Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model
Primary cultures of human glioblastoma were obtained from the surgical material of patients K. (female, 61 years, Ds: relapse of glioblastoma) and Zh. (female, 60 years, Ds: relapse of glioblastoma). The effectiveness of a new therapeutic approach aimed at destroying the cancer cell community was ev...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2018-11-01
|
| Series: | Вавиловский журнал генетики и селекции |
| Subjects: | |
| Online Access: | https://vavilov.elpub.ru/jour/article/view/1717 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832575156517601280 |
|---|---|
| author | E. V. Dolgova A. S. Proskurina E. A. Potter T. V. Tyrinova O. S. Taranov Ya. R. Efremov K. E. Orishchenko S. V. Mishinov V. V. Stupak A. A. Ostanin E. R. Chernykh S. S. Bogachev |
| author_facet | E. V. Dolgova A. S. Proskurina E. A. Potter T. V. Tyrinova O. S. Taranov Ya. R. Efremov K. E. Orishchenko S. V. Mishinov V. V. Stupak A. A. Ostanin E. R. Chernykh S. S. Bogachev |
| author_sort | E. V. Dolgova |
| collection | DOAJ |
| description | Primary cultures of human glioblastoma were obtained from the surgical material of patients K. (female, 61 years, Ds: relapse of glioblastoma) and Zh. (female, 60 years, Ds: relapse of glioblastoma). The effectiveness of a new therapeutic approach aimed at destroying the cancer cell community was evaluated on the primary cell lines of human glioblastoma culture by employing a new strategy of tumor-initiating stem cell synchronization and a domestic strategy of their eradication "3+1". The key elements of the strategy were the following indicator results: (1) evaluation of the presence of tumor-initiating stem cells in a population of cells from analyzed cultures by their ability to internalize double-stranded labeled DNA (TAMRA+ cells); (2) determination of the reference time points of the repair cycle of DNA interstrand cross-links induced by cross-linking cytostatic mitomycin C; (3) evaluation of cell cycle synchronization; (4) determination of the time (day after therapy initiation) when TAMRA+ cells were synchronously present in phase G1/S of the cell cycle, sensitive to the therapy; and (5) establishment of the TAMRA+ (tumor-initiating stem cells) eradication schedule. The cultures were treated with cross-linking cytostatic mitomycin C and a compositional DNA preparation. After the treatments, cell division slows down, and the cultures degrade. The K cell line completely degraded within 30 days of observation. The cell number of the Zh culture fell to nearly one-third of the starting value by day 15 of observation. On day 15, this indicator constituted 1/7.45 for mitomycin C and 1/10.28 for mitomycin C + DNA with reference to the control. The main target of the mitomycin C + DNA regimen was TAMRA+ tumor-initiating stem cells of the glioblastoma cell populations. The action of mitomycin C alone or in the combination with DNA demonstrated effective elimination of TAMRA+ tumor-initiating stem cells and the whole primary cultures of human glioblastomas. |
| format | Article |
| id | doaj-art-5966fbcd74c54d00a4caf582f6992f90 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2018-11-01 |
| 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-5966fbcd74c54d00a4caf582f6992f902025-02-01T09:58:06ZengSiberian 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 селекции2500-32592018-11-0122782583610.18699/VJ18.31-o829Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a modelE. V. Dolgova0A. S. Proskurina1E. A. Potter2T. V. Tyrinova3O. S. Taranov4Ya. R. Efremov5K. E. Orishchenko6S. V. Mishinov7V. V. Stupak8A. A. Ostanin9E. R. Chernykh10S. S. Bogachev11Institute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RASInstitute of Fundamental and Clinical ImmunologyThe State Research Center of Virology and Biotechnology “Vector"Institute of Cytology and Genetics SB RAS; Novosibirsk State UniversityInstitute of Cytology and Genetics SB RASFirst Department of Neurosurgery, Y.L. Tsivian Novosibirsk Research Institute of Traumatology and OrthopaedicsFirst Department of Neurosurgery, Y.L. Tsivian Novosibirsk Research Institute of Traumatology and OrthopaedicsInstitute of Fundamental and Clinical ImmunologyInstitute of Fundamental and Clinical ImmunologyInstitute of Cytology and Genetics SB RASPrimary cultures of human glioblastoma were obtained from the surgical material of patients K. (female, 61 years, Ds: relapse of glioblastoma) and Zh. (female, 60 years, Ds: relapse of glioblastoma). The effectiveness of a new therapeutic approach aimed at destroying the cancer cell community was evaluated on the primary cell lines of human glioblastoma culture by employing a new strategy of tumor-initiating stem cell synchronization and a domestic strategy of their eradication "3+1". The key elements of the strategy were the following indicator results: (1) evaluation of the presence of tumor-initiating stem cells in a population of cells from analyzed cultures by their ability to internalize double-stranded labeled DNA (TAMRA+ cells); (2) determination of the reference time points of the repair cycle of DNA interstrand cross-links induced by cross-linking cytostatic mitomycin C; (3) evaluation of cell cycle synchronization; (4) determination of the time (day after therapy initiation) when TAMRA+ cells were synchronously present in phase G1/S of the cell cycle, sensitive to the therapy; and (5) establishment of the TAMRA+ (tumor-initiating stem cells) eradication schedule. The cultures were treated with cross-linking cytostatic mitomycin C and a compositional DNA preparation. After the treatments, cell division slows down, and the cultures degrade. The K cell line completely degraded within 30 days of observation. The cell number of the Zh culture fell to nearly one-third of the starting value by day 15 of observation. On day 15, this indicator constituted 1/7.45 for mitomycin C and 1/10.28 for mitomycin C + DNA with reference to the control. The main target of the mitomycin C + DNA regimen was TAMRA+ tumor-initiating stem cells of the glioblastoma cell populations. The action of mitomycin C alone or in the combination with DNA demonstrated effective elimination of TAMRA+ tumor-initiating stem cells and the whole primary cultures of human glioblastomas.https://vavilov.elpub.ru/jour/article/view/1717glioblastomaprimary cell linemytomycin ctumor-initiating stem cellstamra-fluorochrom |
| spellingShingle | E. V. Dolgova A. S. Proskurina E. A. Potter T. V. Tyrinova O. S. Taranov Ya. R. Efremov K. E. Orishchenko S. V. Mishinov V. V. Stupak A. A. Ostanin E. R. Chernykh S. S. Bogachev Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model Вавиловский журнал генетики и селекции glioblastoma primary cell line mytomycin c tumor-initiating stem cells tamra-fluorochrom |
| title | Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model |
| title_full | Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model |
| title_fullStr | Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model |
| title_full_unstemmed | Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model |
| title_short | Evaluation of a strategy for tumor-initiating stem cell eradication in primary human glioblastoma cultures as a model |
| title_sort | evaluation of a strategy for tumor initiating stem cell eradication in primary human glioblastoma cultures as a model |
| topic | glioblastoma primary cell line mytomycin c tumor-initiating stem cells tamra-fluorochrom |
| url | https://vavilov.elpub.ru/jour/article/view/1717 |
| work_keys_str_mv | AT evdolgova evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT asproskurina evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT eapotter evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT tvtyrinova evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT ostaranov evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT yarefremov evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT keorishchenko evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT svmishinov evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT vvstupak evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT aaostanin evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT erchernykh evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel AT ssbogachev evaluationofastrategyfortumorinitiatingstemcelleradicationinprimaryhumanglioblastomaculturesasamodel |