Efficacy of a new cancer treatment strategy based on eradication of tumor-initiating stem cells in a mouse model of Krebs-2 solid adenocarcinoma
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Ekaterina A. Potter1,*, Anastasia S. Proskurina1,*, Genrikh S. Ritter1,2, Evgenia V. Dolgova1, Valeriy P. Nikolin1, Nelly A. Popova1,2, Oleg S. Taranov3, Yaroslav R. Efremov1,2, Sergey I. Bayborodin1, Aleksandr A. Ostanin4, Elena R. Chernykh4, Nikolay A. Kolchanov1 and Sergey S. Bogachev1
1Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2Novosibirsk State University, Novosibirsk, Russia
3State Research Center of Virology and Biotechnology “Vector”, Koltsovo, Novosibirsk, Russia
4Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
*These authors have contributed equally to this work
Anastasia S. Proskurina, email: [email protected]
Keywords: DNA internalization; synchronization; cyclophosphamide; seasonal cyclicity; repair cycle
Abbreviations: TISCs, tumor initiating stem cells; ICLs, interstrand cross-links; CP, cyclophosphamide
Received: November 01, 2017 Accepted: May 14, 2018 Published: June 19, 2018
Krebs-2 solid carcinoma was cured using a new “3+1” strategy for eradication of Krebs-2 tumor-initiating stem cells. This strategy was based on synchronization of these cells in a treatment-sensitive phase of the cell cycle. The synchronization mechanism, subsequent destruction of Krebs-2 tumor-initiating stem cells, and cure of mice from a solid graft were found to depend on the temporal profile of the interstrand cross-link repair cycle. Also, the temporal profile of the Krebs-2 interstrand repair cycle was found to have a pronounced seasonal cyclicity at the place of experiments (Novosibirsk, Russia). As a result, the therapeutic effect that is based on application of the described strategy, originally developed for the “winter repair cycle” (November−April), is completely eliminated in the summer period (June−September). We conclude that one of the possible and the likeliest reasons for our failure to observe the therapeutic effects was the seasonal cyclicity in the duration of the interstrand repair cycle, the parameter that is central to our strategy.
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