Limits...
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

Effects of dehydroxymethylepoxyquinomicin (DHMEQ) on cytokines release by monocytes from cancer patients with and without DVT.Monocytes were treated or not with 10 μg/mL DHMEQ, after which the amounts of interleukins (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) secreted were measured by enzyme-linked immunosorbent assay (ELISA). Monocytes were incubated for 24 hr. The treatment with DHMEQ induces the decrease of all molecules in both groups of cancer patients with and without DVT compared to untreated cells (P<0.0001), (t-test). The results are shown as the means ± SD. DVT, Deep Vein thrombosis;
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4507873&req=5

pone.0132496.g004: Effects of dehydroxymethylepoxyquinomicin (DHMEQ) on cytokines release by monocytes from cancer patients with and without DVT.Monocytes were treated or not with 10 μg/mL DHMEQ, after which the amounts of interleukins (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) secreted were measured by enzyme-linked immunosorbent assay (ELISA). Monocytes were incubated for 24 hr. The treatment with DHMEQ induces the decrease of all molecules in both groups of cancer patients with and without DVT compared to untreated cells (P<0.0001), (t-test). The results are shown as the means ± SD. DVT, Deep Vein thrombosis;

Mentions: DHMEQ treatment was used to asses if NF-kB is directly associated with the release of all markers, detected above, from monocytes of cancer patients DVT+ and DVT-. The Fig 4 shows that treatment with DHMQ dramatically decreases the levels of IL-6, TNF-alpha, IL-1beta and VEGF in both groups of cancer patients compared to untreated cells. Similar trend was observed for MMP-9 and TF. In contrast, no differences were observed in the control group in which constitutive NF-kB activation was absent.


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)

Effects of dehydroxymethylepoxyquinomicin (DHMEQ) on cytokines release by monocytes from cancer patients with and without DVT.Monocytes were treated or not with 10 μg/mL DHMEQ, after which the amounts of interleukins (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) secreted were measured by enzyme-linked immunosorbent assay (ELISA). Monocytes were incubated for 24 hr. The treatment with DHMEQ induces the decrease of all molecules in both groups of cancer patients with and without DVT compared to untreated cells (P<0.0001), (t-test). The results are shown as the means ± SD. DVT, Deep Vein thrombosis;
© Copyright Policy
Related In: Results  -  Collection

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

pone.0132496.g004: Effects of dehydroxymethylepoxyquinomicin (DHMEQ) on cytokines release by monocytes from cancer patients with and without DVT.Monocytes were treated or not with 10 μg/mL DHMEQ, after which the amounts of interleukins (IL)-6, tumor necrosis factor alpha (TNF-α), IL-1β and vascular endothelial growth factor (VEGF) secreted were measured by enzyme-linked immunosorbent assay (ELISA). Monocytes were incubated for 24 hr. The treatment with DHMEQ induces the decrease of all molecules in both groups of cancer patients with and without DVT compared to untreated cells (P<0.0001), (t-test). The results are shown as the means ± SD. DVT, Deep Vein thrombosis;
Mentions: DHMEQ treatment was used to asses if NF-kB is directly associated with the release of all markers, detected above, from monocytes of cancer patients DVT+ and DVT-. The Fig 4 shows that treatment with DHMQ dramatically decreases the levels of IL-6, TNF-alpha, IL-1beta and VEGF in both groups of cancer patients compared to untreated cells. Similar trend was observed for MMP-9 and TF. In contrast, no differences were observed in the control group in which constitutive NF-kB activation was absent.

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