cancerspЮжно-Российский онкологический журнал/ South Russian Journal of CancerSouth Russian Journal of Cancer2686-9039АНО "Перспективы онкологии"10.37748/2686-9039-2023-4-1-3GWLSQDcancersp-200Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПоказатели семейства инсулиноподобных факторов роста в ткани легкого больных немелкоклеточным раком легкого перенесших Covid-19 различной степени тяжестиIndices of insulin-like growth factors family in the lung tissue of patients with non-small cell lung cancer after COVID-19 of various severityhttps://orcid.org/0000-0003-3061-6108КитО. И.KitO. I.

 

Кит Олег Иванович – академик РАН, д.м.н., профессор, генеральный директор, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-3061-6108, SPIN: 1728-0329, AuthorID: 343182, ResearcherID:U-2241-2017, Scopus Author ID: 55994103100

 

Oleg I. Kit – Academician at the Russian Academy of Sciences, Dr. Sci. (Med.), professor, general director, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-3061-6108, SPIN: 1728-0329, AuthorID: 343182, ResearcherID:U-2241-2017, Scopus Author ID: 55994103100

rnioi@list.ruhttps://orcid.org/0000-0003-3618-6890ФранциянцЕ. М.FrantsiyantsE. M.

 

Франциянц Елена Михайловна – д.б.н., профессор, заместитель генерального директора по научной работе, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-3618-6890, SPIN: 9427-9928, AuthorID: 462868, ResearcherID: Y-1491-2018, Scopus Author ID: 55890047700

 

Elena M. Frantsiyants – Dr. Sci. (Biol.), professor, deputy general director for science, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-3618-6890, SPIN: 9427-9928, AuthorID: 462868, ResearcherID: Y-1491-2018, Scopus Author ID: 55890047700

super.gormon@yandex.ruhttps://orcid.org/0000-0003-0640-2994ХарагезовД. А.KharagezovD. A.

 

Харагезов Дмитрий Акимович – к.м.н., онколог, хирург, заведующий отделением торакальной онкологии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-0640-2994, SPIN: 5120-0561, AuthorID: 733789, ResearcherID: AAZ-3638-2021, Scopus Author ID: 56626499300

 

Dmitriy A. Kharagezov – Cand. Sci. (Med.), oncologist, surgeon, head of the department of thoracic oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-0640-2994, SPIN: 5120-0561, AuthorID: 733789, ResearcherID: AAZ-3638-2021, Scopus Author ID: 56626499300

dmitr8@mail.ruhttps://orcid.org/0000-0002-2302-8271БандовкинаВ. А.BandovkinaV. A.

 

Бандовкина Валерия Ахтямовна – д.б.н., старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0002-2302-8271, SPIN: 8806-2641, AuthorID: 696989

 

Valeriya A. Bandovkina – Dr. Sci. (Biol.), senior researcher at the laboratory for the study of pathogenesis of malignant tumors, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0002-2302-8271, SPIN: 8806-2641, AuthorID: 696989

valerryana@yandex.ruhttps://orcid.org/0000-0002-3711-8155ЧеряринаН. Д.CheryarinaN. D.

 

Черярина Наталья Дмитриевна – врач-лаборант лаборатории изучения патогенеза злокачественных опухолей, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: http://orcid.org/0000-0002-3711-8155, SPIN: 2189-3404, AuthorID: 558243

 

Natalya D. Cheryarina – MD, laboratory assistant at the laboratory for the study of the pathogenesis of malignant tumors, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: http://orcid.org/0000-0002-3711-8155, SPIN: 2189-3404, AuthorID: 558243

scalolas.92@yandex.ruhttps://orcid.org/0000-0002-2674-9832ПогореловаЮ. А.PogorelovaYu. A.

 

Погорелова Юлия Александровна – к.б.н., старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: http://orcid.org/0000-0002-2674-9832, SPIN: 2168-8737, AuthorID: 558241

 

Yuliya A. Pogorelova – Cand. Sci. (Biol.), senior researcher at laboratory of malignant tumor pathogenesis study, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: http://orcid.org/0000-0002-2674-9832, SPIN: 2168-8737, AuthorID: 558241

flora-73@yandex.ruhttps://orcid.org/0000-0002-6655-7632ЛазутинЮ. Н.LazutinYu. N.

