Department of Tumor Biochemistry and Oncopharmacology

zaletok s-pHead of the Department — Sophia P. Zaletok

Dr.Sci.(Biol.)

Laureate of the O.V. Palladin Prize of NAS of Ukraine

Personal page

Tel
+38 (044) 259-91-95

E-mail sophiazaletok@ukr.net


Priority areas

  • Polyamines' role and molecular pathways in the tumor growth; interrelations between the polyamines metabolism, oncogenes expression and molecular polymorphism of the ribonucleases in the tumor cells
  • Anticancer effect of the polyamines metabolism inhibitors and elaboration of the methods to apply synthetic and natural inhibitors/modulators of the polyamines and arginine metabolism to treatment of the cancer diseases
  • Estimation of prognostic value of the new molecular markers (NF-кB, ODC, etc.) for the cancer patients

Key words

  • polyamines, arginine, inhibitors of polyamines synthesis, oncogenes expression, molecular markers, diagnostics, clinical course prognosis, leukemia, breast cancer, plant polyphenols
Research directions

Main research directions

  • Peculiarities of the polyamines metabolism in the blood cells and bone marrow of the patients with acute and chronic lymphoid leukemia and their role in the disease pathogenesis
  • Evaluation of the polyamines metabolism indices as the diagnostic and prognostic criteria for different forms and cytological variants of the lymphoid neoplasms
  • Estimation of prognostic value of the new molecular markers (NF-кB, ODC, etc.) for the breast cancer patients
  • In vivo anticancer properties of the synthetic inhibitors of the polyamines metabolism and of the natural biologically active compounds

The most significant results for the years 2010-2015

1. It has been determined that inhibition of polyamine synthesis with the help of α-difluoromethylornithine (α-DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG) — inhibitors of key enzymes of polyamine biosynthesis — causes the inhibition of tumor growth and is accompanied with decrease of activity of transcription factor NF-κB, decrease of levels of proteins, products of NF-κB-dependent genes (c-myc,bcl-xl) and increase of p53 protein in tumor cells. Results of these studies show that one of the molecular functions of polyamines in tumor growth may be their impact on the activation and transcriptional activity of NF-κB factor. In turn, it shows that development of schemes of cancer therapy using inhibitors of polyamine metabolism is quite prospective research area.

It has been determined that polyphenols of green tea and red grapes demonstrate antitumor activity and essentially enhance growth-inhibiting effects of synthetic inhibitors (α-DFMO, MGBH and PMG) of polyamine metabolism concerning wide spectrum of experimental tumors of different histogenesis and increase lifespan of animals with transplanted tumors. It has been determined that inhibition of tumor growth under the influence of plant polyphenols is accompanied with reduction of activation of transcription factor NF-κB (р50/р65), decrease of level of expression (on the protein level) of genes odc, c-myc, bcl-xl, inos and cox-2, decrease of polyamine oxidase (PAO) activity and content of polyamines in tumor cells.

For the first time it has been detected that green tea polyphenols alone, as well as in combination with synthetic inhibitors (α-DFMO, MGBG and PMG) of polyamine metabolism significantly increase the level of methylation of promoter areas of ODC genes and genes of р50- and р65-subunits of NF-κB factor and decrease methylation of promoter areas of genes of ODC antizyme in cells of Р-388 and L1210 lymphatic leukemia. The obtained data demonstrate that mechanisms of antitumor action of studied plant polyphenols may be connected with their influence on expression of gene involved in regulation of polyamines synthesis — substances required for the growth and proliferation of cells and their impact on the expression of genes of subunits of transcription factor NF-κB involved in regulation of expression of many important oncogenes of tumor development.

Staff of the Department along with the Institute of Biochemistry and Biotechnology of AN of Georgia have developed 3 plant polyphenol biocomposites and have studied their antitumor, anticancer and antioxidant activity.

High antitumor activity and antioxidant properties of green tea biocomposite has been determined; its capacity to suppress endogenous synthesis of carcinogenic nitro compounds in organism and green tea and red grapes biocomposites' capacity to enhance therapeutic effect of cisplatin and doxorubicin concerning tumors of different histogenesis has been determined; the capacity of biocomposites to neutralize the toxic effects, which accompany chemotherapy of tumors, has been detected. The obtained results show the following:

  • Green tea biocomposite may be applied both as component of complex prophylaxis and complex therapy of cancer patients
  • Green tea and red grapes biocomposite may be applied in clinical oncology for enhancement of therapeutic effect of cisplatin and doxorubicin and decrease of their side toxic effects in patients receiving these drugs
  • Biocomposites also may be used in food industry for improving the quality and biological value of foodstuffs

2. It is known that amino acid arginine is required not only for biosynthesis of proteins. Arginine is precursor of many biologically active compounds (polyamines, agmatine, NO2- and NO3-, etc.), which impact the growth and vitality of cells including malignant cells. Polyamines synthesis in cells is tightly connected with arginine by several intercellular metabolic means and depends not only on activity of ornithine decarboxylase (ODC), S-adenosyl-L-methionine decarboxylase (S-AMDC), spermidine synthase and spermine synthase, but also on activity of arginase. Arginase transforms arginine in ornithine, which is precursor of I polyamine — putrescine, which further serves the biosynthesis of spermidine and spermine. Moreover, under the effect of nitric oxide synthases, the active compounds of nitric oxide are formed of the arginine. The impact of these active compounds on the signal transduction is many-sided. For instance, S-nitrosylation of proteins (including ODC and p50-subunits of NF-κB factor) by cysteine is considered along with phosphorylation as one of the important factors of signal transduction. When arginine decarboxylase affects arginine, the active metabolite agmatine is being formed. Today agmatine is also referred to the polyamines and in contrast to polyamines, it inhibits proliferation.

