Eradication of Krebs-2 primary ascites via a single-injection regimen of cyclophosphamide and double-stranded DNA
Previously, we reported on the development of a therapeutic regimen allowing eradication of primary murine Krebs-2 ascites transplants. This protocol involved multiple injections of dsDNA preparations administered during the NER and HR phases of repair of interstrand DNA cross-links induced by prior...
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
2016-12-01
|
Series: | Вавиловский журнал генетики и селекции |
Subjects: | |
Online Access: | https://vavilov.elpub.ru/jour/article/view/820 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1832575236587913216 |
---|---|
author | E. A. Potter E. V. Dolgova A. M. Minkevich V. P. Nikolin N. A. Popova Ya. R. Efremov S. I. Baiborodin V. A. Rogachev A. S. Proskurina O. S. Taranov E. I. Vereschagin A. A. Ostanin E. R. Chernykh N. A. Kolchanov S. S. Bogachev |
author_facet | E. A. Potter E. V. Dolgova A. M. Minkevich V. P. Nikolin N. A. Popova Ya. R. Efremov S. I. Baiborodin V. A. Rogachev A. S. Proskurina O. S. Taranov E. I. Vereschagin A. A. Ostanin E. R. Chernykh N. A. Kolchanov S. S. Bogachev |
author_sort | E. A. Potter |
collection | DOAJ |
description | Previously, we reported on the development of a therapeutic regimen allowing eradication of primary murine Krebs-2 ascites transplants. This protocol involved multiple injections of dsDNA preparations administered during the NER and HR phases of repair of interstrand DNA cross-links induced by prior cyclophosphamide treatments. Mice treated under this protocol frequently developed secondary ascites, which indicated that some tumor-inducing cancer stem cells could survive the treatment and caused relapse. Further, we observed that animals receiving multiple dsDNA injections developed pronounced systemic inflammatory response. This prompted us to develop a more straightforward treatment regimen based on the synergistic activity of cyclophosphamide and dsDNA preparations, which would allow complete eradication of established primary Krebs-2 ascites and also be less toxic for the treated animals. This protocol relies on a precisely timed single injection of dsDNA during the NER/HR transition period of each repair cycle. Under this protocol, 8-day remission of Krebs-2 engrafted mice was achieved, which was similar to the results of the multiple-injection treatment schedule. We observed an increase in the average life span of Krebs-2- transplanted mice on a single-injection regimen, which was consistent with reduced toxicity of such treatment. |
format | Article |
id | doaj-art-72e755fdce694cac9febfbc60bf7e694 |
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-72e755fdce694cac9febfbc60bf7e6942025-02-01T09:58:03ZengSiberian 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 селекции2500-32592016-12-0120571672210.18699/VJ16.161535Eradication of Krebs-2 primary ascites via a single-injection regimen of cyclophosphamide and double-stranded DNAE. A. Potter0E. V. Dolgova1A. M. Minkevich2V. P. Nikolin3N. A. Popova4Ya. R. Efremov5S. I. Baiborodin6V. A. Rogachev7A. S. Proskurina8O. S. Taranov9E. I. Vereschagin10A. A. Ostanin11E. R. Chernykh12N. A. Kolchanov13S. S. Bogachev14Institute of Cytology and Genetics SB RASInstitute 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 UniversityInstitute 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 Cytology and Genetics SB RASThe State Research Center of Virology and Biotechnology “Vector”Novosibirsk State Medical AcademyScientific Research Institute of Clinical Immunology, SB RAMSScientific Research Institute of Clinical Immunology, SB RAMSInstitute of Cytology and Genetics SB RASInstitute of Cytology and Genetics SB RASPreviously, we reported on the development of a therapeutic regimen allowing eradication of primary murine Krebs-2 ascites transplants. This protocol involved multiple injections of dsDNA preparations administered during the NER and HR phases of repair of interstrand DNA cross-links induced by prior cyclophosphamide treatments. Mice treated under this protocol frequently developed secondary ascites, which indicated that some tumor-inducing cancer stem cells could survive the treatment and caused relapse. Further, we observed that animals receiving multiple dsDNA injections developed pronounced systemic inflammatory response. This prompted us to develop a more straightforward treatment regimen based on the synergistic activity of cyclophosphamide and dsDNA preparations, which would allow complete eradication of established primary Krebs-2 ascites and also be less toxic for the treated animals. This protocol relies on a precisely timed single injection of dsDNA during the NER/HR transition period of each repair cycle. Under this protocol, 8-day remission of Krebs-2 engrafted mice was achieved, which was similar to the results of the multiple-injection treatment schedule. We observed an increase in the average life span of Krebs-2- transplanted mice on a single-injection regimen, which was consistent with reduced toxicity of such treatment.https://vavilov.elpub.ru/jour/article/view/820double-stranded dnacyclophosphamidekrebs-2 ascitestumor-initiating cancer stem cellsrepairremissionnerhomologous recombinationsystemic inflammatory reactionmultiple organ failure |
spellingShingle | E. A. Potter E. V. Dolgova A. M. Minkevich V. P. Nikolin N. A. Popova Ya. R. Efremov S. I. Baiborodin V. A. Rogachev A. S. Proskurina O. S. Taranov E. I. Vereschagin A. A. Ostanin E. R. Chernykh N. A. Kolchanov S. S. Bogachev Eradication of Krebs-2 primary ascites via a single-injection regimen of cyclophosphamide and double-stranded DNA Вавиловский журнал генетики и селекции double-stranded dna cyclophosphamide krebs-2 ascites tumor-initiating cancer stem cells repair remission ner homologous recombination systemic inflammatory reaction multiple organ failure |
title | Eradication of Krebs-2 primary ascites via a single-injection regimen of cyclophosphamide and double-stranded DNA |
title_full | Eradication of Krebs-2 primary ascites via a single-injection regimen of cyclophosphamide and double-stranded DNA |
title_fullStr | Eradication of Krebs-2 primary ascites via a single-injection regimen of cyclophosphamide and double-stranded DNA |
title_full_unstemmed | Eradication of Krebs-2 primary ascites via a single-injection regimen of cyclophosphamide and double-stranded DNA |
title_short | Eradication of Krebs-2 primary ascites via a single-injection regimen of cyclophosphamide and double-stranded DNA |
title_sort | eradication of krebs 2 primary ascites via a single injection regimen of cyclophosphamide and double stranded dna |
topic | double-stranded dna cyclophosphamide krebs-2 ascites tumor-initiating cancer stem cells repair remission ner homologous recombination systemic inflammatory reaction multiple organ failure |
url | https://vavilov.elpub.ru/jour/article/view/820 |
work_keys_str_mv | AT eapotter eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT evdolgova eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT amminkevich eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT vpnikolin eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT napopova eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT yarefremov eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT sibaiborodin eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT varogachev eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT asproskurina eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT ostaranov eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT eivereschagin eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT aaostanin eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT erchernykh eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT nakolchanov eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna AT ssbogachev eradicationofkrebs2primaryascitesviaasingleinjectionregimenofcyclophosphamideanddoublestrandeddna |