Research of the intracranial neoplasia cell sensitivity to chemotherapy drugs
https://doi.org/10.17650/2311-1267-2015-2-4-51-57
Abstract
Introduction. The article is devoted to the personalized selection of chemotherapy for intracranial tumor cell cultures obtained from patients.
Materials and methods. In the primary cell cultures of intracranial tumors (pilocytic astrocytoma, anaplastic astrocytoma, glioblastoma and medulloblastoma), taken from 98 patients aged 3 months to 17 years, were evaluated their sensitivity to chemotherapeutic drugs (vincristine, carboplatin, methotrexate, temozolomide, cytarabine, cyclophosphamide, cisplatin and etoposide) by staining the cells with trypan blue in Goryaev chamber. Using principal component analysis and two-factor analysis of variance was adjusted depending on the chemosensitivity factor ‟patient”, the type of tumor, and the mechanism of action of chemotherapy.
Results. Based on cell sensitivity to chemotherapeutic drugs neuroepithelial tumors particular patient applying statistical methods of analysis allows to identify individual patients at high, moderate or low chemosensitivity, patients with chemotherapy and effectively act unidirectionally or differently and have weak cytotoxic effect on the tumor. Application of the method of two-way analysis of variance revealed that the main factor affecting the sensitivity of tumor cells to chemotherapeutic drugs is a factor of the ‟patient”.
Conclusions. Application of principal component creates a scientific basis for the selection of individual schemes (protocols) therapy in this group of patients.
About the Authors
A. N. ChernovBelarus
28 Akademicheskaya St., Minsk, 220072,
N. N. Yatskov
Belarus
4 Prosp. Nezavisimosti, Minsk, 220030
V. V. Skakun
Belarus
4 Prosp. Nezavisimosti, Minsk, 220030
References
1. Rutkowski S., von Bueren A., von Hoff K. et al. Prognostic relevance of clinical and biological risk factors in childhood medulloblastoma: results of patients treated in the prospective multicenter trail HIT’91. Clin Cancer Res 2007;13(9):2651–7.
2. The World of Health Organization [Electronic resource], 2012. Mode of access: http://www.who.int/cancer/about/facts/ru. Data of access: 23.03.2015.
3. International agency for research of cancer, Globocan, the World of Health Organization [Electronic resource], 2012. Mode of access: http: www.globocan.iarc.fr. Data of access: 23.03.2015.
4. Safdie F., Brandhorst S., Wei M. et al. Fasting enhances the response of glioma to chemo- and radiotherapy. PLoS One 2012;7(9):e44603.
5. Konoplia N.E., Strongin Iu.S., Talabaev M.V., Aleĭnikova O.V. Effectiveness of intensive chemotherapy in the treatment of medulloblastoma/primitive neuroectodermal tumor in children. Vopr Onkol 2008;54(2):157–63.
6. Tomlinson F.H., Lihou M.G., Smith P.J. Comparison of in vitro activity of epipodophyllotoxins with other chemotherapeutic agents in human medulloblastomas. Brit J Cancer 1991;64(6):1051–9.
7. Yung W.K. In vitro chemosensitivity testing and its clinical application in human gliomas. Neurosurg Rev 1989;12(3):197–203.
8. Zendehdel R., Masoudi-Nejad A., Mohammadzadeh J. et al. Cisplatin resistant patterns in ovarian cell line using FTIR and principle component analysis. Iranian J Pharmaceutical Res 2012;11(1):235–40.
9. Иншаков А.Н. Фармакодинамическое моделирование чувствительности опухолевых клеток хронического лимфолейкоза и множественной миеломы к химиопрепаратам in vitro. Автореф. дис. … канд. мед. наук: 14.01.12. ФГБУ РОНЦ им. Н.Н. Блохина РАМН. М., 2012. [Inshakov A.N. Pharmacodynamic modeling of the sensitivity of tumor cell chronic lymphocytic leukemia and multiple myeloma to chemotherapy drugs in vitro. Dissert. PhD: 14.01.12. N.N. Blokhin Russian Cancer Research Center. M., 2012. (In Russ.)].
