Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2015; 61(6): 60-68


A.N. Goltsev1, N.N. Babenko1, Yu.A. Gaevskaya1, O.V. Chelombitko1, N.A. Bondarovich1, T.G. Dubrava1, M.V. Ostankov1, V.K. Klochkov2, N.S. Kavok2, Yu.V. Malyukin2

  1. Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkov;
  2. Institute for Scintillation Materials of the National Academy of Sciences of Ukraine, Kharkov


Tumor development is the consequence of expanding the population of low differentiated cells with unlimited self-maintenance potential, i.e. cancer stem cells (CSCs). Application of new forms of nanocomposites capable of binding to CSCs and inducing the tumor destruction is perspective direction for treating this pathology. There have been developed the methods of obtaining hybrid nanocomplexes containing rare-earth orthovanadates GdYVO4:Eu3+, cholesterol and luminescent dye Dil. By immune fluorescence method using monoclonal antibodies to CD44, CD24, CD117 and Sca-1 markers there has been established the change in the ratio of tumor progenitors of various differentiation levels in a general pool of Ehrlich carcinoma (EC) after treatment with hybrid nanocomplexes. Essential reduction in the concentration of the most tumorogenic CD44high cells with simultaneous rise in the number of CD117+-cells resulted in an increased index of CD44high / CD117+ ratio. It has been demonstrated that application of hybrid nanocomplexes suppressed the tumor growth almost by 80%. The value of cooperative interactions of the cells with different phenotype signs in tumor sites has been proved. The index of CD44high / CD117+ ratio can be used as one of diagnostic and prognostic parameters of development and inactivation rate of tumor process when using different types of anti-tumor therapy.

Keywords: cancer stem cells; nanoparticles; Ehrlich carcinoma; orthovanadates.


