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: 8035155
• 负责人: Timothy Phillips
• 金额: $ 38万
• 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/8035155
• 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

DESCRIPTION (provided by applicant): 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 communities 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). PUBLIC HEALTH RELEVANCE: The findings from this research will be of direct relevance to underserved metropolitan, rural and border communities in Texas where the incidence of liver disease is elevated in the "poor" who are frequently infected with HV and exposed to dietary AF/FB. The long-term goal is to provide an intervention that will improve liver disease management in "high risk" populations by reducing exposure to AF and FB.

描述（由申请人提供）：通过饮食暴露于黄曲霉毒素（AF）的饮食中，肝炎病毒（HV）感染的人类的主要死亡原因（HC）的主要死亡原因显着增强。同样，可以通过暴露于与AF的常见共抗药剂（FB）中“促进” AF的致癌性。重要的是，在贝克萨尔县圣安东尼奥都会区的多个地区，得克萨斯州的HCC大幅增加。在一项试点研究中，我们表明，由于被污染的食物摄入，该人群有暴露AF/FB的风险。因此，预防HV/AF/FB诱导的HCC的创新策略是很高的优先事项。我们使用了一种新颖的方法，它使用绿地（NS）在GI区中有选择地SORBS AF和FB。在德克萨斯州和加纳的临床试验中，我们确认了NS的安全性和功效。在拟议的项目中，我们的目标是基于以下中心假设：与NS的干预将减少Bexar县的研究参与者中的AF/FB暴露。我们的目标着重于确认精制NS的分子机制，并研究了其在啮齿动物模型中降低前肿瘤肝病变发生率的能力。此外，在经过3个月的临床试验后，将在参与者的样品中测量毒素暴露的生物标志物。我们假设该代理人将减少对AF/FB的主要接触，进而减少德克萨斯州脆弱社区中HCC的发生率。在2002年至2006年之间，与德克萨斯州其他县相比，贝克萨尔县人群中HCV感染和HCC的发病率显着高。因此，在这些有HCC风险的人群中，希望减少饮食中的AF/FB暴露。使用毒素肠吸附剂（即NS粘土）来缓解AF/FB暴露是一种创新，实用，可持续和环境良性的方法。此外，这种策略是“开创性的”，因为可以使用精致的绿色粘土来减少有效的癌症引发剂（AF）的生物利用度以及有效的癌症促进剂（FB），从而优先，紧密地隔离了GI型毒素。最终，首选的NS粘土剂量可以通过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）。 公共卫生相关性：这项研究的发现将与德克萨斯州服务不足的大都市，农村和边境社区直接相关，在德克萨斯州，肝病的发病率在“穷人”中升高，他们经常感染HV并暴露于饮食AF/FB。长期目标是提供一种干预措施，以减少对AF和FB的接触，可以改善“高风险”人群的肝病管理。