EFFECTS OF FRUIT & VEGETABLE EXTRACTS ON CANCER MARKERS

水果的功效

• 批准号: 6773362
• 负责人: STEVEN A AKMAN
• 金额: $ 21.53万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-10 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6773362
• 关键词: antioxidants; biomarker; blood chemistry; cancer prevention; carotenoids; cell cycle proteins; chemoprevention; clinical research; clinical trial phase II; dietary supplements; flavonoids; fruit; gel electrophoresis; head /neck neoplasm; human subject; human therapy evaluation; immunocytochemistry; metastasis; neoplasm /cancer nutrition therapy; neoplasm /cancer relapse /recurrence; neoplastic growth; nutrition related tag; patient oriented research; plant extracts; squamous cell carcinoma; vegetables

DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial neoplasm that represents approximately 5% of newly diagnosed noncutaneous malignancies in the United States. While the primary cancers have been successfully treated, the development of second primary tumors (SPTs) is the most important factor determining the survival in early-stage head and neck cancer patients. To improve the survival of head and neck cancer patients, an effective program of chemoprevention for second malignancies is essential. This prospective, randomized double-blind Phase II chemoprevention trial is designed to assess the effects of fruit and vegetable (F&V) extracts on cell cycle regulation, DNA damage/repair, and immune function, which are associated with the development of SPTs in patient with previous HNSCC. We believe that supplementation of F&V extracts may provide efficacy without side effects, a combination that is critical for long-term chemoprevention in both high-risk cancer patients and low-risk healthy populations. The application of such biomarkers will significantly shorten the time required for clinical efficacy evaluation for promising chemopreventive agents. We will have biomarker data on at least 120 subjects (60 each arm) at the end of the 12 week trial period. The primary aim is to test the working hypothesis that F&V extracts can modulate primary intermediate endpoint, the expression of a cell cycle regulatory protein, p27, which is associated with tumor progression, recurrence, and disease-free survival of patients with HNSCC. The secondary endpoints are cell proliferation (Ki-67), DNA damage/repair (Comet assay), and immune function (T-cell activation). The proposed research will use a novel complementary and alternative (CAM) approach to cancer chemoprevention. The results will provide critical information on: (1) the use of surrogate endpoint(s) in monitoring the biological effects of F&V extracts, (2) the mechanisms of F&V in preventing HNSCC, and (3) the feasibility of using supplementation of F&V extract in HNSCC patients. Promising study results from this Phase II trial will lay the groundwork for larger Phase III chemoprevention trial to assess the application of F&V extracts in preventing SPTs for patients with HNSCC.

描述（由申请人提供）：头部和颈部鳞状细胞癌（HNSCC）是一种侵略性的上皮肿瘤，代表了美国新诊断的非直觉恶性肿瘤的约5％。虽然主要癌症已成功治疗，但第二个原发性肿瘤（SPT）的发展是决定早期头颈癌患者生存的最重要因素。为了提高头颈癌患者的存活，对于第二次恶性肿瘤的有效化学预防计划是必不可少的。这项前瞻性双盲阶段II化学预防试验旨在评估果实和蔬菜（F＆V）提取物对细胞周期调节，DNA损伤/修复和免疫功能的影响，这与先前HNSCC患者的SPTS发展有关。我们认为，补充F＆V提取物可以提供疗效而没有副作用，这对于高危癌症患者和低风险健康人群的长期化学预防至关重要。这种生物标志物的应用将大大缩短有希望的化学预防剂临床疗效评估所需的时间。在12周试验期结束时，我们将拥有至少120名受试者（每个ARM）的生物标志物数据。主要目的是检验工作假设，即F＆V提取物可以调节原发性中间端点，细胞周期调节蛋白P27的表达与HNSCC患者患者的肿瘤进展，复发和无病生存有关。次要终点是细胞增殖（KI-67），DNA损伤/修复（彗星测定）和免疫功能（T细胞激活）。拟议的研究将使用一种新颖的补充和替代方法（CAM）进行癌症化学预防。结果将提供有关：（1）在监测F＆V提取物的生物学作用时使用替代端点的关键信息，（2）F＆V在预防HNSCC中的机制，以及（3）在HNSCC患者中使用补充F＆V提取物的可行性。这项II期试验的有前途的研究结果将为大型III期化学预防试验奠定基础，以评估F＆V提取物在预防HNSCC患者的SPT中的应用。