FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2896971428> ?p ?o ?g. }

• W2896971428 endingPage "S26" @default.
• W2896971428 startingPage "S26" @default.
• W2896971428 abstract "Neutrophils are associated with cancer progression and poor prognosis, but the mechanism is poorly understood. In preclinical models, neutrophil extracellular traps (NETs) entrap circulating tumor cells (CTCs) and promote the initiation of metastasis. In these models, NETosis is triggered by exogenous massive inflammatory stimuli, and thus it remains unknown whether cancer hosts under physiologic inflammation-free conditions experience NETosis and consequent cancer metastasis. The objective of this study was to uncover endogenous inflammatory-independent regulators of NETs and cancer metastasis. We hypothesized that a reservoir of free thiol in plasma provided by non-oxidized albumin counteracts the formation of NETs and decreases cancer metastasis. Human neutrophils were cultured with variable albumin and free thiol content. NETs were detected by immunocytochemistry and immunoblotting. Albumin thiols were depleted or chemically oxidized. NET deposition within organs of Albwt/wt and Alb-/- mice was detected by two-photon microscopy. NETs were blocked or degraded by PAD inhibition or DNase I, respectively. To model lung metastasis, Cal33 human head and neck squamous cell carcinoma (HNSCC) cells were injected via tail vein or 4T1 murine breast carcinoma cells were injected into mammary fat pads. Free thiol levels, albumin concentration/oxidation, NET marker proteins, and inflammatory cytokines were measured in plasma from HNSCC patients treated with definitive radiotherapy (RT). Albumin oxidation led to accumulation of intracellular reactive oxygen species within cultured neutrophils, causing NETosis. In mouse models, loss of albumin thiols resulted in enhanced NETosis. NETs were deposited specifically within pulmonary capillary beds where they contributed to the colonization of CTCs and initiation of lung metastases. These effects were abrogated by pharmacologic inhibition of NET formation. Within a cohort of 22 HNSCC patients, 8 developed subsequent lung metastasis. Decreased levels of plasma free thiol (hazard ratio [HR]=5.3, p=0.023) and non-oxidized albumin (HR=9.8, p=0.009) during RT were associated with elevated risk of lung metastasis. Elevated levels of NET markers were observed in plasma from patients with low levels of non-oxidized albumin (p = 0.008), whereas no difference was seen in the plasma concentration of inflammatory cytokines. Plasma albumin thiol content is an endogenous, physiologic, and inflammation-independent regulator of NETosis and pulmonary cancer metastasis. Patients undergoing definitive RT may develop depleted reservoirs of free thiol in plasma that could promote lung metastasis. Strategies that target albumin thiols and NETs could provide new therapeutic and diagnostic opportunities in combating cancer metastasis." @default.
• W2896971428 created "2018-10-26" @default.
• W2896971428 creator A5005859105 @default.
• W2896971428 creator A5008443335 @default.
• W2896971428 creator A5033450333 @default.
• W2896971428 creator A5034148230 @default.
• W2896971428 creator A5040693828 @default.
• W2896971428 creator A5046679576 @default.
• W2896971428 creator A5063472253 @default.
• W2896971428 creator A5063842271 @default.
• W2896971428 creator A5074620324 @default.
• W2896971428 creator A5077482664 @default.
• W2896971428 creator A5084799348 @default.
• W2896971428 date "2018-11-01" @default.
• W2896971428 modified "2023-09-27" @default.
• W2896971428 title "Plasma Redox Imbalance Caused by Albumin Oxidation Promotes Lung-Predominant NETosis and Metastasis in Patients Treated with Definitive Radiation Therapy" @default.
• W2896971428 doi "https://doi.org/10.1016/j.ijrobp.2018.06.150" @default.
• W2896971428 hasPublicationYear "2018" @default.
• W2896971428 type Work @default.
• W2896971428 sameAs 2896971428 @default.
• W2896971428 citedByCount "0" @default.
• W2896971428 crossrefType "journal-article" @default.