Thus, one of the directions of our researches is study of impact of modulators of arginine metabolism and their combined with inhibitors of polyamine metabolism impact on the development of experimental tumors and determination of opportunities of their application in antitumor therapy.

Effect of the arginase inhibitor (norarginine), inhibitors of PA synthesis (DFMO and MGBG) and their combinations on development of experimental tumors (L1210 lymphoid leukemia, ascitic Ehrlich cancer (AEC), Lewis lung carcinoma and its metastasis) was studied in vivo. In vitro was studied effect of arginase, arginine deaminase, DFMO and methotrexate alone and in combinations on growth of LLC and L1210 cell lines.

In vivo, inhibitors/modulators of arginine and PA metabolism caused inhibition of the tumors been tested. The most essential growth inhibition of L1210 leukemia, AEC and Lewis carcinoma in mice was observed under combined application of inhibitors of PA synthesis and arginase inhibitor (DFMO+MGBG+Norarginine). Growth inhibition index under these conditions arrived at 56% for L1210 leukemia, 69% for AEC and 76% for primary Lewis carcinoma. This combination of agents also diminished (by 23%) Lewis carcinoma metastasis number per animal and strongly (12.8-16.3 times versus control) diminished the metastasis volume.

Іn vitro, arginine deaminase and arginase, in dependence of their dose, inhibited growth of LLC cell culture by 16-45%. If α-DFMO was applied in combination with arginase or arginine deaminase, DFMO effect was potentiated by more than 30%.

DFMO and methotrexate in combination inhibited LLC cell culture growth by 2.1-2.4 times stronger than the same agents been applied alone.

Analisis of the results obtained during the study of different branches of the arginine and PA metabolism and other molecular indices in the tumor cells under inhibitors/modulators of PA metabolism have demonstrated the following features. Under individual application of the PA synthesis inhibitors, magnitude and direction of changes of the certain parameters in the tumor cells depended on the stage of PA synthesis been affected with an inhibitor, and this dependence was not identical for different tumor strains. Among the parameters have been studied, the tumors' growth indices had the most manifested correlation with PA content in the tumor cells. This correlation was most stable and highest when the inhibitors of different stages of the PA synthesis were applied in combination.

When DFMO was applied in combination with methotrexate, their cross-potentiating effect on the tumor cell proliferation was accomplished with proapoptotic modulations of total activity and isoenzyme spectra of the RNAases.

Thus, it was established that inhibiting effect on the tumors of different histogenesis and different growth forms was the maximum high and stamle under combined application of the inhibitors affecting different stages of the PA synthesis. Α-DFMO ability to enhance the methotrexate antitumor effect was shown. DFMO and methotrexate in combination demonstrated 2.1-2.4 times stronger inhibition of LLC cell culture growth than the same agents been applied alone.

Tumor growth inhibition correlated with such biochemical and molecular indices as PA content, ODC activity, activity and isoenzyme spectra of the RNAases, methylation level in the promoters of the genes encoding ODC and other enzymes of the PA metabolism, etc. For the first time was shown that tumor growth inhibition with norarginine been included into the treating schemes is associated with the epigenetic modulations (enhanced methylation of the genes encoding the PA-synthesizing enzymes and anti-antizyme of ODC), increased expression of the inducible NO-syntase (iNOS), enhanced production of the nitrogen oxides and diminished expression level of certain oncogenes' proteins (bcl-xl і c-myc) in the tumor cells.
The data obtained elucidate the molecular pathways of antitumor effect of the inhibitors of the PA-metablising anzymes, including their epigenetic effect, and are of the fundamental value.
The practical value of these investigations – there was improved availability of combined inclusion of inhibitors of both arginase and PA-synthesizing enzymes into newly elaborating schemes of antitumor therapy.

3. Expression of numerous molecular-biological markers (levels of expression of subunits of transcription factor NF-κB (p50 and p65), ornithine decarboxylase (ODC), receptors of steroid hormones (estrogens — ER and progesterone — PR), Her2/neu, Ki-67, p53, Bcl-2, E-cadherin) has been studied on tumor samples of more than 130 breast cancer patients (BC). The presence of interrelations between expressions of many of them has been determined.

