Tandem autologous hematopoietic stem cell transplantation for patients with multiple myeloma: a systematic review and meta-analysis.

To evaluate whether patients with multiple myeloma (MM) could benefit from tandem autologous hematopoietic stem cell transplantation (auto-HSCT), PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched, and 10 eligible studies were included after data extraction and quality evaluation. Meta-analysis showed that compared to single autologous hematopoietic stem cell transplantation, tandem auto-HSCT does not improve OS, EFS or efficacy in MM patients, and may even lead to higher treatment-related mortality (TRM). MM patients who received autologous tandem allogeneic HSCT did not achieve better response compared to tandem autologous HSCT. In summary, compared to single autologous hematopoietic stem cell transplantation, tandem autologous hematopoietic stem cell transplantation cannot provide survival advantages for MM patients, and MM patients cannot benefit from autologous tandem allogeneic hematopoietic stem cell transplantation.

Lutein Suppresses Oxidative Stress and Inflammation by Nrf2 Activation in an Osteoporosis Rat Model.

BACKGROUND Osteoporosis is a major health risk for women worldwide. Osteoporosis is caused by an imbalance between bone resorption and formation. Hormonal imbalance and increased redox signaling cause bone deterioration. MATERIAL AND METHODS Oxidative stress was determined through assessment of ROS, lipid peroxide levels, and antioxidant activity. Inflammatory protein markers and Nrf2-related protein expressions were determined through Western blot analysis. Interleukin expressions were determined using ELSA. RESULTS In the present study, we showed that supplementation of lutein protects the ovariectomized (OVX) rats against oxidative stress through its antioxidant protection. OVX rats showed an increase in oxidative stress markers. Lutein treatment significantly decreased the lipid peroxidation levels and ROS in the OVX rats. OVX rats showed inflammatory responses through NF-κB activation and increased inflammatory cytokines (TNF-α, IL-6, IL-8). Further, there was significant upregulation in osteoclast-specific marker NFATc1 in OVX rats compared to sham rats. Lutein supplementation activated Nrf2 driven antioxidant gene expression (HO-1, NQO1) and protected OVX rats against inflammatory responses. CONCLUSIONS We showed the critical role of Lutein in protection against osteoporosis in OVX rats by downregulation of inflammation and osteoclast-specific marker (NFATc1) expression through Nrf2 activation.

ALK-positive anaplastic large cell lymphoma with soft tissue involvement in a young woman.

INTRODUCTION: Anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin lymphoma that has strong expression of CD30. ALCL can sometimes involve the bone marrow, and in advanced stages, it can produce destructive extranodal lesions. But anaplastic large cell lymphoma kinase (ALK)+ ALCL with soft tissue involvement is very rare. CASE REPORT: A 35-year-old woman presented with waist pain for over 1 month. The biopsy of soft tissue lesions showed that these cells were positive for ALK-1, CD30, TIA-1, GranzymeB, CD4, CD8, and Ki67 (90%+) and negative for CD3, CD5, CD20, CD10, cytokeratin (CK), TdT, HMB-45, epithelial membrane antigen (EMA), and pan-CK, which identified ALCL. After six cycles of Hyper-CVAD/MA regimen, she achieved partial remission. Three months later, she died due to disease progression. CONCLUSION: This case illustrates the unusual presentation of ALCL in soft tissue with a bad response to chemotherapy. Because of the tendency for rapid progression, ALCL in young adults with extra-nodal lesions are often treated with high-grade chemotherapy, such as Hyper-CVAD/MA.

Effects of platelet-derived growth factor on chondrocyte proliferation, migration and apoptosis via regulation of GIT1 expression.

The formation of fibrocartilage, cartilaginous and bony calluses is vital for bone healing following a fracture. Fibroblasts, chondrocytes and osteoblasts are critical functional cells that are involved in these three processes, respectively. Platelet­derived growth factor (PDGF), a growth factor that is released from platelet particles and appears during the early stages at the site of fractures, is essential in bone healing via regulation of cell proliferation and differentiation. However, the effects of PDGF on the chondrocytes remain unclear. In the present study, PDGF promoted phosphorylation of Src and upregulated the expression level of G­protein­coupled receptor kinase interacting protein­1 (GIT1) according to the results of the cell culture of chondrocytes in vitro and western blotting. However, the effect of PDGF on the upregulation of GIT1 expression was mostly inhibited by the Src inhibitor, PP2. After knocking down GIT1 expression using siRNA, the phosphorylation of Src continued to be induced by PDGF, although the expression of GIT1 was inhibited. Furthermore, the results indicated that PDGF promoted chondrocyte proliferation and migration, however, the effect on cell apoptosis induction was suppressed after adding the Src inhibitor, PP2. Additionally, when knocking down GIT1 using siRNA, the expression level of GIT1 decreased, which is similar to the effect of the Src inhibitor, PP2. The current study demonstrates that PDGF may initially activate the phosphorylation of Src, and subsequently induce GIT1 expression to promote chondrocyte proliferation and migration, but suppress cell apoptosis.

MicroRNA-128 inhibits EMT of human osteosarcoma cells by directly targeting integrin α2.

Deregulated expression of miRNAs contributes to the development of osteosarcoma. The present study was to evaluate the level of miR-128 and integrin α2 (ITGA2) in osteosarcoma tissues and cells. We further investigated the molecular mechanisms of miR-128 and ITGA2 in osteosarcoma cell lines. In the present study, we found that miR-128 expression was down-regulated in osteosarcoma tissues and MG-63, U2OS, and SAOS-2 cells (all p < 0.001). By contrast, ITGA2 was up-regulated. Furthermore, we found that miR-128 overexpression suppressed cell migration and invasion of MG-63 cells. Mechanically, miR-128 overexpression inhibited epithelial-mesenchymal transition (EMT) of MG-63 cells. Importantly, we identified that the 3'-untranslated region (3'-UTR) of ITGA2 was a direct target of miR-128. Luciferase reporter assays confirmed that miR-128 binding to the 3'-UTR regions of ITGA2 inhibited the expression of ITGA2 in MG-63 cells. At the same time, overexpressed ITGA2 also reversed EMT inhibited by miR-128. In conclusion, this study suggested that high miR-128 expression suppressed osteosarcoma cell migration, invasion, and EMT development through targeting ITGA2, which may be recommended as a therapeutic target for osteosarcoma.

Dimethyl fumarate inhibits the expression and function of hypoxia-inducible factor-1α (HIF-1α).

Osteocyte hypoxia has been induced by skeletal unloading and fracture. Hypoxia-dependent regulation of gene expression is mediated by hypoxia-sensitive transcription factors such as hypoxia-inducible factor-1α (HIF-1α). Dimethyl fumarate (DMF) is a recently approved first-line therapy for multiple sclerosis. However, the role of DMF in regulating HIF-1α expression and function has not been evaluated. In this study, we found that DMF inhibited hypoxia-induced expression of HIF-1α and its target genes such as interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF) in MC3T3 E1 cells. Mechanistically, DMF promoted HIF-1α degradation in a proteasome-dependent but von Hippel-Lindau (VHL) protein-independent manner. Importantly, we found that DMF disrupted the interaction between HIF-1α and its chaperone heat shock protein 90 (Hsp90) but promoted the interaction between HIF-1α and the receptor of activated protein kinase C (RACK1). These data suggest that DMF might promote degradation of HIF-1α by affecting its folding and maturation. Based on these observations, we conclude that DMF is a novel inhibitor of HIF-1α.