Is the progression of tuberculosis possible against the background of antitumor therapy for lung cancer? Results of an experimental study

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Abstract

Aim of the study. The possibility of using antitumor drugs against the background of active tuberculosis is an unresolved problem of modern medicine. The aim of the experimental study was to study the course of tuberculosis infection against the background of antitumor therapy for lung cancer and combined antitumor and anti-tuberculosis chemotherapy.

Material and methods. The study was conducted on two-month-old C57BL/6 mice infected by intravenous injection of the reference strain Mycobacterium tuberculosis H37Rv. On the third day after infection, antitumor drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) and/or a combination of anti-tuberculosis and antitumor drugs were given out. There were 2 control groups (infection control and control of anti-tuberculosis therapy) and 14 experimental groups (in dependence of antitumor drugs of cisplatin, carboplatin, gemcitabine, pemetrexed, etoposide, paclitaxel and docetaxel). Clinical, laboratory, bacteriological, morphological and morphometric parameters, and mortality were evaluated. Nonparametric methods of medical statistics were used.

Results. The isolated use of cisplatin, etoposide and docetaxel led to an increase in the mortality of experimental animals compared with infection control. However, there were no differences in survival between the experimental and control groups in the groups of combined use of antitumor (ATT) and anti-tuberculosis (ATBT) drugs. The combination of ATBT and gemcitabine was accompanied by a significantly lower level of inflammatory response (decreased activity of ceruloplasmin). The maximum inflammatory response was recorded with a combination of ATBT and pemetrexed, which was expressed in an increase in the activity of elastase, transaminases and ADA-1. There was a decrease in the intensity of MTB reproduction in all groups of combined therapy when comparing ATT with a combination of ATT +ATBT. It should be noted that the complete elimination of MTB was achieved only with the combination of ATBT with gemcitabine and etoposide.

Conclusion. The combination of anti-tuberculosis therapy with antitumor drugs does not reliably lead to a fatal progression of the infectious process in the lungs and in some cases makes it possible to achieve complete suppression of the reproduction of Mycobacterium tuberculosis. The most promising schemes of antitumor therapy in conditions of active tuberculosis infection are schemes using carboplatin and gemcitabine, taking into account low mortality, lower toxicity and better effect of anti-tuberculosis therapy against the background of combined use.

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Grigorii G. Kudriashov

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: dr.kudriashov.gg@yandex.com
ORCID iD: 0000-0002-2810-8852
SPIN-code: 9289-6479

Candidate of Medical Sciences, Head of the Department of Pulmonology and Thoracic Surgery, Thoracic Surgeon of the Tuberculosis Pulmonary Surgical (Thoracic) Department No.3

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036

Tatiana I. Vinogradova

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: ti.vinogradova@spbniif.ru
ORCID iD: 0000-0002-5234-349X
SPIN-code: 6354-5070

Doctor of Medical Sciences, Chief Researcher

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036

Yuliya G. Zmitrichenko

N.N. Petrov National Medicine Research Center of oncology

Email: zmitrichenko@gmail.com
ORCID iD: 0000-0002-9137-9532
SPIN-code: 6122-3450

Junior Researcher, Scientific Laboratory of Cancer Chemoprevention and Oncopharmacology

Russian Federation, Leningradskaya str., 68, village Pesochny, St. Petersburg, 197758

Yulia S. Krylova

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: emerald2008@mail.ru
ORCID iD: 0000-0002-8698-7904
SPIN-code: 9729-7872

Candidate of Medical Sciences, Senior Researcher at the Center for Molecular Biomedicine

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036

Marine Z. Dogonadze

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: marine-md@mail.ru
ORCID iD: 0000-0002-9161-466X
SPIN-code: 7475-9828

Candidate of Medical Sciences, Senior Researcher

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036

Natalia V. Zabolotnyh

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: info@spbniif.ru
ORCID iD: 0000-0002-2946-2415
SPIN-code: 7048-8630

Doctor of Medical Sciences, Leading Researcher

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036

Marina Eugenievna Dyakova

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: marinadyakova@yandex.ru
ORCID iD: 0000-0002-7810-880X
SPIN-code: 7858-4573

Doctor of Biological Sciences, Senior Researcher

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036

Dilyara S. Esmedlyaeva

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: diljara-e@yandex.ru
ORCID iD: 0000-0002-9841-0061
SPIN-code: 9402-4487

Candidate of Biological Sciences, Senior Researcher

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036

Grigorii V. Tochilnikov

N.N. Petrov National Medicine Research Center of oncology

Email: gr75@mail.ru
ORCID iD: 0000-0003-4232-8170
SPIN-code: 4366-6930

Candidate of Medical Sciences, Head of the Scientific Laboratory of Cancer Chemoprevention and Oncopharmacology

Russian Federation, Leningradskaya str., 68, village Pesochny, St. Petersburg, 197758

Andrey O. Nefedov

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation

Email: herurg78@mail.ru
ORCID iD: 0000-0001-6228-182X
SPIN-code: 2365-9458

Candidate of Medical Sciences, Senior Researcher, Head of the Department of Thoracic Oncology

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036

Georgiy M. Agafonov

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; Federal State Budgetary Educational Institution of Higher Education “Saint-Petersburg State University”

Email: g.agafonov.98@gmail.com
ORCID iD: 0000-0002-1701-4180
SPIN-code: 4693-8118

Junior Researcher, Resident, Department of Hospital Surgery of the Faculty of Medicine

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036; Universitetskaya emb., 7/9, Saint Petersburg, 199034

Piotr K. Yablonskiy

Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; Federal State Budgetary Educational Institution of Higher Education “Saint-Petersburg State University”

Email: piotr_yablonskii@mail.ru
ORCID iD: 0000-0003-4385-9643
SPIN-code: 3433-2624

Doctor of Medicine, Professor, Head of Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation; Vice-Rector for Medicine

Russian Federation, Ligovskiy ave., 2–4, St. Petersburg, 191036; Universitetskaya emb., 7/9, Saint Petersburg, 199034

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