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，这些亚型占所有确诊癌症的40%。 美国每年一次。美国印第安人/阿拉斯加原住民(AI/AN)有1.6倍的可能性 比一般人群都要肥胖。许多因素都会影响这种高风险，包括贫困、非传统的 食物、健康的相关社会决定因素以及缺乏体力活动。此外，人工智能/人工智能的人最差 美国任何种族的癌症存活率。肥胖相关炎症可能导致癌症风险和不良反应 然而，这是一个可逆的过程。众所周知，AI/AN在临床试验中的代表性不足 研究，更重要的是，它们从未被包括在旨在调节 癌症手术前的炎症。一小部分以生活方式干预为特色的非人工智能/AN研究 在诊断出肥胖相关癌症后，在短期机会窗口(WIO)期间实施 在癌症手术前，一种被称为康复(Prehab)的策略已经显示出一些重要的发现。 这些变化包括血清和肿瘤中炎症标志物的表达水平的变化。 微环境(TME)，可能影响致癌的因素。鉴于肥胖率较高 更糟糕的癌症结果，AI/AN人群可能从这一系列研究中获得最大的收益。我们 假设康复前干预以出版的文献为模型，然后改编成社区 人工智能癌症患者的协作将在调节炎症方面是可行的、可接受的和成功的 生物标志物。拟议的项目是：(1)使用 候选人初步研究，(2)实施针对AI患者的康复前翻译临床试验 准备手术的肥胖相关实体肿瘤以及(3)在手术前和手术前检测炎性生物标记物 干预后评估反应性。研究结果包括血清前后的比较 生物标志物(胰岛素、瘦素、超敏C反应蛋白、IL-6、肿瘤坏死因子α、皮质醇AM、前白蛋白)；组织生物标志物(Ki67、胰岛素 受体、肿瘤坏死因子α、核因子κB、NOS2、裂解半胱氨酸酶-3)；人体测量(血压、体重、 生活方式行为测量(有效的饮食/锻炼工具：REAPS、iPAQ、6MWT、STS)。 拟议的培训计划以申请人在外科肿瘤学、公共卫生和人工智能/AN方面的背景为基础 癌症差异包括以下方面的新培训：(A)临床试验设计和实施，(B)生物标记物 测量和(C)专业发展。严谨的研究和培训策略将促进 候选人的目标是成功转型为独立的、有资金支持的翻译临床试验人员 代表AI/AN缩小癌症差异。这将在一位经验丰富的 为AI/AN服务的亚利桑那大学的指导团队和资源充足的培训环境 该中心是亚利桑那州唯一一家由NCI指定的综合癌症中心的所在地。

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.