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Mp10-08 Decreased Endothelial Proliferation Characterizes the Vascular Defects in Radiation Cystitis

Year: 2018
Type: article
Abstract: You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I1 Apr 2018MP10-08 DECREASED ENDOTHELIAL PROLIFERATION CHARACTERIZES THE VASCULAR DEFECTS IN RADIATION CYSTITIS Bernadette Zwaans, Sarah Bartolone, Michael Chancellor, and Laura Lamb Bernadette ZwaansBernadette Zwaans More articles by this author , Sarah BartoloneSarah Bartolone More articles by this author , Michael ChancellorMichael Chancellor More articles by this author , and Laura LambLaura Lamb More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.354AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Radiation cystitis (RC), characterized by suprapubic pain, hematuria, nocturia, incontinence and frequency, is a debilitating bladder condition caused by radiation therapy directed to the pelvic area. Approximately 5-10% of cancer survivors with a history of pelvic radiation treatment will develop RC. However, the lack of knowledge on the histological and molecular drivers of RC has limited the development of effective therapies. A major histological hallmark of RC is a damaged vascular network that results in varying degrees of hemorrhaging within the bladder. Thus, we hypothesize that radiation-induced vascular damage drives the chronic inflammation, fibrosis and hemorrhaging in radiation cystitis patients. METHODS The effect of radiation on function of endothelial cells was determined in vitro using primary HUVEC. In addition, the bladder vasculature was studied in vivo in our radiation cystitis mouse model. The bladders of C57BL/6 mice received a single dose of 40 Gy irradiation using SARRP. Mice were monitored for urinary frequency and hematuria. Bladders were harvested 1 year post irradiation, processed for histology and analyzed for vascular health, fibrosis and inflammation. RESULTS Radiation decreased endothelial proliferation in a dose-dependent manner by inducing a premature senescent state, resulting in decreased migration in response to stimuli. In vivo, irradiation to the bladder results in loss of functional blood vessels, hemorrhaging, and telangiectasia. Ongoing studies are investigating the underlying mechanism that causes vascular damage in irradiated bladder tissue. CONCLUSIONS Radiation cystitis is a rare but severely debilitating side-effect from pelvic radiation therapy. In this study, we shed light into the involvement of the bladder vasculature, with decreased endothelial proliferation in a dose-dependent manner by inducing a premature senescent state, resulting in decreased migration in response to stimuli. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e118-e119 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Bernadette Zwaans More articles by this author Sarah Bartolone More articles by this author Michael Chancellor More articles by this author Laura Lamb More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Language: English
Field: Medicine
Open Access status: bronze
OpenAlex ID: W2795497738
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