Direct correlation between levels of ODC expression, levels of p53 and E-cadherins has been determined. The inverse correlation has been established between value of Nottingham Prognostic Index (NPI), level of expression of steroid hormones receptors (ER and PR) and Bcl-2, as well as direct correlation — with level of tumor proliferation.

Analysis of peculiarities of tumors with different molecular subtype has showed that compared with luminal and hybrid subtypes of tumors, Her2/neu-positive and basal subtypes are characterized by reliably higher level of proliferation, value of NPI, levels of expression of p53 and p65-subunits of NF-κB and lower level of Bcl-2 expression.

It has been determined that the highest levels of expression of subunits of NF-κB (р50 and р65) have been detected in tumors with negative ER and PR status, hyperexpression of Her2/neu, low Bcl-2, high proliferation and high value of NPI, i.e. in tumors characterized by chemoresistance and unfavorable prognosis. Thus, the obtained data may show that high levels of expression of NF-κB are associated with chemoresistance of BC and unfavorable prognosis.

At present time, the determination of status of steroid hormones receptors and Her2/neu mainly serves the choice of treatment tactics of BC patients. In our opinion, it is expedient to enlarge the spectrum of studied markers, in particular, include in this spectrum such markers as transcription factor NF-κB involved in transcription of many oncogenes and important for progression of tumors, and ODC — product of gene of key enzyme of polyamine biosynthesis needed for proliferation and growth of tumor cells. The determination of NF-κB and ODC will provide us with additional information concerning the tumor, will open the new opportunities for target regulation of polyamine synthesis and activity of NF-κB and will help to individualize therapeutic schemes.

Additional research directions

Staff of the Department along with colleges from Institute of Thermophysics of NAS of Ukraine and Institute of Food Chemistry of NAS of Ukraine have developed new domestic soy products with antitumor activity and have studied them on experimental animals with transplanted tumors of different histogenesis. It has been determined that consumption by animals of the developed soy foodstuffs caused the inhibition of tumor growth. Also it has been detected that developed soy products have antioxidant and anti-inflammatory effect. The obtained results state that there is a possibility to apply developed soy foodstuffs in treatment and prophylactic nutrition of cancer patients and patients from groups of cancer risk.

Modern methods

methods of molecular biology (Western-blotting, gel electrophoresis, surface plasmone resonance (SPR), ELISA, RT-PCR); high-pressure liquid chromatography, biochemical methods to measure enzymes activity; spectrometric, immunohistochemical, statistical (parametric and nonparametric) methods.

Grants
  • STCU grant №4894 «Development of nanotechnology of nanoplant composites and investigation of their antitumor and antioxidant activities» (2011-2013)
  • Project «Impact of ROS-generating systems on the polyamine- and NO-mediated signaling networks in development and metastasis of experimental tumors» (Target Program of Scientific Studies of the Department of Biochemistry, Physiology and Molecular Biology of NAS of Ukraine «Functional Genomics and Metabolomics in Systemic Biology» (2012-2016)
  • Project «Study of Biochemical Mechanisms of Antitumor Activity of Fenugreek (Trigonella foenum graecum L.)» (under the contract between the R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine and ESC «Institute of Biology» of the Taras Shevchenko National University of Kyiv (03.2012-12.2017)
  • Innovative project «Elaboration of Principles of Obtaining, Development of Studied Sample and Pre-clinical Testing of Generic Drug Letrosol» (01.04.2012-31.12.2012)
  • Project «Study of Molecular Mechanisms of Antiblastic Effect of Plant Polyphenols on the Sensitive and Resistant to Cytostatics Tumor Cells» (Program of NAS of Ukraine «Study of Mechanisms of Regulation of Tumor Cells Resistance to Cytostatic Factors and Search for the Methods of Suppression of Expression of Genes Participating in Formation of Drug Resistance» (2007-2011)
  • Project «Impact of Consumption of Soy products on the Growth of Tumors in Experimental Animals and Concomitant Biochemical and Hematological Indexes» (Program of NAS of Ukraine «The Novel Medical and Biological Problems and Human Environment» (2007-2009)
  • STCU grant (Gr_122j) «Creating of plant bioconcentrates with antiradiation and anticarcinogenic action on the base of polyphenols and working out industrial technology for their production» (2005 - 2007)
  • CRDF grant (№ UB1-2446-KV-02) «Role of polyamines in transcriptional regulation of gene involved in neoplastic growth» (2002-2004)
Conferences
  1. VIII Parnas Conference — Warsaw, Poland, August 27-31, 2011.
  2. International Conference and Exhibition on Nutritional Science & Therapy, Aug 27-29, 2012, Hilton Philadelphia Center City, USA.
  3. Congress of Oncologists and Radiologists of СIS, Аstana, 05-07.09. 2012.
  4. Congress «Polyamines: Biological and Clinical Perspectives» Istanbul, Turkey, 2-7 September 2012.
  5. II Ukrainian-Swedish Workshop «Translational Oncology: Old and New Paradigms» — Kyiv, Ukraine, May 20-21, 2013.
  6. IX Jakub K. Parnas conference «Proteins from birth to death» — Jerusalem, Israel, September 29 — October 2, 2013.
  7. Scientific Conference «Biologically active substances: Fundamental and Applied Problems» — Novy Svet, AR Crimea, Ukraine, May 27–June 1, 2013.
  8. XIII International Conference «Primary Therapy of Early Breast Cancer». — Sankt-Gallen, Switzerland, March 13-16, 2013.
  9. 11th International Congress on Targeted Anticancer Therapies, Paris, France, 4-6 March 2013
  10. 9th European Breast Cancer Conference — Glasgow, Scotland, March 19-21, 2014.
  11. XI Biochemical Congress — Kyiv, Ukraine, October 6-10, 2014.
  12. International conference «Cellular hypoxia under tumor disease and its possible correction» — Grodno, Belarus, May14-15, 2014.
  13. ХХ international conference «Theoretical and practical aspects of bioresonance and multiresonance therapy application» — Moscow, Russia, April 11-12, 2014.
  14. 40th FEBS Congress «The biochemical Basis of Life» –– Berlin, Germany, July 4-9, 2015.
  15. JSMO Annual meeting «Fight against Deadly cancer» — Sapporo, Japan, July 16-18, 2015.
  16. Research-and-practice conference «Personification of hormone-dependent tumors treatment» - Yaremche, Ukraine, October 15-16, 2015.
  17. 12th International Conference of the Asian Clinical Oncology Society – New Delhi, India, April 8-10, 2016.
    XIII Congress of Oncologists and Radiologists of Ukraine – Kyiv, Ukraine, May 26-28, 2016.
Publications

