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: 8147016
• 负责人: Timothy Phillips
• 金额: $ 32.33万
• 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/8147016
• 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; public health relevance

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)：饮食中接触黄曲霉毒素(AF)会显著增加患肝细胞癌(HCC)的风险，这是感染肝炎病毒(HV)的人的主要死亡原因。此外，房颤的致癌性可以通过接触伏马菌素(FB)来“促进”，伏马菌素是房颤的常见共同污染物。重要的是，在贝克萨尔县圣安东尼奥大都市区的多个地区，德克萨斯州的肝癌发病率都有显著增加。在一项初步研究中，我们已经表明，由于摄入受污染的食物，这一人群面临着房颤/房颤暴露的风险。因此，预防HV/AF/FB诱导的肝细胞癌的创新策略是高度优先的。我们开发了一种新的方法，使用蒙脱石粘土(NS)，选择性地在胃肠道中吸附AF和FB。在德克萨斯州和加纳的临床试验中，我们证实了NS的安全性和有效性。在拟议的项目中，我们的目标是基于这样一个中心假设，即在贝克萨尔县，对NS的干预将减少研究参与者的房颤/纤维蛋白原暴露。我们的目标是确认精制生理盐水的分子机制，并在啮齿动物模型中研究其降低癌前病变发生率的能力。此外，暴露于毒素的生物标记物将在为期3个月的临床试验后从参与者的样本中进行测量。我们推测，该制剂将减少房颤/房颤的初次暴露，进而降低德克萨斯州易受伤害社区的肝癌发病率。在2002至2006年间，贝克萨尔县人口中的丙型肝炎病毒感染和肝癌的发病率明显高于德克萨斯州的其他县。因此，在这些肝癌高危人群中，减少膳食中的AF/FB暴露是可取的。使用毒素肠道吸附剂(即NS粘土)减轻AF/FB暴露是一种创新、实用、可持续和环境友好的方法。此外，这一策略具有开创性，因为精制的蒙脱石粘土可以通过优先和紧密地将这两种毒素从胃肠道隔离，来降低有效的癌症启动剂(AF)和有效的癌症促进剂(FB)的生物利用度。治疗剂量的NS粘土的首选最终可能是通过将其包含在常见食物中，如花生酱、玉米粉、玉米饼或盐(如碘)。 公共卫生相关性：这项研究的结果将与得克萨斯州服务不足的大都市、农村和边境社区直接相关，在这些社区，肝病的发病率在经常感染HV并暴露于膳食AF/FB的“穷人”中升高。长期目标是提供一种干预措施，通过减少对房颤和纤维蛋白原的暴露，改善“高危”人群的肝病管理。