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Elevated Serum Levels of Inducible Nitric Oxide Synthase, Monocyte Chemoattractant Protein-1, And Cyclooxygenase-2 In Patients with Lung Cancer

Year 2024, Volume: 46 Issue: 3, 388 - 393, 27.05.2024
https://doi.org/10.20515/otd.1386607

Abstract

Lung cancer is a malignant lung tumor characterized by uncontrolled cell growth in lung tissue. Genetic and epigenetic abnormalities can be seen in lung cancer. These abnormalities can lead to activation of oncogene and inactivation of tumor suppressor genes. Inflammation is a powerful mediator of cancer development. Pulmonary inflammation may play a role in the initiation or progression of cancer. The main mediator of inflammation is inducible nitric oxide synthase (iNOS), which synthesizes nitric oxide from L-arginine. Monocyte chemoattractant protein-1 (MCP-1) is one of the important chemokines that regulate the migration and infiltration of monocytes/macrophages. It has been determined that MCP-1 plays an important role in lung allergic inflammation, lung leukocyte infiltration and bronchial hyperresponsiveness in the pathogenesis of asthma. Cyclooxygenases (COX) are responsible for prostaglandin production from arachidonic acid. They contribute to inflammation-induced carcinogenesis. COX2 is the enzyme responsible for inflammation induced by inflammatory stimuli, hormones and growth factors. In line with the information given, in this study, serum levels of COX2, iNOS and MCP-1 were determined using the ELISA method in 90 (36 adenocarcinoma, 36 squamous cell, 18 small cell carcinoma) lung cancer patients and 90 healthy control individuals. It was determined that COX2, iNOS and MCP-1 serum concentrations in lung cancer patients were significantly higher than in control individuals (p<0.001). However, no statistically significant difference was detected between lung cancer histological subtypes (p>0.05). It is thought that our findings may contribute to early diagnosis and development of new treatments for lung cancer.

References

  • 1. Ozbayer C, Yagci E, Ak G, Metintas S, Metintas M, Kurt HJJoEP, Toxicology, et al. Gene Variations of Chemokine and Chemokine Receptor CXCL12/CXCR4 in Lung Cancer. 2023;42(2).
  • 2. Bade BC, Cruz CSDJCicm. Lung cancer 2020: epidemiology, etiology, and prevention. 2020;41(1):1-24. 3. Travis WDJCicm. Lung cancer pathology: current concepts. 2020;41(1):67-85.
  • 4. Wang L, Xia Y, Chen T, Zeng Y, Li L, Hou Y, et al. Sanyang Xuedai enhances the radiosensitivity of human non-small cell lung cancer cells via increasing iNOS/NO production. 2018;102:618-25.
  • 5. Greten FR, Grivennikov SIJI. Inflammation and cancer: triggers, mechanisms, and consequences. 2019;51(1):27-41.
  • 6. Dai M, Hu S, Liu C-F, Jiang L, Yu W, Li Z-L, et al. BPTF cooperates with p50 NF-κB to promote COX-2 expression and tumor cell growth in lung cancer. 2019;11(12):7398.
  • 7. Cinelli MA, Do HT, Miley GP, Silverman RBJMrr. Inducible nitric oxide synthase: Regulation, structure, and inhibition. 2020;40(1):158-89.
  • 8. Kamm A, Przychodzen P, Kuban-Jankowska A, Jacewicz D, Dabrowska AM, Nussberger S, et al. Nitric oxide and its derivatives in the cancer battlefield. 2019;93:102-14.
  • 9. Rani A, Dasgupta P, Murphy JJJTAjop. Prostate cancer: the role of inflammation and chemokines. 2019;189(11):2119-37.
  • 10. Cai Z, Chen Q, Chen J, Lu Y, Xiao G, Wu Z, et al. Monocyte chemotactic protein 1 promotes lung cancer–induced bone resorptive lesions in vivo. 2009;11(3):228-36.
  • 11. Campanholle G, Landgraf R, Gonçalves G, Paiva V, Martins JdO, Wang P, et al. Lung inflammation is induced by renal ischemia and reperfusion injury as part of the systemic inflammatory syndrome. 2010;59:861-9.
  • 12. Han Y, Guo W, Ren T, Huang Y, Wang S, Liu K, et al. Tumor-associated macrophages promote lung metastasis and induce epithelial-mesenchymal transition in osteosarcoma by activating the COX-2/STAT3 axis. 2019;440:116-25.
  • 13. Li H, Huang N, Zhu W, Wu J, Yang X, Teng W, et al. Modulation the crosstalk between tumor-associated macrophages and non-small cell lung cancer to inhibit tumor migration and invasion by ginsenoside Rh2. 2018;18:1-12.
  • 14. Muntané J, De la Mata MJWjoh. Nitric oxide and cancer. 2010;2(9):337.
  • 15. Salamon P, Mekori YA, Shefler IJCI, Immunotherapy. Lung cancer-derived extracellular vesicles: a possible mediator of mast cell activation in the tumor microenvironment. 2020;69:373-81.
  • 16. Sundaram S, Yan LJAR. Adipose-specific monocyte chemotactic protein-1 deficiency reduces pulmonary metastasis of Lewis lung carcinoma in mice. 2019;39(4):1729-38.

