16 research outputs found
Polymorphism of IL‐10 receptor β affects the prognosis of multiple myeloma patients treated with thalidomide and/or bortezomib
学位記番号:保博甲10
XRCC1 Arg194Trp and XRCC1 Arg399Gln Polymorphisms Affect Clinical Features and Prognosis of M yelodysplastic Syndromes
XRCC1 Arg194Trp and XRCC1 Arg399Gln Polymorphisms Affect Clinical Features and Prognosis of M yelodysplastic Syndromes
<I>XRCC1</I> Arg194Trp and <I>XRCC1</I> Arg399Gln Polymorphisms Affect Clinical Features and Prognosis of Myelodysplastic Syndromes
SF3A1 Gene Polymorphism Affects Clinical Features, but not Susceptibility to Myelodysplastic Syndromes
Differences in Expression Patterns of DNMTs and TSG Proteins in Lymphoid Tissue Section Play an Important Role in Their Association
Elemental analysis of erythrocytes in patients with chronic liver diseases positive for hepatitis C virus
Myeloma Microenvironmental TIMP1 Induces the Invasive Phenotype in Fibroblasts to Modulate Disease Progression
Tissue inhibitors of metalloproteinases (TIMPs) are endogenous matrix metalloproteinase inhibitors. TIMP1 is produced by cancer cells and has pleiotropic activities. However, its role and source in multiple myeloma (MM) are unclear. Here, we evaluated TIMP1 protein and mRNA levels in bone marrow (BM) plasma cells and assessed the effects of TIMP1 expression on fibroblast invasive capacity using three-dimensional spheroid cell invasion assays. TIMP1 mRNA and protein levels were elevated when patients progressed from monoclonal gammopathy of undetermined significance or smouldering myeloma to MM. Furthermore, TIMP1 levels decreased at complete response and TIMP1 protein levels increased with higher international staging. TIMP1 mRNA levels were markedly higher in extramedullary plasmacytoma and MM with t(4;14). Overall survival and post-progression survival were significantly lower in MM patients with high TIMP1 protein. Recombinant TIMP1 did not directly affect MM cells but enhanced the invasive capacity of fibroblasts; this effect was suppressed by treatment with anti-TIMP1 antibodies. Fibroblasts supported myeloma cell invasion and expansion in extracellular matrix. Overall, these results suggested that MM-derived TIMP1 induces the invasive phenotype in fibroblasts and is involved in disease progression. Further studies are required to elucidate the specific roles of TIMP1 in MM and facilitate the development of novel therapies targeting the TIMP1 pathway
MYC Causes Multiple Myeloma Progression via Attenuating TP53-Induced MicroRNA-34 Expression
MicroRNAs (miRNAs and miRs) are small (19–25 base pairs) non-coding RNAs with the ability to modulate gene expression. Previously, we showed that the miR-34 family is downregulated in multiple myeloma (MM) as the cancer progressed. In this study, we aimed to clarify the mechanism of miRNA dysregulation in MM. We focused particularly on the interaction between MYC and the TP53-miR34 axis because there is a discrepancy between increased TP53 and decreased miR-34 expressions in MM. Using the nutlin-3 or Tet-on systems, we caused wild-type (WT) p53 protein accumulation in human MM cell lines (HMCLs) and observed upregulated miR-34 expression. Next, we found that treatment with an Myc inhibitor alone did not affect miR-34 expression levels, but when it was coupled with p53 accumulation, miR-34 expression increased. In contrast, forced MYC activation by the MYC-ER system reduced nutlin-3-induced miR-34 expression. We also observed that TP53 and MYC were negatively correlated with mature miR-34 expressions in the plasma cells of patients with MM. Our results suggest that MYC participates in the suppression of p53-dependent miRNA expressions. Because miRNA expression suppresses tumors, its inhibition leads to MM development and malignant transformation