 

Лазутин Юрий Николаевич – к.м.н., доцент, ведущий научный сотрудник отдела торакальной хирургии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0002-6655-7632, SPIN: 5098-7887, AuthorID: 364457

 

Yuriy N. Lazutin – Cand. Sci. (Med.), associate professor, leading researcher of the department of thoracic surgery, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0002-6655-7632, SPIN: 5098-7887, AuthorID: 364457

lazutin.jurij@yandex.ruhttps://orcid.org/0000-0002-2589-7606МилакинА. Г.MilakinA. G.

 

Милакин Антон Григорьевич – онколог отделения торакальной хирургии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0002-2589-7606, SPIN: 7737-4737, AuthorID: 794734

 

Anton G. Milakin – MD, oncologist of the department of thoracic surgery, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0002-2589-7606, SPIN: 7737-4737, AuthorID: 794734

amilakin@yandex.ruhttps://orcid.org/0000-0003-2572-1624ЛейманИ. А.LeymanI. A.

 

Лейман Игорь Александрович – к.м.н., врач-онколог отделения торакальной хирургии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-2572-1624, SPIN: 2551-0999, AuthorID: 735699

 

Igor A. Leyman – Cand. Sci. (Med.), MD, oncologist of the department of thoracic surgery, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-2572-1624, SPIN: 2551-0999, AuthorID: 735699

toraxrnioi@yandex.ruhttps://orcid.org/0000-0003-4513-7548СтатешныйО. Н.StateshnyO. N/

 

Статешный Олег Николаевич – онколог отделения торакальной хирургии, ФГБУ «НМИЦ онкологии» Минздрава России, г. Ростов-на-Дону, Российская Федерация.

ORCID: https://orcid.org/0000-0003-4513-7548, SPIN: 9917-1975, AuthorID: 1067071

 

Oleg N. Stateshniy – MD, oncologist at the department of thoracic surgery, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation.

ORCID: https://orcid.org/0000-0003-4513-7548, SPIN: 9917-1975, AuthorID: 1067071

stateshny@rambler.ruФГБУ «НМИЦ онкологии» Минздрава РоссииРоссияNational Medical Research Centre for OncologyRussian Federation202301022023412333Copyright © Кит О.И., Франциянц Е.М., Харагезов Д.А., Бандовкина В.А., Черярина Н.Д., Погорелова Ю.А., Лазутин Ю.Н., Милакин А.Г., Лейман И.А., Статешный О.Н., 20232023Кит О.И., Франциянц Е.М., Харагезов Д.А., Бандовкина В.А., Черярина Н.Д., Погорелова Ю.А., Лазутин Ю.Н., Милакин А.Г., Лейман И.А., Статешный О.Н.Kit O.I., Frantsiyants E.M., Kharagezov D.A., Bandovkina V.A., Cheryarina N.D., Pogorelova Y.A., Lazutin Y.N., Milakin A.G., Leyman I.A., Stateshny O.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cancersp.com/jour/article/view/200Цель исследования

Цель исследования. Изучить содержание IGF и их белков-переносчиков в тканях легкого больных немелкоклеточным раком легкого (НМРЛ) в зависимости от тяжести перенесенного COVID-19.

Пациенты и методы

Пациенты и методы. В исследование включены 60 больных с гистологически подтвержденным НМРЛ стадии T1–3NхM0, проходивших лечение в торакальном отделении ФГБУ «НМИЦ онкологии» Минздрава России с 2020 по 2021 гг.

В контрольную группу вошли 30 больных раком легкого с бессимптомными или легкими случаями COVID-19 (15 мужчин и 15 женщин), в основную группу – 30 больных (15 мужчин и 15 женщин), перенесших болезнь в тяжелой или среднетяжелой форме. Средний возраст больных составил 59,11 ± 2,89 года, значимых отличий между контрольной и основной группами не отмечали. Перед началом исследования от участников было получено письменное информированное согласие, одобренное советом по этике ФГБУ «НМИЦ онкологии» Минздрава России. Количественную оценку содержания в ткани опухоли, перифокальной зоне и линии резекции IGF-I, IGF-II и IGFBP-1,2,3 выполняли методом иммуноферментного анализа (ИФА методом (Mediagnost, Германия)). Статистический анализ проводили с использованием программы Statistica 10, значение p < 0,05 рассматривалось как показатель статистической значимости.

Результаты

Результаты. У больных основной группы, по сравнению с контрольной группой, вне зависимости от пола, в образцах опухоли и линии резекции уровень IGF-I и IGF-II был выше в среднем в 1,5–2,2 раза, а IGFBP-1 в опухоли был ниже в 1,3 раза у мужчин и в 5 раз у женщин. Соотношение IGF и IGFBP-1-3 у больных контрольной группы в ткани перифокальной зоны изменялись в сторону показателей ткани опухоли. В основной группе у мужчин IGF/IGFBP-1-3 оказались ниже или не отличались от условно интактной ткани, а у женщин повышались, как и в ткани опухоли.

