Carfilzomib Inhibits Constitutive NF-κB Activation in Mantle Cell Lymphoma B Cells and Leads to the Induction of Apoptosis.
Acta Haematol. 2017 Feb 17;137(2):106-112
Authors: Zhang YL, Guang MH, Zhuo HQ, Min XH, Yao Q, Gu AQ, Wu SH, Zhang DB, Lu JY, Chen Y, Chen YH, Zhang KJ
Mantle cell lymphoma (MCL) remains incurable and new treatments are needed, especially in the relapsed/refractory setting. We therefore investigated the effects of carfilzomib, a novel, long-acting, second-generation proteasome inhibitor, in MCL cells. Eight established MCL cell lines and freshly isolated primary MCL cells were treated with carfilzomib. Cell proliferation was assessed by a 3H-thymidine incorporation assay. Cell apoptosis was evaluated by flow cytometry with annexin V and propidium iodide. Electrophoresis mobility shift (EMSA), Western blot, and luciferase assays were used to analyze NF-κB activation and related signaling proteins. Carfilzomib inhibited growth and induced apoptosis in both established MCL cell lines and freshly isolated primary MCL cells in a dose-dependent manner. In contrast, carfilzomib was less toxic to normal peripheral blood mononuclear cells from healthy individuals. The carfilzomib-induced apoptosis of MCL cells occurred in a caspase-dependent manner through both intrinsic and extrinsic caspase pathways. In addition, carfilzomib inhibited constitutive activation of the NF-κB signaling cascade, both in MCL cell lines and primary MCL cells, by completely blocking the phosphorylation of IκBα. Our results demonstrate that carfilzomib can induce growth arrest and apoptosis in MCL cells and that the mechanism may involve the NF-κB signaling pathway.
PMID: 28208145 [PubMed - as supplied by publisher]
Mean Platelet Volume in Heterozygous Beta Thalassaemia.
Acta Haematol. 2017 Feb 17;137(2):100-105
Authors: Cikrikcioglu MA, Celik K, Ekinci I, Nasifov M, Toprak AE, Cetin G, Genc S
BACKGROUND/AIM: It is not known why cerebrovascular and cardiovascular ischaemic events are less frequently observed in heterozygous beta thalassaemia (HBT) patients than in the general population. However, we previously reported that serum levels of some platelet function markers, i.e. soluble CD40 ligand and soluble P-selectin, are lower in patients with HBT than in controls. A high mean platelet volume (MPV) is an indicator of in vivo platelet activation and may indicate a tendency to thrombosis. We investigated whether MPV is lower in HBT patients than in controls.
METHODS: Forty-eight patients with HBT were compared with 51 controls matched for gender, age, and BMI for MPV in a cross-sectional study.
RESULTS: The MPV was within the normal range and higher in the HBT group (9.64 ± 1.20 vs. 9.07 ± 082 fL, p = 0.006). The 2 groups were similar in terms of atherosclerosis risk factors and medications. After linear regression analysis, the MPV was correlated with HBT, sensitive CRP, and BMI.
CONCLUSION: The higher MPV in patients with HBT could indicate platelet activation, and this may represent a dilemma. Higher MPV in the HBT group might have resulted from higher sympathetic nervous system activity, mild ineffective erythropoiesis, and haemolysis.
PMID: 28208125 [PubMed - as supplied by publisher]