Mast cells (MCs) are a part of the innate immune system. The MC functions toward cancer are partially based on the release of chymase and tryptase. However, the MC effect on breast cancer is controversial. The aim of our study was to investigate the presence of MCs in breast cancer tumors of different molecular subtypes and their relationships with other pathological prognostic factors. Tryptase- and chymase-positive mast cell densities were evaluated by immunohistochemistry in 108 primary invasive breast cancer tissue samples. Positive cells were counted within the tumor bed and at the invasive margin. For all analyzed MC subpopulations, we observed statistically significant differences between individual molecular subtypes of breast cancer. The significantly higher numbers of intratumoral chymase- and tryptase-positive mast cells were observed in luminal A and luminal B tumors compared to triple-negative and HER2+ non-luminal lesions. A denser MC infiltration was associated with lower tumor grade, higher ER and PR expression, lower proliferation rate as well as the lack of HER2 overexpression. The results obtained in our study indicate a possible association of chymase- and tryptase-positive MCs with more favorable cancer immunophenotype and with beneficial prognostic indicators in breast cancer.
Background: Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID-exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation, and increased production of pro-inflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous. Objective:We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA).Methods: A total of 95 asthma patients with aspirin hypersensitivity underwent sputum induction. High-performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids in induced sputum supernatant (ISS). Sixteen variables covering clinical characteristics, IS inflammatory cells, and eicosanoids were considered in the LCA.Results: Three classes (subphenotypes) were distinguished within the NERD cohort.Class 1 subjects had mild-to-moderate asthma, an almost equal distribution of inflammatory cell patterns, the lowest concentrations of eicosanoids, and logLTE 4 /logPGE 2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher pro-inflammatory LTE 4 in ISS and the highest logLTE 4 /logPGE 2 ratio. Class 3 subjects had mild-to-moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro-(LTE 4 , PGD 2 and 11-dehydro-TBX 2 ) was balanced by
Background Aspirin desensitization followed by daily aspirin use is an effective treatment for aspirin‐exacerbated respiratory disease (AERD). Objective To assess clinical features as well as genetic, immune, cytological and biochemical biomarkers that might predict a positive response to high‐dose aspirin therapy in AERD. Methods We enrolled 34 AERD patients with severe asthma who underwent aspirin desensitization followed by 52‐week aspirin treatment (650 mg/d). At baseline and at 52 weeks, clinical assessment was performed; phenotypes based on induced sputum cells were identified; eicosanoid, cytokine and chemokine levels in induced sputum supernatant were determined; and induced sputum expression of 94 genes was assessed. Responders to high‐dose aspirin were defined as patients with improvement in 5‐item Asthma Control Questionnaire score, 22‐item Sino‐Nasal Outcome Test (SNOT‐22) score and forced expiratory volume in 1 second at 52 weeks. Results There were 28 responders (82%). Positive baseline predictors of response included female sex (p = .002), higher SNOT‐22 score (p = .03), higher blood eosinophil count (p = .01), lower neutrophil percentage in induced sputum (p = .003), higher expression of the hydroxyprostaglandin dehydrogenase gene, HPGD (p = .004) and lower expression of the proteoglycan 2 gene, PRG2 (p = .01). The best prediction model included Asthma Control Test and SNOT‐22 scores, blood eosinophils and total serum immunoglobulin E. Responders showed a marked decrease in sputum eosinophils but no changes in eicosanoid levels. Conclusions and Clinical Relevance Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high HPGD expression and low PRG2 expression may predict a positive response to long‐term high‐dose aspirin therapy in patients with AERD.
Background:A special regulatory role for prostaglandin E 2 (PGE 2 ) has been postulated in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD).Objective: To investigate the effect of systemic aspirin (acetylsalicylic acid) administration on airway PGE 2 biosynthesis in induced sputum supernatant (ISS) among subjects with NERD or aspirin-tolerant asthma with chronic rhinosinusitis with nasal polyposis (ATA-CRSwNP), as well as healthy controls (HC). Methods:Induced sputum (IS) was collected from patients with NERD (n = 26), ATA-CRSwNP (n = 17), and HC (n = 21) at baseline and after aspirin challenge. Sputum differential cell count and IS supernatant (ISS) levels of prostanoids, PGE 2 , 8-iso-PGE 2 , tetranor-PGE-M, 8-iso-PGF 2 α, and leukotriene C 4 , D 4 , and E 4 , were determined using mass spectrometry. Urinary excretion of LTE 4 was measured by ELISA.Results: NERD subjects had elevated sputum eosinophilic count as compared to ATA-CRSwNP and HC (median NERD 9.1%, ATA-CRSwNP 2.1%, and HC 0.4%; P < 0.01). Baseline ISS levels of PGE 2 were higher in asthmatics as compared to HC at baseline (NERD vs HC P = 0.04, ATA-CRSwNP vs HC P < 0.05). Post-challenge ISS levels of PGE 2 compared to baseline significantly decreased in NERD and HC (P < 0.01 and P = 0.01), but not in ATA-CRSwNP. In NERD, a similar decrease in PGE 2 as in HC resulted from 2.8 times lower dose of aspirin. Conclusion:Aspirin-precipitated bronchoconstriction is associated with a decrease in airway PGE 2 biosynthesis. These results support the mechanism of PGE 2 biosynthesis inhibition as a trigger for bronchoconstriction in NERD. K E Y W O R D Seicosanoids, induced sputum, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, oral aspirin challenge, prostaglandins Abbreviations: ATA-CRSwNP, aspirin-tolerant asthma with chronic rhinosinusitis with nasal polyposis; COX, cyclooxygenase; Cys-LTs, cysteinyl leukotrienes; HC, healthy control; LTC4, leukotriene C4; LTD4, leukotriene D4; LTE4, leukotriene E4; NERD, nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease; NSAIDs, nonsteroidal anti-inflammatory drugs; PGE2, prostaglandin E2; Tetranor-PGE-M, 9,15-dixo-11α-hydroxy-2,3,4,5-tetranor-prostan-1,20-dioic acid.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.