Заключение

Заключение. Повышение соотношения IGF и белков-переносчиков в ткани опухоли больных основной группы свидетельствовало об избыточном накоплении в ней IGF, что может способствовать более агрессивному росту злокачественной опухоли. Наиболее выраженные нарушения в системе инсулиноподобных факторов роста мы обнаружили в ткани опухоли и интактного легкого больных, перенесших COVID-19 в тяжелой и среднетяжелой форме.

Purpose of the study

Purpose of the study. An analysis of levels of IGF and their carrying proteins in lung tissues of cancer patients depending on the severity of the previous COVID-19 infection.

Patients and methods

Patients and methods. The study included 60 patients with histologically verified non-small cell lung cancer (NSCLC) T1–3NхM0 receiving treatment at the Thoracic Department, National Medical Research Centre for Oncology, in 2020–2021. The control group included 30 NSCLC patients after asymptomatic or mild COVID-19 disease (15 males and 15 females); the main group included 30 (15 men and 15 women) patients after severe or moderate to severe COVID-19 infection. The mean age of patients was 59.11 ± 2.89 years; no significant differences were noted between the control and main groups. All participants gave their informed consent prior to the study approved by the Ethics Committee of National Medical Research Centre for Oncology. Qualitative assessment of IGF-I, IGF-II and IGFBP-1,2,3 levels in the tissues of the tumor, peritumoral area and resection line were measured by ELISA (Mediagnost, Germany). The statistical analysis was performed in the Statistica 10 program, the differences were considered statistically significant at p < 0.05.

Results

Results. Regardless of the gender, levels of IGF-I and IGF-II in tumor and resection line samples in patients of the main group were higher than in the control group on average by 1.5–2.2 times, and IGFBP-1 in the tumor was lower by 1.3 times in men and by 5 times in women. The ratio of IGF and IGFBP-1-3 in patients of the control group in perifocal tissues changed towards the parameters in the tumor tissue. IGF/IGFBP-1-3 in men of the main group were lower or did not differ from the indices in the intact tissue, while in women they increased, similarly to the tumor tissue.

Conclusion

Conclusion. An increase in the ratio of IGF and carrier proteins in the tumor tissue of patients in the main group indicated an excessive accumulation of IGF in it, which may contribute to more aggressive growth of malignant tumors. The most pronounced disorders in the system of insulin-like growth factors were found in the tissues of the tumor and intact lung of patients with previous severe and moderate to severe COVID-19.