  1. Ambasta RK, Sharma A, Kumar P. Nanoparticle mediated targeting of VEGFR and cancer stem cells for cancer therapy. Vasc Cell. 2011;3:26. CrossRef PubMed PubMedCentral
  2.   CrossRef   PubMed PubMedCentral  
  3. Prylutska SV, Burlaka AP, Prylutskyy YI, Ritter U, Scharff P. Pristine C(60) fullerenes inhibit the rate of tumor growth and metastasis. Exp Oncol. 2011 ;33(3):162–4.
  5. Panchuk RR, Prylutska SV, Chumak VV, Skorokhyd NR, Lehka LV, Evstigneev MP, Prylutskyy YuI, Berger W, Heffeter P, Scharff P, Ritter U, Stoika RS. Application of C60 fullerene-doxorubicin complex for tumor cell treatment in vitro and in vivo J Biomed. Nanotechnol. 2015 (7):1139–52.
  7. Kopf-Maier P, Krahl D. Tumor inhibition by metallocenes: ultrastructural localisationof titanium and vanadium, in treated tumor cells by electron energy loss spectroscopy. Chem Biol Interact. 1983;44(3):317–28. CrossRef" id="ref_href_id" target="blank"">CrossRef   CrossRef  
  8. Navara CS, Benyumov A, Vassilev A, Narla RK, Ghosh P, Uckun FM. Vanadocenes as potent anti-proliferative agents disrupting mitotic spindle formation in cancer cells. Anticancer Drugs. 2001;12(4):369–76. CrossRef PubMed
  9.   CrossRef   PubMed  
  10. Goltsev AN, Babenko NN, Gayevskaya YuA, Bondarovich NA, Ostankov MV, Chelombytko OV, Dubrava TG, Klochkov VK, Kavok NS, Malyukin YuV. Capability of orthovanadate-based nanoparticles to in vitro identification and in vivo inhibition of cancer stem cells. Nanosystems, nanomaterials, nanotechnologies. 2013; 11(4): 729–39. [Ukrainian].
  12. Goltsev AN, Chelombitko OV, Babenko NN, Gayevskaya YuA, Dubrava TG, Bondarovich NO, Ostankov MV, Dimitrov AYu, Klochkov VK, Kavok NS, Malyukin YuV. Functional activity of Ehrlich carcinoma cancer stem cells after treatment by orthovanadate-based nanoparticles. Ann Oncol. 2014; 25(suppl 4):iv569.
  14. Karpenko NA, Malukin YuV, Koreneva E M, Klochkov VK, Kavok NS, Smolenko NP, Pochernyaeva SS. The effects of chronic intake of nanoparticles of cerium dioxide or gadolinium ortovanadate into aging male rats. Proceedings of the 3rd Int. Conf. «Nanomaterials: Applications and Properties '2013», September 16-21, 2013: Abstract book - Alushta (Ukraine), 2013; 2(4):04NAMB28- 1–04NAMB28-4.
  16. Al - Jarallah A, Trigatti BL. A role for the scavenger receptor, class B type I in high density lipoprotein dependent activation of cellular signaling pathways. Biochim Biophys Acta. 2010; 1801(12):1239-48. CrossRef PubMed
  17.   CrossRef   PubMed  
  18. Clayman RV, Bilhartz LE, Buja LM, Spady DK, Dietschy JM. Renal cell carcinoma in the Wistar-Lewis rat: a model for studying the mechanisms of cholesterol acquisition by a tumor in vivo. Cancer Res. 1986 ;46(6):2958–63.
  20. Lebed AS, Efimova SL, Guralchuk GYa, Sorokin AV, Borovoy IA. Study of complex formation processes in "fluorescent probe - surface active agent" system in aqueous solutions at the concentration of surface active agents below and under CCM. Biophysical bulletin. 2010; 24(1):46-55. [Ukrainian].
  22. Goltsev AN, Babenko NN, Gayevskaya YuA, Dubrava TG, Ostankov MV, Chelombitko OV, Klochkov VK, Kavok NS. Identification of tumour cells with hybrid complexes based on non-organic nanoparticles and organic biologically active compounds: Collection of 16th International Scientific and Practical Conference "Fundamental and Applied Research, Design and Application of High Technologies in Industry and Economy", St. Petersburg, December 5-6, 2013. St. Petersburg: Publishing House of Polytechnic University, P.121-31 [Russian].
  24. Al-Hajj M., Clarke M. F. Self-renewal and solid tumor stem cells. Oncogene. 2004 Sep 20;23(43):7274-82.
  26. Ghebeh H, Sleiman GM, Manogaran PS, Al-Mazrou A, Barhoush E, Al-Mohanna FH, Tulbah A, Al-Faqeeh K, Adra CN. Profiling of normal and malignant breast tissue show CD44high/CD24low phenotype as a predominant stem/progenitor marker when used in combination with Ep-CAM/CD49f markers. BMC Cancer. 2013; 13:289. CrossRef PubMed PubMedCentral
  27.   CrossRef   PubMed PubMedCentral  
  28. Yan W, Chen Y, Yao Y, Zhang H, Wang T. Increased invasion and tumorigenicity capacity of CD44+/CD24- breast cancer MCF7 cells in vitro and in nude mice. Cancer Cell Int. 2013 Jun 24;13(1):62.
  30. Li Y, Welm B, Podsypanina K, Huang S. Chamorro M, Zhang X, Rowlands T, Egeblad M, Cowin P, Werb Z, Tan LK, Rosen JM, Varmus HE. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci USA. 2003; 100(26):15853–8. CrossRef PubMed PubMedCentral
  31.   CrossRef   PubMed PubMedCentral  
  32. Huang R, Wu D, Yuan Y, Li X, Holm R, Trope CG, Nesland JM, Suo Z. CD117 expression in fibroblasts-like stromal cells indicates unfavorable clinical outcomes in ovarian carcinoma patients. PLoS One. 2014; 9 (11):e112209.
  34. Chui X, Egami H, Yamashita J, Kurizaki T, Ohmachi H, Yamamoto S, Ogawa M. Immunohistochemical expression of the c-kit proto-oncogene product in human malignant and non-malignant breast tissues. Br J Cancer. 1996;73(10):1233-6. CrossRef PubMed PubMedCentral
  35.   CrossRef   PubMed PubMedCentral  
  36. Kondi-Pafiti A, Arkadopoulos N, Gennatas C, Michalaki V, Frangou-Plegmenou M, Chatzipantelis P. Expression of c-kit in common benign and malignant breast lesions. Tumori. 2010 Nov-Dec;96(6):978-84.
  38. Ozaslan M, Karagoz I D, Kilic I H, Guldur ME. Ehrlich ascites carcinoma. African J Biotechnology. 2011; 10(13): 2375–8.
  40. Goltsev AN, Chelombytko OV, Bondarovich NA, Ostankov MV, Dimitrov AYu. Cryopreservation effect on pluripotency gene expression in Ehrlich carcinoma cells cells: Abstracts Annual Scientific Conference & AGM of the Society for Low Temperature Biology (STBL) «Freezing biological time 50th Anniversary Celebration». London, UK, October 8-10, 2014, P.84.
  42. Goltsev AM, Safranchuk OV, Bondarovich MO, Ostankov MV. Change in cryolability of tumour stem cells depending on adenocarcinoma growth phase. Fiziol Zh. 2011; 57(4): 68–76 [Ukrainian].
  44. Goltsev AM, Safranchuk OV, Bondarovich MO, Ostankov MV, Babenko NN, Gayevskaya YuA, Chelombitko OV. Methodical approaches to the stabilization of structural and functional states of cryopreserved cells of Ehrlich carcinoma. Reports National Acad Sci of Ukraine. 2012; (8):115-22. [Ukrainian].
  46. Klochkov VK, 2015. Method of obtaining of an aqueous dispersion of cholesterol. Ukraine. The decision on handing over of UA patent 14.01.2015. [Ukrainian] .
  48. Klochkov VK. Aqueous colloid solutions of nanoluminophores nReVO4:Eu3+ (Re = Y, Gd, La). Material Science of Nanostructures. 2009; (2):3–8. [Ukrainian].
  50. Charpin C, Giusiano S, Charfi S, Secq V, Carpentier S, Andrac L, Lavaut MN, Allasia C, Bonnier P, Garcia S. Quantitative immunohistochemical expression of c-Kit in breast carcinomas is predictive of patients' outcome. Br J Cancer. 2009 Jul 7; 101(1): 48–54.
  52. Betker JL, Kullberg M, Gomez J, Anchordoquy TJ. Cholesterol domains enhance transfection. Ther Deliv. 2013 ;4(4):453-62. CrossRef PubMed PubMedCentral

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.