1-LMP-1 or LMP-1 siRNA. Compared with the blank control, the cell apoptosis rates were decreased by 10.31 and 12.05% after pcDNA3.1-LMP-1 transfection and increased by 41.48 and 35.63% after lentiviral LMP-1 siRNA infection in the SNK-6 and SNT-8 cells. Survivin expression was induced by Selonsertib concentration LMP-1, and the effect was attenuated by inhibitors of survivin, NF-kappa B and PI3K/Akt. Reduction in cell apoptosis by LMP-1 was also inhibited by inhibitors of survivin, NF-kappa B and PI3K/Akt. For the in vivo assay, tumor-bearing mice were established
by subcutaneous injection with differentially treated SNT-8 cells into the back of the nude mice, and the tumor growth in the different groups was recorded. The results revealed that tumor formation and growth were also inhibited by treatment with survivin, NF-kappa B and PI3K/Akt inhibitors. Collectively, LMP-1-induced survivin expression inhibited cell apoptosis through the NF-kappa B and PI3K/Akt pathways, and survivin may be a new target for the treatment of NKTL induced by EBV.”
“Mutations in the additional sex comb-like 1 (ASXL1) gene were
recently shown in various myeloid malignancies, but they have not been comprehensively investigated in acute myeloid leukemia (AML). In this study, we analyzed ASXL1 mutations in exon 12 in 501 adults with de novo AML. ASXL1 mutations were detected in 54 patients (10.8%), 8.9% among those with normal karyotype and 12.9% among those with abnormal cytogenetics. The mutation was closely associated with older age, male sex, isolated trisomy 8, RUNX1 mutation, and expression of human leukocyte antigen-DR and CD34, but inversely associated selleck chemical with t(15; 17), complex cytogenetics, FLT3-internal tandem duplication, selleck compound NPM1 mutations, WT1 mutations, and expression of CD33 and CD15. Patients with ASXL1 mutations had a shorter overall survival than patients without, but the mutation was not an independent adverse prognostic factor in multivariate analysis. Sequential analyses showed that the original ASXL1 mutations were lost at relapse and/or refractory status in 2 of the 6 relapsed ASXL1-mutated patients studied, whereas 2 of the 109 ASXL1-wild patients acquired a novel ASXL1
mutation at relapse. In conclusion, AML bearing ASXL1 mutations showed distinct clinical and biological features. The ASXL1 mutation status can change during disease evolution in a few patients. (Blood.2010;116(20):4086-4094)”
“Osteoblasts undergo apoptosis both in vitro and in vivo in response to high dose glucocorticoid (GC) treatment. However, the molecular mechanisms remain elusive, hindering the prevention and treatment of this side-effect. Apoptosis was induced by dexamethasone (Dex) in murine MBA-15.4 osteoblasts within 24-48 h of treatment. We found dose- and time-dependent upregulation of Bim protein, a pro-apoptotic Bcl-2 family member, with highest levels at 24-48 h for 1 mu M Dex. This was also observed in primary human bone marrow stromal cells.