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Increased Levels of NF-kB-Dependent Markers in Cancer-Associated Deep Venous Thrombosis.

Malaponte G, Signorelli SS, Bevelacqua V, Polesel J, Taborelli M, Guarneri C, Fenga C, Umezawa K, Libra M - PLoS ONE (2015)

Bottom Line: However, their combined role in cancer-associated deep vein thrombosis (DVT) and the molecular mechanisms, involved in its pathophysiology, needs further investigations.Accordingly, significantly higher NF-kB activity was observed in cancer patients DVT+ than DVT-.NF-kB inhibition was associated with decreased levels of all molecules in both cancer DVT+ and DVT-.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Biotechnological Sciences, Section of General & Clinical Pathology and Oncology, University of Catania, Catania, Italy.

ABSTRACT
Several studies highlight the role of inflammatory markers in thrombosis as well as in cancer. However, their combined role in cancer-associated deep vein thrombosis (DVT) and the molecular mechanisms, involved in its pathophysiology, needs further investigations. In the present study, C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), matrix metalloproteases-9 (MMP-9), vascular endothelial growth factor (VEGF), tissue factor (TF), fibrinogen and soluble P-selectin, were analyzed in plasma and in monocyte samples from 385 cancer patients, of whom 64 were concomitantly affected by DVT (+). All these markers were higher in cancer patients DVT+ than in those DVT-. Accordingly, significantly higher NF-kB activity was observed in cancer patients DVT+ than DVT-. Significant correlation between data obtained in plasma and monocyte samples was observed. NF-kB inhibition was associated with decreased levels of all molecules in both cancer DVT+ and DVT-. To further demonstrate the involvement of NF-kB activation by the above mentioned molecules, we treated monocyte derived from healthy donors with a pool of sera from cancer patients with and without DVT. These set of experiments further suggest the significant role played by some molecules, regulated by NF-kB, and detected in cancer patients with DVT. Our data support the notion that NF-kB may be considered as a therapeutic target for cancer patients, especially those complicated by DVT. Treatment with NF-kB inhibitors may represent a possible strategy to prevent or reduce the risk of DVT in cancer patients.

No MeSH data available.


Related in: MedlinePlus

Cytokines secretion in monocytes from cancer patients with and without DVT.Levels of IL-6, TNF-α, IL-1β, and VEGF were measured in supernatants of purified monocytes from cancer patients with and without DVT by a sensitive enzyme-linked immunosorbent assay (ELISA). The results are shown as the means ± SD.
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pone.0132496.g001: Cytokines secretion in monocytes from cancer patients with and without DVT.Levels of IL-6, TNF-α, IL-1β, and VEGF were measured in supernatants of purified monocytes from cancer patients with and without DVT by a sensitive enzyme-linked immunosorbent assay (ELISA). The results are shown as the means ± SD.

Mentions: The secretion of these markers analyzed in monocytes supernatant showed similar trend to that observed in plasma. Spontaneous production of cytokines, such as IL-6, TNF-α, Il-1β and VEGF were significantly higher in both groups of cancer patients with and without DVT than those from healthy controls (p<0.0001) (Fig 1). Compared to DVT- cancer patients, DVT+ showed an increased fold change of 1.28 (95% CI: 1.20–1.37; p<0.0001), 1.34 (95% CI: 1.23–1.46; p<0.0001), 1.41 (95% CI: 1.30–1.54; p<0.0001), and 1.61 (95% CI: 1.45–1.78; p<0.0001) for IL-6, TNF-α, Il-1β, and VEGF, respectively. In addition to cytokines, also MMP-9 production and TF activity were higher in DVT+ cancer patients than in those DVT- and in healthy controls (mean ± SD, 103 ± 23, 73 ± 24, 8.8 ± 4, for MMP-9 and mean ± SD, 35.6 ± 6.4, 28 ± 5, 3.3 ± 0.7 for TF activity, respectively). As expected, strong correlations between levels of IL-6, TNF-α, IL-1β, VEGF, MMP-9 and TF in plasma from cancer patients DVT+ and DVT- and those released from monocytes of the same patients were observed (Table 3).