Monographs (Selected)

  1. S.P. Zaletok, S.V. Gogol, O.O. Klenov, G.B. Artamonova, Yu.V. Yanish, V.V. Bentrad, O.V. Karnaushenko, Knyrik M.V. Norarginine enhances the antitumor activity of inhibitors of polyamines synthesis in vivo. Oncology 2017; 19: (In Ukrainian).
  2. V.O. Shlyakhovenko. Ribonucleases. Possible new approach in cancer therapy. Exp Oncol 2016; 38: 2-8.
  3. Yu.V. Yanish, A.B. Artamonova, S.P. Zaletok. Impact of arginine and polyamines metabolism modulators on the arginaze activity and nitrogen oxides production by cells of Ehrlich carcinoma in vivo. Clinical Oncology (Kyiv) 2016; №3: 89-91 (In Ukrainian).
  4. Orlovsky О.А., Samoylenko О.А., Shlyakhovenko V.O. «Transcription factor binding sites in a structural gene: what may be this? East European Scientific Journal (EESJ) 2016; 6 (10), Part 3: 62-8.
  5. Bentrad V.V., Zaletok S.P., Makai S. The role of Methi (fenugreek) on growth of grafted tumors in experimental animals. J. of Carcinogenesis 2016;1: 61-2.
  6. V.O. Shlyakhovenko, S.P. Zaletok, S.V. Gogol, A.A. Klenov, Yu.V. Janish, A.P. Burlaka, O.A. Glavin, M.O. Druzhina, A.V. Verbynenko, E.V. Karnaushenko. Antitumor effect of reactive oxygen species in artificial ROS-generating systems. Oncology 2016; 18: 283-8.
  7. Berdynskykh N.K., Kuryshchuk K.V., Lyalyushko N.M., Ryads'ka L.S., Vorobyova H.M., Chekhun V.F. Ceruloplasmin: from biotechnology to clinical application // Kyiv: Vyd-vo med. Literatury, 2006. — 173 p. (In Ukrainian)
  8. Mosienko V.S., Kurtseitov L.K. Integral approaches to the treatment of tumor disease. — Kyiv: Shkol'nyj mir, 2010. — 448 p. (In Russian)

Articles (Selected)

