title: Increased Levels of NF-kB-Dependent Markers in Cancer-Associated Deep Venous Thrombosis.
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.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of General & Clinical Pathology and Oncology, University of Catania, Catania, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Malaponte
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, Medical Angiology Unit, Garibaldi Hospital, Catania, Italy.
authors.forename: Salvatore S
authors.initials: SS
authors.lastname: Signorelli
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of General & Clinical Pathology and Oncology, University of Catania, Catania, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bevelacqua
authors.affiliation: Epidemiology and Biostatistics Unit, Centro di Riferimento Oncologico-National Cancer Institute, Aviano, Italy.
authors.forename: Jerry
authors.initials: J
authors.lastname: Polesel
authors.affiliation: Epidemiology and Biostatistics Unit, Centro di Riferimento Oncologico-National Cancer Institute, Aviano, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Taborelli
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, Messina, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Guarneri
authors.affiliation: Department of Environmental and Health Sciences (S.A.S.T.A.S.), University of Messina, Messina, Italy.
authors.forename: Concettina
authors.initials: C
authors.lastname: Fenga
authors.affiliation: Department of Molecular Target Medicine Screening, Aichi Medical University, Nagakute, Japan.
authors.forename: Kazou
authors.initials: K
authors.lastname: Umezawa
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Section of General & Clinical Pathology and Oncology, University of Catania, Catania, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000150:complications / Q000378:metabolism*; D012907:Smoking; D013925:Thromboplastin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D020246:Venous Thrombosis / Q000150:complications / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D005340:Fibrinogen; D002097:C-Reactive Protein; D013925:Thromboplastin; D020780:Matrix Metalloproteinase 9