Increased Levels of NF-kB-Dependent Markers in Cancer-Associated Deep Venous Thrombosis.

Malaponte G, Signorelli SS, Bevelacqua V, Polesel J, Taborelli M, Guarneri C, Fenga C, Umezawa K, Libra M - PLoS ONE (2015)

Cytokines secretion in monocytes from cancer patients with and without DVT.Levels of IL-6, TNF-α, IL-1β, and VEGF were measured in supernatants of purified monocytes from cancer patients with and without DVT by a sensitive enzyme-linked immunosorbent assay (ELISA). The results are shown as the means ± SD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507873&req=5

pone.0132496.g001: Cytokines secretion in monocytes from cancer patients with and without DVT.Levels of IL-6, TNF-α, IL-1β, and VEGF were measured in supernatants of purified monocytes from cancer patients with and without DVT by a sensitive enzyme-linked immunosorbent assay (ELISA). The results are shown as the means ± SD.
Mentions: The secretion of these markers analyzed in monocytes supernatant showed similar trend to that observed in plasma. Spontaneous production of cytokines, such as IL-6, TNF-α, Il-1β and VEGF were significantly higher in both groups of cancer patients with and without DVT than those from healthy controls (p<0.0001) (Fig 1). Compared to DVT- cancer patients, DVT+ showed an increased fold change of 1.28 (95% CI: 1.20–1.37; p<0.0001), 1.34 (95% CI: 1.23–1.46; p<0.0001), 1.41 (95% CI: 1.30–1.54; p<0.0001), and 1.61 (95% CI: 1.45–1.78; p<0.0001) for IL-6, TNF-α, Il-1β, and VEGF, respectively. In addition to cytokines, also MMP-9 production and TF activity were higher in DVT+ cancer patients than in those DVT- and in healthy controls (mean ± SD, 103 ± 23, 73 ± 24, 8.8 ± 4, for MMP-9 and mean ± SD, 35.6 ± 6.4, 28 ± 5, 3.3 ± 0.7 for TF activity, respectively). As expected, strong correlations between levels of IL-6, TNF-α, IL-1β, VEGF, MMP-9 and TF in plasma from cancer patients DVT+ and DVT- and those released from monocytes of the same patients were observed (Table 3).

Bottom Line: However, their combined role in cancer-associated deep vein thrombosis (DVT) and the molecular mechanisms, involved in its pathophysiology, needs further investigations.Accordingly, significantly higher NF-kB activity was observed in cancer patients DVT+ than DVT-.NF-kB inhibition was associated with decreased levels of all molecules in both cancer DVT+ and DVT-.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical and Biotechnological Sciences, Section of General & Clinical Pathology and Oncology, University of Catania, Catania, Italy.

ABSTRACT
Several studies highlight the role of inflammatory markers in thrombosis as well as in cancer. However, their combined role in cancer-associated deep vein thrombosis (DVT) and the molecular mechanisms, involved in its pathophysiology, needs further investigations. In the present study, C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), matrix metalloproteases-9 (MMP-9), vascular endothelial growth factor (VEGF), tissue factor (TF), fibrinogen and soluble P-selectin, were analyzed in plasma and in monocyte samples from 385 cancer patients, of whom 64 were concomitantly affected by DVT (+). All these markers were higher in cancer patients DVT+ than in those DVT-. Accordingly, significantly higher NF-kB activity was observed in cancer patients DVT+ than DVT-. Significant correlation between data obtained in plasma and monocyte samples was observed. NF-kB inhibition was associated with decreased levels of all molecules in both cancer DVT+ and DVT-. To further demonstrate the involvement of NF-kB activation by the above mentioned molecules, we treated monocyte derived from healthy donors with a pool of sera from cancer patients with and without DVT. These set of experiments further suggest the significant role played by some molecules, regulated by NF-kB, and detected in cancer patients with DVT. Our data support the notion that NF-kB may be considered as a therapeutic target for cancer patients, especially those complicated by DVT. Treatment with NF-kB inhibitors may represent a possible strategy to prevent or reduce the risk of DVT in cancer patients.

No MeSH data available.


Related in: MedlinePlus