Eradication of Krebs-2 primary ascites via a single-injection regimen of cyclophosphamide and double-stranded DNA

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...

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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:
double-stranded dna
cyclophosphamide
krebs-2 ascites
tumor-initiating cancer stem cells
repair
remission
ner
homologous recombination
systemic inflammatory reaction
multiple organ failure
Online Access:https://vavilov.elpub.ru/jour/article/view/820
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Summary: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.
ISSN:2500-3259

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