Development of the therapeutic regimen based on the synergistic activity of cyclophosphamide and double-stranded DNA preparation which results in complete cure of mice engrafted with Krebs-2 ascites
Cumulative evidence obtained in this series of studies has guided the logic behind the development of a novel composite dsDNA-based preparation whose therapeutic application according to the specific regimen completely cures the mice engrafted with otherwise lethal Krebs-2 ascites. The likely mechan...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2016-12-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/821 |
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| author | E. A. Potter E. V. Dolgova A. S. Proskurina Ya. R. Efremov O. S. Taranov V. P. Nikolin N. A. Popova T. D. Dubatolova D. D. Petrova E. I. Vereschagin A. M. Minkevich O. M. Andrushkevich S. I. Baiborodin V. A. Rogachev A. A. Ostanin E. R. Chernykh N. A. Kolchanov S. S. Bogachev |
| author_facet | E. A. Potter E. V. Dolgova A. S. Proskurina Ya. R. Efremov O. S. Taranov V. P. Nikolin N. A. Popova T. D. Dubatolova D. D. Petrova E. I. Vereschagin A. M. Minkevich O. M. Andrushkevich S. I. Baiborodin V. A. Rogachev A. A. Ostanin E. R. Chernykh N. A. Kolchanov S. S. Bogachev |
| author_sort | E. A. Potter |
| collection | DOAJ |
| description | Cumulative evidence obtained in this series of studies has guided the logic behind the development of a novel composite dsDNA-based preparation whose therapeutic application according to the specific regimen completely cures the mice engrafted with otherwise lethal Krebs-2 ascites. The likely mechanism involves elimination of TAMRA+ tumor-inducing stem cells (TISCs) from Krebs-2 tumors. We performed quantitative analysis of TISC dynamics in Krebs-2 ascites following treatment with the cytostatic drug cyclophosphamide (CP) and untreated control cells. In intact ascites, TISC percentage oscillates around a certain value. Following CP treatment and massive apoptosis of committed cancer cell subpopulation, we observed relative increase in TISC percentage, which is consistent with reduced susceptibility of TISCs to CP. Nonetheless, this treatment apparently synchronizes TISCs in a cell cycle phase when they become sensitive to further drug treatments. We describe the regimen of synergistic DNA + CP activity against Krebs-2 ascites. This protocol results in a complete cure of 50 % of Krebs-2 engrafted mice and involves three metronomic injections of CP exactly at the timepoints when repair cycles are about to finish combined with dsDNA injections 18 hours following each CP injection. The “final shot” uses CP + DNA treatment, which targets the surviving yet highly synchronized and therefore treatmentsensitive cells. The first three CP/DNA injections appear to arrest Krebs-2 cells in late S-G2-M phase and result in their simultaneous progression into G1-S phase. The timing of the “final shot” is crucial for the successful treatment, which eradicates tumorigenic cell subpopulation from Krebs-2 ascites. Additionally, we quantified the changes in several biochemical, cellular and morphopathological parameters in mice throughout different treatment stages. |
| format | Article |
| id | doaj-art-e7fd54bf5cf44d82ae8553d602bbce45 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2016-12-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-e7fd54bf5cf44d82ae8553d602bbce452025-02-01T09:58:03ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592016-12-0120572373510.18699/VJ16.162536Development of the therapeutic regimen based on the synergistic activity of cyclophosphamide and double-stranded DNA preparation which results in complete cure of mice engrafted with Krebs-2 ascitesE. A. Potter0E. V. Dolgova1A. S. Proskurina2Ya. R. Efremov3O. S. Taranov4V. P. Nikolin5N. A. Popova6T. D. Dubatolova7D. D. Petrova8E. I. Vereschagin9A. M. Minkevich10O. M. Andrushkevich11S. I. Baiborodin12V. A. Rogachev13A. A. Ostanin14E. R. Chernykh15N. A. Kolchanov16S. S. Bogachev17Institute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RAS Novosibirsk State UniversityThe State Research Center of Virology and Biotechnology “Vector”Institute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RAS Novosibirsk State UniversityInstitute of Molecular and Cellular BiologyThe Specialized Educational Scientific Center at Novosibirsk State UniversityNovosibirsk State Medical AcademyInstitute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RAS Novosibirsk State UniversityInstitute of Cytology and Genetics SB RAS Novosibirsk State UniversityInstitute