Mast cells and macrophages infiltrate healing myocardial infarcts and may play an important role in regulating fibrous tissue deposition and extracellular matrix remodelling. This study examined the time-course of macrophage and mast cell accumulation in healing infarcts and studied the histological characteristics and protease expression profile of mast cells in a canine model of experimental infarction. Although macrophages were more numerous than mast cells in infarct granulation tissue, macrophage density decreased during maturation of the scar, whereas mast cell numbers remained persistently elevated. During the inflammatory phase of infarction, newly recruited leucocytes infiltrated the injured myocardium and appeared to be clustered in close proximity to degranulating cardiac mast cells. During the proliferative phase of healing, mast cells had decreased granular content and were localized close to infarct neovessels. In contrast, macrophages showed no selective localization. Mast cells in healing canine infarcts were alcian blue/safranin-positive cells that expressed both tryptase and chymase. In order to explain the pro-inflammatory and angiogenic actions of tryptase--the major secretory protein of mast cells--its effects on endothelial chemokine expression were examined. Chemokines are chemotactic cytokines that play an important role in leucocyte trafficking and angiogenesis and are highly induced in infarcts. Tryptase, a proteinase-activated receptor (PAR)-2 agonist, induced endothelial expression of the angiogenic chemokines CCL2/MCP-1 and CXCL8/IL-8, but not the angiostatic chemokine CXCL10/IP-10. Endothelial PAR-2 stimulation with the agonist peptide SLIGKV induced a similar chemokine expression profile. Mast cell tryptase may exert its angiogenic effects in part through selective stimulation of angiogenic chemokines.
IMPORTANCE Stereotactic body radiotherapy is a hypofractionated, cost-effective treatment option for localized prostate cancer. OBJECTIVE To characterize US national trends and the clinical and socioeconomic factors associated with the use of stereotactic body radiotherapy in prostate cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data collected by the National Cancer Database to assess the clinical and socioeconomic factors among 106 926 men diagnosed as having prostate cancer from 2010 to 2015 who underwent definitive radiotherapy and the trends in the use of this therapy. The initial analysis was performed between January and February 2018, with final updates performed August 2019. EXPOSURE Stereotactic body radiotherapy, defined as 5 fractions of radiotherapy. MAIN OUTCOMES AND MEASURES Temporal trends and clinical and sociodemographic factors associated with stereotactic body radiotherapy use. RESULTS In total, 106 926 patients diagnosed as having localized prostate cancer between 2010 and 2015 and receiving definitive radiotherapy were identified. White patients composed 77.3% of this cohort, whereas black patients composed 18.7%. Government-issued insurance was used by 61.2% of patients. More than 80% of patients had a Charlson-Deyo Comorbidity Index score of 0 (range, 0 to Ն3, with lower numbers indicating fewer comorbidities). In the study population, 25.7% had low-risk disease; 26.3%, favorable intermediate-risk disease; 23.3%, unfavorable intermediaterisk disease; and 24.7%, high-risk disease. The proportion of patients who underwent radiotherapy and received stereotactic body radiotherapy (a total of 5395 patients) increased from 3.1% in 2010 to 7.2% in 2015 (odds ratio, 0.36; 95% CI, 0.33-0.40; P < .001). Among the entire cohort, patients received a median dose of 36.25 Gy (range, 30.00-50.00 Gy). Androgen deprivation therapy use increased significantly as disease risk level increased among all patients receiving radiotherapy (9.5% with low risk to 76.6% with high risk; P = .02) and among those receiving stereotactic body radiotherapy (4.1% with low risk to 33.2% with high risk; P = .04) or not receiving stereotactic body radiotherapy (9.9% with low risk to 77.6% with high risk; P = .04). Patients treated at an academic center, living in an urban area, or possessing higher incomes and those who were healthier, white individuals, or were diagnosed as having lower-risk prostate cancer had higher odds of receiving stereotactic body radiotherapy. CONCLUSIONS AND RELEVANCE This study found that stereotactic body radiotherapy use in prostate cancer more than doubled from 2010 to 2015 but accounted for less than 10% of all patients undergoing radiotherapy. Androgen deprivation therapy use increased with disease risk among patients overall, regardless of receiving stereotactic body radiotherapy. Socioeconomic and clinical (continued) Key Points Question Does an association exist between clinical or socioeconomic factors and selecting stereotactic body radiosurgery to treat pro...
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.