10. Свирновский А.И., Сергиенко Т.Ф., Пасюков В.В. и др. Разработка принципов создания диагностического набора для оценки лекарственной чувствительности лейкозных клеток. Проблемы здоровья и экологии 2011;3:94–100. [Svirnovskiy A.I., Sergienko T.F., Pasyukov V.V. et al. Development of guidelines for creating a diagnostic kit for evaluating drug sensitivity of leukemic cells. Problemy zdoroviya i ecologii = Problems of Health and Environment 2011;3:94–100. (In Russ.)].
11. Jordan J.P., Hand C.M., Markowitz R.S. et al. Test for chemotherapeutic sensitivity of cerebral gliomas: use of colorimetric MTT assay. J Neurooncol 1992;14(1):19–35.
12. Fiebig H.H., Maier A., Burger A.M. Clonogenic assay with established human tumour xenografts. Eur J Cancer 2004;40(6):802–20.
13. Апшкалне Д.Л., Круминия Г.А., Кикут Р.П. и др. Результаты клинического применения методов индивидуальной чувствительности химиотерапевтических препаратов для лечения глиом. Вопросы нейрохирургии им. Н.Н. Бурденко 1980;6:7–12. [Apshkalne D.L., Kruminiya G.A., Kikut R.P. et al. The clinical application of individual sensitivity of chemotherapeutic agents for the treatment of gliomas. Voprosy neirokhirurgii im. N.N. Burdenko = Problems of Neurosurgery named after N.N. Burdenko 1980;6:7–12. (In Russ.)].
14. Чернов А.Н., Калюнов В.Н. Оценка индивидуальной чувствительности клеток нейроэпителиальных опухолей к химиопрепаратам in vitro. Евразийский онкологический журнал 2015;1:84–96. [Chernov A.N., Kalyunov V.N. Evaluation of the sensitivity of individual cell neuroepithelial tumors to chemotherapy drugs in vitro. Yevraziyskiy onkologicheskiy zhurnal = Eurasian Journal of Oncology 2015;1:84–96. (In Russ.)].
15. Bredel M., Bredel C., Juric D. et al. Tumor necrosis factor-α-induced protein 3 as a putative regulator of nuclear factor-κB–mediated resistance to O6 -alkylating agents in human glioblastomas. J Clin Oncol 2006;24:274–87.
16. Божкова В.П., Викторов И.В., Брежестовский Л.А. и др. Руководство по культивированию нервной ткани. Методы. Техника. Проблемы. М.: Наука, 1988. [Bozhkova V.P., Viktorov I.V., Brezhestovskiy L.A. et al. Guide culturing neural tissue. Methods. Equipment. Problems. M.: Nauka, 1988. (In Russ.)].
17. Руководство по проведению доклинических исследований лекарственных средств. Часть первая. Под редакцией А.Н. Миронова. М.: Гриф и К, 2012. [Guidelines for conducting pre-clinical studies of drugs. Part one. Ed.: A.N. Mironov. M.: Grif & K, 2012. (In Russ.)].
18. Biostatistics: A Methodology for the Health Sciences (G. van Belle, P.J. Heagerty, L.D. Fisher, T.S. Lumley, eds.). Jonh Wiley and Sons Inc., 2004.
19. Айвазян С.А., Бухштабер В.М., Енюков И.С. и др. Прикладная статистика. Классификация и снижение размерности. М.: Финансы и статистика, 1989. [Ayvazyan S.A., Bukhshtaber V.M., Yenyukov I.S. et al. Applied statistics. Classification and dimension reduction. M.: Finansy i statistika, 1989. (In Russ.)].
20. Grunda J.M., Fiveash J., Palmer Ch.A. et al. Rationally designed pharmacogenomic treatment using concurrent capecitabine and radiotherapy for glioblastoma; gene expression profiles associated with outcome. Clin Cancer Res 2010;16:2890–2.
21. Watanabe T., Suzuki T., Natsume M. et al. Discrimination of genotoxic and nongenotoxic hepatocarcinogens by statistical analysis based on gene expression profiling in the mouse liver as determined by quantitative real-time PCR. Mutation Res 2012;747:164–75.
Review
For citations:
Chernov A.N., Yatskov N.N., Skakun V.V. Research of the intracranial neoplasia cell sensitivity to chemotherapy drugs. Russian Journal of Pediatric Hematology and Oncology. 2015;2(4):51-57. (In Russ.) https://doi.org/10.17650/2311-1267-2015-2-4-51-57