of Cytology and Genetics SB RASInstitute of Clinical Immunology, SB RAMSInstitute of Clinical Immunology, SB RAMSInstitute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RASCumulative evidence obtained in this series of studies has guided the logic behind the development of a novel composite dsDNA-based preparation whose therapeutic application according to the specific regimen completely cures the mice engrafted with otherwise lethal Krebs-2 ascites. The likely mechanism involves elimination of TAMRA+ tumor-inducing stem cells (TISCs) from Krebs-2 tumors. We performed quantitative analysis of TISC dynamics in Krebs-2 ascites following treatment with the cytostatic drug cyclophosphamide (CP) and untreated control cells. In intact ascites, TISC percentage oscillates around a certain value. Following CP treatment and massive apoptosis of committed cancer cell subpopulation, we observed relative increase in TISC percentage, which is consistent with reduced susceptibility of TISCs to CP. Nonetheless, this treatment apparently synchronizes TISCs in a cell cycle phase when they become sensitive to further drug treatments. We describe the regimen of synergistic DNA + CP activity against Krebs-2 ascites. This protocol results in a complete cure of 50 % of Krebs-2 engrafted mice and involves three metronomic injections of CP exactly at the timepoints when repair cycles are about to finish combined with dsDNA injections 18 hours following each CP injection. The “final shot” uses CP + DNA treatment, which targets the surviving yet highly synchronized and therefore treatmentsensitive cells. The first three CP/DNA injections appear to arrest Krebs-2 cells in late S-G2-M phase and result in their simultaneous progression into G1-S phase. The timing of the “final shot” is crucial for the successful treatment, which eradicates tumorigenic cell subpopulation from Krebs-2 ascites. Additionally, we quantified the changes in several biochemical, cellular and morphopathological parameters in mice throughout different treatment stages.https://vavilov.elpub.ru/jour/article/view/821double-stranded dnacyclophosphamidekrebs-2 ascitestumor-initiating stem cellsrepairremissionnerhomologous recombinationsystemic inflammatory reactionmultiple organ failure |
| spellingShingle | E. A. Potter E. V. Dolgova A. S. Proskurina Ya. R. Efremov O. S. Taranov V. P. Nikolin N. A. Popova T. D. Dubatolova D. D. Petrova E. I. Vereschagin A. M. Minkevich O. M. Andrushkevich S. I. Baiborodin V. A. Rogachev A. A. Ostanin E. R. Chernykh N. A. Kolchanov S. S. Bogachev Development of the therapeutic regimen based on the synergistic activity of cyclophosphamide and double-stranded DNA preparation which results in complete cure of mice engrafted with Krebs-2 ascites Вавиловский журнал генетики и селекции double-stranded dna cyclophosphamide krebs-2 ascites tumor-initiating stem cells repair remission ner homologous recombination systemic inflammatory reaction multiple organ failure |
| title | Development of the therapeutic regimen based on the synergistic activity of cyclophosphamide and double-stranded DNA preparation which results in complete cure of mice engrafted with Krebs-2 ascites |
| title_full | Development of the therapeutic regimen based on the synergistic activity of cyclophosphamide and double-stranded DNA preparation which results in complete cure of mice engrafted with Krebs-2 ascites |
| title_fullStr | Development of the therapeutic regimen based on the synergistic activity of cyclophosphamide and double-stranded DNA preparation which results in complete cure of mice engrafted with Krebs-2 ascites |
| title_full_unstemmed | Development of the therapeutic regimen based on the synergistic activity of cyclophosphamide and double-stranded DNA preparation which results in complete cure of mice engrafted with Krebs-2 ascites |
| title_short | Development of the therapeutic regimen based on the synergistic activity of cyclophosphamide and double-stranded DNA preparation which results in complete cure of mice engrafted with Krebs-2 ascites |
| title_sort | development of the therapeutic regimen based on the synergistic activity of cyclophosphamide and double stranded dna preparation which results in complete cure of mice engrafted with krebs 2 ascites |
| topic | double-stranded dna cyclophosphamide krebs-2 ascites tumor-initiating stem cells repair remission ner homologous recombination systemic inflammatory reaction multiple organ failure |
| url | https://vavilov.elpub.ru/jour/article/view/821 |
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