Circulating osteopontin: a dual marker of bone destruction and angiogenesis in patients with multiple myeloma

The matrix protein osteopontin has been shown to be a marker of osteoclastic activity in multiple myeloma patients, as well as a regulator of angiogenesis. We measured serum levels of osteopontin in 50 untreated multiple myeloma patients (in 25, also after treatment) and examined the relation to markers of osteolytic and angiogenic activity. The median (range) of serum osteopontin was 85 (5-232) in the patient group vs. 36 (2-190) ng/ml in the control group. Serum osteopontin levels were significantly higher in patients with advanced stage or grade of myeloma disease. All patients with serum osteopontin levels >100 ng/ml had advanced stage (II or III) or high grade bone disease, whereas stage I or low grade patients had serum osteopontin levels <100ng/ml. Serum osteopontin levels significantly decreased after treatment. There was a positive correlation of osteopontin with the bone turnover marker N-terminal propeptide of procollagen type I (NTx) and the angiogenic markers vascular endothelial growth factor (VEGF) and bone marrow microvessel density (r: 0.35, 0.47 and 0.30 respectively, p < 0.05). These results support osteopontin as a dual marker of bone destruction and angiogenic activity in myeloma patients. Osteopontin represents a useful biomarker for monitoring myeloma disease activity

Relationship between serum levels of vascular endothelial growth factor, hepatocyte growth factor and matrix metalloproteinase-9 with biochemical markers of bone disease in multiple myeloma

Background: Multiple myeloma is characterized by accumulation of plasma cells in the bone marrow, with osteolysis and increased marrow angiogenesis. We studied molecules involved in angiogenesis (MMP-9, HGF, VEGF) in relation to disease stage, extent of bone destruction, and markers of bone turnover (Ntx and PICP). Methods: MMP-9, HGF, VEGF were measured in the serum of 42 newly diagnosed myeloma patients and 24 controls with commercial ELISA kits. Urinary levels of Ntx were measured by ELISA, and serum PICP with RIA. Extent of radiological bone disease was graded into low and high score. Stage was estimated according to the Durie-Salmon criteria. Results: HGF, VEGF and Ntx were higher in patients than controls ( pb0.001). MMP-9 and PICP did not differ between patients and controls. HGF, VEGF, MMP-9 and Ntx increased significantly with disease stage (I to III, pb0.001) and PICP decreased significantly with advancing stage ( pb0.05). There was a positive correlation between HGF and MMP-9 (r: 0.36, pb0.01), VEGF and MMP-9 (r: 0.38, pb0.01), Ntx and MMP-9 (r: 0.39, pb0.01) and an inverse correlation between PICP and MMP-9 (r: −0.66, pb0.0001). Conclusions: Angiogenesis and bone destruction are closely interrelated in myeloma, and cytokine levels (MMP-9, VEGF and HGF) may be useful in monitoring progression

Serum interleukin-17 and its relationship to angiogenic factors in multiple myeloma

Background: Interleukin-17 (IL-17) is a CD4 T-cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and regulates the production of a variety of proangiogenic factors, such as tumor necrosis factor-α (TNF-α) and vascular endothelial cell growth factor (VEGF). Angiogenesis is implicated in the progression of multiple myeloma (MM). Methods: We measured serum levels of IL-17, TNF-α, and VEGF, as well as microvessel density (MVD) in 40 untreated MM patients. Results: Levels of IL-17 in the sera of patients with MM were higher than those in matched controls; however, the difference did not reach statistical significance. Serum levels of both TNF-α and VEGF in MM patients were significantly higher than those in controls (

Serum levels of Interleukin-15 and Interleukin-10 and their correlation with proliferating cell nuclear antigen in multiple myeloma

