Carfilzomib Inhibits Constitutive NF-κB Activation in Mantle Cell Lymphoma B Cells and Leads to the Induction of Apoptosis.

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.

[The efficacy and complication analysis of interspinous dynamic device (Wallis) in patients of degenerative lumbar disease].

OBJECTIVES: To review degenerative lumbar disease treated with Wallis and the re-herniation cases after the implantation of Wallis, so as to evaluate the effect of the device. METHODS: From January 2009 to June 2010, a retrospective analysis was done and 48 patients (30 males and 18 females) with an average age of 43 years (ranging from 17 to 69 years), who received stabilization of the segment using the Wallis device, were reviewed. The involved segments included: 4 cases at L(3-4), 38 cases at L(4-5), 6 cases at L(5)-S(1). Preoperative and postoperative visual analogue scales (VAS) and Oswestry disability index (ODI) were recorded to evaluate the clinical efficiency, imageology diversity was assessed by X-rays and MRI. RESULTS: All cases received fenestration and the implantation of Wallis. No surgery related complications were recorded. There were 48 cases were followed up. The average follow-up period was (20 ± 4) months (12 - 30 months). The average ODI score dropped from 46 ± 10 to 24 ± 7 (t = 12.765, P < 0.05). The average VAS for back and leg pain dropped from 8.1 ± 1.6 to 2.1 ± 1.1(t = 21.881, P < 0.05). Six patients with recurrent lower back and leg pain were diagnosed by MRI, as recurrent herniation (6/48, 12.5%). All re-herniation occurred at L(4-5) level, between 2 and 13 months after the surgery. Three of the 6 patients underwent additional discectomy and fusion, others received conservative treatment. CONCLUSIONS: Although existing problems such as recurrence after surgery, the clinical outcome of Wallis in treating protrusion of lumbar intervertebral disc and lumbar stenosis is satisfied in middle-early stage.