  1. S.Zaletok, L.Gulua, L. Wicker, S.Gogol, O.Orlovsky, O.Karnaushenko, A.Verbinenko, V.Milinevska, O. Samoylenko, I.Todor, T. Turmanidze. Extracts of green tea, red wine and lemon reduce in vivo growth of experimental tumors and toxicity of anticancer drugs. Experim Oncol 2015; 37: 262-71.
  2. Samoilenko О.А., Milinevska O.A., Karnaushenko O.V., Shlyakhovenko V.A., Zaletok S.P. Effect of the polyamine metabolism inhibitors on tumor growth and metastasis of Lewis lung carcinoma in mice. Experim. Оncol 2015; 37: 154-5.
  3. Yu.V. Yanish, M.V. Gonchar, A.B. Artamonova, O.V. Karnaushenko. Impact of modulators of arginine and polyamines level on the metabolic activity of macrophages, the cytolytic activity of splenocytes and their electrokinetic properties in mice with L1210 leukemia. Clinical Oncology (Kyiv) 2015; № 2: 47-51 (In Ukrainian).
  4. Yu.V. Yanish, M.V. Gonchar, S.V. Gogol, O.A. Klenov, V.V. Bentrad. Influence of arginine and polyamines metabolism modulators on the surface electric charge of Lewis lung carcinoma (LLC) cells in vivo and their proliferative activity in the culture. Clinical Oncology (Kyiv) 2015; № 2: 52-4 (In Ukrainian).
  5. Mosienko V.S., Kushchevska N.F., Burlaka A.P., Shlyakhovenko V.O., Lukin S.M., Kurtseitov L.K., Karnaushenko O.V., Verbinenko A.V. Study of anticancer properties of iron oxide nanoparticles and their composites in grafted mouse tumors. Pharmacology and medical toxicology (Kyiv) 2015; №1: 59-67 (in Ukrainian).
  6. V.S. Mosienko, N.F. Kushchevskaya, V.O. Shlyakhovenko, A.P. Burlaka, L.K. Kurtseyitov, O.V. Karnaushenko, A.V. Verbynenko. Effect of ferromagnetic iron nanoparticles and their composites on the growth and metastasis of Lewis lung carcinoma and solid Ehrlich carcinoma. Clinical Oncology (Kyiv) 2015; №2: 55-9 (In Ukrainian).
  7. Mosienko V.S., Kurtseitov L.K., Mysyak S.A., et al. Approaches to development of integrated therapy, prophylaxis and rehabilitation of cancer patients. Contemporary aspects of military medicine 2015; 22: 199-206 (in Ukrainian).
  8. Shapochka D.O., Zaletok S.P., Gnidyuk М.І. Features of NF-κB and ODC expression in tumors of patients with dreast cancer with different molecular profiles. Oncology 2014; 16: 33-9.
  9. Shlyakhovenko V.O., Orlovsky O.А., Zaletok S.P. Simple methods for screening of potential anticancer agents and other remedies. Physics of the alive 2014; №1-2: 56-60.
  10. Shlyakhovenko V.O., Verbinenko A.V., Milinevska V.O. Epigenetic changes in cells of experimental leukemia under the blocking of polyamine synthesis. Oncology 2014; 16:17-22.
  11. Orlovsky A.A., Klenov O.A., Zaletok .S., Chekhun V.F. Application of cancerolysis reaction to primary screening of clinical foods activity. Siberian J. Oncol 2014; 61: 29-32 (in Russian).
  12. Shlyakhovenko V.O., Milinevska V.O. Determination of ornithine decarboxylase. Lab. diagnostics 2014; 1: 36-8.
  13. Ivanova T.S., Krupodorova T.A., Barshteyn V.Y., Artamonova A.B., Shlyakhovenkо V.A. Anticancer substances of mushroom origin. Exp. Oncol 2014; 36: 58-66.
  14. Shapochka D.O., Zaletok S.P., Gnidyuk M.I. Molecular and biological features of breast cancer. Clinical oncology 2013; № 2: 138-42 (In Ukrainian).
  15. Lukianova N.Yu., Naleskina L.A., Bezdenezhnykh N.O., Kunskaya L.M., Demash D.V., Yanish Yu.V., Todor I.N., Chekhun V.F. Reactive changes of cytophysiological properties, molecular-biological profile and functional metabolic status of cells in vitro with different sensitivity to cytostatic agents under the influence of magnetic fluid. Cancer Research Journal 2013; 1: 7-14.
  16. Zhylenko V.V., Zaletok S.P. Impact of fenugreek on the level of malondialdehyde in organs and some hematological indexes of animals with transplanted tumors Sibirskij onkologicheskij zhurnal 2013; №.2: 58-61 (In Russian).
  17. Yanish Yu.V., Artamonova G.B., Shlyakhovenko V.O. Glycopeptide vaccine on DNA-histone carrier and its impact on ζ-potential of effector cells for experimental treatment of lymphoblastic leukemia. Exp. Oncol 2013; 35: 198-201.
  18. Mosienko V.S., Shlyakhovenko V.A., Yanish Yu.V., Karanaushenko E.V., Kurtseinov L.K., Milinevska V.A., Verbinenko A.V. Biotherapy of tumor disease. Luchevaja diagnostika. Luchevaja terapija 2013; № 2-3: 76-87 (In Russian).
  19. Samoilenko O., Zaletok S., Chekhun V. The 11th International Congress on Targeted Anticancer Therapies. Paris, 4-6 March 2013 (TAT 2013). Exp. Oncol 2013; 35: 231-5.