немелкоклеточный рак легкогоCovid-19IGF-IIGF-IIIGFBPnon-small cell lung cancerCOVID-19IGF-IIGF-IIIGFBPReferencesHammoudeh A, Hammoudeh M, Bhamidimarri PM, Mahboub B, Halwani R, Hamid Q, et al. Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology. World J Gastroenterol. 2021;27(21):2850– 2870. https://doi.org/10.3748/wjg.v27.i21.2850Hammoudeh A, Hammoudeh M, Bhamidimarri PM, Mahboub B, Halwani R, Hamid Q, et al. Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology. World J Gastroenterol. 2021;27(21):2850– 2870. https://doi.org/10.3748/wjg.v27.i21.2850Lemos AEG, Silva GR, Gimba ERP, Matos ADR. Susceptibility of lung cancer patients to COVID-19: A review of the pandemic data from multiple nationalities. Thorac Cancer. 2021 Oct;12(20):2637–2647. https://doi.org/10.1111/1759-7714.14067Lemos AEG, Silva GR, Gimba ERP, Matos ADR. Susceptibility of lung cancer patients to COVID-19: A review of the pandemic data from multiple nationalities. Thorac Cancer. 2021 Oct;12(20):2637–2647. https://doi.org/10.1111/1759-7714.14067Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol. 2020 Jun 16;11:1446. https://doi.org/10.3389/fimmu.2020.01446Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immu- nol. 2020 Jun 16;11:1446. https://doi.org/10.3389/fimmu.2020.01446Ruggiero V, Aquino RP, Del Gaudio P, Campiglia P, Russo P. Post-COVID Syndrome: The Research Progress in the Treatment of Pulmonary sequelae after COVID-19 Infection. Pharmaceutics. 2022 May 26;14(6):1135. https://doi.org/10.3390/pharmaceutics14061135Ruggiero V, Aquino RP, Del Gaudio P, Campiglia P, Russo P. Post-COVID Syndrome: The Research Progress in the Treatment of Pulmonary sequelae after COVID-19 Infection. Pharmaceutics. 2022 May 26;14(6):1135. https://doi.org/10.3390/pharma- ceutics14061135Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020 Mar;21(3):335–337. https://doi.org/10.1016/s1470-2045(20)30096-6Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 2020 Mar;21(3):335–337. https://doi.org/10.1016/s1470-2045(20)30096-6Yu J, Ouyang W, Chua MLK, Xie C. SARS-CoV-2 Transmission in Patients With Cancer at a Tertiary Care Hospital in Wuhan, China. JAMA Oncol. 2020 Jul 1;6(7):1108–1110. https://doi.org/10.1001/jamaoncol.2020.0980Yu J, Ouyang W, Chua MLK, Xie C. SARS-CoV-2 Transmission in Patients With Cancer at a Tertiary Care Hospital in Wuhan, China. JAMA Oncol. 2020 Jul 1;6(7):1108-1110. https://doi.org/10.1001/jamaoncol.2020.0980ThyagaRajan S, Priyanka HP. Bidirectional communication between the neuroendocrine system and the immune system: relevance to health and diseases. Ann Neurosci. 2012 Jan;19(1):40–46. https://doi.org/10.5214/ans.0972.7531.180410ThyagaRajan S, Priyanka HP. Bidirectional communication between the neuroendocrine system and the immune system: rel- evance to health and diseases. Ann Neurosci. 2012 Jan;19(1):40–46. https://doi.org/10.5214/ans.0972.7531.180410Hazrati E, Gholami M, Farahani RH, Ghorban K, Ghayomzadeh M, Rouzbahani NH. The effect of IGF-1 plasma concentration on COVID-19 severity. Microb Pathog. 2022 Mar;164:105416. https://doi.org/10.1016/j.micpath.2022.105416Hazrati E, Gholami M, Farahani RH, Ghorban K, Ghayomzadeh M, Rouzbahani NH. The effect of IGF-1 plasma concentration on COVID-19 severity. Microb Pathog. 2022 Mar;164:105416. https://doi.org/10.1016/j.micpath.2022.105416Chen YM, Qi S, Perrino S, Hashimoto M, Brodt P. Targeting the IGF-Axis for Cancer Therapy: Development and Validation of an IGF-Trap as a Potential Drug. Cells. 2020 Apr 29;9(5):1098. https://doi.org/10.3390/cells9051098Chen YM, Qi S, Perrino S, Hashimoto M, Brodt P. Targeting the IGF-Axis for Cancer Therapy: Development and Validation of an IGF-Trap as a Potential Drug. Cells. 2020 Apr 29;9(5):1098. https://doi.org/10.3390/cells9051098Blyth AJ, Kirk NS, Forbes BE. Understanding IGF-II Action through insights into receptor binding and activation. Cells. 2020;9(10):2276. https://doi.org/10.3390/cells9102276Blyth AJ, Kirk NS, Forbes BE. Understanding IGF-II Action through insights into receptor binding and activation. Cells. 