• W2896971428 hasAuthorship W2896971428A5005859105 @default.
• W2896971428 hasAuthorship W2896971428A5008443335 @default.
• W2896971428 hasAuthorship W2896971428A5033450333 @default.
• W2896971428 hasAuthorship W2896971428A5034148230 @default.
• W2896971428 hasAuthorship W2896971428A5040693828 @default.
• W2896971428 hasAuthorship W2896971428A5046679576 @default.
• W2896971428 hasAuthorship W2896971428A5063472253 @default.
• W2896971428 hasAuthorship W2896971428A5063842271 @default.
• W2896971428 hasAuthorship W2896971428A5074620324 @default.
• W2896971428 hasAuthorship W2896971428A5077482664 @default.
• W2896971428 hasAuthorship W2896971428A5084799348 @default.
• W2896971428 hasBestOaLocation W28969714281 @default.
• W2896971428 hasConcept C121608353 @default.
• W2896971428 hasConcept C126322002 @default.
• W2896971428 hasConcept C134897094 @default.
• W2896971428 hasConcept C142724271 @default.
• W2896971428 hasConcept C165616093 @default.
• W2896971428 hasConcept C2776125364 @default.
• W2896971428 hasConcept C2776530083 @default.
• W2896971428 hasConcept C2776833033 @default.
• W2896971428 hasConcept C2776914184 @default.
• W2896971428 hasConcept C2779013556 @default.
• W2896971428 hasConcept C28406088 @default.
• W2896971428 hasConcept C502942594 @default.
• W2896971428 hasConcept C71924100 @default.
• W2896971428 hasConcept C86803240 @default.
• W2896971428 hasConcept C95444343 @default.
• W2896971428 hasConcept C96232424 @default.
• W2896971428 hasConceptScore W2896971428C121608353 @default.
• W2896971428 hasConceptScore W2896971428C126322002 @default.
• W2896971428 hasConceptScore W2896971428C134897094 @default.
• W2896971428 hasConceptScore W2896971428C142724271 @default.
• W2896971428 hasConceptScore W2896971428C165616093 @default.
• W2896971428 hasConceptScore W2896971428C2776125364 @default.
• W2896971428 hasConceptScore W2896971428C2776530083 @default.
• W2896971428 hasConceptScore W2896971428C2776833033 @default.
• W2896971428 hasConceptScore W2896971428C2776914184 @default.
• W2896971428 hasConceptScore W2896971428C2779013556 @default.
• W2896971428 hasConceptScore W2896971428C28406088 @default.
• W2896971428 hasConceptScore W2896971428C502942594 @default.
• W2896971428 hasConceptScore W2896971428C71924100 @default.
• W2896971428 hasConceptScore W2896971428C86803240 @default.
• W2896971428 hasConceptScore W2896971428C95444343 @default.
• W2896971428 hasConceptScore W2896971428C96232424 @default.
• W2896971428 hasIssue "3" @default.
• W2896971428 hasLocation W28969714281 @default.
• W2896971428 hasOpenAccess W2896971428 @default.
• W2896971428 hasPrimaryLocation W28969714281 @default.
• W2896971428 hasRelatedWork W2154708791 @default.
• W2896971428 hasRelatedWork W3028926318 @default.
• W2896971428 hasRelatedWork W3032091224 @default.
• W2896971428 hasRelatedWork W3196980365 @default.
• W2896971428 hasRelatedWork W4224256108 @default.
• W2896971428 hasRelatedWork W4226146528 @default.
• W2896971428 hasRelatedWork W4283771460 @default.
• W2896971428 hasRelatedWork W4296716094 @default.
• W2896971428 hasRelatedWork W4304116770 @default.
• W2896971428 hasRelatedWork W4312078103 @default.
• W2896971428 hasVolume "102" @default.
• W2896971428 isParatext "false" @default.
• W2896971428 isRetracted "false" @default.
• W2896971428 magId "2896971428" @default.
• W2896971428 workType "article" @default.