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).
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 studies therefore demonstrate that VEGF-induced MM cell proliferation and survival are mediated via Mcl-1, providing the preclinical framework for novel therapeutics targeting Mcl-1 and/or VEGF to improve patient outcome in MM.
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.
Relationship between tumour necrosis factor-related apoptosis inducing ligand (TRAIL) and vascular endothelial growth factor in human multiple myeloma patients.
We show that pazopanib is the first-in-class VEGF receptor inhibitor to inhibit in vivo tumor cell growth associated with increased MM cell apoptosis, decreased angiogenesis, and prolonged survival in a mouse xenograft model of human MM.
In the present study, we demonstrated that bortezomib attenuated the hypoxic induction of erythropoietin and vascular endothelial growth factor at subnanomolar concentrations in multiple myeloma and liver cancer cell lines, regardless of cytotoxic concentrations of bortezomib.
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.
The results confirmed that 3 micromol/l dihydroartemisinin could significantly decrease vascular endothelial growth factor secretion by RPMI8226 cells (P<0.05), which correlated well with the reduction of multiple myeloma-induced angiogenesis on chicken chorioallantoic membranes.
IL-6 did not protect against beta-lapachone-induced apoptosis in MM.1S cells, and dexamethasone showed additive cytotoxicity. beta-lapachone also decreased binding of MM.1S cells to BMSCs; abrogated IL-6 and VEGF secretion triggered by adhesion of BMSCs to MM.1S cells; reduced proliferation of MM.1S cells adherent to BMSCs; and decreased intracellular adhesion molecule-1 (ICAM-1) expression on MM.1S cells.
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).
Transduction of MM cells with a luciferase reporter under the control of a human VEGF promoter further indicated that CD40-induced VEGF expression was mediated through a transcriptional control mechanism.
In this study, we demonstrate increased expression and production levels of VEGF in myeloma compared to non-myelomatous hematological lines, resistance to hypoxia and enhancement of VEGF-A production by hypoxia in myeloma, and direct growth inhibition of myeloma cells due to apoptosis and G1 arrest caused by TNFalpha upregulation induced by thalidomide.
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).
This study explores the effect of adenovirus-mediated delivery of soluble vascular endothelial growth factor receptor Fms-like tyrosine kinase-1 (sFLT-1) on the growth of MM cell line KM3 in nude mice. sFLT-1 cDNA was amplified by reverse transcription-polymerase chain reaction from human umbilical vein endothelial cells and was used as a transgene to construct an adenoviral vector carrying sFLT-1 (ADV-sFLT).