Study of the influence of the drug amixin in vitro on the level of expression of lymphocyte activation markers in the peripheral blood of patients with uveal melanoma
L. N. Velichko, A. V. Bordanova
SI «Filatov’s Institute of eye diseases and tissue therapy of NAMN of Ukraine», Odessa (Ukraine)
Introduction. Individual choice of the immunomodulatory drugs and rational combination of physical therapeutic factors with immunomodulatory therapy is an important task of clinical immunology. At present empiric approaches to administration of the immunomodulatory drugs in immunotherapy of oncologic patients.
The investigation of the role of some molecules in realization of positive treatment effect of the combined therapy of patients with uveal melanoma allowed to develop new approaches to search and development of complex schemes of treatment with the use of immunomodulators. The imvestigations of the molecular mechanisms of the immunocompetent cell activation will allow to develop pathogenetically substantiated approaches to treatment of patients with uveal melanoma.
Objective. To study the influence of the drug amixin in vitro on the expression of molecular markers of lymphoid cell activation CD7+, CD25+, CD38+, CD45+, CD54+, CD95+, CD150+ in patients with uveal melanoma.
Material and methods. The level of the expression of molecular markers of lymphocyte activation was studied using immunohistochemical PAP- method with the help of the panel of monoclonal antibodies CD7+, CD25+, CD38+, CD45+, CD54+, CD95+, CD150+ before and after cultivation with the drug amixin. The study was conducted in vitro with lymphocytes of the peripheral blood of patients with uveal melanoma (N=30). The statistic processing was made by the computer program Statistica 6.0 using Newman-Keuls criterium.
Results. The studies made on the effect of the drug amixin in vitro on the expression state of molecular markers of lymphocyte activation in the peripheral blood of patients with uveal melanoma revealed authentic increase of the expression indices CD7+, CD25+, CD54+, CD95+ after using the above-mentioned drug.
The level of the expression CD7+ reliably increased from 26.4±3.8 % to 34.1±2.6 % (p<0.05); CD25+ — from 19.4±3.3 % to 28.8±3.1 %, (p<0.01); CD54+ — from 18.3±5.1 % to 32.7±2.2 %, (p<0.01); CD95+ -from 24.2±6.3 % to 36.5±5.4 %, (p<0.05).
Conclusion. The method of the investigation of the influence of immunomodulatory drugs on the molecular profile of lymphocytes in the peripheral blood developed in the immunology laboratory of SI» Filatov’s Institute of eye diseases and tissue therapy of NAMN of Ukraine» can be used in the clinical practice for choosing adequate immunocorrection therapy. The interferon inductor amixin can be applied in the process of combined therapy (photocoagulation + β-application therapy) in patients with uveal melanoma or immunocorrection.
Key words: Uveal melanoma, amixin, molecular markers of lymphocyte activation, complex treatment
1.Berezhnaia NM, Chekhun VF. Interleukins system and cancer. Kiev: DIA; 2002. 224 p.
2.Berezhnaia NM, Chekhun VF. Immunology of malignant growth. Kiev: Naukova dumka; 2005. 790 p.
3.Velichko LN. The expression level of lymphocyte activation molecular markers in peripheral blood of patients with uveal melanoma with varying efficiency preserving therapy. Oftalmol Zh. 2013;5:9–13. In Russian.
4.Vit VV. Prognostic significance of morphological features of the immune response of uveal melanoma with different cell types. Arkh Patol. 1983;7:25–30. In Russian.
5.Vorontsova AL, Kudryavets YuI. Interferon as an important element of optimizing the treatment of cancer patients. Onkologiia. 2000;2(1–2):16–20. In Russian.
6.Vorontsova AL. The role of interferon in antitumor resistance. Eksperimentalnaiia onkologiia. 1989;11(6):49–54. In Russian.
7.Gavrilova TV, Shilov YuI, Churina VV et al. Mechanisms of immune disorders and immune myelopeptides correction in penetrating wounds of the eye. Refraktsionnaia khirurgiia I oftalmologiia. 2009;4:29–35. In Russian.
8.Egorova EA, Lysenko ON, Strizhova NV. Influence of amiksin on the immune and hormone receptor status in patients with endometrial hyperplasia Winter J. on Immunoreabilitation. 1999;15:73. In Russian.
9.Ershov FI. Antiviral medications. M.:Meditsina; 1998. 200 p.
10.Ziangirova GG, Likhvantseva VG. Tumor of the vascular tract of the eye. Moscow: Posledneie slovo; 2003. 456 p.
11.Likhvantseva VG. The role of cytokines in the pathogenesis, prognosis and treatment of uveal melanoma: thesis for Doctor of Med Science. M.; 2001. 475 p.
12.Rabson A, Roitt A, Delves P. Really Essential Medical Immunology. M.:Binom; 2006. 319p.
13.Bialasiewicz AA, Ma J-X, Richard G. Clinical and histopathological aspects of 113 necrotizing malignant melanomas of the choroid. Part 2: Immunogenetic characterization of T-cell receptor — positive tumor — infiltrating lymphocytes and survival of patients with necrotizing melanomas of the choroids. Klin. Monatsbl Augenheilkd. 1998;213(11):271–7.
14.Bialasiewicz A A, Ma J-X, Richard G. α/β — and γ/δ TCR+ lymphocyte infiltration in necrotising choroidal melanomas. Br. J. Ophthalmol. 1999;83:1069–73.
15.Dunne BM, McNamara M, Clynes M et al. MDR1 expression is associated with adverse survival in melanoma of the uveal tract. Hum. Pathol. 1998;29(6):594–8.
16.Ferguson TA, Herndon JM. The immune response and the eye: The ACAID inducing signal is dependent on the nature of the antigen. Invest. Ophthalmol. Vis. Sci. 1994;35(7):3085–95.
17.Karre K, Ljunggren HG, Piontek G, Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986;319:675–8.
18.Niederkorn JY. Exogenous recombinant interleukin-2 abrogates anterior-chamber- associated immune deviation.Transplantation. 1987;43(4):523–8.
19.Niederkorn JY. Immune privilege and immune regulation in the eye. Adv. Immunol. 1990;48(1):191–226.
20.Owen-Schaub LB, Gutterman JU, Grimm EA. Lymphokine-activated killer cell cytotoxicity necrosis factor a and interleukin 2 in the generation of human activation of human cytotoxic lymphocytes: Effect of tumor synergy of tumor necrosis factor and interleukin 2 in the generation of human lymphokine-activated killer cell cytotoxicity. Cancer Res. 1988;48(5):788–92.
21.Streilein JW. Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nature Reviews Immunology. 2003;3(11):879–89.
22.Streilin JW. Immune regulation and the eye: a dangerous compromise. FASEB J. 1987;1:199–208.
23.Wilbanks GA, Streilein JW. Studies on the induction of anterior chamber — associated immune deviation (ACAID). 1. Evidence that an antigen — specific, ACAID — inducing, cell — associated signal exists in the peripheral blood. J. Immunol. 1991;146(8):2610–7.
24.Williamson JS, Streilein JW. Induction of delayed hypersensitivity to alloantigens coinjected with Langerhans cells into the anterior chamber of the eye. Abrogation of anterior chamber — associated immune deviation. Transplantation. 1989;47(3):519–24.
25.Wissing MD, Dadon T, Kim E et al. Small — molecule screening of PC3 prostate cancer cells identifies tilorone dihydrochloride to selectively inhibit cell growth based on cyclin — dependent kinase 5 expression. Oncol. Rep. 2014;32(1):419–24.