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dc.creatorLuo, Haitao
dc.date.available2012-06-01T15:37:37Z
dc.date.issued2005-08
dc.identifier.urihttp://hdl.handle.net/2346/1364
dc.description.abstractHepatocellular carcinoma (HCC) is the third leading cause of cancer deaths in the developing world, and major risk factors have been identified as chronic infection with hepatitis B virus (HBV) and dietary exposure to aflatoxin B1 (AFB1). One of the current challenges in this field is how to manage high-risk individuals who have been exposed to these risk factors for many years. Chemoprevention was proposed as a good tool to target these individuals. Among various chemopreventive agents, green tea polyphenols (GTP) have been shown to be safe and effective in most in vitro and in vivo studies. To further investigate GTP¡¯s safety and efficacy in humans, a randomized, double-blind, and placebo-controlled phase IIa chemoprevention trial with GTP was carried out in a highrisk population of HCC in Fusui, Guangxi, China. After screening 1200 sera samples from local residents, a total of 124 healthy adults who were sero-positive for HBV and AFB1 was voluntarily recruited, randomized into 3 groups, and received either placebo, 500-mg GTP, or 1,000-mg GTP daily for 3 months. Urine and blood samples at baseline, 1 month, and 3 months of the intervention were collected from these participants and were analyzed for various GTP biomarkers and carcinogen specific biomarkers to assess the efficacy of the trial. An overall compliance of 99% with mild and insignificant sideeffects was observed. Baseline data for all biomarkers analyzed showed homogeneity among the 3 study groups. The placebo group had slight fluctuations in biomarker levels during the course of intervention, whereas urinary excretion of (-)-epigallocatechin (EGC) and (-)-epicatechin (EC) and plasma concentration of (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) were dose-dependently elevated in the GTP-treated groups. Urinary excretion of AFB1-mercapturic acid, a detoxified metabolite of AFB1, was significantly increased, while the serum levels of AFB1-albumin adduct, a macromolecule damaged by AFB1, was significantly diminished after GTP intervention. The oxidative DNA damage biomarker, urinary 8-hydroxy-2¡¯-deoxyguanosine, was also significantly decreased by GTP intervention. This study validated GTP biomarkers and proved the relative safety of GTP in humans. GTP intervention significantly inhibited carcinogen biomarkers and enhanced activities of detoxifying enzymes.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.subjectGreen tea polyphenols
dc.subjectHigh-risk population
dc.subjectChemoprevention
dc.titlePHASE IIa chemoprevention trial with green tea polyphenols in high-risk population of liver cancer
dc.typeDissertation
thesis.degree.nameDoctor of Philosophy
thesis.degree.levelDoctoral
thesis.degree.disciplineEnvironmental Toxicology
thesis.degree.grantorTexas Tech University
thesis.degree.departmentEnvironmental Toxicology
dc.contributor.committeeMemberTheodorakis, Christopher W.
dc.contributor.committeeMemberShen, Chwan-Li (Leslie)
dc.contributor.committeeMemberPence, Barbara
dc.contributor.committeeMemberAnderson, Todd A.
dc.contributor.committeeChairWang, Jia-Sheng
dc.degree.departmentEnvironmental Toxicology
dc.rights.availabilityUnrestricted.


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