It has been established previously that up to 40% of mouse CD34+ hematopoietic stem cells are capable of internalizing exogenous dsDNA fragments both in vivo and ex vivo. Importantly, when mice are...

Background: Immunization of mice with tumor homogenate after combined treatment with cyclophosphamide (CP) and double-stranded DNA (dsDNA) preparation is effective at inhibition of growth of tumor challenged after the treatment. It was assumed that this inhibition might be due to activation of the antigen-presenting cells. The purpose was to develop improved antitumor strategy using mice. We studied the combined action of cytostatics doxorubicin (Dox) plus CP with subsequent dsDNA preparation on tumor growth.Methods: Three-month old CBA/Lac mice were used in the experiments. Mice were injected with CP and human dsDNA preparation. The percentage of mature dendritic cells (DCs) was estimated by staining of mononuclear cells isolated from spleen and bone marrow 3, 6, and 9 days later with monoclonal antibodies CD34, CD80, and CD86. In the next set of experiments, mice were given intramuscularly injections of 1-3 × 10⁵tumor cells. Four days later, they were injected intravenously with 6-6.7 mg/kg Dox and intraperitoneally with 100-200 mg/kg CP; 200 mkg human DNA was injected intraperitoneally after CP administration. Differences in tumor size between groups were analyzed for statistical significance by Student's t-test. The MTT-test was done to determine the cytotoxic index of mouse leucocytes from treated groups.Results: The conducted experiments showed that combined treatment with CP and dsDNA preparation produce an increase in the total amount of mature DCsin vivo. Treatment of tumor bearers with preparation of fragmented dsDNA on the background of pretreatment with Dox plus CP demonstrated a strong suppression of tumor growth in two models. RLS, a weakly immunogenic, resistant to alkalyting cytostatics tumor, grew 3.4-fold slower when compared with the control (p < 0.001). In experiment with Krebs-2 tumor, only 2 of the 10 mice in the Dox+CP+DNA group had a palpable tumor on day 16. The cytotoxic index of leucocytes was 86.5% in the Dox+CP+DNA group, but it was 0% in the Dox+CP group.Conclusions: Thus, the set of experiments we performed showed that exogenous dsDNA, when administered on the background of pretreatment with Dox plus CP, has an antitumor effect possibly due to DC activation.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Ekaterina A. Potter1, Evgenia V. Dolgova1, Anastasia S. Proskurina1, Alexandra M. Minkevich1, Yaroslav R. Efremov1, 2, Oleg S. Taranov3, Vladimir V. Omigov3, Valeriy P. Nikolin1, Nelly A. Popova1, 2, Sergey I. Bayborodin1, 2, Alexander A. Ostanin4, Elena R. Chernykh4, Nikolay A. Kolchanov1, Mikhail A. Shurdov5, Sergey S. Bogachev1 1Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia 2Department of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia 3The State Research Center of Virology and Biotechnology VECTOR, Novosibirsk 630559, Russia 4Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk 630099, Russia 5LLC Panagen, Gorno-Altaisk 649000, Russia Correspondence to: Sergey S. Bogachev, e-mail: labmolbiol@mail.ru Keywords: ascites Krebs-2, cyclophosphamide, extracellular dsDNA, tumor-initiating stem cells, repair Received: December 18, 2015 Accepted: January 26, 2016 Published: February 10, 2016

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Ekaterina A. Potter1, *, Evgenia V. Dolgova1, *, Anastasia S. Proskurina1, *, Yaroslav R. Efremov1, 2, Alexandra M. Minkevich1, Aleksey S. Rozanov1, Sergey E. Peltek1, Valeriy P. Nikolin1, Nelly A. Popova1, 2, Igor A. Seledtsov3, Vladimir V. Molodtsov2, 3, Evgeniy L Zavyalov1, Oleg S. Taranov4, Sergey I. Baiborodin1, Alexander A. Ostanin5, Elena R. Chernykh5, Nikolay A. Kolchanov1, Sergey S. Bogachev1 1Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia 2Novosibirsk State University, Novosibirsk 630090, Russia 3Softberry Inc., New York 10549, USA 4The State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk 630559, Russia 5Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, Russia *These authors contributed equally to this work Correspondence to: Sergey S. Bogachev, email: labmolbiol@mail.ru Keywords: tumor-initiating stem cells, DNA internalization, RNAseq, Real Time PCR, TAMRA Received: August 29, 2016 Accepted: December 15, 2016 Published: December 23, 2016