA, HL-60R significantly over-expressed both the mRNAs and the proteins of all the IAPs studied, i.e. c-IAP-1, c-IAP-2, XIAP, NAIP and survivin. Determination of the DNA-binding capacity of NF-kappaB (p50 or p65 subunits) indicated that, while HL-60 cells sho…
Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their possible relat…
2005
The hepatic cancer HA22T/VGH cell line, which constitutively expresses activated nuclear factor-kappaB (NF-kB), was chosen as a model to examine the antitumor activity of curcumin, also in relationship to its possible influences on the activation of the transcription factor and on the expression of the inhibitory of apoptosis proteins (IAPs) and of other NF-kB target genes. Curcumin exerted cell growth inhibitory and apoptotic effects, related, at least part, to free radical generation and mainly dependent on caspase-9 and -3 activation. The combination of curcumin with cisplatin resulted in a synergistic antitumor activity and that with doxorubicin in additivity or sub-additivity. Curcumin…
cIAP1 regulates TNF-mediated cdc42 activation and filopodia formation
2013
International audience; umour necrosis factor-α (TNF) is a cytokine endowed with multiple functions, depending on the cellular and environmental context. TNF receptor engagement induces the formation of a multimolecular complex including the TNFR-associated factor TRAF2, the receptor-interaction protein kinase RIP1 and the cellular inhibitor of apoptosis cIAP1, the latter being essential for NF-κB activation. Here, we show that cIAP1 also regulates TNF-induced actin cytoskeleton reorganization through a cdc42-dependent, NF-κB-independent pathway. Deletion of cIAP1 prevents TNF-induced filopodia and cdc42 activation. The expression of cIAP1 or its E3-ubiquitin ligase-defective mutant restore…
Altered Expression of c-IAP1, Survivin, and Smac Contributes to Chemotherapy Resistance in Thyroid Cancer Cells
2006
Abstract Resistance to chemotherapy predicts an unfavorable outcome for patients with radioiodine-insensitive thyroid cancer. To investigate the mechanisms underlying this resistance, we evaluated the expression of four different inhibitor of apoptosis proteins, and their antagonist, Smac, in thyroid cancer cells that survived 48 hours of exposure to cisplatin, doxorubicin, or taxol. We found high levels of c-IAP1 after cisplatin treatment and increased expression of survivin following exposure to doxorubicin. Cells that endured treatment with taxol showed reduced expression of Smac and released minimal amounts of this protein from the mitochondria. Down-regulation of c-IAP1 and survivin in…
Targeting apoptosis proteins in hematological malignancies
2010
The apoptotic machinery plays a key role in hematopoietic cell homeostasis. Terminally differentiated cells are eliminated, at least in part, by apoptosis, whereas part of the apoptotic machinery, including one or several caspases, is required to go through very specific steps of the differentiation pathways. A number of hematological diseases involve a deregulation of this machinery, which in most cases is a decrease in cell sensitivity to pro-apoptotic signals through over-expression of anti-apoptotic molecules. In some situations however, e.g. in the erythroid lineage of low grade myelodysplastic syndromes, cell sensitivity to apoptosis is increased in a death receptor-dependent manner a…
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…
Resistance to diverse apoptotic triggers in multidrug resistant HL60 cells and its possible relationship to the expression of P-glycoprotein, Fas and…
2002
We studied the human HL60 leukemia cell line and its multidrug resistant (MDR) variant HL60R. In contrast to the HL60, HL60R showed an inability to undergo apoptosis from doxorubicin (Dox) or other different stimuli, including cisplatin, Fas ligation and serum withdrawal. HL60R cells lost surface Fas expression, but we found no evidence that Fas/FasL mediates the apoptotic effects of Dox in HL60. P-glycoprotein (P-gp) did not seem to play a major role as a specific inhibitor of apoptosis. In fact, the P-gp inhibitor verapamil reversed only partially the resistance to Dox-induced apoptosis of the MDR cells. In addition, it did not modify the rate of apoptosis induced from the other stimuli i…