Cancer Survivorship Research and Training in Radiation Cystitis

癌症幸存者在放射治疗后有患放射性膀胱炎(RC)的风险。RC是一种令人衰弱的 膀胱，并可能危及生命。目前的治疗方法是不充分的，可能会产生严重的改变生活的副作用。 缺乏可靠的治疗和早期诊断标记物的部分原因是对 与这种情况的进展有关的组织和分子变化。 我假设是辐射对膀胱血管的损伤导致了慢性炎症， 与RC相关的纤维化和血尿。这一假设将通过三个具体目标来解决：1. 确定放射治疗对膀胱血管功能的影响，2.评估和靶向炎症 建立RC动物模型；3.验证尿液候选生物标志物早期检测RC的可行性。 研究设计包括评估内皮细胞的功能变化和确定 ICAM-1的表达及其在辐射反应中免疫细胞募集中的作用。非辐照和 环磷酰胺处理的细胞将分别作为阴性对照和阳性对照。使用RC的鼠标模型， 将确定分子和组织学膀胱对辐射的反应的时间线。未辐照 用小鼠膀胱和环磷酰胺诱导的膀胱炎作为阴性和阳性对照。 分别进行了研究。最后，有前列腺癌或宫颈癌病史的RC患者的尿样将被使用。 开发RC的生物标记物。对照组由年龄匹配的男性和女性尿样组成。 作为一名癌症幸存者和一名科学家，我的最终职业目标是提高癌症患者的生活质量 幸存者通过我的研究。我计划通过成为一名独立的翻译调查员来实现这一目标， 将我的研究重点放在癌症治疗的泌尿系统并发症上，并将我的研究成果落实到 诊所。 通过我过去的研究记录，我在血管基础科学技术方面有丰富的经验 和癌症生物学。成功完成本研究和培训计划所需的其他必要技能将 通过翻译研究、辐射和生物统计学方面的指导和课程学习获得。此外，我 将接受病毒感染和病理学方面的实践培训。我将从以下公司获得持续指导 夏尔博士和兰姆博士。金井博士和威尔逊博士将担任共同导师。我的导师有一段成功的历史 NIH科学家的指导，我们在博蒙特研究公司拥有一流的支持性培训环境 研究所和奥克兰大学威廉·博蒙特医学院。 我们的研究结果可以显著提高许多癌症幸存者的生活质量 因放射治疗而出现严重的膀胱并发症。这些研究可能会导致找到有效的 RC的治疗以及早期检测RC的尿液生物标志物。这项研究研究具有很大的潜力 改善患有这种衰弱疾病的癌症幸存者的生活质量。

Cancer survivors are at risk for developing radiation cystitis (RC) after radiation therapy. RC is a debilitating bladder and may be life-threatening. Current therapies are inadequate and can have severe life changing side-effects. The absence of reliable treatment and early diagnostic markers is in part due to limited comprehension of the histological and molecular changes associated with the progression of this condition. I hypothesize that radiation-induced damage to the bladder vasculature drives the chronic inflammation, fibrosis and hematuria associated with RC. This hypothesis will be addressed through three specific aims: 1. Determine the effect of radiation therapy on bladder vasculature function, 2. Assess and target the inflammation in an animal model of RC, and 3. Validate urinary candidate biomarkers for early detection of RC. The study design includes assessing functional changes of endothelial cells and determining changes in ICAM-1 expression and its role in immune cell recruitment in response to irradiation. Non-irradiated and cyclophosphamide treated cells will serve as negative and positive controls respectively. Using a mouse model of RC, a timeline of molecular and histological bladder changes in response to radiation will be determined. Non-irradiated bladders and cyclophosphamide-induced cystitis in mice will be used as negative and positive controls for these studies respectively. Finally urine samples from RC patients with a history of prostate or cervical cancer will be used to develop a biomarker for RC. Controls consist of age-matched male and female urine samples. As a cancer survivor and a scientist, my ultimate career goal is to improve the quality of life of cancer survivors through my research. I plan on achieving this goal by becoming an independent translation investigator, focusing my research on urological complications from cancer therapies, and implementing my research findings into the clinic. Through my past research track record, I have extensive experience in basic science techniques in vascular and cancer biology. The additional necessary skills to successfully complete this research and training proposal will be acquired through mentorship and coursework in translational research, radiation, and biostatistics. In addition, I will be receiving practical training in viral infections and pathology. I will be receiving continuous mentorship from Drs. Chancellor and Lamb. Drs. Kanai and Wilson will serve as co-mentors. My mentors have a history of successful mentorship of NIH scientists and we have a superb and supportive training environment here at Beaumont Research Institute and Oakland University William Beaumont School of Medicine. The outcome of our studies can significantly improve the quality of life of many cancer survivors that are suffering with severe bladder complications due to radiation therapy. These studies could lead to finding effective therapy for RC as well as a urine biomarker for early detection of RC. This research study has great potential to improve the quality of life of cancer survivors suffering from this debilitating condition.