Podium Session

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PD12-11: Decreased Vascular Endothelial Growth Factor in Radiation Cystitis

Friday, May 12
5:10 PM - 5:20 PM
Location: BCEC: Room 159

Presentation Authors: Bernadette Zwaans*, Sarah Bartolone, Royal Oak, MI, Heinz Nicholai, Santiago de Chile, Chile, Michael Chancellor, Laura Lamb, Royal Oak, MI

Introduction: Radiation cystitis (RC) is a severely debilitating and inflammatory condition of the bladder resulting from radiation therapy to the pelvic area for which there is no curative therapy. 5-10% of cancer patients who have received pelvic radiation will develop RC, though little is known about the histological and molecular changes that drive the disease progression. A major histological hallmark of RC is vascular damage and hemorrhaging. Therefore, our study focuses on identifying early molecular changes that drive the vascular defect observed in RC using a mouse model of RC. In addition, we aim to identify potential urine biomarkers that could identify RC development prior to the appearance of symptoms.

Methods: Female C57BL/6 mice received a single dose of 40 Gy radiation delivered specifically to the bladder using a Small Animal Radiation Research Platform, a technique that simulates radiation treatment in human patients. Bladder tissues were harvested at 2 and 12 weeks post irradiation and processed for histology or molecular analysis. In addition, changes in vascular endothelial growth factor (VEGF) and cytokine/chemokine expression were analyzed in human urine samples from cancer survivors that received pelvic radiation.

Results: Bladder irradiation was well tolerated by mice. By 12 weeks, decreased bladder vascularization was detected in irradiated animals as was an increase in inflammatory cells clustered around blood vessels. This vascularization defect coincided with a loss of VEGF levels. Decreased VEGF expression was also identified in urine from symptomatic RC patients, in comparison to age-matched controls.

Conclusions: Radiation therapy for the treatment of pelvic tumors can cause severe damage to the bladder that can develop into radiation (hemorrhagic) cystitis. Blood loss through the urine is a major hallmark of RC and is caused by vascular defects that are currently not well understood. In this study irradiated mouse bladders developed reduced vascularization which coincided with a loss of VEGF expression. In addition, low levels of VEGF were also identified in the urine of symptomatic RC patients. Our findings suggest VEGF as a potential therapeutic target to treat the vascular defect in RC.

Source Of Funding: This research was supported by the Aikens Center for Neurology Research and the Urology Care Foundation Research Scholars Program (Bernadette M.M. Zwaans).

Bernadette Zwaans, PhD

Beaumont Health


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PD12-11: Decreased Vascular Endothelial Growth Factor in Radiation Cystitis

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