  20. Shapochka D.O., Zaletok S.P., Gnidyuk M.I. Expression of Molecular Markers in Tumours of Patients with Breast Cancer. J. Cytol. Histol 2013; 4: 184-9.
  21. Mosienko V.S. Tissue hypoxia in tumor-bearing organism and its possible role in cancer therapy. Oncology 2013; 15: 313-9.
  22. Klenov O.O. Impact of consumption by animals of soy products with various content of biologically active substances (polyphenols) on the level of ornithine decarboxylase and content of polyamines in experimental tumors. Farmakolohiya ta likars'ka toksykolohiya 2012; № 2: 37-43 (In Ukrainian).
  23. Zhylenko V.V., Zaletok S.P. Study of impact of fenugreek extract on the growth of Ca755 mammary gland carcinoma in mice. Ukr. zhurnal klin. i lab. Medytsyny 2012; 4: 96-101 (In Ukrainian).
  24. Shapochka D.O., Zaletok S.P., Gnidyuk M.I. Relationship between NF-κB expression and molecular profile (ER, PR, Her2/neu, Ki67, p53) in tumors of patients with breast cancer. Exp. Oncol 2012; 34: 358-63.
  25. Zaletok S.P., Shlyakhovenko V.O., Verbinenko A.I., Gogol S.V., Klenov O.O., Gulua L.K. Impact of synthetic and natural modifiers of polyamine metabolism on the development of experimental leucosis in mice and level of DNA methylation in leucosis cells. Oncology 2012; 14: 145-9 (In Ukrainian).
  26. Samoilenko O., Zaletok S., Orlovsky O., Gogol S. Additive antitumor effect of plant polyphenols and synthetic inhibitors of polyamines biosynthesis. Experim. Oncol 2011; 33: 186-9.
  27. Shlyakhovenko V.O., Artamonova G.B., Yanish Yu.V. Antimetastatic effect of glycopeptide antitumor vaccine. Farmakolohiya ta likars'ka toksykolohiya 2011; №6: 12-24 (In Ukrainian).
  28. Zaletok S.P., Shlyakhovenko V.O., Orlovsky O.A., Gogol S.V., Klenov O.O., Karnaushenko O.V., Verbinenko A.V., Samoilenko O.A., Milinevska V.O. Study of possibility of enhancement of antitumor effect of glycopeptide vaccines using plant polyphenols. Visnyk farmakolohiyi ta farmatsiyi 2010; № 7: 13-8 (In Ukrainian).
    Zaletok S.P. Role of polyamines in carcinogenesis and tumor growth // Oncology. Selected lections for students and doctors / ed. V.F. Chekhun. — Kyiv, 2010. — P. 354-69 (In Ukrainian).
  29. Shlyakhovenko V., Mosienko V., Yanish Yu. et al. Impact of microfragments of reconstructed chromatin, antitumor vaccine and their combinations on growth of melanoma in experiment. Visnyk farmakolohiyi ta farmatsiyi 2010; № 9: 28-32 (In Russian).
  30. Zaletok S., Gulua L., Gogol S., Orlovsky A., Samoilenko E., Klenov O., Chekhun V., Mchedishvili N., Omiadze N., Abutidze M. Antioxidant, antitumor and antitoxic activities of green tea and red wine lees biocomposite. Sovremennaja medicina 2010; 16: 29-32.
  31. Shlyakhovenko V.O. Enzymes and cancer // Oncology. Selected lections for students and doctors / ed. V.F. Chekhun. — Kyiv, 2010. — P. 321-34 (In Ukrainian)
  32. Zaletok S.P., Orlovsky O.A., Gogol S.V., Alexandrova N.O., Samoilenko O.A., Ihnatenko N.A., Klenov O.A., Zhylenko V.V. Molecular functions of polyamines at neoplastic growth, their role in regulation of functioning of transcription factor NF-κB in cells of experimental tumors. Likars'ka Sprava 2009; № 1-2: 68-79 (In Ukrainian).
  33. Shlyakhovenko V.A. Rybonucleases in tumor growth. Exp. Oncol 2009; 31: 127-33.
  34. Zaletok S.P., Orlovsky A.A., Gogol S.V., Samoilenko E.A., Klenov O.A., Malitska I.V., Gulua L.K. Influence of plant polyphenols on polyamines metabolism and expression of proteins, products of some oncogenes in experimental tumors. Ukr. zhurnal klin. lab. Medytsyny 2009; 4: 96-101.
  35. Klenov O.V., Zaletok S.P., Orlovsky O.A., Gogol S.V., Burlaka D.P. Prospects of application of soy products in treatment nutrition of cancer patients. Oncology 2009; 11: 232-6 (In Ukrainian).
  36. Orlovsky O.A., Zaletok S.P., Sharkova N.O. Experimental data concerning the issue of differential approach to the soy clinical nutrition at tumors of different hormone-dependence. Ukr. zhurnal klin. lab. Medytsyny 2009; 4: 152-7 (In Ukrainian).
  37. Glavin O.A., Mikhailenko P.M., Zaletok S.P., Gulua L. Effects of biocomposites from green tea and black tea on endogenous synthesis, metabolism and genotoxic effects of carcinogenic N-nitrosodimethylamine. Еxp. Oncol 2008; 30: 306-14.
  38. Samoilenko О.А., Orlovsky О.А., Alexandrova N.O., Ushenin Y.V., Zaletok S.P. Development of a method to immobilize DNA on the «Biosuplar-5» SPR-spectrometer sensory chip for the study of polyamines effect on functional activity of transcription factors and oncogenes expression dependent on them. Ukrayins'kyy medychnyy al'manakh 2008; 11: 95-105.

