Analysis of the Metabolic Characteristics of Serum Samples in Patients With Multiple Myeloma

Aims: This study aimed to identify potential, non-invasive biomarkers for diagnosis and monitoring of the progress in multiple myeloma (MM) patients.Methods: MM patients and age-matched healthy controls (HC) were recruited in Discovery phase and Validation phase, respectively. MM patients were segregated into active group (AG) and responding group (RG). Serum samples were collected were conducted to non-targeted metabolomics analyses. Metabolites which were significantly changed (SCMs) among groups were identified in Discovery phase and was validated in Validation phase. The signaling pathways of these SCMs were enriched. The ability of SCMs to discriminate among groups in Validation phase was analyzed through receiver operating characteristic curve. The correlations between SCMs and clinical features, between SCMs and survival period of MM patients were analyzed.Results: Total of 23 SCMs were identified in AG compared with HC both in Discovery phase and Validation phase. Those SCMs were significantly enriched in arginine and proline metabolism and glycerophospholipid metabolism. 4 SCMs had the discriminatory ability between MM patients and healthy controls in Validation phase. Moreover, 12 SCMs had the ability to discriminate between the AG patients and RG patients in Validation phase. 10 out of 12 SCMs correlated with advanced features of MM. Moreover, 8 out of 12 SCMs had the negative impact on the survival of MM. 5′-Methylthioadenosine may be the only independent prognostic factor in survival period of MM.Conclusion: 10 SCMs identified in our study, which correlated with advanced features of MM, could be potential, novel, non-invasive biomarkers for active disease in MM

Daintain/AIF-1 Plays Roles in Coronary Heart Disease via Affecting the Blood Composition and Promoting Macrophage Uptake and Foam Cell Formation

Background: Daintain/AIF-1 is an inflammatory polypeptide factor/allograft inflammatory factor 1 derived from macrophages. It is characterized in APOE-/- mice as a novel inflammatory factor associated with atherosclerosis. The purpose of this study was to characterize its function in human atherosclerosis. Methods: Immunohistochemistry was used to identify the expression of daintain/AIF-1 in vessel segments within and far from atherosclerotic plaques; High-performance liquid chromatography (HPLC) was used to display the effects of daintain/AIF-1 on C-reactive protein (CRP), oxidative capacity and superoxide dismutase (SOD) in vivo; Oil Red O Staining was used to show the effects of daintain/AIF-1 on uptake of oxidized low density lipoprotein (ox-LDL) into U937 cells, a macrophage line; Western Blot was used to test scavenger receptor A (SRA) expression. Results: A high density of daintain/AIF-1 was observed in the tunica intima and media of coronary artery with atherosclerotic plaque, and fewer daintain/AIF-1 in the vessels without atherosclerotic plaque; Daintain/AIF-1 injected intravenously into BALB/c mice boosted oxidative capacity, significantly impaired SOD activities and augmented the CRP level in blood. According to the oil red O test, daintain/AIF-1 profoundly facilitated the uptake of ox-LDL in U937 macrophages and formation of foam cells in the endothelium. We also found that the molecular mechanisms are effective by promoting overexpression of SRA on macrophages. Conclusion: These findings implicate that the inflammatory factor daintain/AIF-1 is closely associated with atherogenesis, and could be further characterized as a novel risk factor for atherosclerosi

Experimental Verification of Phase Noise Robust Spiral Constellation for THz and Optical Communication

This paper proposes a series of spiral constellations that allows optimal constellation design to minimize phase noise impact in THz and optical communication systems. The spiral constellation performance is verified through simulations and experiments at millimeter wave band

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial

Abstract Background Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed. Methods Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR). Results A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49–0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55–0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors. Conclusions Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients. Trial registration The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014