Therapeutic effects of cyclophosphamide, dsDNA preparations and combinations thereof against Krebs-2 ascites cancer cells and various cancer transplants
Existence of a small subset of cancer cells referred to as tumor initiating stem cells (TISCs) largely responsible for tumor progression and resistance to chemotherapeutic cytostatic drugs reperesent an important recent paradigm shift. The present work is the first report in the series of papers fro...
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| Format: | Article |
| Language: | English |
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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
2016-03-01
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| Series: | Вавиловский журнал генетики и селекции |
| Subjects: | |
| Online Access: | https://vavilov.elpub.ru/jour/article/view/467 |
| _version_ | 1826550260408778752 |
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| author | E. A. Potter E. V. Dolgova A. M. Minkevich Ya. R. Efremov O. S. Taranov V. V. Omigov V. P. Nikolin N. A. Popova A. S. Proskurina E. I. Vereschagin A. V. Kozel V. A. Rogachev D. B. Petrov A. A. Ostanin E. R. Chernykh N. A. Kolchanov S. S. Bogachev |
| author_facet | E. A. Potter E. V. Dolgova A. M. Minkevich Ya. R. Efremov O. S. Taranov V. V. Omigov V. P. Nikolin N. A. Popova A. S. Proskurina E. I. Vereschagin A. V. Kozel V. A. Rogachev D. B. Petrov A. A. Ostanin E. R. Chernykh N. A. Kolchanov S. S. Bogachev |
| author_sort | E. A. Potter |
| collection | DOAJ |
| description | Existence of a small subset of cancer cells referred to as tumor initiating stem cells (TISCs) largely responsible for tumor progression and resistance to chemotherapeutic cytostatic drugs reperesent an important recent paradigm shift. The present work is the first report in the series of papers from our group where we describe the development of anticancer therapy based on the selective targeting of TISCs. Here were characterize a cytoreductive activity of cyclophosphamide (CP), double-stranded DNA (dsDNA) and combinations thereof against the TISC population present in mouse Krebs-2 ascites. We evaluated engraftment potential of Krebs-2 cancer cells treated in ascites-bearing mice in vivo, followed by re-engraftment to congenic recipient mice in a form of a solid graft. These data indicate that with our approach TISCs can be completely eliminated even from a well-established ascites. We demonstrate that dsDNA-internalizing and CD34-positive cells are more sensitive to the synergistic effects of CP and dsDNA. When Krebs-2 ascites are treated with human DNA 1-12 hours post CP injection, this results in either elimination of cells that internalize TAMRA-labeled DNA (TISCs) or alters their phenotype, which is accompanied with the loss of surface expression of CD34. Next, we show that the timepoint 18 hrs post CP treatment is critical to the ongoing repair process in that it divides the repair into two phases: nucleotide excision repair + dsDNA break repair and homologous recombination. Importantly, both of these phases can be conveniently used for targeting the tumorigenic potential of the graft. In the context of monotherapy, CP is most effective against ascites grafts when administered as serial injections. To achieve maximum efficiency, the timing of consecutive injections must match the time when cancer cells found at G2/M during the first injection enter G1/S and/or the time of active repair via homologous recombination. |
| first_indexed | 2024-03-07T16:06:52Z |
| format | Article |
| id | doaj.art-286909d4625d482ead65a231e57499c6 |
| institution | Directory Open Access Journal |
| issn | 2500-3259 |
| language | English |
| last_indexed | 2025-03-14T06:34:30Z |
| publishDate | 2016-03-01 |
| 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-286909d4625d482ead65a231e57499c62025-03-05T07:59:21ZengSiberian 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 селекции2500-32592016-03-012019610710.18699/VJ15.116450Therapeutic effects of cyclophosphamide, dsDNA preparations and combinations thereof against Krebs-2 ascites cancer cells and various cancer transplantsE. A. Potter0E. V. Dolgova1A. M. Minkevich2Ya. R. Efremov3O. S. Taranov4V. V. Omigov5V. P. Nikolin6N. A. Popova7A. S. Proskurina8E. I. Vereschagin9A. V. Kozel10V. A. Rogachev11D. B. Petrov12A. A. Ostanin13E. R. Chernykh14N. A. Kolchanov15S. S. Bogachev16Institute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, Russia Novosibirsk State University, Novosibirsk, RussiaThe State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, RussiaThe