title: A strategy to eradicate well-developed Krebs-2 ascites in mice.
abstract: We describe the strategy, which allows curing experimental mice engrafted with Krebs-2 ascites. The strategy is based on the facts that i) Krebs-2 tumor-initiating stem cells (TISCs) are naturally capable of internalizing fragments of extracellular double-stranded DNA (dsDNA); ii) upon delivery into TISCs, these dsDNA fragments interfere with the on-going DNA repair process so that TISCs either die or lose their tumorigenic potential. The following 3-step regimen of therapeutic procedures leading to eradication of Krebs-2 ascites is considered. Firstly, three timed injections of cyclophosphamide (CP) exactly matching the interstrand cross-link (ICL) repair phases that lead to synchronization of ascites cells in late S/G2/M. Secondly, additional treatment of ascites 18 hours post each CP injection (at NER/HR transition timepoint) with a composite dsDNA-based preparation interfering with the NER and HR repair pathways, so that tumorigenic properties of ascites cells are compromised. Thirdly, final treatment of mice with a combination of CP and dsDNA injections as ascites cells undergo apoptotic destruction, and the surviving TAMRA+ TISCs arrested in late S/G2/M phases massively enter into G1/S, when they regain sensitivity to CP+dsDNA treatment. Thus, this regimen assures that no viable cells, particularly Krebs-2 TISCs, remain.
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Potter
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors.forename: Evgenia V
authors.initials: EV
authors.lastname: Dolgova
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors.forename: Anastasia S
authors.initials: AS
authors.lastname: Proskurina
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Minkevich
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.|Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.
authors.forename: Yaroslav R
authors.initials: YR
authors.lastname: Efremov
authors.affiliation: The State Research Center of Virology and Biotechnology VECTOR, Novosibirsk 630559, Russia.
authors.forename: Oleg S
authors.initials: OS
authors.lastname: Taranov
authors.affiliation: The State Research Center of Virology and Biotechnology VECTOR, Novosibirsk 630559, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Omigov
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors.forename: Valeriy P
authors.initials: VP
authors.lastname: Nikolin
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.|Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.
authors.forename: Nelly A
authors.initials: NA
authors.lastname: Popova
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.|Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia.
authors.forename: Sergey I
authors.initials: SI
authors.lastname: Bayborodin
authors.affiliation: Institute of Clinical Immunology, Siberian Branch of The Russian Academy of Medical Sciences, Novosibirsk 630099, Russia.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Ostanin
authors.affiliation: Institute of Clinical Immunology, Siberian Branch of The Russian Academy of Medical Sciences, Novosibirsk 630099, Russia.
authors.forename: Elena R
authors.initials: ER
authors.lastname: Chernykh
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Kolchanov
authors.affiliation: LLC Panagen, Gorno-Altaisk 649000, Russia.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Shurdov
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of The Russian Academy of Sciences, Novosibirsk 630090, Russia.
authors.forename: Sergey S
authors.initials: SS
authors.lastname: Bogachev
mesh_terms: D000818:Animals; D001201:Ascites / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002287:Carcinoma, Krebs 2 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D014162:Transfection
chemical_list: D003520:Cyclophosphamide; D004247:DNA
keywords: ascites Krebs-2; cyclophosphamide; extracellular dsDNA; repair; tumor-initiating stem cells