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

对美洲印第安人癌症患者炎症生物标志物的营养和运动预康复干预

• 批准号: 10739958
• 负责人: JENNIFER A ERDRICH
• 金额: $ 27.16万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10739958
• 关键词: Activities of Daily Living; Age; Alaska Native; American Indians; Anti-Inflammatory Agents; Arizona; Biological Markers; Blood Pressure; CASP3 gene; Cancer Patient; Cancer Survivor; Carcinogenesis Mechanism; Clinical Oncology; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Collection; Communities; Comprehensive Cancer Center; Data; Development; Diagnosis; Diet; Dietary Intervention; Enrollment; Environment; Excision; Exercise; Fitness Centers; Food; Funding; Future; General Population; Goals; Habilitation; High Prevalence; Home; Hydrocortisone; Incidence; Inflammation; Inflammatory; Institution; Institutional Review Boards; Insulin; Insulin Receptor; Interleukin-6; Intervention; Intervention Studies; Intervention Trial; Interview; Juglans; Leptin; Life Style; Life Style Modification; Link; Literature; Malignant Neoplasms; Measurement; Measures; Mentorship; Metabolic dysfunction; Modeling; NOS2A gene; Native-Born; Obesity; Obesity associated cancer; Operative Surgical Procedures; Outcome; Outcome Measure; Outcome Study; Participant; Patients; Pattern; Phase; Physical activity; Population; Positioning Attribute; Postoperative Period; Poverty; Prealbumin; Process; Public Health; Publishing; Qualitative Research; Reporting; Research; Research Personnel; Resources; Risk; Sampling; Schedule; Serum; Serum Markers; Solid Neoplasm; Structure; Surgical Oncology; Surveys; Survival Rate; TNF gene; Testing; Time; Tissue Sample; Tissues; Training; Translations; Treatment-Related Cancer; Tribal Council; Tribes; Underrepresented Populations; United States; Universities; Walking; Weight; Work; Writing; adverse outcome; behavior change; behavior measurement; biomarker selection; cancer diagnosis; cancer health disparity; cancer risk; cancer subtypes; cancer surgery; cancer survival; carcinogenesis; career; clinical translation; diet and exercise; exercise intervention; experience; feasibility testing; functional improvement; health equity; improved; inflammatory marker; inflammatory milieu; inflammatory modulation; lifestyle intervention; mortality; novel; nutrition; obese patients; operation; peer; physical inactivity; post intervention; programs; psychologic; racial population; skills; smoking cessation; social health determinants; study population; therapy design; tissue biomarkers; tool; translational clinical trial; trial design; tribal Nation; tribal member; tumor; tumor microenvironment; waist circumference

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.

项目摘要 有13种与肥胖有关的癌症亚型，这些占所有被诊断出的癌症的40％ 每年美国。美洲印第安人/阿拉斯加本地人（AI/AN）人口的可能性高1.6倍 肥胖比普通人群。许多因素会影响这种较高的风险，包括贫困，非传统 食物，相关的健康社会决定者和身体不活动。此外，AI/AN人的最糟糕 任何美国种族组的癌症存活率。与肥胖相关的炎症可能会导致癌症风险和不利 结果，但是这是一个可逆的过程。众所周知，AI/AN在临床试验中的人数不足，并且 研究，更重要的是，它们从未被包括在旨在调节的干预措施中 癌症手术前的炎症。少数在非AI/具有生活方式干预措施的研究 诊断出与肥胖相关癌症的诊断，并在机会短途窗口（WOO）中实施 在癌症手术之前，一种称为预居住（Prehab）的策略已显示出一些重要的发现。 这些包括改变血清和肿瘤中炎症标记的表达水平 微环境（TME），可能影响致癌的因素。鉴于肥胖的患病率较高 而且癌症的结果更糟糕，AI/A人群可能从这一研究中获得最大的收益。我们 假设是以出版的文献进行建模的预先干预措施，然后与社区改编 AI癌症患者的协作将是可行的，可接受且成功调节炎症的 生物标志物。拟议的项目是（1）使用 候选人的初步研究，（2）为AI患者实施了预先翻译的临床试验 肥胖相关的实体瘤癌为手术做准备，（3）测量炎症生物标志物的前和 干预后评估响应能力。研究结果包括序列的前后比较 生物标志物（胰岛素，瘦素，HSCRP，IL-6，TNFα，皮质醇AM，prealbumin）;组织生物标志物（KI67，胰岛素 受体，TNFα，NFκB，NOS2，裂解caspase-3）;人体测量值（血压，体重， 腰圈）;生活方式行为措施（经过验证的饮食/运动工具：REAP，IPAQ，6MWT，STS）。 拟议的培训计划以手术肿瘤学，公共卫生和AI/AN的申请人背景为基础 癌症分布以包括（a）临床试验设计和实施中的新培训，（b）生物标志物 测量和（c）专业发展。严格的研究和培训策略将促进 候选人成功地转变为独立的，资助的翻译临床试验者的目标 代表AI/AN到狭窄的癌症差异。这将在经验丰富的支持下实现 AI/AN-AN-Servaning Arizona大学的Menorship团队和资源良好的培训环境 机构和亚利桑那州唯一的NCI指定综合癌症中心的所在地。