A Nutrition and Exercise Prehabilitation Intervention on Inflammatory Biomarkers in American Indian Cancer Patients

项目摘要 有13种癌症亚型与肥胖有关，占所有癌症诊断的40%。 美国每年。美国印第安人/阿拉斯加原住民（AI/AN）人口的死亡率是其他人的1.6倍。 比一般人群肥胖。许多因素影响这种高风险，包括贫困，非传统 食物、健康的相关社会决定因素和缺乏身体活动。此外，AI/AN的人有最糟糕的 美国任何种族的癌症存活率。肥胖相关的炎症可能会导致癌症风险和不良反应 结果，然而，这是一个可逆过程。已知AI/AN在临床试验中代表性不足， 研究，更重要的是，他们从来没有被包括在一个干预，旨在调节 癌症手术前的炎症。少数非AI/AN研究以生活方式干预为特征 在诊断出肥胖相关癌症后，并在短期机会窗口（WOO）期间实施 在癌症手术之前，一种被称为prehab（prehab）的策略已经显示出一些重要的发现。 这些包括血清和肿瘤中炎症标记物表达水平的改变 微环境（TME），可能影响致癌作用的因素。考虑到肥胖症的高发率 和更糟糕的癌症结果，AI/AN人群可能从这一研究中获得最大的收益。我们 假设根据已发表的文献建立的预治疗干预模型， AI癌症患者的合作将是可行的，可接受的，并成功地调节炎症 生物标志物。拟议的项目是（1）使用 候选人的初步研究，（2）实施AI患者的prehab转化临床试验， 准备手术的肥胖相关实体瘤癌症，以及（3）测量术前和术后的炎性生物标志物， 干预后评估反应性。研究结果包括血清中的前和后比较， 生物标志物（胰岛素、瘦素、hsCRP、IL-6、TNFα、皮质醇AM、前白蛋白）;组织生物标志物（Ki 67、胰岛素 受体，TNFα，NFκB，NOS 2，裂解的半胱天冬酶-3）;人体测量（血压，体重， 腰围）;生活方式行为测量（经验证的饮食/运动工具：REAPS、IPAQ、6 MWT、STS）。 拟议的培训计划建立在申请人在外科肿瘤学，公共卫生和AI/AN的背景之上 癌症差异包括（a）临床试验设计和实施，（B）生物标志物 （c）专业发展。严格的研究和培训战略将促进 候选人的目标是成功地转变为一个独立的，资助的翻译临床试验工作 代表AI/AN缩小癌症差异。这将在一位经验丰富的 导师团队和亚利桑那大学资源充足的培训环境，一个AI/AN服务 该机构是亚利桑那州唯一一家NCI指定的综合癌症中心。

PROJECT ABSTRACT There are 13 cancer subtypes that are linked to obesity and these account for 40% of all cancers diagnosed in the United States annually. American Indian/Alaska Native (AI/AN) populations are 1.6 times more likely to be obese than the general population. Many factors influence this elevated risk including poverty, nontraditional foods, related social determinants of health, and physical inactivity. Furthermore, AI/AN people have the worst cancer survival rates of any US racial group. Obesity-related inflammation likely drives cancer risk and adverse outcomes, and yet, this is a reversible process. AI/AN are known to be underrepresented in clinical trials and research, and even more importantly, they have never been included in an intervention designed to modulate inflammation prior to cancer surgery. A small handful of studies in non-AI/AN featuring lifestyle interventions following diagnosis of obesity-related cancer and implemented during the short window of opportunity (WOO) before cancer surgery, a strategy known as prehabilitation (prehab), have shown some significant findings. These include alterations in the expression levels of inflammatory markers in serum and the tumor microenvironment (TME), factors that may influence carcinogenesis. Given the higher prevalence of obesity and worse cancer outcomes, the AI/AN population may have the greatest gains from this line of research. We hypothesize that a prehab intervention modeled after published literature then adapted with community collaboration for AI cancer patients will be feasible, acceptable, and successful at modulating inflammatory biomarkers. The proposed project is to (1) complete the adaptation of a prehab intervention using the candidate’s preliminary research, (2) implement the prehab translational clinical trial for AI patients with obesity-related solid tumor cancer preparing for surgery, and (3) measure inflammatory biomarkers pre and post-intervention to assess responsiveness. Study outcomes include pre and post comparisons of serum biomarkers (insulin, leptin, hsCRP, IL-6, TNFα, cortisol AM, prealbumin); tissue biomarkers (Ki67, insulin receptor, TNFα, NFκB, NOS2, cleaved caspase-3); anthropometric measurements (blood pressure, weight, waist circumference); lifestyle behavioral measures (validated diet/exercise tools: REAPS, IPAQ, 6MWT, STS). The proposed training plan builds on the applicant’s background in surgical oncology, public health, and AI/AN cancer disparities to include new training in (a) clinical trial design and implementation, (b) biomarker measurement and (c) professional development. The rigorous research and training strategies will promote the candidate’s goal of successfully transforming into an independent, funded translational clinical trialist working on behalf of AI/AN to narrow cancer disparities. This will be achieved with the support of a highly experienced mentorship team and the well-resourced training environment of The University of Arizona, an AI/AN-serving institution and home to the only NCI-designated Comprehensive Cancer Center in the state of Arizona.