Pathogenetic aspects of endothelial dysfunction in patients with diffuse large В-cell lymphoma

The functional state of the vascular endothelium as well as the serum level of TNF-α и IL-4 in 30 patients with diffuse large B-cell lymphoma (DLBCL) before and after chemotherapy (PCT) have been investigated. The prevalence of factors vaso-constriction (von Willebrand factor and endothelin-1) over the stable metabolites of nitric oxide as well as the significant predominance of proinflammatory cytokines TNF-a over the content of IL-4 has been revealed in blood serum of patients with DLBCL before chemotherapy. It testifies to the presence of the cytokine imbalance and endothelial dysfunction already in the debut of the disease. After the course the content of PCTs Willebrand factor and endothelin-1 as well as TNF-a and IL-4 in the serum of patients decreased while the nitrogen oxide level increased, thereat these changes did not reach the level of corresponding factors and mediators in healthy donors. The findings testify to the formation of endothelial dysfunction in patients with DLBCL, requiring further rehabilitation measures to improve the quality of life of patients DLBCL.

1.Amosova E.N., Yaremenko O.B., Matiyashchuk I.G., et al. State of the endothelium-dependent and endothelium-independent vazoregulyatsii in patients with systemic lupus erythematosus / / Ukr. revmatol. Journal. 2008. 4 (34). Р. 4–9. (In Russian)

2.Antonov V.G., Kozlov V.K. The pathogenesis of cancer: immune and biochemical phenomena and mechanisms. Extracellular and cellular mechanisms of general immunosuppression and immune resistance / / Cytokines and Inflammation. 2004. T. 3. Number 1. Pp. 8-19. (In Russian)

3.Baluda V.P., Barkagan Z.S., Goldberg E.D., et al. Laboratory methods of hemostasis / / Tomsk Univ. University Press, 1980. 314. (In Russian)

4.Berezhnaya N.M., Chekhun V.F.  Interleukins system and cancer (New aspects of the interaction of the tumor and the body) / / Kiev: DIA, 2000. 224 p. (In Russian)

5.Borovikov V.P. STATISTICA: the art of analyzing data on a computer / / St. Petersburg.: Peter, 2003. 688. (In Russian)

6.Verzhbitskaya N.E., Magarill J.A. Comparative characteristics of the frequency of certain types of malignant non-Hodgkin's lymphoma in the Kemerovo region and other geographical regions / / Siberian Journal of Oncology. 2007. Number 4. Pp. 96-100. (In Russian)

7.Grebennicpva L.G. The use of occlusive test to assess endothelial function in patients with rheumatoid arthritis / / InVestRegion. 2008. Number 3. Pp. 60-64. (In Russian)

8.Davydov M.I., Aksel E.M. Malignant neoplasms in Russia and the CIS in 2006 / / Bulletin RCRC. NN RAMS. 2008. T. 19, № 2 (Suppl 1). 152. (In Russian)

9.Domashenko M.A., Orlova S.V., Kostyreva M.V., et al. Endothelial dysfunction in ischemic cerebrovascular disorders for CHD / / Heart. 2007. T. 5, № 7. Pp. 376-378. (In Russian)

10.Dorokhin K.M., Spas V.V. Pathophysiological aspects of endogenous intoxication / / Anesthesiology and Critical Care Medicine. 1994. Number 1. Pp. 56-60. (In Russian)

11.Kadagidze Z.G. Cytokines / / Practical Oncology. 2003. Volume 4, № 3. Pp. 131-139. (In Russian)

12.Kareva N.P. Clinical and pathogenetic aspects of the mechanism of action of electromagnetic radiation in the millimeter range chemotherapy complications of lymphoma: Author. dis. Dr. med. Science. Novosibirsk, 2007. 42. (In Russian)

13.Ketlinskiy S.A., Simbirtsev A.S. Cytokines. SPb.: Folio, 2008. 552 s. (In Russian)

14.ESMO Clinical Recommendations for diagnosis, treatment and monitoring with primary non-Hodgkin's lymphoma diagnosed large-/ / Minimum clinical recommendations of the European Society for Medical Oncology (ESMO). Moscow: RCRC. NN Blokhin, 2003. Pp. 25-27. (In Russian)

15.Loseva M.I., Pospelova T.I., Soldatova G.S., et al. Remote consequences of anticancer therapy Leukemia. Novosibirsk: IPP «Art-Avenue», 2005. 364 p. (In Russian)

16.Lysenko N.V. Endothelin-1 and cyclic guanosine monophosphate in the blood plasma of patients with rheumatoid arthritis associated with Raynaud's syndrome / / Ukr. revmatol. Journal. 2002. № 1 (7). Pp. 57-60. (In Russian)

17. Nebieridze D.V. Endothelial dysfunction and its correction for hypertension / / Russian Journal of Medicine. 2006. T. 14, № 2. Pp. 127-131. (In Russian)

18. Podoltseva E.I. Features of treatment of aggressive lymphomas / / Practical Oncology. 2004. T. 5, № 3. Pp. 194-202. (In Russian)

19. Shilkina N.P., Molodkina O.A., Vinogradov A.A. Changes in vascular and endothelial function in systemic vasculitis / / Scientific and practical rheumatology. 2007. Number 2. Pp. 19-23. (In Russian)

20. Aukrust P., Shardal A.M., Muller F. et al. Decreased levels of total and reduced glutathione in CD4 lymphocytes in common variable immunodeficiency are associated with activation of the tumor necrosis factor system: possible immunopathogenetic role of oxidative stress // Blood. 1995. Vol. 86. P. 1383–1391.

21. Hennessy B.T., Hanraban E.O., Daly P.A. Non Hodgkin's lymphoma; an update // Lancet Oncol.  2004. Vol. 5. P. 341–353.

22. Nedeljkovic Z.S., Gokce N., Loscalzo J. Mechanisms of oxidative stress and vascular dysfunction // Postgrad. Med. J. 2003. Vol. 79 (930). P. 195–199.

23. Schmitt M., Mengele K., Schueren E. et al. European Organi- sation for Research and Treatment of Cancer (EORTC) Pathobiology Group standard operating procedure for the preparation of human tumour tissue extracts suited for the quantitative analysis of tissue as- sociated biomarkers // Eur. J. Cancer. 2007. Vol. 43 (5). P. 835–844.

24. Szlosarek P., Kellie A.C., Balkwill F.R. Tumour necrosis factor α as a tumor promoter // Eur. J. Cancer. 2006. Vol. 42 (6). Р. 745–750.

Dolgushina Yu.V. – postgraduate student of the chair for therapy, hematology and transfusiology,
e-mail: post_gem@mail.ru