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A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation

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 a...

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Autores principales: Alyamkina, Ekaterina A, Nikolin, Valeriy P, Popova, Nelly A, Dolgova, Evgenia V, Proskurina, Anastasia S, Orishchenko, Konstantin E, Efremov, Yaroslav R, Chernykh, Elena R, Ostanin, Alexandr A, Sidorov, Sergey V, Ponomarenko, Dmitriy M, Zagrebelniy, Stanislav N, Bogachev, Sergey S, Shurdov, Mikhail A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987767/
https://www.ncbi.nlm.nih.gov/pubmed/21040569
http://dx.doi.org/10.1186/1479-0556-8-7
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author Alyamkina, Ekaterina A
Nikolin, Valeriy P
Popova, Nelly A
Dolgova, Evgenia V
Proskurina, Anastasia S
Orishchenko, Konstantin E
Efremov, Yaroslav R
Chernykh, Elena R
Ostanin, Alexandr A
Sidorov, Sergey V
Ponomarenko, Dmitriy M
Zagrebelniy, Stanislav N
Bogachev, Sergey S
Shurdov, Mikhail A
author_facet Alyamkina, Ekaterina A
Nikolin, Valeriy P
Popova, Nelly A
Dolgova, Evgenia V
Proskurina, Anastasia S
Orishchenko, Konstantin E
Efremov, Yaroslav R
Chernykh, Elena R
Ostanin, Alexandr A
Sidorov, Sergey V
Ponomarenko, Dmitriy M
Zagrebelniy, Stanislav N
Bogachev, Sergey S
Shurdov, Mikhail A
author_sort Alyamkina, Ekaterina A
collection PubMed
description 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 × 10(5 )tumor 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 DCs in 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.
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spelling pubmed-29877672010-11-23 A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation Alyamkina, Ekaterina A Nikolin, Valeriy P Popova, Nelly A Dolgova, Evgenia V Proskurina, Anastasia S Orishchenko, Konstantin E Efremov, Yaroslav R Chernykh, Elena R Ostanin, Alexandr A Sidorov, Sergey V Ponomarenko, Dmitriy M Zagrebelniy, Stanislav N Bogachev, Sergey S Shurdov, Mikhail A Genet Vaccines Ther Research 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 × 10(5 )tumor 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 DCs in 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. BioMed Central 2010-11-01 /pmc/articles/PMC2987767/ /pubmed/21040569 http://dx.doi.org/10.1186/1479-0556-8-7 Text en Copyright ©2010 Alyamkina et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Alyamkina, Ekaterina A
Nikolin, Valeriy P
Popova, Nelly A
Dolgova, Evgenia V
Proskurina, Anastasia S
Orishchenko, Konstantin E
Efremov, Yaroslav R
Chernykh, Elena R
Ostanin, Alexandr A
Sidorov, Sergey V
Ponomarenko, Dmitriy M
Zagrebelniy, Stanislav N
Bogachev, Sergey S
Shurdov, Mikhail A
A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation
title A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation
title_full A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation
title_fullStr A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation
title_full_unstemmed A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation
title_short A strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded DNA preparation
title_sort strategy of tumor treatment in mice with doxorubicin-cyclophosphamide combination based on dendritic cell activation by human double-stranded dna preparation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987767/
https://www.ncbi.nlm.nih.gov/pubmed/21040569
http://dx.doi.org/10.1186/1479-0556-8-7
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