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（由申请方提供）：头颈部鳞状细胞癌（HNSCC）是一种侵袭性上皮肿瘤，约占美国新诊断非皮肤恶性肿瘤的5%。虽然原发性肿瘤已被成功治疗，但第二原发性肿瘤（SPT）的发展是决定早期头颈癌患者生存的最重要因素。为提高头颈部恶性肿瘤患者的生存率，对第二恶性肿瘤进行有效的化学预防至关重要。这项前瞻性、随机双盲II期化学预防试验旨在评估水果和蔬菜（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，这些影响与既往HNSCC患者发生SPT相关。我们认为，补充F&V提取物可以提供有效性而没有副作用，这种组合对于高风险癌症患者和低风险健康人群的长期化学预防至关重要。这些生物标志物的应用将大大缩短有前途的化学预防剂的临床疗效评价所需的时间。在12周试验期结束时，我们将获得至少120例受试者（每组60例）的生物标志物数据。主要目的是检验F&V提取物可以调节主要中间终点的工作假设，即细胞周期调节蛋白p27的表达，其与HNSCC患者的肿瘤进展、复发和无病生存相关。次要终点为细胞增殖（Ki-67）、DNA损伤/修复（彗星试验）和免疫功能（T细胞活化）。这项研究将使用一种新的补充和替代（CAM）方法来进行癌症化学预防。结果将提供以下方面的关键信息：（1）使用替代终点监测F&V提取物的生物学效应，（2）F&V预防HNSCC的机制，以及（3）在HNSCC患者中使用F&V提取物补充剂的可行性。这项II期试验的有希望的研究结果将为更大的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SPT中的应用。