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.

理论基础：以食物为基础的癌症化学预防方法强调了复杂混合物的可能性 在整个食品中使用预防性药物，以抑制多种致癌过程。支持这一点的有几个 已进行的临床前动物研究表明，阿魏酸具有显著的化学预防活性。 冷冻干燥的黑色覆盆子[LBR]对肿瘤的发展，包括口腔癌。我们提供的初步数据 证明LBR的短期原位传递可以调节关键调控基因的表达 癌前患者的癌细胞和“高危正常”口腔粘膜可能有利于预防 癌症的发展。假设：手术后头颈部长期每日暴露于LBR[HN] 癌症患者将调节口腔癌发展过程中关键基因的表达。这种调制 可以预测LBR在人类口腔癌发生中的预防潜力。实验方法：IBIIA阶段 将在210名手术切除I期或II期HN的患者中进行手术后临床试验 癌症。在两个递送系统中每天给予LBR剂量(0，4，8克)，为期6个月。口头的 在选定的时间点收集口腔刮片、血液、尿液和唾液，并对结果进行评估。 黏附/暴露、安全/毒性和调节与以下相关的特定基因表达的能力 致癌进展。具体目标：目标1.确定术后患者对临床的依从性 试验设计期望和确定长期服用LBR的耐受性和潜在的不良影响。 目的2.确定暴露、剂量和递送工具与LBR摄取之间的相互关系 口腔组织中的成分。目的3.评估LBR在高危人群口腔中调节基因表达的能力 口腔癌术后粘膜。目的4.分析以下调制基因的持久性 停止LBR治疗。这项新颖的翻译研究将提供必要的数据，建立科学的 为纳入未来第三阶段随机临床试验的实验和设计参数奠定基础 并首次研究了长期服用LBR对高危口腔粘膜的分子效应。 手术后的癌症患者。它还将提供与关键基因调控相关的有价值的见解 这可能会导致口腔癌的预防。

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