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Antimetastatic Activity of Combined Topotecan and Tyrosyl-DNA Phosphodiesterase-1 Inhibitor on Modeled Lewis Lung Carcinoma

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The antimetastatic activity of combined or individual administration of topotecan and tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitor was examined under various administration schedules in mice with Lewis lung carcinoma modeled by intravenous injection of 200,000 clone/mouse. The greatest antimetastatic effect was observed after combined use of topotecan and Tdp1 inhibitor as documented by macroscopic study of the lungs that revealed the decreased metastatic scores by 76, 91, or 74% at the respective inhibitor doses of 2, 4, or 6 mg/mouse, respectively, in parallel with inhibition of metastasis up to 98% (at inhibitor dose of 4 mg/mouse) and morphological and morphometric analyses of the lung sections, which revealed elevation of metastasis growth delay index to 86 and 63% at the respective inhibitor doses of 4 and 6 mg/mouse, respectively. The combined administration of topotecan and Tdp1 inhibitor is viewed as the most effective way to eliminate the metastatic formations with possible restitution of focal lesions.

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Authors and Affiliations

  1. Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia

    E. V. Koldysheva & E. L. Lushnikova

  2. Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia

    N. A. Popova, V. I. Kaledin & V. P. Nikolin

  3. Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia

    A. L. Zakharenko & O. I. Lavrik

  4. N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia

    O. A. Luzina & N. F. Salakhutdinov

  5. Novosibirsk National Research State University, Novosibirsk, Russia

    A. P. Men’shchikova, N. A. Popova, N. F. Salakhutdinov & O. I. Lavrik

Authors
  1. E. V. Koldysheva
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  2. A. P. Men’shchikova
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  3. E. L. Lushnikova
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  4. N. A. Popova
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  5. V. I. Kaledin
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  6. V. P. Nikolin
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  7. A. L. Zakharenko
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  8. O. A. Luzina
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  9. N. F. Salakhutdinov
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  10. O. I. Lavrik
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Correspondence to E. V. Koldysheva.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 166, No. 11, pp. 609-615, November, 2018

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Koldysheva, E.V., Men’shchikova, A.P., Lushnikova, E.L. et al. Antimetastatic Activity of Combined Topotecan and Tyrosyl-DNA Phosphodiesterase-1 Inhibitor on Modeled Lewis Lung Carcinoma. Bull Exp Biol Med 166, 661–666 (2019). https://doi.org/10.1007/s10517-019-04413-3

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  • DOI: https://doi.org/10.1007/s10517-019-04413-3

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