2020;9(10):2276. https://doi.org/10.3390/cells9102276Krein PM, Sabatini PJB, Tinmouth W, Green FHY, Winston BW. Localization of insulin-like growth factor-I in lung tissues of patients with fibroproliferative acute respiratory distress syndrome. Am J Respir Crit Care Med. 2003;167(1):83–90. https://doi.org/10.1164/rccm.2201012Krein PM, Sabatini PJB, Tinmouth W, Green FHY, Winston BW. Localization of insulin-like growth factor-I in lung tissues of patients with fibroproliferative acute respiratory distress syndrome. Am J Respir Crit Care Med. 2003;167(1):83–90. https://doi.org/10.1164/rccm.2201012Kasprzak A, Kwasniewski W, Adamek A, Gozdzicka-Jozefiak A. Insulin-like growth factor (IGF) axis in cancerogenesis. Mutat Res Rev Mutat Res. 2017 Apr-Jun;772:78–104. https://doi.org/10.1016/j.mrrev.2016.08.007Kasprzak A, Kwasniewski W, Adamek A, Gozdzicka-Jozefiak A. Insulin-like growth factor (IGF) axis in cancerogenesis. Mutat Res Rev Mutat Res. 2017 Apr-Jun;772:78–104. https://doi.org/10.1016/j.mrrev.2016.08.007Soliman AR, Sadek KM. Relation between insulin growth factor 1 and survival after SARS-CoV-2(COVID 19) infection in elderly kidney transplant recipients. Ren Fail. 2021 Dec;43(1):388–390. https://doi.org/10.1080/0886022x.2021.1886115Soliman AR, Sadek KM. Relation between insulin growth factor 1 and survival after SARS-CoV-2(COVID 19) infection in el- derly kidney transplant recipients. Ren Fail. 2021 Dec;43(1):388–390. https://doi.org/10.1080/0886022x.2021.1886115Ahasic AM, Tejera P, Wei Y, Su L, Mantzoros CS, Bajwa EK, et al. Predictors of circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in critical illness. Crit Care Med. 2015;43(12):2651–2659. https://doi.org/10.1097/ccm.0000000000001314Ahasic AM, Tejera P, Wei Y, Su L, Mantzoros CS, Bajwa EK, et al. Predictors of circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in critical illness. Crit Care Med. 2015;43(12):2651–2659. https://doi.org/10.1097/ccm.0000000000001314Li G, Zhou L, Zhang C, Shi Y, Dong D, Bai M, et al. Insulin-Like Growth Factor 1 Regulates Acute Inflammatory Lung Injury Mediated by Influenza Virus Infection. Front Microbiol. 2019 Nov 26;10:2541. https://doi.org/10.3389/fmicb.2019.02541Li G, Zhou L, Zhang C, Shi Y, Dong D, Bai M, et al. Insulin-Like Growth Factor 1 Regulates Acute Inflammatory Lung Injury Me- diated by Influenza Virus Infection. Front Microbiol. 2019 Nov 26;10:2541. https://doi.org/10.3389/fmicb.2019.02541Luo J, Rizvi H, Preeshagul IR, Egger JV, Hoyos D, Bandlamudi C, et al. COVID-19 in patients with lung cancer. Ann Oncol. 2020 Oct;31(10):1386–1396. https://doi.org/10.1016/j.annonc.2020.06.007Luo J, Rizvi H, Preeshagul IR, Egger JV, Hoyos D, Bandlamudi C, et al. COVID-19 in patients with lung cancer. Ann Oncol. 2020 Oct;31(10):1386–1396. https://doi.org/10.1016/j.annonc.2020.06.007Varma Shrivastav S, Bhardwaj A, Pathak KA, Shrivastav A. Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unravelingthe Role in Mediating IGF-Independent Effects Within the Cell. Front Cell Dev Biol. 2020 May 5;8:286. https://doi.org/10.3389/fcell.2020.00286Varma Shrivastav S, Bhardwaj A, Pathak KA, Shrivastav A. Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell. Front Cell Dev Biol. 2020 May 5;8:286. https://doi.org/10.3389/fcell.2020.00286Munoz K, Wasnik S, Abdipour A, Bi H, Wilson SM, Tang X, et al. The Effects of Insulin-Like Growth Factor I and BTP-2 on Acute Lung Injury. Int J Mol Sci. 2021 May 15;22(10):5244. https://doi.org/10.3390/ijms22105244Munoz K, Wasnik S, Abdipour A, Bi H, Wilson SM, Tang X, et al. The Effects of Insulin-Like Growth Factor I and BTP-2 on Acute Lung Injury. Int J Mol Sci. 2021 May 15;22(10):5244. https://doi.org/10.3390/ijms22105244Feizollahi P, Matin S, Roghani SA, Mostafaei S, Safarzadeh E, Taghadosi M. Evaluation serum levels of Insulin Growth Factor-1 (IGF-1) and its association with clinical parameters in severe COVID-19. Inflammopharmacology. 