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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.

SUBMITTER: Potter EA

PROVIDER: S-EPMC4905495 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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A strategy to eradicate well-developed Krebs-2 ascites in mice.

Potter Ekaterina A EA Dolgova Evgenia V EV Proskurina Anastasia S AS Minkevich Alexandra M AM Efremov Yaroslav R YR Taranov Oleg S OS Omigov Vladimir V VV Nikolin Valeriy P VP Popova Nelly A NA Bayborodin Sergey I SI Ostanin Alexander A AA Chernykh Elena R ER Kolchanov Nikolay A NA Shurdov Mikhail A MA Bogachev Sergey S SS

Oncotarget 20160301 10

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 leadin ...[more]

PMID: 26872383

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Project description:BackgroundThe socioeconomic inequalities in child health continue to widen despite improved economy.ObjectiveTo investigate the correlation between socio-economic factors and health risk behaviors and psychosocial well-being of children in Hong Kong.HypothesisThe null hypothesis is that for this particular developed region, there exists little or no correlation between social-economic factors and health risk behaviors and psychosocial well-being of children.DesignCross sectional territory wide survey.ParticipantsCaregivers of 7,000 children in kindergartens in Hong Kong.Measuring toolsYouth Risk Behavior Surveillance questionnaire, health-related knowledge and hygienic practice questionnaire, and Children Behavior Checklist (CBCL).ResultsChildren were less likely to have somatic complaints and anxiety/depression as reflected by CBCL scores coming from families of higher income, not being recipients of social assistance, with fathers in employment, and with higher parental education. Children with only mother or father as caretakers had lower odds ratios (ORs) 0.71 (95% CI 0.58-0.89) and 0.53 (95% CI 0.33-0.84) respectively to have the habit of eating breakfast, whilst parental education at post-secondary level and higher family income had higher ORs 1.91 (95% CI 1.31-2.78), and 1.63 (95% CI 1.11-2.39). Fathers unemployed, relatives as main caretakers and living in districts with low median household inome incurred higher ORs, as 1.46 (95% CI 1.10-1.94),1.52 (95% CI 1.27-1.83) and 1.17 (95% CI 1.02-1.34) respectively, of watching television over two hours daily, whilst children with parental education at secondary level or above incurred lower OR 0.33 (95% CI 0.24-0.45). Children with parental education at post-secondary level and higher family income had lower ORs of 0.32 (95% CI 0.48-0.97) and 0.52 (95% CI 0.34-0.79) respectively, with regard to exposing to passive smoking, and reversed for those living in districts with lower median household income, lower family income and recipient of CSSA with ORs 1.24 (95% CI 1.06-1.44) and 1.6 (95% CI 1.09-2.37) respectively.ConclusionNull hypothesis was not supported. A strong gradient was still found to exist among different socio-economic groups for various health-related behaviors in developed society like Hong Kong.

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A strategy to eradicate well-developed Krebs-2 ascites in mice.

Publications

A strategy to eradicate well-developed Krebs-2 ascites in mice.

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