Higher serum nitrate levels are associated with poor survival in lung cancer patients

Çolakoğulları, Mukaddes; Ulukaya, Engin; Yılmaztepe, Arzu; Ocakoğlu, Gökhan; Yilmaz, Meryem; Karadağ, Mehmet; Tokullugil, Asuman

doi:10.1016/j.clinbiochem.2006.06.008

Cited by 18 publications

(17 citation statements)

References 31 publications

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“…In serum NO levels correlate with staging in lung cancer [18] and its increase in patients with small cell and non-small cell lung cancer has been associated with a poor survival rate [9]. We found a significantly higher expression of NO in the serum from the mice evaluated 20 days after Urethane injection.…”

Section: Discussionmentioning

confidence: 86%

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Identification of myeloid-derived suppressor cells and T regulatory cells in lung microenvironment after Urethane-induced lung tumor

Rosin

Pedregosa

Almeida

et al. 2011

International Immunopharmacology

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Section: Discussionmentioning

confidence: 86%

“…As NO is highly reactive and unstable in vivo, nitrite/nitrate in serum is most often used as a measure of NO production in blood stream [8]. Nitrite/nitrate higher levels have been associated with poor survival rate in patients with lung cancer [9].…”

Section: Introductionmentioning

confidence: 99%

Identification of myeloid-derived suppressor cells and T regulatory cells in lung microenvironment after Urethane-induced lung tumor

Rosin

Pedregosa

Almeida

et al. 2011

International Immunopharmacology

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“…Clinical data further support the role of NO in lung cancer and metastasis. A high level of NO was observed in the lung of patients with lung cancer (43, 49), and a positive correlation has been reported between NO, its stable endproducts nitrite and nitrate, and its generator NOS with advanced cancer staging and poor survival in patients with lung cancer (2,15,24). Animal studies further showed that genetic ablation of NOS suppressed lung tumor formation in mice (35).…”

mentioning

confidence: 96%

Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells

Yongsanguanchai

Pongrakhananon

Mutirangura

et al. 2015

American Journal of Physiology-Cell Physiology

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Yongsanguanchai N, Pongrakhananon V, Mutirangura A, Rojanasakul Y, Chanvorachote P. Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells. Am J Physiol Cell Physiol 308: C89 -C100, 2015. First published November 19, 2014; doi:10.1152/ajpcell.00187.2014.-Even though tremendous advances have been made in the treatment of cancers during the past decades, the success rate among patients with cancer is still dismal, largely because of problems associated with chemo/radioresistance and relapse. Emerging evidence has indicated that cancer stem cells (CSCs) are behind the resistance and recurrence problems, but our understanding of their regulation is limited. Rapid reversible changes of CSC-like cells within tumors may result from the effect of biological mediators found in the tumor microenvironment. Here we show how nitric oxide (NO), a key cellular modulator whose level is elevated in many tumors, affects CSC-like phenotypes of human non-small cell lung carcinoma H292 and H460 cells. Exposure of NO gradually altered the cell morphology toward mesenchymal stem-like shape. NO exposure promoted CSC-like phenotype, indicated by increased expression of known CSC markers, CD133 and ALDH1A1, in the exposed cells. These effects of NO on stemness were reversible after cessation of the NO treatment for 7 days. Furthermore, such effect was reproducible using another NO donor, S-nitroso-Nacetylpenicillamine. Importantly, inhibition of NO by the known NO scavenger 2-(4-carboxy-phenyl)-4,4,5,5 tetramethylimidazoline-1-oxy-3-oxide strongly inhibited CSC-like aggressive cellular behavior and marker expression. Last, we unveiled the underlying mechanism of NO action through the activation of caveolin-1 (Cav-1), which is upregulated by NO and is responsible for the aggressive behavior of the cells, including anoikis resistance, anchorage-independent cell growth, and increased cell migration and invasion. These findings indicate a novel role of NO in CSC regulation and its importance in aggressive cancer behaviors through Cav-1 upregulation.cancer stem cells; nitric oxide; caveolin-1; CD133; ALDH1A1; nonsmall cell lung carcinoma ACCORDING TO THE AMERICAN CANCER SOCIETY 2013 annual cancer statistics, lung cancer remains one of the most common malignancies and is the leading cause of cancer-related deaths worldwide (61). Increasing evidence has indicated the role of cancer stem cells (CSCs) in cancer aggressiveness, chemoresistance, and relapse; they are being considered as the underlying causes of the high mortality rate of cancer (29,47,50,55). The concept of a tumor having a heterogeneous cancer cell population with a subpopulation of cells possessing a high tumorigenic potential and stem-like property was first described in 1997 (5). This subpopulation is commonly known as tumor-initiating cells, tumor-propagating cells, or CSCs and has been identified in many types of cancer (16,23,40,46,56,58,63). CSCs have been suggested as the rationale behind chemo/radioresistance and cancer relapse (3,4,18,39,68) an...

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“…Peroxynitrite can induce cell damage by developing lipid peroxidation, causing DNA damage and mitochondrial dysfunction. In contrast, Colakogullari and coworkers (40) did not observe high concentrations of NO as an early effect of cisplatin therapy. This variation can be attributed to different study protocols.…”

Section: Discussionmentioning

confidence: 96%

The Platinum(II) Complexes Induced Oxidative Stress of Isolated Rat Heart

Radonjić

Milosavljevic

Živković

et al. 2017

Serbian Journal of Experimental and Clinical Research

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Higher serum nitrate levels are associated with poor survival in lung cancer patients

Cited by 18 publications

References 31 publications

Identification of myeloid-derived suppressor cells and T regulatory cells in lung microenvironment after Urethane-induced lung tumor

Identification of myeloid-derived suppressor cells and T regulatory cells in lung microenvironment after Urethane-induced lung tumor

Nitric oxide induces cancer stem cell-like phenotypes in human lung cancer cells

The Platinum(II) Complexes Induced Oxidative Stress of Isolated Rat Heart

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