Department of Molecular Medicine, Iran University of Medical Science, 14496-14530, Tehran, Iran.
ATRAB-Applied and Translational Radiobiology, Department of Radiation Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Strahlenther Onkol. 2019 Oct;195(10):934-939. doi: 10.1007/s00066-019-01497-8. Epub 2019 Jul 30.
The urinary bladder is one major organ at risk in radiotherapy of pelvic malignancies. The radiation response manifests in early and chronic changes in bladder function. These are based on inflammatory effects and changes in urothelial cell function and proliferation. This study evaluates the effect of bortezomib as an anti-proliferative and anti-inflammatory compound in an established mouse bladder model. The early radiation-induced bladder dysfunction in the mouse occurs in two phases during the first month after irradiation (phase I: day 0-15, phase II: days 16-30).
Daily bortezomib injections (0.02 mg/ml, subcutaneously) were administered between days 0-15 or 15-30 in separate groups. Single graded radiation doses were administered in five dose groups. Cystometry was carried out before (individual control) and during the first month after irradiation. When bladder capacity was decreased by ≥50%, mice were considered as responders. Statistical analysis was performed by the SPSS software version 24.
Daily bortezomib injections between days 0-15 resulted in a significant decrease in responders for phase I. There was no significant effect with daily bortezomib injections between days 16-30.
Two separate waves of acute radiation-induced urinary bladder dysfunction have distinct mechanisms that need further biological studies.
膀胱是盆腔恶性肿瘤放疗中易受影响的主要器官之一。放射反应表现为膀胱功能的早期和慢性变化。这些变化基于炎症效应以及尿路上皮细胞功能和增殖的改变。本研究评估了硼替佐米作为一种抗增殖和抗炎化合物在已建立的小鼠膀胱模型中的作用。在照射后第一个月内，小鼠早期的放射性膀胱功能障碍分为两个阶段（I 期：第 0-15 天，II 期：第 16-30 天）。
分别在第 0-15 天或第 15-30 天的两组中给予每日硼替佐米注射（0.02mg/ml，皮下注射）。在五个剂量组中给予单次递增剂量的照射。在照射前（个体对照）和照射后第一个月进行尿动力学检查。当膀胱容量减少≥50%时，将小鼠视为反应者。使用 SPSS 软件版本 24 进行统计分析。
在第 0-15 天期间每日给予硼替佐米注射可显著减少 I 期反应者。在第 16-30 天期间每日给予硼替佐米注射没有显著影响。
急性放射性膀胱功能障碍的两个独立波具有不同的机制，需要进一步的生物学研究。
