Furthermore, the combination of MPT0G413 and BTZ enhanced polyubiquitinated protein accumulation and synergistically reduced MM viability, increased caspase-3, caspase-8, caspase-9 levels, and cleaved poly (ADP) ribosome polymerase and also inhibited adherence of MM cells to bone marrow stromal cells (BMSC) and reduced VEGF and IL-6 levels and cell growth in a co-culture system.
Moreover, it inhibits endothelial cell growth and tubule formation, abrogates both VEGF secretion and VEGF-induced MM cell migration, inhibits osteoclastogenesis, and shows synergistic cytotoxicity with dexamethasone, the immunomodulatory drug pomalidomide, and the p110δ inhibitor idelalisib.
The T-VAD regimen also reduced VEGF to a greater extent in newly diagnosed MM patients than it did in recurrent patients ([MD=-120.20, [-164.60--39.80], P<0.01).
The aim of the present study was designed to determine the effects of rHuEpo on cancer-associated fibroblasts (CAFs) from monoclonal gammopathy of undetermined significance (MGUS) and MM patients by means of in vitro and in vivo assays. rHuEpo treatment reduces the expression of mRNA levels of fibroblast activation markers, namely alpha smooth actin (αSMA) and fibroblast activation protein (FAP) in MGUS and MM CAFs, and of pro-inflammatory and pro-angiogenic cytokines, including interleukin (IL)-6 and IL-8, vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor-2 (FGF-2), and hepatocyte growth factor (HGF) in MM CAFs.
DCZ3301 retained its activity against MM cells in the presence of exogenous cytokines (IL-6 or VEGF) or bone marrow stromal cells (BMSCs) and reduced activity of multiple signaling pathways (STAT3, NFκB, AKT, ERK1/2) in MM but not normal cells.
We found that the A allele of rs699947 within VEGF and T allele of rs2228570 within VDR gene, interaction between rs699947 and rs2228570, rs2228570 andsmoking were all associated with increased MM risk.
In this study, we examined the association between bone marrow angiogenesis estimated as micro-vessel density (MVD) and gene expression of SDC1, HGF, VEGF and IL6 in whole bone marrow biopsies from healthy volunteers (n = 10), patients with monoclonal gammopathy of undetermined significance (MGUS) (n = 35) and MM (n = 65).
Relationship between tumour necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor in human multiple myeloma patients.
The aim of this pilot study was to determine the plasma levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) and find possible association between them and main clinical features and parameters of tumor burden in patient with multiple myeloma (MM).
Our data suggest that mTOR inhibition and silencing of VEGF expression is associated with synergistic antitumor activity and this combination treatment might be a suitable strategy for new therapeutic approaches using RNA interference in MM.
Using a stem-loop quantitative reverse transcription-PCR, we analyzed miR-15a/16 expressions in bone marrow samples from newly diagnosed MM patients and a panel of MM cell lines. miRNA transfection, western blotting analysis and assay of luciferase activity were used to examine whether vascular endothelial growth factor (VEGF) is the target of miR-15a/16.
Compared to healthy controls, the levels of VEGF, bFGF, Ang-2, HiF-1α and cEPCs were significantly higher and Ang-1 and Ang-1/Ang-2 were lower in MM (p < 0.01). cEPC numbers correlated with Ang-1 (p = 0.03), Ang-2 (p = 0.01) and VEGF (p = 0.002).
Our data demonstrate that the secretion of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and cell-to-cell contact with microenvironment-derived stromal cells from patients with multiple myeloma (MM-BMSCs) significantly decreased the sensitivity of myeloma cells to bortezomib treatment.
Bone marrow (BM) neovascularization and vascular endothelial growth factor (VEGF) expression in multiple myeloma (MM) correlate with disease progression.
In addition, our own results show that under normoxic conditions oncogenic c-Myc is required for constitutive high HIF-1 protein levels and activity in Multiple Myeloma (MM) cells, thereby influencing VEGF secretion and angiogenic activity within the bone marrow microenvironment.