Akciğer Kanserli Hastalarda İndüklenebilir Nitrik Oksit Sentaz, Monosit Kemoatraktan Protein-1 ve Siklooksijenaz-2'nin Yüksek Serum Düzeyleri

Year 2024, Volume: 46 Issue: 3, 388 - 393, 27.05.2024
https://doi.org/10.20515/otd.1386607

Abstract

Akciğer kanseri, akciğer dokusunda kontrolsüz hücre büyümesi ile karakterize kötü huylu bir akciğer tümörüdür. Akciğer kanserinde genetik ve epigenetik anormallikler görülebilir. Bu anormallikler, onkogenin aktivasyonuna ve tümör supresör genlerin inaktivasyonuna neden olabilir. İnflamasyon kanser gelişiminde güçlü bir aracıdır, tümörün büyümesine ve vücuda yayılmasına yardımcı olur. İnflamatuar hücrelerden salınan reaktif azot veya oksijen türleri DNA'ya bağlanabilir ve genetik değişikliklere neden olabilir. Böylece, pulmoner inflamasyon kanserin başlamasında veya ilerlemesinde rol oynayabilir. İnflamasyonun ana aracısı, nitrik oksidi L-arginin'den sentezlenen indüklenebilir nitrik oksit sentazdır (iNOS). iNOS'un tümör ilerlemesindeki rolü çok karmaşıktır, hem promotör hem de inhibitör etkiler belirlenmiştir. Akut ve kronik inflamatuar reaksiyonlarda lökosit göçü ve kemokinlerin aktivasyonu önemli fonksiyonlardır. Monosit kemoatraktan protein-1 (MCP-1), monosit/makrofajların migrasyonunu ve infiltrasyonunu düzenleyen önemli kemokinlerden biridir. MCP-1'in astım patogenezinde akciğer allerjik inflamasyonu, akciğer lökosit infiltrasyonu, bronş aşırı duyarlılığı ve eozinofillerin alınmasında önemli rol oynadığı tespit edilmiştir. Siklooksijenazlar (COX), araşidonik asitten prostaglandin üretiminden sorumludur. Prostaglandinlerin sentezi inflamatuar bölgede önemli ölçüde artar. Ayrıca, inflamasyona bağlı karsinogeneze katkıda bulunurlar. Siklooksijenaz 2 (COX2), inflamasyon uyaranları, hormonlar ve büyüme faktörleri tarafından indüklenen inflamasyondan sorumlu olan enzimdir. Verilen bilgiler doğrultusunda bu çalışmada, COX2, iNOS ve MCP-1’in serum seviyeleri 90 (36 adenokarsinom, 36 skuamöz hücreli, 18 küçük hücreli karsinom) akciğer kanseri hastası ve 90 sağlıklı kontrol bireyde ELISA yöntemi kullanılarak belirlendi. Akciğer kanserli hastalarda COX2, iNOS ve MCP-1 serum konsantrasyonlarının kontrol bireylere göre anlamlı derecede yüksek olduğu belirlenmiştir (p<0.001). Ancak akciğer kanseri histolojik alt tipleri arasında istatistiksel olarak anlamlı fark tespit edilememiştir (p>0.05). Bulgularımızın akciğer kanserinde erken teşhise ve yeni tedavilerin geliştirilmesine katkıda bulunabileceği düşünülmektedir.

Ethical Statement

Research and publication ethics were complied with in the study.

Thanks

We thank all consultants,staff and interviewees who participated in the study.

