Prevention of hepatocellular carcinoma in vulnerable communities in Texas

德克萨斯州弱势社区的肝细胞癌预防

• 批准号: 8288643
• 负责人: Timothy Phillips
• 金额: $ 32.97万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8288643
• 关键词: Acute; Affinity; Aflatoxins; Albumins; Animals; Area; Benign; Binding; Biological; Biological Availability; Biological Markers; Blood; Butter; Cause of Death; Cirrhosis; Clinical Trials; Communities; County; Diet; Disease Management; Dose; Effectiveness; Enterosorption; Exposure to; Food; Fumonisin B1; Fumonisins; Future; Gastrointestinal tract structure; Ghana; Goals; Hepatic; Hepatitis C; Hepatitis Viruses; Hispanics; Human; In Vitro; Incidence; Intake; Intervention; Iodine; Lesion; Liquid substance; Liver; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Measures; Modeling; Molecular; Monitor; Nodule; Parents; Participant; Peanuts - dietary; Phase; Pilot Projects; Population; Populations at Risk; Prevention; Prevention strategy; Primary carcinoma of the liver cells; Process; Protocols documentation; Rattus; Research; Riboflavin; Risk; Rodent Model; Rural; Safety; Sampling; Sequential Treatment; Sodium Chloride; Staging; Swelling; Texas; Therapeutic; Tissues; Toxin; Trace metal; Transferase; Treatment Efficacy; Urine; Vitamin A; Water-Soluble Vitamin; adduct; base; carcinogenicity; clay; high risk; improved; in vivo; innovation; male; metropolitan; novel strategies; promoter

Project Summary The risk of developing hepatocellular carcinoma (HCC), a leading cause of death in humans infected with hepatitis virus (HV), is significantly enhanced by dietary exposure to aflatoxin (AF). Also, the carcinogenicity of AF can be "promoted" with exposure to fumonisin (FB), a common co-contaminant with AF. Importantly, a significant increase in HCC in Texas has been documented in multiple regions of the San Antonio metropolitan area of Bexar County. In a pilot study, we have shown this population is at risk for AF/FB exposure due to the intake of contaminated foods. Thus, innovative strategies for the prevention of HV/AF/FB-induced HCC are high priorities. We have developed a novel approach using a smectite clay (NS) that selectively sorbs AF and FB in the GI tract. In clinical trials in Texas and Ghana, we confirmed the safety and efficacy of NS. In the proposed project, our aims are based on the central hypothesis that intervention with NS will decrease AF/FB exposure in study participants in Bexar County. Our objectives focus on confirming the molecular mechanisms of refined NS and investigating its ability to diminish the incidence of preneoplastic hepatic lesions in a rodent model. Also, biomarkers of toxin exposure will be measured in samples from participants following a 3-month clinical trial. We postulate that this agent will reduce primary exposure to AF/FB and, in turn, reduce the incidence of HCC in vulnerable commumnities in Texas. Between 2002 and 2006, the incidence of HCV infection and HCC in populations in Bexar County was significantly higher compared to other counties in Texas. Therefore, in these populations at risk for HCC, it is desirable to decrease dietary exposure to AF/FB. Mitigating AF/FB exposure using a toxin enterosorbent (i.e., NS clay) represents an innovative, practical, sustainable and environmentally benign approach. Moreover, this strategy is "ground-breaking" in that a refined smectite clay can be used to decrease the bioavailability of a potent cancer initiator (AF) as well as a potent cancer promoter (FB) by preferentially and tightly sequestering both toxins from the GI tract. The preferred delivery of a therapeutic dose of NS clay may eventually be through its inclusion in common foods such as peanut butter, corn meal, tortillas, or salt (like iodine).

项目摘要 发展肝细胞癌（HCC）的风险，这是人类死亡的主要原因 饮食中的黄曲霉毒素（AF）感染了肝炎病毒（HV），从而显着增强。 同样，AF的致癌性可以“促进”，暴露于Fumonisin（FB），这是一种常见 与AF共同抗议。重要的是，德克萨斯州的HCC显着增加 记录在贝克萨尔县圣安东尼奥都会区的多个地区。在飞行员中 研究，我们已经表明，由于摄入 受污染的食物。因此，预防HV/AF/FB诱导的HCC的创新策略 是高度优先事项。我们已经使用了一种新的方法，该方法使用了绿色粘土（NS） 在胃肠道中有选择性地SORBS AF和FB。在德克萨斯州和加纳的临床试验中，我们确认 NS的安全性和功效。在拟议的项目中，我们的目标是基于中央 假设NS的干预将减少BEXAR研究参与者的AF/FB暴露 县。我们的目标着重于确认精制NS的分子机制和 调查其降低啮齿动物中肿瘤性肝病变的发生率的能力 模型。此外，将在参与者的样品中测量毒素暴露的生物标志物 经过3个月的临床试验。我们假设该代理将减少主要接触 AF/FB，反过来降低了德克萨斯州脆弱的宿舍中HCC的发病率。 在2002年至2006年之间，BEXAR中HCV感染和HCC的发生率 与德克萨斯州其他县相比，县的高度要高得多。因此，在这些中 有可能患有HCC的人群，希望减少饮食中的AF/FB暴露。缓解 使用毒素肠吸附剂（即NS粘土）的AF/FB暴露是一种创新，实用的， 可持续和环境良性的方法。此外，该策略是“开创性的” 因为可以使用精致的绿色粘土来减少有效癌症的生物利用度 通过优先隔离 两种毒素都来自胃肠道。首选的NS粘土治疗剂量可能 最终将其包含在普通食品中，例如花生酱，玉米粉，玉米饼， 或盐（如碘）。