Anticoagulant drugs increase natural killer cell activity in lung cancer

In preclinical studies in animal models and in initial clinical trials, anticoagulation drugs have been shown to be effective in the prevention and treatment of haematogenous metastasis, and in the prolongation of survival in animal models. However, only a few studies have been performed on the dire...

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Bibliographic Details
Published in:	Lung cancer (Amsterdam, Netherlands) Vol. 47; no. 2; pp. 215 - 223
Main Authors:	Bobek, V., Boubelik, M., Fišerová, A., L’uptovcová, M., Vannucci, L., Kacprzak, G., Kolodzej, J., Majewski, A.M., Hoffman, R.M.
Format:	Journal Article
Language:	English
Published:	Shannon Elsevier Ireland Ltd 01-02-2005 Elsevier Science
Subjects:	Aged Animals Anticoagulants Anticoagulants - pharmacology Anticoagulants - therapeutic use Biological and medical sciences Cancer Carcinoma, Lewis Lung - immunology Carcinoma, Non-Small-Cell Lung - immunology Case-Control Studies Female Heparin Humans Killer Cells, Natural - immunology Lewis lung cancer LMWHs Lung Neoplasms - immunology Male Medical sciences Mice Middle Aged Natural killer cell NK activity Pneumology Tumor Cells, Cultured Tumors of the respiratory system and mediastinum Warfarin Natural killer cell Anticoagulants LMWHs Warfarin Lewis lung cancer Heparin NK activity Cancer Drug Lung disease Respiratory disease Lung cancer Activity Anticoagulant Increase Malignant tumor Natural Natural iller cell Blood group Bronchus disease
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Summary:	In preclinical studies in animal models and in initial clinical trials, anticoagulation drugs have been shown to be effective in the prevention and treatment of haematogenous metastasis, and in the prolongation of survival in animal models. However, only a few studies have been performed on the direct influence of anticoagulation drugs on the immune system. The purpose of this study is to determine the effect of warfarin, unfractioned heparin, low molecular weight heparins (LMWHs), and acetylsalicylic acid anticoagulants on the functional activity of natural killer (NK) cells. Cytotoxic activity in patients with early, operable stages of non-small-cell lung cancer was compared with healthy volunteers. Cytotoxic studies were also carried out in tumor-bearing animals. Lung-cancer patients were characterized by significantly lower NK cell cytotoxicity (7.07 ± 3.15) than healthy donors (44.12 ± 10.62, P < 0.001). NK cell activation was found in both in vitro experiments using peripheral blood mononuclear cells (PBMC) from healthy donors and ex vivo in lung carcinoma patients after treatment with unfractionated heparin and fraxiparine. Similarly, potentiation of NK cell activity in Lewis lung carcinoma-bearing mice was found after therapy with unfractionated heparin. NK cell activity is lower in lung cancer patients than in normal subjects. NK cell activation was increased by LMWHs. Other anticoagulants augment the effector function of NK cells in cancer patients and in an animal model of lung cancer. This is a novel effect of these compounds, which were thought previously to exert their effect only via their anticoagulant properties.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0169-5002 1872-8332
DOI:	10.1016/j.lungcan.2004.06.012