Insulin resistance in the development and progression of invasive bladder cancer

浸润性膀胱癌发生和进展中的胰岛素抵抗

• 批准号: 9284276
• 负责人: Ronac Mamtani
• 金额: $ 17.44万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-06 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9284276
• 关键词: Accounting; Address; Award; Benefits and Risks; Biological Markers; Biometry; Bladder; Bladder Neoplasm; Blood specimen; Case-Control Studies; Clinical; Clinical Data; Collaborations; Curative Surgery; Cystectomy; Data; Data Quality; Data Set; Databases; Development; Development Plans; Diabetes Mellitus; Diagnosis; Disease; Endocrinology; Enrollment; Epidemiology; Functional disorder; Future; Goals; Growth; Health; Incidence; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Integration Host Factors; Intervention; Intervention Studies; K-Series Research Career Programs; Knowledge; Lead; Link; Malignant Neoplasms; Malignant neoplasm of urinary bladder; Measures; Medical; Medicine; Mentors; Mentorship; Metabolic; Metabolism; Methods; Modeling; Modernization; Modification; Morbidity - disease rate; Muscle; Neoplasms; Obesity; Observational Study; Operative Surgical Procedures; Outcome; Pathological Staging; Patient Care; Patient Selection; Patients; Pennsylvania; Performance; Play; Population; Positioning Attribute; Prevalence; Prior Chemotherapy; Prospective cohort; Prospective cohort study; Radical Cystectomy; Recurrence; Research; Research Methodology; Research Personnel; Risk; Risk Assessment; Risk Factors; Role; Selection for Treatments; Senior Scientist; Specimen; Staging; Structure; System; Testing; Time; Training; Translational Research; Tumor Pathology; Universities; Urogenital Cancer; aggressive therapy; base; biobank; biomarker discovery; cancer care; cancer recurrence; cancer therapy; career; career development; chemotherapy; clinical epidemiology; clinical practice; cohort; design; economic cost; experience; experimental study; improved; improved outcome; insight; interest; mortality; novel; oncology; patient oriented; patient oriented research; personalized approach; population based; professor; prognostic; prospective; public health relevance; response; risk selection; skills; success; theories; tool; tumor; tumor progression

 DESCRIPTION (provided by applicant): This application proposes a career development award for an Assistant Professor of Medicine in Oncology at the University of Pennsylvania with scientific interest in understanding the role of host factors, and their modification, on genitourinary cancer outcomes. During the course of this award, he will identify metabolic predictors of poor outcome in patients with muscle-invasive bladder cancer. This award will enable him to evolve into an independent investigator, conducting both population-based and patient-oriented research to inform a more personalized approach to genitourinary cancer therapy. New skills and further knowledge will be obtained in a 5-year career development plan that spans the fields of epidemiology, oncology, and endocrinology through (1) advanced training in epidemiology and biostatistics; (2) new training in translational research methodology; (3) new hands-on experience in prospective observational research; (4) intensive mentorship and collaboration with senior scientists; and (5) the performance of original research. To achieve these goals, the candidate has assembled a mentoring team with expertise in clinical epidemiology, bladder cancer care, metabolism, translational science, and biostatistics, all of whom are not only accomplished researchers but also successful mentors and leaders in their respective fields. Muscle-invasive tumor is the major cause of morbidity and mortality from bladder cancer. Pre-operative chemotherapy is associated with improved survival, but responses are seen in only 30-40% of patients. Current methods for predicting bladder cancer recurrence rely on tumor pathology, which is available only after surgery (cystectomy) and therefore cannot inform decisions about use of chemotherapy prior to cystectomy. Host-related factors associated with tumor recurrence have not yet been identified, although insulin resistance may play a role. This research will first employ a novel database to conduct a case-control study assessing clinical insulin resistance, defined as a diagnosis with diabetes and/or obesity, as a risk factor for the development of bladder cancer recurrence after cystectomy (AIM 1). Next, the candidate will conduct a prospective cohort study in patients treated with cystectomy to examine risk of bladder cancer recurrence in relation to subclinical insulin resistance (AIM 2), measured by homeostatic model assessment (HOMA). Results from these studies could be implemented into clinical practice to improve individualized prognostication and selection of patients likely to benefit from risk-reducing pre-operative chemotherapy. Finally, the candidate will create a biobank of bladder tumor specimens and blood samples from enrolled cohort patients which will be available for later biomarker discovery studies related to the applicant's current and future hypotheses. This training will enable the candidate to transition seamlessly between population- and patient-oriented methods, selecting the design best suited to answer each question. A structured training plan with rigorously mentored scientific study is proposed to position the candidate for independence at the end of five years.

 描述（由申请人提供）：本申请为宾夕法尼亚大学肿瘤学医学助理教授提供职业发展奖，该教授对理解宿主因素及其修饰对泌尿生殖系统癌症结果的作用有科学兴趣。获得该奖项后，他将确定肌肉浸润性膀胱癌患者预后不良的代谢预测因素。该奖项将使他能够发展成为一名独立研究者，开展基于人群和以患者为导向的研究，以提供更个性化的治疗方法。通过（1）流行病学和生物统计学的高级培训（2）转化研究方法的新培训，将在跨越流行病学、肿瘤学和内分泌学领域的五年职业发展计划中获得新的技能和知识； ; （3）前瞻性观察研究的新实践经验；（4）与资深科学家的深入指导和合作；以及（5）原创研究的表现为了实现这些目标，候选人组建了一支具有临床专业知识的指导团队。流行病学、膀胱癌护理、新陈代谢、转化科学和生物统计学，他们不仅是各自领域的杰出研究人员，也是成功的导师和领导者。肌肉侵袭性肿瘤是膀胱癌发病和死亡的主要原因。 - 手术化疗是与提高生存率相关，但目前预测膀胱癌复发的方法仅依赖于肿瘤病理学，而肿瘤病理学仅在手术（膀胱切除术）后可用，因此无法为化疗前的使用决策提供依据。膀胱切除术。尽管胰岛素抵抗可能发挥作用，但与肿瘤复发相关的宿主相关因素尚未确定。这项研究将首先使用一个新的数据库来进行评估临床胰岛素抵抗（定义为糖尿病的诊断）的病例对照研究。和/或肥胖，作为危险因素接下来，候选人将对膀胱切除术患者进行前瞻性队列研究，以检查膀胱癌复发与亚临床胰岛素抵抗的关系（AIM 2），通过稳态模型评估进行测量。 (HOMA)。这些研究的结果可以应用于临床实践，以改善个体化预后并选择可能受益于降低风险的术前化疗的患者。 候选人将创建一个膀胱肿瘤标本和来自入组患者的血液样本的生物库，这些样本将可用于与申请人当前和未来假设相关的后续生物标志物发现研究。该培训将使候选人能够在面向人群和面向患者之间无缝过渡。方法，选择最能回答每个问题的设计，提出一个经过严格指导的科学研究的结构化培训计划，以便在五年后为候选人提供独立的定位。