Efficacy of antitumor therapy schemes with carboplatin in an experimental model of lung carcinoma and drug-resistant tuberculosis
- Authors: Kudriashov G.G.1, Krylova Y.S.1, Zmitrichenko Y.G.2, Tochilnikov G.V.2, Agafonov G.M.1,3, Vinogradova T.I.1, Yablonskii P.K.1,3
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Affiliations:
- Saint Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation
- N.N. Petrov National Medicine Research Center of oncology
- Federal State Budgetary Educational Institution of Higher Education “Saint Petersburg State University”
- Issue: Vol 23, No 1 (2025)
- Pages: 34-40
- Section: Original research
- URL: https://bakhtiniada.ru/1728-2918/article/view/312089
- DOI: https://doi.org/10.29296/24999490-2025-01-04
- ID: 312089
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Abstract
Introduction. Up to 20% of tuberculosis patients suffer from malignant neoplasms. In this case, the combination of both diseases in the lung is a particular problem. More than 60% of patients cannot complete combination therapy due to drug-resistant MBT. The aim of the study was a preclinical study of the efficacy and safety of combination regimens of antitumor therapy using carboplatin and antituberculosis therapy for drug-resistant tuberculosis. The study was supported by grant No.22-15-00470 from the Russian Science Foundation (https://rscf.ru/project/22-15-00470/)
Material and methods. The study was conducted on 40 C57BL/6 mice aged two months with pre-modeled combined pathology of lung carcinoma and tuberculosis. Depending on the therapy, 4 groups were formed: I – control without treatment (n = 10), II – antitumor (carboplatin + paclitaxel) + antituberculosis therapy (n = 10), III – antitumor (carboplatin + pemetrexed) + antituberculosis therapy (n = 10), IV – antitumor (carboplatin + gemcitabine) + antituberculosis therapy (n = 10). The antituberculosis therapy regimen included moxifloxacin, linezolid, bedaquiline and perchlozone. The antitumor effect (tumor growth index, tumor growth inhibition), antituberculosis effect (CFU per lung weight), toxicity (biometric parameters of internal organs), and survival were assessed. Statistical processing was performed using non-parametric statistics methods.
Results. The lowest average body weight was recorded in the control group. The average body weight of the experimental animals correlated with the tumor node volume. The smallest tumor volume was recorded in the control, and the largest in group IV. The optimal anti-tuberculosis effect was achieved in all experimental groups. At the same time, significantly better survival, as well as signs of lower toxicity were noted in the group where anti-tuberculosis therapy was used in combination with carboplatin and gemcitabine.
Conclusion. A preclinical study of the efficacy and safety of combined anti-tuberculosis and antitumor therapy with carboplatin based on a combination model of Lewis pulmonary carcinoma and drug-resistant tuberculosis showed an optimal anti-tuberculosis effect in all groups. At the same time, acceptable toxicity and better survival indicate a greater safety of the combination of anti-tuberculosis therapy with carboplatin and gemcitabine.
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##article.viewOnOriginalSite##About the authors
Grigorii G. Kudriashov
Saint Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation
Email: dr.kudriashov.gg@yandex.com
ORCID iD: 0000-0002-2810-8852
Leading Researcher, Thoracic Surgeon, Head of the Department of Pulmonology and Thoracic Surgery, Candidate of Medical Sciences
Russian Federation, Ligovsky ave., 2–4, St. Petersburg, 191036Yulia 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
Senior Researcher, Center for Molecular Biomedicine, Candidate of Medical Sciences
Russian Federation, Ligovsky ave., 2–4, St. Petersburg, 191036Yuliya G. Zmitrichenko
N.N. Petrov National Medicine Research Center of oncology
Email: zmitrichenko@gmail.com
ORCID iD: 0000-0002-9137-9532
Junior Researcher, Scientific Laboratory of Cancer Chemoprevention and Oncopharmacology
Russian Federation, Leningradskaya str., 68, village Pesochny, St. Petersburg, 197758Grigorii V. Tochilnikov
N.N. Petrov National Medicine Research Center of oncology
Email: gr75@mail.ru
ORCID iD: 0000-0003-4232-8170
Head of Laboratory, Scientific Laboratory of Cancer Chemoprophylaxis and Oncopharmacology
Russian Federation, Leningradskaya str., 68, village Pesochny, St. Petersburg, 197758Georgiy 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
Research Intern, Clinical resident of the Department of Hospital Surgery
Russian Federation, Ligovsky ave., 2–4, St. Petersburg, 191036; Universitetskaya embankment, 7/9, Saint Petersburg, 199034Tatiana 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
Chief Researcher, Doctor of Medical Sciences
Russian Federation, Ligovsky ave., 2–4, St. Petersburg, 191036Piotr K. Yablonskii
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”
Author for correspondence.
