TY - JOUR

T1 - Efficacy of the new therapeutic approach in curing malignant neoplasms on the model of human glioblastoma

AU - Dolgova, Evgeniya V.

AU - Andrushkevich, Oleg M.

AU - Kisaretova, Polina E.

AU - Proskurina, Anastasia S.

AU - Ritter, Genrikh S.

AU - Dubatolova, Tatyana D.

AU - Romanenko, Margarita V.

AU - Taranov, Oleg S.

AU - Efremov, Yaroslav R.

AU - Zavyalov, Evgeniy L.

AU - Romaschenko, Alexandr V.

AU - Mishinov, Sergey V.

AU - Kirikovich, Svetlana S.

AU - Levites, Evgeniy V.

AU - Potter, Ekaterina A.

AU - Ostanin, Alexandr A.

AU - Chernykh, Elena R.

AU - Roshchin, Stanislav Yu

AU - Bervitskiy, Anatoliy V.

AU - Moysak, Galina I.

AU - Rzaev, Jamil A.

AU - Bogachev, Sergey S.

N1 - Funding Information: This study was supported by the Russian Ministry of Science and High Education, State Budgeted Project 0259-2021-0013 for the Institute of Cytology and Genetics, Novosibirsk and the Russian Foundation for Basic Research (Grant No. 18-34-20016). Microscopic examination of bone marrow cells was supported by the Russian Ministry of Science and High Education, State Budgeted Project 0246-2021-0017 for the Institute of Molecular and Cellular Biology, Novosibirsk. The authors are also grateful to Inga N. Zaitseva, Dmitriy B. Petrov, and Mikhail A. Shurdov for additional funding. Publisher Copyright: Copyright © 2021 by Cancer Biology & Medicine.

PY - 2021/8

Y1 - 2021/8

N2 - Objective: Glioma is a highly invasive tumor, frequently disposed in essential areas of the brain, which makes its surgical excision extremely difficult; meanwhile adjuvant therapy remains quite ineffective. Methods: In the current report, a new therapeutic approach in curing malignant neoplasms has been performed on the U87 human glioblastoma model. This approach, termed "Karanahan", is aimed at the eradication of cancer stem cells (CSCs), which were recently shown to be capable of internalizing fragments of extracellular double-stranded DNA. After being internalized, these fragments interfere in the process of repairing interstrand cross-links caused by exposure to appropriate cytostatics, and such an interference results either in elimination of CSCs or in the loss of their tumorigenic potency. Implementation of the approach requires a scheduled administration of cytostatic and complex composite double-stranded DNA preparation. Results: U87 cells treated in vitro in accordance with the Karanahan approach completely lost their tumorigenicity and produced no grafts upon intracerebral transplantation into immunodeficient mice. In SCID mice with developed subcutaneous grafts, the treatment resulted in reliable slowing down of tumor growth rate (P < 0.05). In the experiment with intracerebral transplantation of U87 cells followed by surgical excision of the developed graft and subsequent therapeutic treatment, the Karanahan approach was shown to reliably slow down the tumor growth rate and increase the median survival of the mice twofold relative to the control. Conclusions: The effectiveness of the Karanahan approach has been demonstrated both in vitro and in vivo in treating developed subcutaneous grafts as well as orthotopic grafts after surgical excision of the tumor.

AB - Objective: Glioma is a highly invasive tumor, frequently disposed in essential areas of the brain, which makes its surgical excision extremely difficult; meanwhile adjuvant therapy remains quite ineffective. Methods: In the current report, a new therapeutic approach in curing malignant neoplasms has been performed on the U87 human glioblastoma model. This approach, termed "Karanahan", is aimed at the eradication of cancer stem cells (CSCs), which were recently shown to be capable of internalizing fragments of extracellular double-stranded DNA. After being internalized, these fragments interfere in the process of repairing interstrand cross-links caused by exposure to appropriate cytostatics, and such an interference results either in elimination of CSCs or in the loss of their tumorigenic potency. Implementation of the approach requires a scheduled administration of cytostatic and complex composite double-stranded DNA preparation. Results: U87 cells treated in vitro in accordance with the Karanahan approach completely lost their tumorigenicity and produced no grafts upon intracerebral transplantation into immunodeficient mice. In SCID mice with developed subcutaneous grafts, the treatment resulted in reliable slowing down of tumor growth rate (P < 0.05). In the experiment with intracerebral transplantation of U87 cells followed by surgical excision of the developed graft and subsequent therapeutic treatment, the Karanahan approach was shown to reliably slow down the tumor growth rate and increase the median survival of the mice twofold relative to the control. Conclusions: The effectiveness of the Karanahan approach has been demonstrated both in vitro and in vivo in treating developed subcutaneous grafts as well as orthotopic grafts after surgical excision of the tumor.

KW - Cancer stem cells

KW - Glioblastoma

KW - Mytomycin C

KW - TAMRA

KW - U87 cell line

UR - http://www.scopus.com/inward/record.url?scp=85109319396&partnerID=8YFLogxK

U2 - 10.20892/j.issn.2095-3941.2020.0511

DO - 10.20892/j.issn.2095-3941.2020.0511

M3 - Article

C2 - 34259424

AN - SCOPUS:85109319396

VL - 18

SP - 910

EP - 930

JO - Cancer Biology and Medicine

JF - Cancer Biology and Medicine

SN - 2095-3941

IS - 3

ER -