In order to determine prognostic factors characterizing multiple myeloma (MM) cell kinetics, bone marrow proliferative activity and serum Interleukin-10 (IL-10), and Interleukin-15 (IL-15) levels were measured in 40 newly diagnosed MM patients, compared with 10- age and sex-matched-healthy controls. Cell proliferation was evaluated by employing a monoclonal antibody directed against the proliferating cell nuclear antigen (PCNA), whereas IL-10 and IL-15 were measured with quantitative sandwich enzyme immunoassay methods. IL-15, IL-10 and PCNA were higher in the patient group than in controls (P \u3c 0.001). IL-10 levels, and PCNA increased significantly with increasing Durie-Salmon disease stage (I-III, P \u3c 0.002, and P = 0.001, respectively). Serum IL-15 levels in MM stage III patients were elevated in comparison with stages I and II, the difference however, did not reach statistical significance. There was a significant positive correlation between serum IL-15 and IL-10 levels (r: 0.372, P \u3c 0.01), and between serum IL-10 and PCNA (r: 0.608, P \u3c 0.0001), as well as a positive correlation of serum IL-15 with PCNA, which marginally failed to reach statistical significance. Serum IL-15 levels are elevated in MM patients, increase with advancing stage, and correlate with Il-10 and PCNA. These proliferative factors may be useful in assessing disease progression in MM

Serum interleukin-17 and its relationship to angiogenic factors in multiple myeloma

Background: Interleukin-17 (IL-17) is a CD4 T-cell-derived mediator of angiogenesis that stimulates vascular endothelial cell migration and regulates the production of a variety of proangiogenic factors, such as tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial cell growth factor (VEGF). Angiogenesis is implicated in the progression of multiple myeloma (MM). Methods: We measured serum levels of IL-17, TNF-alpha, and VEGF, as well as microvessel density (MVD) in 40 untreated MM patients. Results: Levels of IL-17 in the sera of patients with MM were higher than those in matched controls; however, the difference did not reach statistical significance. Serum levels of both TNF-alpha and VEGF in MM patients were significantly higher than those in controls (P&lt;0.001 in both instances). Levels of IL-17 in MM patients, both stage 11 and stage 111, were significantly higher than those of stage I patients (p=0.001 and p&lt;0.001, respectively). Similarly, higher values of VEGF (p&lt;0.001), TNF-a (p&lt;0.001), and MVD (p&lt;0.035) were associated with advanced disease stage. Serum values of IL-17 in MM patients correlated positively not only with VEGF (Spearman’s rho=0.606) and TNF-alpha (r=0.552; p&lt;0.001 in both instances), but also with MVD (r=0.385, p=0.014). In addition, a positive correlation was found between serum values of VEGF and TNF-alpha (r=0.657, p&lt;0.001), MVD and VEGF (r=0.353, p=0.026), and between MVD and TNF-alpha (r=0.506,p=0.001) in MM patients. Conclusion: These results suggest that IL-17 plays a role in the promotion of angiogenesis and associated disease progression in MM. (C) 2006 European Federation of Internal Medicine. Published by Elsevier B.V All rights reserved

Long-term serial changes in platelet activation indices following sirolimus elution and bare metal stent implantation in patients with stable coronary artery disease

Background: Platelet activation is crucial in the development of stent thrombosis following percutaneous coronary intervention (PCI). We carried out a long-term assessment of multiple factors implicated in the thrombotic process and monitored markers of platelet activation after the implantation of sirolimus-eluting stents (SES) in patients with stable coronary artery disease (CAD). Additionally, we compared these findings with those after bare-metal stent (BMS) implantation. Methods: A cohort of 47 consecutive patients, aged 70% narrowing of the lumen) of one major epicardial coronary artery and stable CAD underwent successful elective PCI. Patients were randomly allocated to SES (n = 25) or BMS (n = 22). Venous blood was obtained 24 hours before and 24 hours, 48 hours, 1 month, and 6 months after PCI for measurements of plasma levels of sP-selectin, von Willebrand Factor (vWF), fibrinogen, d-dimer, sCD40, factor VIII, b-thromboglobulin (b-TG) and platelet factor 4 (PF-4). Results: There were no significant differences between the two groups in levels of fibrinogen or d-dimers in peripheral blood. However, we observed a significant kinetic effect (p<0.001) and stent-effect (p<0.015) on vWF levels and a significant kinetic effect (p = 0.012) on factor VIII, sP-selectin (p = 0.04), b-TG (p<0.001), and PF4 (p = 0.016). A trend towards a significant stent effect on sCD40 was also detected (p = 0.06). Conclusions: SES and BMS did not show significant differences in relationship to markers of platelet activation and coagulation in patients with stable CAD. Although some markers showed an increase after stent implantation, they returned to the initial levels 6 months later. Keywords: Stents, Platelet activation, Coronary artery diseas