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: 8495791
• 负责人: Timothy Phillips
• 金额: $ 30.83万
• 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 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8495791
• 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

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 通过优先且紧密地隔离引发剂（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）。

项目成果

Physiologically based toxicokinetics of serum aflatoxin B1-lysine adduct in F344 rats.

• DOI: 10.1016/j.tox.2012.10.020
• 发表时间: 2013-01-07
• 期刊: TOXICOLOGY
• 影响因子: 4.5
• 作者: Qian, Guoqing;Tang, Lili;Wang, Franklin;Guo, Xia;Massey, Michael E.;Williams, Jonathan H.;Phillips, Timothy D.;Wang, Jia-Sheng
• 通讯作者: Wang, Jia-Sheng

Integrative toxicopathological evaluation of aflatoxin B₁ exposure in F344 rats.

• DOI: 10.1177/0192623313477256
• 发表时间: 2013
• 期刊: Toxicologic pathology
• 影响因子: 1.5
• 作者: Qian G;Wang F;Tang L;Massey ME;Mitchell NJ;Su J;Williams JH;Phillips TD;Wang JS
• 通讯作者: Wang JS

Common African cooking processes do not affect the aflatoxin binding efficacy of refined calcium montmorillonite clay.

• DOI: 10.1016/j.foodcont.2013.08.037
• 发表时间: 2014-03
• 期刊: Food control
• 影响因子: 6
• 作者: Elmore SE;Mitchell N;Mays T;Brown K;Marroquin-Cardona A;Romoser A;Phillips TD
• 通讯作者: Phillips TD

Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction.

• DOI: 10.1016/j.fct.2016.07.017
• 发表时间: 2016-09
• 期刊: FOOD AND CHEMICAL TOXICOLOGY
• 影响因子: 4.3
• 作者: Qian, Guoqing;Tang, Lili;Lin, Shuhan;Xue, Kathy S.;Mitchell, Nicole J.;Su, Jianjia;Gelderblom, Wentzel C.;Riley, Ronald T.;Phillips, Timothy D.;Wang, Jia-Sheng
• 通讯作者: Wang, Jia-Sheng

Aflatoxin B1 modulates the expression of phenotypic markers and cytokines by splenic lymphocytes of male F344 rats.

• DOI: 10.1002/jat.2866
• 发表时间: 2014-03
• 期刊: JOURNAL OF APPLIED TOXICOLOGY
• 影响因子: 3.3
• 作者: Qian, Guoqing;Tang, Lili;Guo, Xia;Wang, Franklin;Massey, Michael E.;Su, Jianjia;Guo, Tai L.;Williams, Jonathan H.;Phillips, Timothy D.;Wang, Jia-Sheng
• 通讯作者: Wang, Jia-Sheng