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      Value of circulating neutrophil elastase for detecting recurrence of differentiated thyroid cancer

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          Abstract

          Objective

          The inflammatory microenvironment has been implicated in differentiated thyroid cancer (DTC). Inflammatory stimuli induce the release of components of neutrophils into extracellular space, leading to formation of neutrophil extracellular trap (NET), which can stimulate growth and progression of cancer. Generation of activated factor XII and thrombin is also involved in cancer progression. This study attempted to determine whether the level of circulating markers of NET, activated factor XII, and endogenous thrombin potential may be useful for detecting the recurrence of DTC.

          Methods

          A total of 122 patients with DTC were recruited during the postoperative follow-up period. Measurement of the levels of circulating markers of NET (neutrophil elastase, histone–DNA complex, cell-free dsDNA), activated factor XII, and endogenous thrombin potential was performed.

          Results

          A significantly elevated level of neutrophil elastase was detected in patients with recurrence ( n = 12) compared to those without recurrence ( n = 110), while significant elevation of the levels of other markers was not observed. The value for area under the curve (0.717, P = 0.018) of neutrophil elastase for detecting recurrence of DTC was superior to that (0.661, P = 0.051) of serum thyroglobulin. An elevated level of neutrophil elastase was significantly associated with recurrence of DTC independent of serum thyroglobulin.

          Conclusions

          Because an elevated level of neutrophil elastase was detected in patients with recurrence of DTC and showed a significant association with recurrence of DTC, it can be proposed as a novel biomarker for use in detecting recurrence of DTC along with other tests.

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          Most cited references43

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          2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

          Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer.
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            Neutrophil extracellular traps kill bacteria.

            Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria. These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria. NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation. NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria.
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              Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice

              Cancer cells from a primary tumor can disseminate to other tissues, remaining dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to awaken, resume proliferating, and develop into metastases. Studying mouse models, we found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Sustained inflammation induced the formation of neutrophil extracellular traps (NETs), and these were required for awakening dormant cancer. Mechanistic analysis revealed that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin α3β1 signaling. Antibodies against NET-remodeled laminin prevented awakening of dormant cells. Therapies aimed at preventing dormant cell awakening could potentially prolong the survival of cancer patients.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                31 October 2023
                31 October 2023
                01 December 2023
                : 12
                : 12
                : e230400
                Affiliations
                [1 ]Department of Laboratory Medicine , Seoul National University College of Medicine, Seoul, Republic of Korea
                [2 ]Department of Laboratory Medicine , Seoul National University Hospital, Seoul, Republic of Korea
                [3 ]Cancer Research Institute , Seoul National University College of Medicine, Seoul, Republic of Korea
                [4 ]Department of Internal Medicine , Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
                Author notes
                Correspondence should be addressed to E S Kim or H K Kim: grace10@ 123456uuh.ulsan.kr or lukekhk@ 123456snu.ac.kr

                *(H Lee and T-S Kim contributed equally to this work)

                Author information
                http://orcid.org/0000-0002-5962-1499
                http://orcid.org/0000-0002-9311-4642
                http://orcid.org/0000-0003-2401-3933
                Article
                EC-23-0400
                10.1530/EC-23-0400
                10692691
                37909732
                de65cef7-0879-48f3-ac92-c3de9aa1edd2
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 25 September 2023
                : 31 October 2023
                Categories
                Research

                differentiated thyroid cancer,neutrophil elastase,recurrence,biomarker

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