2022 Feb;30(1):199–205. https://doi.org/10.1007/s10787-021-00908-6Feizollahi P, Matin S, Roghani SA, Mostafaei S, Safarzadeh E, Taghadosi M. Evaluation serum levels of Insulin Growth Fac- tor-1 (IGF-1) and its association with clinical parameters in severe COVID-19. Inflammopharmacology. 2022 Feb;30(1):199–205. https://doi.org/10.1007/s10787-021-00908-6Mu M, Gao P, Yang Q, He J, Wu F, Han X, et al. Alveolar epithelial cells promote IGF-I production by alveolar macrophages through TGF-β to suppress endogenous inflammatory signals. Front Immunol. 2020 Jul 21;11:1585. https://doi.org/10.3389/fimmu.2020.01585Mu M, Gao P, Yang Q, He J, Wu F, Han X, et al. Alveolar epithelial cells promote IGF-I production by alveolar macrophages through TGF-β to suppress endogenous inflammatory signals. Front Immunol. 2020 Jul 21;11:1585. https://doi.org/10.3389/fimmu.2020.01585He J, Mu M, Wang H, Ma H, Tang X, Fang Q, et al. Upregulated IGF-I in the lungs of asthmatic mice originates from alveolar macrophages. Mol Med Rep. 2019 Feb;19(2):1266–1271. https://doi.org/10.3892/mmr.2018.9726He J, Mu M, Wang H, Ma H, Tang X, Fang Q, et al. Upregulated IGF-I in the lungs of asthmatic mice originates from alveolar macrophages. Mol Med Rep. 2019 Feb;19(2):1266–1271. https://doi.org/10.3892/mmr.2018.9726Kasprzak A, Kwasniewski W, Adamek A, Gozdzicka-Jozefiak A. Insulin-like growth factor (IGF) axis in cancerogenesis. Mutat Res Rev Mutat Res. 2017 Apr-Jun;772:78–104. https://doi.org/10.1016/j.mrrev.2016.08.007Kasprzak A, Kwasniewski W, Adamek A, Gozdzicka-Jozefiak A. Insulin-like growth factor (IGF) axis in cancerogenesis. Mu- tat Res Rev Mutat Res. 2017 Apr-Jun;772:78–104. https://doi.org/10.1016/j.mrrev.2016.08.007Shin J, Toyoda S, Nishitani S, Onodera T, Fukuda S, Kita S, Fukuhara A, Shimomura I. SARS-CoV-2 infection impairs the insulin/IGF signaling pathway in the lung, liver, adipose tissue, and pancreatic cells via IRF1. Metabolism. 2022 Aug;133:155236. https://doi.org/10.1016/j.metabol.2022.155236Shin J, Toyoda S, Nishitani S, Onodera T, Fukuda S, Kita S, Fukuhara A, Shimomura I. SARS-CoV-2 infection impairs the in- sulin/IGF signaling pathway in the lung, liver, adipose tissue, and pancreatic cells via IRF1. Metabolism. 2022 Aug;133:155236. https://doi.org/10.1016/j.metabol.2022.155236Kelesidis T, Mantzoros CS. Cross-talk between SARS-CoV-2 infection and the insulin/IGF signaling pathway: Implications for metabolic diseases in COVID-19 and for post-acute sequelae of SARS-CoV-2 infection. Metabolism. 2022 Jul 25;134:155267. https://doi.org/10.1016/j.metabol.2022.155267Kelesidis T, Mantzoros CS. Cross-talk between SARS-CoV-2 infection and the insulin/IGF signaling pathway: Implications for metabolic diseases in COVID-19 and for post-acute sequelae of SARS-CoV-2 infection. Metabolism. 2022 Jul 25;134:155267. https://doi.org/10.1016/j.metabol.2022.155267Fang J, Feng C, Chen W, Hou P, Liu Z, Zuo M, et al. Redressing the interactions between stem cells and immune system in tissue regeneration. Biol Direct. 2021 Oct 20;16(1):18. https://doi.org/10.1186/s13062-021-00306-6Fang J, Feng C, Chen W, Hou P, Liu Z, Zuo M, et al. Redressing the interactions between stem cells and immune system in tissue regeneration. Biol Direct. 2021 Oct 20;16(1):18. https://doi.org/10.1186/s13062-021-00306-6Varma Shrivastav S, Bhardwaj A, Pathak KA, Shrivastav A. Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell. Front Cell Dev Biol. 2020 May 5;8:286. https://doi.org/10.3389/fcell.2020.00286Varma Shrivastav S, Bhardwaj A, Pathak KA, Shrivastav A. Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unravel- ing the Role in Mediating IGF-Independent Effects Within the Cell. Front Cell Dev Biol. 2020 May 5;8:286. https://doi.org/10.3389/fcell.2020.00286Velcheti V, Govindan R. Insulin-like growth factor and lung cancer. J Thorac Oncol. 2006 Sep;1(7):607–610. https://doi.org/10.1016/s1556-0864(15)30370-1Velcheti V, Govindan R. Insulin-like growth factor and lung cancer. J Thorac Oncol. 2006 Sep;1(7):607–610. https://doi.org/10.1016/s1556-0864(15)30370-1

The authors declare that there are no conflicts of interest present.