Prevention of hepatocellular carcinoma in vulnerable communities in Texas

项目摘要 罹患肝细胞癌的风险，这是人类的主要死亡原因 感染肝炎病毒(HV)的人因饮食中接触黄曲霉毒素(AF)而显著增加。 此外，房颤的致癌性可以通过暴露于伏马菌素(FB)而增强，伏马菌素是一种常见的 与房颤共污染。重要的是，德克萨斯州肝癌的显著增加是 在贝克萨尔县圣安东尼奥大都市区的多个地区有记录。在试行中 研究表明，这一人群有房颤/纤维蛋白原暴露的风险，原因是摄入了 受污染的食物。因此，预防HV/AF/FB诱导的肝癌的创新策略 都是高度优先的。我们开发了一种使用蒙皂石粘土(NS)的新方法 选择性地吸收胃肠道内的房颤和房颤。在德克萨斯州和加纳的临床试验中，我们证实 生理盐水的安全性和有效性。在拟议的项目中，我们的目标是基于 Bexar研究参与者接受NS干预将减少AF/FB暴露的假说 县里。我们的目标集中在确认精制NS和 研究其降低啮齿动物肝脏癌前病变发生率的能力 模特。此外，暴露毒素的生物标记物将在参与者的样本中进行测量。 经过3个月的临床试验。我们推测，这种制剂将减少主要的接触 房颤/房颤，进而降低得克萨斯州易受感染社区的肝癌发病率。 2002-2006年间，贝克萨尔人群中丙型肝炎病毒感染和肝癌的发病率 与德克萨斯州的其他县相比，县明显更高。因此，在这些 对于肝细胞癌的高危人群，减少膳食中的AF/FB暴露是可取的。减轻 使用毒素肠道吸附剂(即NS粘土)暴露AF/FB代表了一种创新的、实用的、 可持续和环境友好的方法。此外，这一战略是“开创性的” 因为精制的蒙脱石粘土可以用来降低一种强有力的癌症的生物利用度 引发剂(AF)和有效的癌症促进剂(FB)通过优先和紧密隔离 两种毒素都来自胃肠道。优选递送治疗量的NS粘土可以 最终通过将其添加到花生酱、玉米粉、玉米饼等常见食物中， 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).