AUXILIARY ENDOTHELIUM-TROPHIC THERAPY AT HEPATOCELLULAR CARCINOMA
Introduction. Endothelial dysfunction is the universal pathological process which is observed in particular at oncological diseases. Its correction can provide clinical effect.
Research objective was determination of results of correction of endothelial dysfunction at patients with hepatocellular carcinoma.
Materials and Methods. A prospective experimental clinical study was conducted according to the "experience-control" scheme.
78 patients with hepatocellular cancer carcinoma of II and III clinical stages which were exposed to radical surgical treatment are examined. The status of vascular endothelium and results of treatment depending on the carried-out correction of endothelial dysfunction (NO-group donator L-arginine and ACE inhibitors) was investigated.
Comparison of quantitative traits was carried out with the help of the Student's test. If the boundary criteria for the applicability of parametric methods are not met (the criterion for the equality of Fisher variances and the normality of the Kolmogorov-Smirnov distribution), the Mann-Whitney method is used. The frequencies were compared using a two-sided Fisher exact test. The level of statistical significance for the refutation of the null hypothesis was p <0.05.
Results. Existence of significant disturbances of indicators of endothelial function in patients hepatocellular carcinoma in the initial period and their aggravation when performing treatment is revealed. In particular, acute increase of the contents of the circulating endotheliocytes and Villebrand's factor, decrease in an endothelium-dependent vazodilyatation was observed. This analysis at hepatocellular carcinoma is carried out for the first time.
It is also established for the first time that application of L-arginine and its combination to inhibitors of angiotensin converting enzyme has allowed achieving partial correction of endothelial dysfunction, including decrease in a endothelium damage rate and restoration of his functional activity. Also decrease in frequency of complications in the early and remote postoperative period was observed. So, number of early postoperative complications and a recurrence and metastasises at implementation of correction of endothelial dysfunction on average decreased twice.
Conclusion. Correction of endothelial dysfunction can be recommended in oncological practice in the perioperative period for prevention of postoperative complications development.
Keywords: hepatocellular carcinoma; surgical treatment; endothelial dysfunction; L-arginine; correction.
Sayakhat T. Olzhayev 1,
Aleksandr V. Lazarev 2
1 Almaty Regional Oncological Clinic, Almaty, Republic of Kazakhstan;
2 Altai branch Russian Cancer Research Center of N.N. Blochin of the Russian Academy of Medical Science, Barnaul, Russian Federation.
1. Balogh J., Victor D., Asham E.H. et al. Hepatocellular carcinoma: a review // J Hepatocell Carcinoma. 2016. Vol.3. P.41-53.
2. Basudhar D., Glynn S.A., Greer M. et al. Coexpression of NOS2 and COX2 accelerates tumor growth and reduces survival in estrogen receptor-negative breast cancer // Proc Natl Acad Sci U S A. 2017. Vol.114(49). P.13030-13035.
3. Blazejczyk A., Papiernik D., Porshneva K., Sadowska J., Wietrzyk J. Endothelium and cancer metastasis: Perspectives for antimetastatic therapy // Pharmacol Rep. 2015. Vol.67(4). P.711-718.
4. Connolly G.C., Khorana A.A., Kuderer N.M. et al. Leukocytosis, thrombosis and early mortality in cancer patients initiating chemotherapy. Thromb Res. 2010. Vol.126(2). P.113-118.
5. de Oliveira G.A., Cheng R.Y.S., Ridnour L.A. et al. Inducible Nitric Oxide Synthase in the Carcinogenesis of Gastrointestinal Cancers // Antioxid Redox Signal. 2017. Vol.26(18). P.1059-1077.
6. Elyamany G., Alzahrani A.M., Bukhary E. Cancer-associated thrombosis: an overview // Clin Med Insights Oncol. 2014. Vol.8. P.129-137.
7. Fukumura D., Kashiwagi S., Jain R.K. The role of nitric oxide in tumour progression // Nat Rev Cancer. – 2006. – Vol.6. – P.521-534.
8. Gallo O., Masini E., Morbidelli L. et al. Role of nitric oxide in angiogenesis and tumor progression in head and neck cancer // J Natl Cancer Inst. 1998. Vol.90. P.587-596.
9. Halámková J., Penka M. Current Recommendations for the Prevention and Treatment of Venous Thromboembolism in Cancer Patients. Klin Onkol. 2017. Vol.30(2). P.100-105.
10. Hickok J.R., Thomas D.D. Nitric oxide and cancer therapy: the emperor has NO clothes. Curr Pharm Des. 2010;16:381–91.
11. Hui G., Meng M. Prognostic value of vascular endothelial growth factor expression in women with ovarian cancer: A meta-analysis // J BUON. 2015. Vol.20(3). P.870-878.
12. Lee S.Y., Rim Y., McPherson D.D., Huang S.L., Kim H. A novel liposomal nanomedicine for nitric oxide delivery and breast cancer treatment // Biomed Mater Eng. 2014. Vol.24. P.61-67.
13. Levi M. Cancer-related coagulopathies // Thromb Res. 2014. Vol.133. Suppl 2: S70-75.
14. Leon L., Jeannin J.F., Bettaieb A. Post-translational modifications induced by nitric oxide (NO): implication in cancer cells apoptosis // Nitric Oxide. 2008. Vol.19. P.77-83.
15. Lo H.W., Hsu S.C., Ali-Seyed M. et al. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway // Cancer Cell. 2005. Vol.7. P.575-589.
16. Riess H., Habbel P., Jühling A., Sinn M., Pelzer U. Primary prevention and treatment of venous thromboembolic events in patients with gastrointestinal cancers // World J Gastrointest Oncol. 2016. Vol.8(3). P.258-270.
17. Qiu M., Ke L., Zhang S. et al. JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin // Cancer Chemother Pharmacol. 2017. Vol.80(2). P.275-286.
18. Singleton P.A. Hyaluronan regulation of endothelial barrier function in cancer // Adv Cancer Res. 2014. Vol.123. P.191-209.
19. Søndergaard E.S., Fonnes S., Gögenur I. Endothelial dysfunction after non-cardiac surgery: a systematic review // Acta Anaesthesiol Scand. 2015. Vol.59(2). P.140-146.
20. Reymond N., d'Água B.B., Ridley A.J. Crossing the endothelial barrier during metastasis // Nat Rev Cancer. 2013. Vol.13(12). P.858-870.
21. Tomczyk M., Nowak W., Jaźwa A. Endothelium in physiology and pathogenesis of diseases // Postepy Biochem. 2013. Vol.59(4). P.357-364.
22. Vannini F., Kashfi K., Nath N. The dual role of iNOS in cancer // Redox Bio. 2015. Vol.6. P.334-343.
23. Yamashita Y. Hypercoagulable State in Cancer // Rinsho Byori. 2015. Vol.63(12). P.1435-1442.
24. Zhou L., Zhang H., Wu J. Effects of nitric oxide on the biological behavior of HepG2 human hepatocellular carcinoma cells // Exp Ther Med. 2016. Vol.11(5). P.1875-1880.
25. Wolberg A.S., Mast A.E. Tissue factor and factor VIIa--hemostasis and beyond // Thromb Res. 2012. Vol.129. Suppl 2:S1-4.
Bibliography link
Olzhayev S.T., Lazarev A.V. Auxiliary endothelium-trophic therapy at hepatocellular carcinoma. Nauka i Zdravookhranenie [Science & Healthcare]. 2017, 6, pp. 43-52.