State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk region, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, Russia Novosibirsk State University, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaNovosibirsk State Medical Academy, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, Russia Novosibirsk State University, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaLLC «Тermorobot» Novosibirsk, RussiaInstitute of Clinical Immunology, SB RAMS, Novosibirsk, RussiaInstitute of Clinical Immunology, SB RAMS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaExistence of a small subset of cancer cells referred to as tumor initiating stem cells (TISCs) largely responsible for tumor progression and resistance to chemotherapeutic cytostatic drugs reperesent an important recent paradigm shift. The present work is the first report in the series of papers from our group where we describe the development of anticancer therapy based on the selective targeting of TISCs. Here were characterize a cytoreductive activity of cyclophosphamide (CP), double-stranded DNA (dsDNA) and combinations thereof against the TISC population present in mouse Krebs-2 ascites. We evaluated engraftment potential of Krebs-2 cancer cells treated in ascites-bearing mice in vivo, followed by re-engraftment to congenic recipient mice in a form of a solid graft. These data indicate that with our approach TISCs can be completely eliminated even from a well-established ascites. We demonstrate that dsDNA-internalizing and CD34-positive cells are more sensitive to the synergistic effects of CP and dsDNA. When Krebs-2 ascites are treated with human DNA 1-12 hours post CP injection, this results in either elimination of cells that internalize TAMRA-labeled DNA (TISCs) or alters their phenotype, which is accompanied with the loss of surface expression of CD34. Next, we show that the timepoint 18 hrs post CP treatment is critical to the ongoing repair process in that it divides the repair into two phases: nucleotide excision repair + dsDNA break repair and homologous recombination. Importantly, both of these phases can be conveniently used for targeting the tumorigenic potential of the graft. In the context of monotherapy, CP is most effective against ascites grafts when administered as serial injections. To achieve maximum efficiency, the timing of consecutive injections must match the time when cancer cells found at G2/M during the first injection enter G1/S and/or the time of active repair via homologous recombination.https://vavilov.elpub.ru/jour/article/view/467double-stranded dnacyclophosphamidekrebs-2 ascitestumor-initiating cancer stem cellsnerhomologous recombinationengraftment potential |
| spellingShingle | E. A. Potter E. V. Dolgova A. M. Minkevich Ya. R. Efremov O. S. Taranov V. V. Omigov V. P. Nikolin N. A. Popova A. S. Proskurina E. I. Vereschagin A. V. Kozel V. A. Rogachev D. B. Petrov A. A. Ostanin E. R. Chernykh N. A. Kolchanov S. S. Bogachev Therapeutic effects of cyclophosphamide, dsDNA preparations and combinations thereof against Krebs-2 ascites cancer cells and various cancer transplants Вавиловский журнал генетики и селекции double-stranded dna cyclophosphamide krebs-2 ascites tumor-initiating cancer stem cells ner homologous recombination engraftment potential |
| title | Therapeutic effects of cyclophosphamide, dsDNA preparations and combinations thereof against Krebs-2 ascites cancer cells and various cancer transplants |
| title_full | Therapeutic effects of cyclophosphamide, dsDNA preparations and combinations thereof against Krebs-2 ascites cancer cells and various cancer transplants |
| title_fullStr | Therapeutic effects of cyclophosphamide, dsDNA preparations and combinations thereof against Krebs-2 ascites cancer cells and various cancer transplants |
| title_full_unstemmed | Therapeutic effects of cyclophosphamide, dsDNA preparations and combinations thereof against Krebs-2 ascites cancer cells and various cancer transplants |
| title_short | Therapeutic effects of cyclophosphamide, dsDNA preparations and combinations thereof against Krebs-2 ascites cancer cells and various cancer transplants |
| title_sort | therapeutic effects of cyclophosphamide dsdna preparations and combinations thereof against krebs 2 ascites cancer cells and various cancer transplants |
| topic | double-stranded dna cyclophosphamide krebs-2 ascites tumor-initiating cancer stem cells ner homologous recombination engraftment potential |
| url | https://vavilov.elpub.ru/jour/article/view/467 |
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