Food-Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer

基于食物的口腔癌高风险人体组织中生物标志物的调节

• 批准号: 8197486
• 负责人: CHRISTOPHER M WEGHORST
• 金额: $ 30.19万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197486
• 关键词: Address; Adherence; Adverse effects; Adverse event; Animals; Berry; Biological; Biological Markers; Biopsy; Blood; Cancer Patient; Cells; Chemopreventive Agent; Chronic; Clinical Trials; Clinical Trials Design; Collection; Common Terminology Criteria for Adverse Events; Complex Mixtures; Consumption; Data; Detection; Development; Diagnosis; Dose; Epithelial; Epithelial Cells; Excision; Experimental Designs; Food; Foundations; Frequencies; Future; Gene Expression; Gene Expression Profile; Genes; Head and Neck Cancer; High Pressure Liquid Chromatography; Human; In Situ; Individual; Interview; Lead; Lesion; Long-Term Effects; Mass Spectrum Analysis; Methods; Molecular; Molecular Profiling; Normal tissue morphology; Operative Surgical Procedures; Oral; Oral cavity; Oral health; Oral mucous membrane structure; Outcome; Pathway interactions; Patients; Phase; Plasma; Preventive; Principal Investigator; Process; Randomized Clinical Trials; Raspberries; Recurrence; Regulator Genes; Regulatory Pathway; Reverse Transcriptase Polymerase Chain Reaction; Risk; Safety; Saliva; Sampling; Schedule; Self Administration; Series; Severities; Staging; System; Testing; Time; Tissues; Toxic effect; Urine; base; cancer cell; cancer chemoprevention; cancer prevention; carcinogenesis; cohort; diaries; expectation; head and neck cancer patient; high risk; human tissue; insight; malignant mouth neoplasm; medical appointment; novel; oral cancer prevention; oral carcinogenesis; oral tissue; pre-clinical; programs; translational study; tumor; uptake

Rationale: A food-based approach to cancer chemoprevention emphasizes the potential for complex mixtures of preventive agents in whole foods to inhibit multiple processes of carcinogenesis. Supporting this, several preclinical animal studies have been conducted that demonstrate the remarkable chemopreventive activity of lyophilyzed black raspberries [LBR] on tumor development, including oral cancer. Preliminary data by us demonstrate that short-term in situ delivery of LBR can modulate the expression of key regulatory genes in cancer cells and "at-risk normal" oral mucosa of pre-surgical cancer patients that may favor the prevention of cancer development. Hypothesis: Long-term daily exposure of LBR by post-surgical head and neck [HN] cancer patients will modulate expression of genes critical in the development of oral cancer. This modulation may predict the preventive potential of LBR in human oral carcinogenesis. Experimental Approach: Phase IBIIA post-surgical clinical trials will be conducted in 210 individuals following surgical resection of stage I or II HN cancers. Daily LBR doses (0, 4, 8 gm) in two delivery systems will be given for a period of six months. Oral cavity scrapings, blood, urine, and saliva will be collected at selected time points and evaluated for outcomes of adherance/exposure, safety/toxicity, and capacity to modulate specific gene expressions associated with carcinogenic progression. Specific Aims: Aim 1. Determine the adherence of post-surgical patients to clinical trial design expectations and define tolerability and, potential adverse effects of long-term LBR administration. Aim 2. Determine the interrelationships between exposure, dose and delivery vehicle, and uptake of LBR components in oral tissues. Aim 3. Evaluate the ability of LBR to modulate gene expression in ¿high-risk¿ oral mucosa of post-surgical oral cancer. Aim 4. Analyze for the persistence of modulation genes following cessation of LBR treatment. This novel translational study will provide essential data establishing the scientific foundation for experimental and design parameters to be included in a future Phase III randomized clinical trial and is the first to examine the molecular effects of long-term LBR administration on ¿at-risk¿ oral mucosa in post-surgical cancer patients. It will also provide valuable insights related to the modulation of critical genes that might lead to oral cancer prevention.

理由：基于食物的癌症化学预防方法强调了复杂混合物的潜力 天然食品中的预防剂可以抑制多种致癌过程，这支持了这一点。 已进行的临床前动物研究证明了显着的化学预防活性 我们提供的冻干黑树莓 [LBR] 对肿瘤发展（包括口腔癌）的初步数据。 证明短期原位递送 LBR 可以调节关键调控基因的表达 术前癌症患者的癌细胞和“有风险的正常”口腔粘膜可能有利于预防 假设：术后头颈部长期每日接触 LBR [HN] 癌症患者会调节对口腔癌发展至关重要的基因的表达。 可以预测 LBR 在人类口腔癌发生中的预防潜力：IBIIA 期。 术后临床试验将在 210 名 I 期或 II 期 HN 手术切除后的个体中进行 癌症患者将通过两种给药系统每日口服 LBR 剂量（0、4、8 克），为期六个月。 将在选定的时间点收集口腔刮屑、血液、尿液和唾液并评估结果 依从性/暴露、安全性/毒性以及调节与相关的特定基因表达的能力 具体目标： 目标 1. 确定术后患者对临床的依从性。 试验设计预期并确定长期 LBR 给药的耐受性和潜在副作用。 目标 2. 确定暴露、剂量和递送载体与 LBR 摄取之间的相互关系 目标 3. 评估 LBR 调节 ¿ 基因表达的能力。高风险??口服 目标 4. 分析术后口腔癌粘膜的调节基因的持续性。 这项新颖的转化研究将提供建立科学依据的重要数据。 为未来 III 期随机临床试验中包含的实验和设计参数奠定基础 并且是第一个研究长期 LBR 给药对 ¿有风险??口腔粘膜在 它还将为术后癌症患者提供与关键基因调节相关的宝贵见解。 这可能有助于预防口腔癌。

项目成果

Storage conditions modulate the metabolomic profile of a black raspberry nectar with minimal impact on bioactivity.

储存条件可调节黑树莓花蜜的代谢组学特征，而对生物活性的影响极小。

• DOI: 10.1039/c8fo00639c
• 发表时间: 2018
• 期刊: Food & function
• 影响因子: 6.1
• 作者: Teegarden,MatthewD;Knobloch,ThomasJ;Weghorst,ChristopherM;Cooperstone,JessicaL;Peterson,DevinG
• 通讯作者: Peterson,DevinG