Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Chronometric Administration of Cyclophosphamide and a Double-Stranded DNA-Mix at Interstrand Crosslinks Repair Timing, Called “Karanahan” Therapy, Is Highly Efficient in a Weakly Immunogenic Lewis Carcinoma Model. / Ruzanova, Vera; Proskurina, Anastasia; Efremov, Yaroslav и др.
в: Pathology and Oncology Research, Том 28, 1610180, 27.05.2022.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Chronometric Administration of Cyclophosphamide and a Double-Stranded DNA-Mix at Interstrand Crosslinks Repair Timing, Called “Karanahan” Therapy, Is Highly Efficient in a Weakly Immunogenic Lewis Carcinoma Model
AU - Ruzanova, Vera
AU - Proskurina, Anastasia
AU - Efremov, Yaroslav
AU - Kirikovich, Svetlana
AU - Ritter, Genrikh
AU - Levites, Evgenii
AU - Dolgova, Evgenia
AU - Potter, Ekaterina
AU - Babaeva, Oksana
AU - Sidorov, Sergey
AU - Taranov, Oleg
AU - Ostanin, Alexandr
AU - Chernykh, Elena
AU - Bogachev, Sergey
N1 - Funding Information: The work was supported by the Russian Ministry of Science and Higher Education via the Institute of Cytology and Genetics under State Budget Project No. FWNR-2022-0016 and the Russian Foundation for Basic Research under Grant No. 18-29-09045. Publisher Copyright: Copyright © 2022 Ruzanova, Proskurina, Efremov, Kirikovich, Ritter, Levites, Dolgova, Potter, Babaeva, Sidorov, Taranov, Ostanin, Chernykh and Bogachev.
PY - 2022/5/27
Y1 - 2022/5/27
N2 - Background and Aims: A new technology based on the chronometric administration of cyclophosphamide and complex composite double-stranded DNA-based compound, which is scheduled in strict dependence on interstrand crosslinks repair timing, and named “Karanahan”, has been developed. Being applied, this technology results in the eradication of tumor-initiating stem cells and full-scale apoptosis of committed tumor cells. In the present study, the efficacy of this novel approach has been estimated in the model of Lewis carcinoma. Methods: To determine the basic indicative parameters for the approach, the duration of DNA repair in tumor cells, as well as their distribution along the cell cycle, have been assessed. Injections were done into one or both tumors in femoral region of the engrafted mice in accordance with the developed regimen. Four series of experiments were carried out at different periods of time. The content of poorly differentiated CD34+/TAMRA+ cells in the bone marrow and peripheral blood has been determined. Immunostaining followed by the flow cytometry was used to analyze the subpopulations of immune cells. Results: The high antitumor efficacy of the new technology against the developed experimental Lewis carcinoma was shown. It was found that the therapy efficacy depended on the number of tumor growth sites, seasonal and annual peculiarities. In some experiments, a long-term remission has been reached in 70% of animals with a single tumor and in 60% with two tumors. In mice with two developed grafts, mobilization capabilities of both poorly differentiated hematopoietic cells of the host and tumor stem-like cells decrease significantly. Being applied, this new technology was shown to activate a specific immune response. There is an increase in the number of NK cell populations in the blood, tumor, and spleen, killer T cells and T helper cells in the tumor and spleen, CD11b+Ly-6C+ and CD11b+Ly-6G+ cells in the tumor. A population of mature dendritic cells is found in the tumor. Conclusion: The performed experiments indicate the efficacy of the Karanahan approach against incurable Lewis carcinoma. Thus, the discussed therapy is a new approach for treating experimental neoplasms, which has a potential as a personalized anti-tumor therapeutic approach in humans.
AB - Background and Aims: A new technology based on the chronometric administration of cyclophosphamide and complex composite double-stranded DNA-based compound, which is scheduled in strict dependence on interstrand crosslinks repair timing, and named “Karanahan”, has been developed. Being applied, this technology results in the eradication of tumor-initiating stem cells and full-scale apoptosis of committed tumor cells. In the present study, the efficacy of this novel approach has been estimated in the model of Lewis carcinoma. Methods: To determine the basic indicative parameters for the approach, the duration of DNA repair in tumor cells, as well as their distribution along the cell cycle, have been assessed. Injections were done into one or both tumors in femoral region of the engrafted mice in accordance with the developed regimen. Four series of experiments were carried out at different periods of time. The content of poorly differentiated CD34+/TAMRA+ cells in the bone marrow and peripheral blood has been determined. Immunostaining followed by the flow cytometry was used to analyze the subpopulations of immune cells. Results: The high antitumor efficacy of the new technology against the developed experimental Lewis carcinoma was shown. It was found that the therapy efficacy depended on the number of tumor growth sites, seasonal and annual peculiarities. In some experiments, a long-term remission has been reached in 70% of animals with a single tumor and in 60% with two tumors. In mice with two developed grafts, mobilization capabilities of both poorly differentiated hematopoietic cells of the host and tumor stem-like cells decrease significantly. Being applied, this new technology was shown to activate a specific immune response. There is an increase in the number of NK cell populations in the blood, tumor, and spleen, killer T cells and T helper cells in the tumor and spleen, CD11b+Ly-6C+ and CD11b+Ly-6G+ cells in the tumor. A population of mature dendritic cells is found in the tumor. Conclusion: The performed experiments indicate the efficacy of the Karanahan approach against incurable Lewis carcinoma. Thus, the discussed therapy is a new approach for treating experimental neoplasms, which has a potential as a personalized anti-tumor therapeutic approach in humans.
KW - cancer stem cells
KW - committed tumor cells
KW - cytostatic agent
KW - dsDNA
KW - interstrand crosslink repair
KW - Karanahan approach
KW - Lewis lung carcinoma
KW - tumor growth site
KW - Antigens, CD34
KW - Cyclophosphamide/pharmacology
KW - Humans
KW - Mice, Inbred C57BL
KW - Neoplastic Stem Cells/pathology
KW - DNA/genetics
KW - Animals
KW - Carcinoma/pathology
KW - Mice
UR - http://www.scopus.com/inward/record.url?scp=85131852523&partnerID=8YFLogxK
U2 - 10.3389/pore.2022.1610180
DO - 10.3389/pore.2022.1610180
M3 - Article
C2 - 35693632
AN - SCOPUS:85131852523
VL - 28
JO - Pathology and Oncology Research
JF - Pathology and Oncology Research
SN - 1219-4956
M1 - 1610180
ER -
ID: 36560974