Original experimental model of tuberculosis and lung cancer

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Abstract

BACKGROUND: The potential relationship between pulmonary tuberculosis and lung cancer has been the subject of intense interest over the past few decades. Nevertheless, the features of the pathogenesis of concomitant pathology remain poorly studied.

AIM: The ain of the study to develop an experimental model of the concomitant pathology of tuberculosis and lung cancer.

MATERIALS AND METHODS: The study was performed on mice of the C57BL/6 line at the age of two months in four groups: 1st — intact mice (n = 12), 2nd — mice without a tumor infected with tuberculosis (n = 24), 3rd — tumor-bearing mice not infected with tuberculosis (n = 23), 4th — tumor-bearing mice infected with tuberculosis (n = 24). Individual and group parameters were evaluated using the SPSS Statistica v23 software package.

RESULTS: Tumor was developed at the site of primary transplantation in all mice from groups 3 and 4, which was confirmed by visual assessment and the results of histological examination. Tumor growth in the main group was significantly less than in the control group of the tumor, which may be due to intoxication against the background of tuberculosis infection. All infected mice from groups 2 and 4 developed pulmonary tuberculosis, confirmed by computed tomography of the lungs, bacteriological and histological examination of lung samples. Mycobacterial load in the lungs was the highest in animals with concomitant pathology of tuberculosis and tumor. The survival rate of mice was determined to a large extent by tumor growth rather than by the progression of tuberculosis infection.

CONCLUSIONS: The results of the study indicate the possibility of creating an experimental biological model of the concomitant pathology of tuberculosis and lung cancer in mice. The features of the course of the concomitant pathology were revealed: Lewis lung epidermoid carcinoma develops more slowly in tuberculosis infected animals than in the tumor control group; the development of the tuberculosis process in mice with a tumor occurs more intensively than in the tuberculosis infection control group. The survival rate of mice with concomitant pathology is determined more by the intensity of tumor growth than by the progression of tuberculosis.

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About the authors

Grigorii G. Kudriashov

St. Petersburg Research Institute of Phthisiopulmonology

Author for correspondence.
Email: dr.kudriashov.gg@yandex.com

MD, PhD, Senior Research Associate, Thoracic Surgery Center

Russian Federation, Saint Petersburg

Andrey O. Nefedov

St. Petersburg Research Institute of Phthisiopulmonology

Email: herurg78@mail.ru

MD, PhD, Senior Research Associate, Thoracic Surgery Center

Russian Federation, Saint Petersburg

Grigorii V. Tochilnikov

N.N. Petrov Oncology Research Institute

Email: gr75@mail.ru

MD, PhD, Head of the Scientific Laboratory of Cancer Chemoprophylaxis and Oncopharmacology

Russian Federation, Saint Petersburg

Yuliya G. Zmitrichenko

N.N. Petrov Oncology Research Institute

Email: zmitrichenko@gmail.com

Junior Research Associate, Scientific Laboratory of Cancer Chemoprophylaxis and Oncopharmacology

Russian Federation, Saint Petersburg

Yuliya S. Krylova

St. Petersburg Research Institute of Phthisiopulmonology

Email: emerald2008@mail.ru

MD, PhD, Senior Research Associate, Center for Molecular Biomedicine

Russian Federation, Saint Petersburg

Marine Z. Dogonadze

St. Petersburg Research Institute of Phthisiopulmonology

Email: marine-md@mail.ru

MD, PhD, Senior Research Associate

Russian Federation, Saint Petersburg

Nataliya V. Zabolotnyh

St. Petersburg Research Institute of Phthisiopulmonology

Email: info@spbniif.ru

MD, PhD, Dr. Sci. (Med.), Leading Research Associate

Russian Federation, Saint Petersburg

Marina E. Dyakova

St. Petersburg Research Institute of Phthisiopulmonology

Email: info@spbniif.ru

MD, PhD, Senior Research Associate

Russian Federation, Saint Petersburg

Dilyara S. Esmerdyaeva

St. Petersburg Research Institute of Phthisiopulmonology

Email: info@spbniif.ru

MD, PhD, Senior Research Associate

Russian Federation, Saint Petersburg

Maria L. Vitovskaya

St. Petersburg Research Institute of Phthisiopulmonology

Email: mariavit72@mail.ru

MD, PhD, Senior Research Associate

Russian Federation, Saint Petersburg

Pavel V. Gavrilov

St. Petersburg Research Institute of Phthisiopulmonology

Email: spbniifrentgen@mail.ru

MD, PhD, Leading Research Associate

Russian Federation, Saint Petersburg

Artem A. Azarov

St. Petersburg Research Institute of Phthisiopulmonology

Email: azardoc0@gmail.com

Postgraduate Student

Russian Federation, Saint Petersburg

Vyacheslav Yu. Zhuravlev

St. Petersburg Research Institute of Phthisiopulmonology

Email: vy.zhuravlev@spbniif.ru

MD, PhD, Leading Research Associate

Russian Federation, Saint Petersburg

Tatyana I. Vinogradova

St. Petersburg Research Institute of Phthisiopulmonology

Email: ti.vinogradova@spbniif.ru

MD, PhD, Dr. Sci. (Med.), Project Leader

Russian Federation, Saint Petersburg

Piotr K. Yablonskii

St. Petersburg Research Institute of Phthisiopulmonology

Email: piotr_yablonskii@mail.ru

MD, PhD, Dr. Sci. (Med.), Director

Russian Federation, Saint Petersburg

References

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Dynamics of body weight of mice in the study groups. TB — tuberculosis

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3. Fig. 2. Computed tomograms of the mice lungs: a — the lungs of an intact animal (group 1), b — tuberculous infiltration in the upper third of the right lung (group 2), c — metastatic focus in the lower third of the left lung (group 3), d — subtotal infiltration in the lungs of a mouse (group 4)

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4. Fig. 3. Histological examination of the tumor node of a tumor-bearing mice not infected with TB (×200, Hematoxylin and eosin): a — the femur; b — the soft tissue of the thigh. The arrow shows tumor structures, the asterisk marks the bone marrow cavity

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5. Fig. 4. Histological examination of lung tissue of tumor-bearing mice infected with TB (×200, Hematoxylin and eosin): a — tumor metastasis to the lung; b — site of productive pneumonia; c — fuchsin-positive rods in macrophages (indicated by the arrows, ×600, Zil – Nielsen)

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6. Fig. 5. Dynamics of mycobacterial load (CFU per lung mass) in tumor-bearing mice infected with TB and mice without a tumor infected with TB. When comparing groups of animals using the Mann–Whitney criterion on the 14th, 21st and 28th days of the experiment, the significance level was equal to р = 0.522, р = 0.004 and р = 0.011, respectively

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7. Fig. 6. Survival rate of C57BL/6 mice in four study groups. TB — tuberculosis

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