Selected technical recommendations

  1. Tatischev R.K., Mjasoyedov D.V., Abramenko І.V., Shlyakhovenko V.О. Kryoautovaccination inbrest cancer treatment. Technical recommendations of Ministry of Health of Ukraine №37, 2015.
Patents
  1. Patent for useful model of Ukraine № 40714 (2009) «Application of biocomposite on the basis of green tea polyphenols in the treatment of cancer diseases» / Zaletok S.P., Orlovsky O.A., Gogol S.V., Khaetsky I.K., Todor I.M., Chekhun V.F. // Bull № 8, 2009
  2. Patent for useful model of Ukraine № 45097 (2009) «Method of treatment of malignant tumors» / Zaletok S.P., Samoylenko O.A., Orlovsky O.A., Klenov O.O., Gogol S.V., Malytska I.V., Jylenko V.V. // Bull № 20, 2009
  3. Patent for useful model of Ukraine № 45210 (2009) «Method of integral evaluation of non-specific resistance of organism concerning malignant tumors using reaction of carcinolysis» / Orlovsky O.A., Chekhun V.F. // Bull № 20, 2009
  4. Patent for useful model of Ukraine № 49686 (2010) «Method of testing of food products for antitumor activity» / Orlovsky O.A., Zaletok S.P., Klenov O.O., Samoylenko O.A., Chekhun V.F. // Bull № 9, 2010
  5. Patent for useful model of Ukraine № 51141 (2010) «Method of testing of non-cytotoxic treatment drugs for the antitumor activity» / Orlovsky O.A., Zaletok S.P., Chekhun V.F. // Bull № 13, 2010
  6. Patent for useful model of Ukraine № 53314 (2010) «Soy food product with antitumor activity and method of its obtaining» / Chekhun V.F., Dolinsky A.A., Orlovsky O.A., Terletska Ya.T., Zaletok S.P., Sharkova N.O., Klenov O.O., Zhukotsky E.K. // Bull № 19, 2010
  7. Patent for useful model of Ukraine № 48694 (2010) «Antitumor vaccine on the basis of micellar complex of glycopeptides CpG-DNA» / Shlyakhovenko V.O., Olishevsky S.V., Yanish Yu.V., Milinevska V.O., Kozak V.V. // Bull № 6, 2010
  8. Patent for useful model of Ukraine № 69292 (2012) «Method of enhancing the effectiveness of chemotherapy of resistant to chemotherapy malignant tumors» / Zaletok S.P., Orlovsky O.A., Shlyakhovenko V.O., Klenov O.O., Samoylenko O.A., Gogol S.V., Karanushenko O.V., Verbinenko A.V. // Bull № 8, 2012
  9. Patent for useful model of Ukraine № 74937 (2012) «Method of evaluation of sensitivity of malignant tumors to the treatment factors» / Shlyakhovenko V.O., Orlovsky O.A. // Bull № 21, 2012
  10. Patent for useful model of Ukraine № 75710 (2012) «Standardized method of experimental evaluation of side toxicity of treatment factors» / Shlyakhovenko V.O., Orlovsky O.A. // Bull № 23, 2012
  11. Patent for useful model of Ukraine № 100000 (2012) «Method of increase of effectiveness of chemotherapy of resistant to chemotherapy malignant tumors» / Zaletok S.P., Orlovsky O.A., Shlyakhovenko V.O., Klenov O.O., Samoylenko O.A., Gogol S.V., Karanushenko O.V., Verbinenko A.V. // Bull № 21, 2012
  12. 12. Invention patent of Ukraine №104343 (2014) «Method for evaluation of sensitivity of malignant tumors to the treatment factors» / Shlyakhovenko V.O., Orlovsky O.A. // Bull. №2, 2014.
  13. Invention patent of Ukraine №104495 (2014) «Standardized method of experimental evaluation of side toxicity of treatment factors» / Shlyakhovenko V.O., Orlovsky O.A. // Bull. №3, 2014.
  14. Utility patent of Ukraine № 101382 “Method to inhibite malignant tumor growth” /Zaletok S.P., Shlyakhovenko V.O., Orlovsky О.А., Yanish Yu.V., Gogol S.V., Bentrad V.V., Karnaushenko O.V., Verbinenko A.V., Samoylenko O.A., Klenov О.О. // Bull. №17/2015.
  15. Invention patent of Ukraine №112021 (2016) «Method for evaluation of sensitivity of malignant tumors to the treatment factors» / Shlyakhovenko V.O., Milinevska V.O., Orlovsky O.A., Zaletok S.P. // Bull. №13, 2016.
Innovations
  • It was created a natural drug made of waste of human blood plasma — Ceruloplasmin. This drug was first time registered in Ukraine at October 11, 1996 (registration certificate № П/96/322/6) and named as «Ceruloplasmin freeze-dried for injections». Under contemporary name «Biocerulin» the drug was registered at March, 2009, registration certificate № UA/0763/01/01. In 2007, development contractors of the drug were awarded with the State prize of Ukraine «For elaboration of production technique of Ceruloplasmin and investigation of its biological and pharmacological properties».
  • The conception proposed to apply composite of green tea polyphenols in complex treatment of oncologic diseases.
Collaboration
  • The University of Arizona (Tucson, USA; theme of studies «Study of Molecular Mechanisms of Impact of Polyamines on the Growth of Malignant Tumors»)
  • The Durmishidze Institute of Biochemistry and Biotechnology of AS of Georgia (Tbilisi, Georgia; theme of studies: «Study of Antitumor and Antioxidant Properties of Plant Polyphenol Biocomposites»)
  • V.E. Lashkarov Institute of semiconductors physics, NAS of Ukraine
  • Institute of molecular biology and genetics, NAS of Ukraine
Staff
  • Zaletok Sophia, Doctor of Biology, Senior staff scientist, head of dept.
  • Shlyakhovenko Volodymir, Doctor of Medicine, professor, Principal staff scientist
  • Gogol Sergiy, Ph.D. (Biol.), Senior staff scientist
  • Orlovsky Olexiy, Ph.D. (Biol.), Staff scientist
  • Yanish Yury, н.с., Ph.D. (Biol.), Staff scientist
  • Bentrad Veronika, Ph.D (Biol.), Junior staff scientist
  • Klenov Oleg, Ph.D (Biol.), Junior staff scientist.
  • Samoylenko Olena, Principal engineer
  • Karnaushenko Olena, Principal engineer
  • Verbinenko Alla, Principal engineer
  • Garkavenko Ganna, Technician

