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

基本信息

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
项目类别：
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

项目摘要

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).

项目概要罹患肝细胞癌 (HCC) 的风险，肝细胞癌是人类死亡的主要原因饮食中暴露于黄曲霉毒素 (AF) 会显着增强感染肝炎病毒 (HV) 的风险。此外，接触伏马菌素 (FB) 会“促进”房颤的致癌性，伏马菌素是一种常见的物质。与 AF 共同污染。重要的是，德克萨斯州的 HCC 病例显着增加贝克萨尔县圣安东尼奥都市区的多个地区都有记录。在飞行员中研究表明，该人群因摄入 AF/FB 而面临暴露风险受污染的食物。因此，预防 HV/AF/FB 诱发的 HCC 的创新策略是高度优先事项。我们开发了一种使用蒙脱石粘土 (NS) 的新方法，在胃肠道中选择性吸附 AF 和 FB。在德克萨斯州和加纳的临床试验中，我们证实 NS 的安全性和有效性。在拟议的项目中，我们的目标是基于中央假设 NS 干预将减少 Bexar 研究参与者的 AF/FB 暴露县。我们的目标集中于确认精制 NS 的分子机制和研究其降低啮齿动物癌前肝脏病变发生率的能力模型。此外，还将在参与者的样本中测量毒素暴露的生物标志物经过3个月的临床试验。我们假设该药物将减少主要暴露 AF/FB 反过来又降低了德克萨斯州脆弱社区的 HCC 发病率。 2002 年至 2006 年间，Bexar 人群中 HCV 感染和 HCC 的发病率与德克萨斯州其他县相比，该县的比例明显更高。因此，在这些对于有 HCC 风险的人群，最好减少膳食中对 AF/FB 的暴露。缓解使用毒素肠吸附剂（即 NS 粘土）进行 AF/FB 暴露代表了一种创新、实用、可持续且环境友好的方法。而且，这个策略是“开创性的” 因为精炼的蒙脱石粘土可用于降低强效癌症的生物利用度通过优先和紧密隔离，作为引发剂 (AF) 以及有效的癌症促进剂 (FB) 两种毒素均来自胃肠道。治疗剂量的 NS 粘土的优选递送可以最终通过将其添加到花生酱、玉米粉、玉米饼等常见食品中，或盐（如碘）。