Email: glhirurgb2@mail.ru
ORCID iD: 0000-0003-4385-9643
Head, Vice-Rector for Medicine, Doctor of Medical Sciences, professor
Russian Federation, Ligovsky ave., 2–4, St. Petersburg, 191036; Universitetskaya embankment, 7/9, Saint Petersburg, 199034References
- Крылова Ю.С., Кудряшов Г.Г., Нефедов А.О., Дохов М.А., Захарченко А.О., Яблонский П.К. Сигнальные молекулы опухолевой трансформации при туберкулезе. Молекулярная медицина. 2022; 20 (6): 12–5. https://doi.org/10.29296/24999490-2022-06-02. [Krylova Yu.S., Kudriashov G.G., Nefedov A.O., Dokhov M.A., Zakharchenko A.O., Yablonskii P.K. Signaling molecules of tumor transformation in tuberculosis. Molekulyarnaya meditsina. 2022; 20 (6): 12–15. https://doi.org/10.29296/24999490-2022-06-02 (in Russian)].
- Кудряшов Г.Г., Нефедов А.О., Точильников Г.В., Змитриченко Ю.Г., Крылова Ю.С., Догонадзе М.З., Заболотных Н.В., Дьякова М.Е., Эсмедляева Д.С., Витовская М.Л., Гаврилов П.В., Азаров А.А., Журавлев В.Ю., Виноградова Т.И., Яблонский П.К. Оригинальная экспериментальная модель туберкулеза и рака легкого. Педиатр. 2022: 13 (5): 33–42. DOI: https://doi.org/10.17816/PED13533-42. [Kudrjashov G.G., Nefedov A.O., Tochil’nikov G.V., Zmitrichenko Ju.G., Krylova Ju.S., Dogonadze M.Z., Zabolotnyh N.V., D’jakova M.E., Jesmedljaeva D.S., Vitovskaja M.L., Gavrilov P.V., Azarov A.A., Zhuravlev V.Ju., Vinogradova T.I., Jablonskij P.K. Original’naja jeksperimental’naja model’ tuberkuleza i raka legkogo. Pediatr. 2022: 13 (5): 33–42. DOI: https://doi.org/10.17816/PED13533-42 (in Russian)].
- Кудряшов Г.Г., Виноградова Т.И., Змитриченко Ю.Г., Догонадзе М.З., Заболотных Н.В., Дьякова М.Е., Эсмедляева Д.С., Гаврилов П.В., Азаров А.А., Точильников Г.В., Нефедов А.О., Крылова Ю.С., Яблонский П.К. Влияние противоопухолевых препаратов на течение туберкулеза в эксперименте. Молекулярная медицина. 2023; 21 (2): 25–32. https://doi.org/10.29296/24999490-2023-02-04. [Kudrjashov G.G., Vinogradova T.I., Zmitrichenko Ju.G., Dogonadze M.Z., Zabolotnyh N.V., D’jakova M.E., Jesmedljaeva D.S., Gavrilov P.V., Azarov A.A., Tochil’nikov G.V., Nefedov A.O., Krylova Ju.S., Jablonskij P.K. Vlijanie protivoopuholevyh preparatov na techenie tuberkuleza v jekspe-rimente. Molekuljarnaja medicina. 2023; 21 (2): 25–32. https://doi.org/10.29296/24999490-2023-02-04 (in Russian)].
- Вершинина С.Ф., Стуков А.Н. Экспериментальные опухоли: Практическое руководство. СПб.: Изд-во Галаника, 2018. [Vershinina S. F., Stukov A. N. Jeksperimental’nye opuholi: Prakticheskoe rukovodstvo. SPb.: Izd-vo Galanika, 2018 (in Russian)]
- Стуков А.Н., Иванова М.А., Никитин А.К., Сорокин Г.М., Коньков С.А. Индекс роста опухоли как интегральный критерий эффективности противоопухолевой терапии в эксперименте. Вопросы онкологии. 2001: 47 (5): 616–8. [Stukov A.N., Ivanova M.A., Nikitin A.K., Sorokin G.M., Kon’kov S.A. Indeks rosta opuholi kak integral’nyj kriterij jeffektivnosti protivoopuholevoj terapii v jeksperimente. Voprosy onkologii. 2001: 47 (5): 616–8 (in Russian)].
- Lee C.S., Shu C.C., Chen Y.C., Liao K.M., Ho C.H. Tuberculosis treatment incompletion in patients with lung cancer: occurrence and predictors. International J. of Infectious Diseases. 2021: 113: 200–6. DOI: https://doi.org/10.1016/j.ijid.2021.09.072
- Leung C.Y., Huang H.L., Rahman M.M., Nomura S., Krull Abe S., Saito E., Shibuya K. Cancer incidence attributable to tuberculosis in 2015: global, regional, and national estimates. BMC cancer. 2020; 20: 1–13. DOI: https://doi.org/10.1186/s12885-020-06891-5
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