Cancer Survivorship Research and Training in Radiation Cystitis

放射性膀胱炎的癌症生存研究和培训

• 批准号: 9768473
• 负责人: Bernadette Margaretha Maria Zwaans
• 金额: $ 12.95万
• 依托单位: WILLIAM BEAUMONT HOSPITAL RESEARCH INST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9768473
• 关键词: Address; Adhesions; Age; Albumins; Animal Model; Animals; Anti-inflammatory; Basic Science; Biological Assay; Biological Markers; Biometry; Bladder; Blood Vessels; Blood coagulation; Cancer Biology; Cancer Survivor; Cancer Survivorship; Cell Aging; Cell physiology; Cells; Chronic; Climacteric; Clinic; Clinical; Collaborations; Comprehension; Cyclophosphamide; Cystectomy; Cystitis; Development; Disease Progression; Early Diagnosis; Endothelial Cells; Endothelium; Environment; Exposure to; Female; Fibrosis; Formalin; Goals; Grant; Hematuria; Hemorrhage; Histologic; Human; Immune; In Vitro; Increased frequency of micturition; Inflammation; Inflammatory; Inflammatory Response; Intercellular adhesion molecule 1; Interleukin-1; Interstitial Collagenase; Intervention; Knowledge; Lead; Leukocytes; Life; Ligands; Malignant neoplasm of cervix uteri; Malignant neoplasm of prostate; Maps; Medical; Mentors; Mentorship; Mesenchymal; Microscopic; Molecular; Molecular Diagnostic Testing; Mus; Outcome; Outcome Study; PGF gene; Pain; Pathology; Patient Care; Patients; Pelvic Cancer; Pharmaceutical Preparations; Property; Proteins; Quality of life; Radiation; Radiation Dosage; Radiation Oncology; Radiation exposure; Radiation induced damage; Radiation therapy; Recording of previous events; Research; Research Design; Research Institute; Research Personnel; Research Training; Risk; Rodent; Rodent Model; Role; Sampling; Scientist; Site; Symptoms; TNF gene; Tacrolimus; Techniques; Testing; TimeLine; Training; Translating; Translational Research; Translations; Tube; United States; United States National Institutes of Health; Universities; Urge Incontinence; Urine; Urology; Vascular Endothelial Growth Factors; Virus Diseases; base; cancer complication; cancer therapy; candidate marker; career; chemokine; cohort; connective tissue growth factor; conventional therapy; cytokine; diagnostic biomarker; early detection biomarkers; effective therapy; experience; experimental study; improved; in vivo Model; irradiation; male; medical schools; migration; mouse model; novel therapeutics; pre-clinical; radiation cystitis; radiation effect; radiation response; recruit; research study; response; side effect; skills; urinary; urologic

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.

癌症幸存者在放射治疗后有发生放射性膀胱炎（RC）的风险。RC是一种使人衰弱的 膀胱，可能危及生命。目前的治疗是不够的，可能有严重的改变生活的副作用。 缺乏可靠的治疗和早期诊断标志物，部分原因是对 组织学和分子变化与这种情况的进展。 我假设放射线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。评估和靶向炎症， RC动物模型; 3.用于早期检测RC的尿液候选生物标志物。 研究设计包括评估内皮细胞的功能变化，并确定 ICAM-1的表达及其在免疫细胞对辐射的反应中的作用。未辐照和 环磷酰胺处理的细胞将分别用作阴性和阳性对照。使用RC小鼠模型， 将确定响应于辐射的分子和组织膀胱变化的时间轴。未辐照 小鼠膀胱和环磷酰胺诱导的膀胱炎将用作这些的阴性和阳性对照 分别研究。最后，将使用来自具有前列腺癌或宫颈癌病史的RC患者的尿样 开发RC的生物标志物。对照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，并将我的研究成果应用于 诊所 通过我过去的研究记录，我在血管基础科学技术方面拥有丰富的经验， 和癌症生物学。成功完成本研究和培训提案所需的其他必要技能将 通过导师和课程在转化研究，辐射和生物统计学获得。另外我 将接受病毒感染和病理学方面的实践培训。我将获得来自以下人士的持续指导 Drs.校长和兰姆金井博士和威尔逊博士将担任共同导师。我的导师们有着成功的 在博蒙研究所，我们有一个一流的和支持性的培训环境， 研究所和奥克兰大学威廉博蒙医学院。 我们的研究结果可以显着改善许多癌症幸存者的生活质量， 由于放射治疗而患有严重的膀胱并发症。这些研究可能会发现有效的 用于RC的治疗以及用于RC的早期检测的尿生物标志物。这项研究具有很大的潜力， 改善癌症幸存者的生活质量。