Chemoprevention of Green Tea Polyphenol on Liver Cancer

绿茶多酚对肝癌的化学预防作用

• 批准号: 7062103
• 负责人: JIA-SHENG WANG
• 金额: $ 31.74万
• 依托单位: TEXAS TECH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-16 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7062103
• 关键词: China; DNA damage; aflatoxins; bioassay; biomarker; biotransformation; blood chemistry; cancer prevention; cancer risk; chemical carcinogenesis; chemoprevention; clinical research; clinical trials; flavonoids; genotype; hepatitis B; hepatitis B virus group; hepatocellular carcinoma; high performance liquid chromatography; human subject; human therapy evaluation; oxidative stress; questionnaires; statistics /biometry; tea; urinalysis

DESCRIPTION (provided by applicant): The long-term goal of this revised application is to design effective prevention strategies for reducing the incidence of liver cancer in high-risk populations. Primary liver cancer, mainly hepatocellular carcinoma (HCC), is one of the most common cancers in Asia and Africa. The poor prognosis of this malignancy results in it being the third most common cause of cancer deaths in the world. Chronic infection with hepatitis B viruses (HBV) and dietary aflatoxin exposure are two major etiologic risk factors for HCC in high-risk areas. The great challenge in cancer prevention and control is how to manage those who have already been exposed to carcinogens, such as individuals who are HBsAg carriers and have long-term aflatoxin exposure. Chemoprevention has been proposed as the good tool to target these high-risk populations. Among various identified chemopreventive agents, green tea polyphenols (GTP) have been shown to be safe and high effective in inhibition of carcinogen-induced mutagenesis and tumorigenesis in bioassays and animal models for different target organ sites, including aflatoxin-induced liver tumors. The specific aims for this study are (1) to incorporate molecular biomarkers analysis for aflatoxin exposure, HBV infection, and oxidative DNA damage into an on-going randomized, double blinded, and placebo-controlled intervention trial of GTP in 1,800 residents who are double seropositive of HBsAg and aflatoxin-albumin adduct in Fusui County, Guangxi Zhuang Autonomous Region, People's Republic of China; efficacy of the chemopreventive trial will be determined by monitoring changes of levels of risk-factor specific molecular biomarkers and the actual incidence of HCC in the studied population. (2) to examine and assess the efficacy of GTP in reducing aflatoxin biomarkers by measuring aflatoxin-albumin adducts in serum and various aflatoxin biomarkers in urine collected from 300 participants in different time of the study. Difference in metabolic phenotypes/genotypes as they related to aflatoxin biomarker levels will be determined. (3) to evaluate the inhibitory effect of GTP on HBV-associated markers including HBV-DNA replication and HBV-induced immunologic changes in serum samples. (4) to determine antioxidative role of GTP in inhibition of the level of 8-hydroxy-2'-deoxyguanosine in urine samples collected from the study participants and (5) to determine and assess long-term bioavailability and biotransformation of GTP and the long-term toxicological effect of GTP on study participants. The results of this study would help to evaluate the chemoprotective effect of GTP against human HCC and to understand the molecular mechanisms of GTP in chemoprevention of human HCC caused by well-defined major risk factors.

描述（由申请人提供）：本次修订申请的长期目标是设计有效的预防策略，以降低高危人群肝癌的发病率。原发性肝癌，主要是肝细胞癌（HCC），是亚洲和非洲最常见的癌症之一。这种恶性肿瘤的预后不良，使其成为世界上第三大癌症死亡原因。乙型肝炎病毒（HBV）慢性感染和饮食中黄曲霉毒素暴露是高危地区肝癌的两个主要病因危险因素。癌症防治的巨大挑战是如何管理那些已经接触致癌物的人，例如HBsAg携带者和长期接触黄曲霉毒素的人。化学预防被认为是针对这些高危人群的良好工具。在各种已确定的化学预防剂中，绿茶多酚（GTP）已被证明在不同靶器官部位（包括黄曲霉毒素诱导的肝脏肿瘤）的生物测定和动物模型中安全且高效地抑制致癌物诱导的突变和肿瘤发生。本研究的具体目标是 (1) 将黄曲霉毒素暴露、乙型肝炎病毒感染和氧化性 DNA 损伤的分子生物标志物分析纳入一项正在进行的随机、双盲和安慰剂对照的 GTP 干预试验中，该试验在 1,800 名患有双盲的居民中进行。中华人民共和国广西壮族自治区扶绥县HBsAg和黄曲霉毒素-白蛋白加合物血清阳性；化学预防试验的有效性将通过监测危险因素特异性分子生物标志物水平的变化以及研究人群中 HCC 的实际发病率来确定。 (2)通过测量从研究的不同时间收集的300名参与者的血清中的黄曲霉毒素-白蛋白加合物和尿液中的各种黄曲霉毒素生物标志物来检查和评估GTP减少黄曲霉毒素生物标志物的功效。将确定与黄曲霉毒素生物标志物水平相关的代谢表型/基因型的差异。 (3)评估GTP对HBV相关标志物的抑制作用，包括血清样本中HBV-DNA复制和HBV诱导的免疫学变化。 (4) 确定 GTP 在抑制研究参与者尿液样本中 8-羟基-2'-脱氧鸟苷水平方面的抗氧化作用，以及 (5) 确定和评估 GTP 的长期生物利用度和生物转化以及长期生物利用度和生物转化。 -GTP 对研究参与者的长期毒理学影响。本研究的结果将有助于评估 GTP 对人类 HCC 的化学保护作用，并了解 GTP 在化学预防由明确的主要危险因素引起的人类 HCC 中的分子机制。