Issue 1 (199), article 5


Cybernetics and Computer Engineering, 2020, 1(199)

Azarkhov O.Yu.1, DSc. (Medicine),
Head of the Biomedical Engineering Department

Chernyshova T.A.2, Physician,

1Pryazovsky State Technical University of the Ministry of Education and Science of Ukraine,
7, University st., Mariupol, 87555, Ukraine

2Aviation Medical Center of the National Aviation University,
1, Komarova av., Kyiv, 03058, Ukraine


Introduction. The study of the possibility of using the circulating tumor cells (CTC) definition in the patients` blood with different localization of malignant tumors as a diagnostic criterion and the criterion of the effectiveness of specific treatment tactics is one of the topical issues in modern oncology.

The purpose of the paper is to analyze the results of using the developed information technology for identification of circulating tumor cells for the study of blood samples of patients in order to confirm or reject the initial diagnosis of cancer of different localization.

Results. Our information technology is based on the use of an advanced method of isolation of intact circulating cells, the difference of which is to supplement the structure of the basic ISET method (Isolation by Sizе of Tumor Cells) with new modes: 100% sealing chamber with hemolysate and providing it with the necessary and constant pressure during the filtration process by introducing a negative pressure gauge, as well as the mode of three-level filtering of the CTC on consecutive polycarbonate membranes with micropore diameters of 8 μm, 5 μm and 3 μm. To assess the malignancy of selected cells, the information technology used the method of determining the CTC according to the set of criteria, formed databases with created template CTC masks and control templates in the automated mode. Blood samples from patients were tested using IT. Taking into account each step of the technique (using different filters), analysis of the results showed that of the total proportion of samples, which additionally detected the CTC using not only an 8 μm filter, but also filters 5 μm and 3 μm, was 20.66 %.

Conclusions. The use of information technology to identify circulating tumor cells improves the efficiency of detecting these cells by reducing the testing time and expanding the range of research due to the ability to detect cells of small size. Improvement of IT by supplementing the knowledge base (complex of template mask masks and relevant expert findings) makes it possible to apply it in screening of patients’ blood, including at the preclinical stage of the examination.

Keywords: information technology, circulating tumor cells, method of isolation of circulating tumor cells, automated system, screening of patients’ blood.

Download full text!


1. Goeminne J.C., Guillaume T., Symann M. Pitfalls in the de- tection of disseminated non-hematological tumor cells. Ann Oncol. 2000, no. 11, pp.785-792.

2. Pantel K., Woelfle U. Detection and molecular characterisa- tion of disseminated tumour cells: implications for anticancer therapy. Biochim Biophys Acta. 2005, no. 1756, pp. 53-64.

3. Smerage J.B., Hayes D.F. The measurement and therapeutic implications of circulating tumour cells in breast cancer. Br J Cancer. 2006, no. 94, pp. 8-12.

4. Grudinskaya T.V., Kovalev A.A., Kovalev K.A., Kuznetsova T.P. Heterogeneity of circulating tumor cells. Oncology. 2012, Vol. 14, no. 2, pp. 126-129. (in Russian)

5. Keith O.I., Novikova I.A., Selyutina O.N., Duritsky M.N., Dontsov V.A., Chernikova E.N., Samaneva N.Yu., Nistratova O.V. Research of the CTC level in epitital tumors of different localizations. International Journal of Applied and Fundamental Research. 2015, no.12 (Part 5), pp. 817-820. (in Russian).

6. Bzhadug O.B. Grivtsova L.Y., Tupitsh N.N., Tyulandin S.A. Circulating tumor cells in the blood of patients with locally distributed and disseminated breast cancer. RONC Newsletter. 2007, Vol. 18, no. 3, pp. 19-22. (in Russian)

7. Balic M., Dandachi N., Hofmann G. Comparison of two methods for enumerating circulating tumor cells in carcinoma patients. Clin Cytom. 2005, no.68, pp. 25-30.

8. Ashworth T. A case of cancer in which cells similar to those in the tumors were seen in the blood after death. Aust Med J. 1869, no. 14, pp. 146-149.

9. Goeminne J.C., Guillaume T., Symann M. Pitfalls in the detection of disseminated non-hematological tumor cells. Ann Oncol. 2000, no. 11, pp. 785-92.

