Prevention of hepatocellular carcinoma in vulnerable communities in Texas

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 感染肝炎病毒（HV）的人，通过饮食暴露于黄曲霉毒素（AF）而显著增强。 此外，AF的致癌性可以通过暴露于伏马菌素（FB）而“促进”，伏马菌素是一种常见的致癌物质。 重要的是，德克萨斯州HCC的显着增加， 在贝克萨尔县的圣安东尼奥大都市区的多个地区都有记录。以试点 我们的研究表明，由于摄入以下物质，该人群存在AF/FB暴露的风险： 被污染的食物。因此，预防HV/AF/FB诱导的HCC的创新策略 是高度优先的。我们开发了一种使用蒙皂石粘土（NS）的新方法， 选择性吸收胃肠道中的AF和FB。在德克萨斯州和加纳的临床试验中， 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干预将降低贝克萨尔研究受试者的AF/FB暴露 县我们的目标集中在确认精制NS的分子机制， 研究其降低啮齿动物中癌前肝病变发生率的能力 模型此外，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，这种药剂将减少初级暴露于 AF/FB，并反过来降低德克萨斯州弱势社区HCC的发病率。 2002年至2006年，贝克萨尔人群中HCV感染和HCC的发病率 与德克萨斯州其他县相比，该县的发病率明显较高。因此，在这些 因此，对于处于HCC风险的人群，期望减少对AF/FB的饮食暴露。减轻 使用毒素肠吸附剂的AF/FB暴露（即，NS粘土）代表了一种创新，实用， 可持续和无害环境方法。而且，这一战略具有“开创性” 因为精制的绿土粘土可用于降低强效癌症的生物利用度 引发剂（AF）以及有效的癌症促进剂（FB）， 都是胃肠道的毒素治疗剂量的NS粘土的优选递送可 最终通过将其包含在普通食品中，如花生酱，玉米粉，玉米饼， 或盐（如碘）。

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).