Science personnel training

  • Zhylenko V.V. — Candidate of Biological Sciences, specialty 03.00.04 — «Biochemistry», theme of dissertation «Biochemical mechanisms of antitumor activity of fenugreek (Trigonella foenum graecum L.)», (24.02.2014)
  • Klenov O.O. — Candidate of Biological Sciences, specialty 14.00.07 - “Oncology”, theme of dissertation: «Tumor growth in laboratory animals under soybean products being included into their diet» (2015)
  • Shapochka D.O. — a principal engineer of the department — implements dissertation on the theme: “Predictive and prognostic value of molecular biological markers (NF-κB and others) for the breast cancer patients” (preliminary thesis presentation is planned in October 2016)
  • Samoylenko О.А. — a junior staff scientist of the department — implements dissertation on the theme: «Modification of polyamines metabolism by natural polyphenolics in experimental tumor growth» (preliminary thesis presentation is planned in October 2016)

In the department were performed students' degree works:

  • Klymchuk Yu.Yu. — on the basis of the Department has performed and defended Master's Thesis «Impact of plant polyphenols on the level of expression of proteins — products of genes in tumor cells of different genesis upon the conditions of exhaustion of polyamines» (2013)
  • Knyrik М.А. (4-th year student of the Department of biotechnology and biotechnique in Kyiv National Technical University) — «Activity and expression level of iNOS in tumor cells under synthetic and natural inhibitors of polyamines synthesis» (2015 р.)
  • Gordienko І.S. (4-th year student of the Department of biotechnology and biotechnique in Kyiv National Technical University) — «Arginase activity and ODC expression in tumor cells under synthetic and natural inhibitors of polyamines synthesis» (2015 р.)
Awards
  • The O.V. Palladin Prize of Presidium of AS of Ukraine (1989) for the monograph «Polyamines and tumor growth» — Berdynskykh N.K., Zaletok S.P. — Kyiv, «Naukova Dumka», 1987. — 141 p.
  • State Prize of Ukraine in sphere of Science and Technology «For the development of technology of the production of ceruloplasmin and study of its biological and pharmacological properties» (V.F. Chekhun, V.O. Shlyakhovenko, N.K. Berdynskykh, V.M. Pivnyuk, N.M. Lyalyushko) (2007).Diploma of Verkovna Rada of Ukraine of Merits for Ukrainian people (2010) (Zaletok S.P.)
  • Zaletok S.P. — Diploma of Verkovna Rada of Ukraine of Merits for Ukrainian people (2010)
  • Artamonova G.B. — 2-nd Prize for the best paper «Antimetastatic effect of polysaccharide fraction extracted from fruit body of mushroom Lentinus edodes» in the VII International Scientific and Technical Conference «Topical Issues of Biological Physics and Chemistry», April, 2011, Sevastopol, Ukraine.
  • Klymchuk Yu.Yu. — Diploma for the best paper «Impact of glycopeptide vaccine and polyphenols of green tea on the growth of lymphatic leukemia L1210 in mice and expression in leukemia cells of proteins, products of genes c-myc and p53» in the VII International Scientific Conference of Students and Postgraduate Students «Youth and Progress in Biology», April, 2011. Lviv, Ukraine.
  • Mosienko V.О. — Diploma №549 (02.12.2014) of NAS of Ukraine for professional merit.
  • Zhylenko (Bentrad) V.V. — Diploma of Golosievo aldermanry in Kyiv for professional merit (2014)

Research grants for young scientists

  • Zhylenko (Bentrad) V.V. — Ukrainian President's research grant for young scientists (2014-2016)

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