10. Christiansen J.J., Rajasekaran A.K. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006, no. 66, pp. 8319-26.

11. Ring I, Smith E, Dowsett M. Circulating tumour cells in breast cancer. Lancet Oncol. 2004, no. 5, pp. 79-88.

12. Andreopoulou E., Yang L.-Y., Rangel K., Reuben J., Hsu L., Krishnamurthy S., Valero V. Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect™ versus Yeridex CellSearch™ system. Int. journal of cancer. 2012, Vol. 130, no.7, pp. 1590-1597.

13. Kagan M., Howard D., Bendele Т., Mayes J., Silvia J., Repollet M., Doyle J. A Sample Preparation and Analysis System for Identification of Circulating Tumor Cells. Journal of Clinical Ligand Assay. 2002, Vol. 25, no. 1, pp. 104-110.

14. Nezos A., Pissimisis N., Lembessis P., Sourla A., Dimopoulos P., Dimopoulos Т., Tzelepis K. Detection of circulating tumor cells in bladder cancer patients. Cancer treatment reviews. 2009, Vol. 35, no.3, pp. 272-279.

15. Ignatiadis M., Kallergi G., Ntoulia M., Perraki M., Apostolaki S., Kafousi M., Chlouverakis G. Prognostic value of the molecular detection of circulating tumor cells using a multimarker reverse transcription-PCR assay for cytokeratin 19, mammaglobin A, and HER2 in early breast cancer. Clinical cancer research: an official journal of the American Association for Cancer Research. 2008, Vol. 14, no9, pp. 2593-2600.

16. Van der Auwera I., Peeters D., Benoy I. Circulating tumour cell detection: a direct comparison between the CellSearch System, the AdnaTest and CK-19/mammaglobin RT-PCR in patients with metastatic breast cancer. British journal of cancer. 2010, Vol.102, no. 2, pp. 276-284.

17. Nagrath S., Sequist L., Maheswaran S., Bell D., Irimia D., Ulkus L., Smith M. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007, Vol. 450, no.7173, pp. 1235-1239.

18. Chen L., Bode A. M., Dong Z. Circulating Tumor Cells: Moving Biological Insights into Detection. Theranostics. 2017.

19. Laget S., Broncy L., Hormigos K., Dhingra D.M., BenMohamed F., Capiod T. Technical Insights into Highly Sensitive Isolation and Molecular Characterization of Fixed and Live Circulating Tumor Cells for Early Detection of Tumor Invasion. PLOS ONE. 2017, 12 (1): e0169427. URL:

20. Zlepko S.M., Chernyshova T.A., Mayevsky A.Ye., Krivonosov V.Ye., Azarkhov A.Yu. Information technology for the determination of circulating tumor cells in human blood. Kibernetika i vyčislitel’naâ tehnika. 2018, no. 2 (192), pp. 84-98. (in Ukrainian).

21. Vona G., Sabile A., Louha M., Sitruk V., Romana S., Schutze K., Capron F. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulatingtumor cells. The American journal of pathology. 2000, Vol. 156, no. 1, pp. 57-63.

22. Paterlini-Bréchot P., Benali-Furet N.L. Circulating tumor cells (CTC) detection : Clinical impact and future directions. Cancer Letter. 2007, no. 253, pp. 180-204.

23. Ismailova G., Laget S., Paterlini-Brechot P. Diagnosis of circulating tumor cells using ISET technology and their molecular characteristics for fluid biopsy. Clinical medicine of Kazakhstan. 2015, no. 1 (35), pp. 15-20. (in Russian).

24. Pavlov S.V., Kozhemyako V.P., Burdenyuk I.I., Rami Rebhi Hamdi. Opto-electronic technologies of biomedical image analysis. Vinnitsa, 2011, 166 p. (in Ukrainian).

25. Zlepko S.M., Pavlov S.V., Koval L.G., Timchyk I.S. Fundamentals of biomedical radioelectronic apparatus. Vinnitsa, 2011, 133 p. (in Ukrainian).

26. Chernyshova T.A. Criteria and Method for Detection of Circulating Tumor Cells. Cybernetics and computer engineering. 2019, no.1 (195), pp.85-98.

27. Pat. 127486 UA, MPK C12M 3/06, G01N 33/574, G01N 33/49. Device for detecting circulating tumor cells in the blood / S.M. Zlepko, V.E. Krivonosov, S.V. Timchyk, T.A. Chernyshova, O.S. Zlepko, O.Yu. Azarkhov, V.S. Pavlov, V.V. Krivonosov (Ukraine). 2018 00060; claimed 02.01.2018; publ. 08/10/2018, Bul. № 15. – 7 p. (in Ukrainian).

Recieved 11.12.2019