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...

Full description

Saved in:
Bibliographic Details
Main Authors: 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
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