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.

作者简介

E. Koldysheva

Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine

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俄罗斯联邦, Novosibirsk

A. Men’shchikova

Novosibirsk National Research State University

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俄罗斯联邦, Novosibirsk

E. Lushnikova

Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational Medicine

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俄罗斯联邦, Novosibirsk

N. Popova

Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences; Novosibirsk National Research State University

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俄罗斯联邦, Novosibirsk; Novosibirsk

V. Kaledin

Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences

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俄罗斯联邦, Novosibirsk

V. Nikolin

Federal Research Center Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences

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俄罗斯联邦, Novosibirsk

A. Zakharenko

Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences

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俄罗斯联邦, Novosibirsk

O. Luzina

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

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俄罗斯联邦, Novosibirsk

N. Salakhutdinov

N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of the Russian Academy of Sciences; Novosibirsk National Research State University

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俄罗斯联邦, Novosibirsk; Novosibirsk

O. Lavrik

Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences; Novosibirsk National Research State University

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俄罗斯联邦, Novosibirsk; Novosibirsk


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