References

  • 1. Ozbayer C, Yagci E, Ak G, Metintas S, Metintas M, Kurt HJJoEP, Toxicology, et al. Gene Variations of Chemokine and Chemokine Receptor CXCL12/CXCR4 in Lung Cancer. 2023;42(2).
  • 2. Bade BC, Cruz CSDJCicm. Lung cancer 2020: epidemiology, etiology, and prevention. 2020;41(1):1-24. 3. Travis WDJCicm. Lung cancer pathology: current concepts. 2020;41(1):67-85.
  • 4. Wang L, Xia Y, Chen T, Zeng Y, Li L, Hou Y, et al. Sanyang Xuedai enhances the radiosensitivity of human non-small cell lung cancer cells via increasing iNOS/NO production. 2018;102:618-25.
  • 5. Greten FR, Grivennikov SIJI. Inflammation and cancer: triggers, mechanisms, and consequences. 2019;51(1):27-41.
  • 6. Dai M, Hu S, Liu C-F, Jiang L, Yu W, Li Z-L, et al. BPTF cooperates with p50 NF-κB to promote COX-2 expression and tumor cell growth in lung cancer. 2019;11(12):7398.
  • 7. Cinelli MA, Do HT, Miley GP, Silverman RBJMrr. Inducible nitric oxide synthase: Regulation, structure, and inhibition. 2020;40(1):158-89.
  • 8. Kamm A, Przychodzen P, Kuban-Jankowska A, Jacewicz D, Dabrowska AM, Nussberger S, et al. Nitric oxide and its derivatives in the cancer battlefield. 2019;93:102-14.
  • 9. Rani A, Dasgupta P, Murphy JJJTAjop. Prostate cancer: the role of inflammation and chemokines. 2019;189(11):2119-37.
  • 10. Cai Z, Chen Q, Chen J, Lu Y, Xiao G, Wu Z, et al. Monocyte chemotactic protein 1 promotes lung cancer–induced bone resorptive lesions in vivo. 2009;11(3):228-36.
  • 11. Campanholle G, Landgraf R, Gonçalves G, Paiva V, Martins JdO, Wang P, et al. Lung inflammation is induced by renal ischemia and reperfusion injury as part of the systemic inflammatory syndrome. 2010;59:861-9.
  • 12. Han Y, Guo W, Ren T, Huang Y, Wang S, Liu K, et al. Tumor-associated macrophages promote lung metastasis and induce epithelial-mesenchymal transition in osteosarcoma by activating the COX-2/STAT3 axis. 2019;440:116-25.
  • 13. Li H, Huang N, Zhu W, Wu J, Yang X, Teng W, et al. Modulation the crosstalk between tumor-associated macrophages and non-small cell lung cancer to inhibit tumor migration and invasion by ginsenoside Rh2. 2018;18:1-12.
  • 14. Muntané J, De la Mata MJWjoh. Nitric oxide and cancer. 2010;2(9):337.
  • 15. Salamon P, Mekori YA, Shefler IJCI, Immunotherapy. Lung cancer-derived extracellular vesicles: a possible mediator of mast cell activation in the tumor microenvironment. 2020;69:373-81.
  • 16. Sundaram S, Yan LJAR. Adipose-specific monocyte chemotactic protein-1 deficiency reduces pulmonary metastasis of Lewis lung carcinoma in mice. 2019;39(4):1729-38.
There are 15 citations in total.

Details

Primary Language English
Subjects Chest Diseases, Medical Genetics (Excl. Cancer Genetics)
Journal Section ORİJİNAL MAKALE
Authors

Emine Yağcı 0000-0003-2179-1318

Cansu Özbayer 0000-0002-1120-1874

Güntülü Ak 0000-0001-8849-193X

Hülyam Kurt 0000-0003-2433-9925

Selma Metintaş 0000-0002-5002-5041

Muzaffer Metintaş 0000-0002-4812-0170

Publication Date May 27, 2024
Submission Date November 6, 2023
Acceptance Date April 1, 2024
Published in Issue Year 2024 Volume: 46 Issue: 3

Cite

Vancouver Yağcı E, Özbayer C, Ak G, Kurt H, Metintaş S, Metintaş M. Elevated Serum Levels of Inducible Nitric Oxide Synthase, Monocyte Chemoattractant Protein-1, And Cyclooxygenase-2 In Patients with Lung Cancer. Osmangazi Tıp Dergisi. 2024;46(3):388-93.


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