Transitioning from preclinical to clinical chemopreventive assessments of lyophilized black raspberries: interim results show berries modulate markers of oxidative stress in Barrett's esophagus patients.
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AuthorsKresty, Laura A.
Frankel, Wendy L.
Hammond, Cynthia D.
Baird, Maureen E.
Mele, Jennifer M.
Stoner, Gary D.
Fromkes, John J.
MetadataShow full item record
AbstractIncreased fruit and vegetable consumption is associated with decreased risk of a number of cancers of epithelial origin, including esophageal cancer. Dietary administration of lyophilized black raspberries (LBRs) has significantly inhibited chemically induced oral, esophageal, and colon carcinogenesis in animal models. Likewise, berry extracts added to cell cultures significantly inhibited cancer-associated processes. Positive results in preclinical studies have supported further investigation of berries and berry extracts in high-risk human cohorts, including patients with existing premalignancy or patients at risk for cancer recurrence. We are currently conducting a 6-mo chemopreventive pilot study administering 32 or 45 g (female and male, respectively) of LBRs to patients with Barrett's esophagus (BE), a premalignant esophageal condition in which the normal stratified squamous epithelium changes to a metaplastic columnar-lined epithelium. BE's importance lies in the fact that it confers a 30- to 40-fold increased risk for the development of esophageal adenocarcinoma, a rapidly increasing and extremely deadly malignancy. This is a report on interim findings from 10 patients. To date, the results support that daily consumption of LBRs promotes reductions in the urinary excretion of two markers of oxidative stress, 8-epi-prostaglandin F2alpha (8-Iso-PGF2) and, to a lesser more-variable extent, 8-hydroxy-2'-deoxyguanosine (8-OHdG), among patients with BE.
CitationNutr. Cancer 2006, 54 (1):148-156
JournalNutrition and Cancer
DescriptionDietary modulation of cancer & cancer biomarkers; Dietary modulation of carcinogenesis-related pathwaysDietary item or component studied: black raspberries. Outcome studied: 8-epi-prostaglandin F2alpha (8-Iso-PGF2); 8-hydroxy-2'-deoxyguanosine (8-OHdG)Study type: humansStudy design: cohort study. Study size: 10 Barrett's esophagus (BE) cases. Tissue/biological material/sample size: urine. Mode of exposure: dietary. Impact on outcome (including dose-response): Mean concentrations of 8-Iso-PGF2 levels at baseline, Week 12, and Week 26 of study were 1.56E-10, 1.26E-10, and 1.15E-10 mg/ml of urine, respectively. Levels of urinary 8-Iso-PGF2 were significantly reduced following 26 wk of daily LBRs administration (P < 0.05). 60% of subjects experienced significant individual level decreases in 8-Iso-PGF2 levels following the 26-wk dietary intervention (P < 0.05). There was no significant change in mean levels of urinary 8-OHdG following treatment with LBRs; however, at the individual level, five patients experienced significant declines in 8-OHdG. In addition, all five patients experiencing significant declines in 8-OHdG also had significant declines in 8-Iso-PGF2. Thus, a significant correlation (r = 0.7; P = 0.024) was noted between levels of these two markers of oxidative stress following berry administration. However, in contrast to changes in urinary levels of 8-Iso-PGF2, four patients experienced significant increases in urinary 8-OhdG levels over the course of the intervention.Quality control: Levels of urinary 8-OHdG and 8-Iso-PGF2 were divided by levels of urinary creatinine to control for potential differences in urine volume between patients. KEYWORDS - CLASSIFICATION: administration & dosage;Aged;analogs & derivatives;analysis;Anticarcinogenic Agents;Barrett Esophagus;Biological Markers;chemically induced;chemistry;complications;Deoxyguanosine;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;Dinoprost;Esophageal Neoplasms;Female;Food Preservation;Freeze Drying;Fruit;Gastroesophageal Reflux;history;Humans;Male;Middle Aged;Oxidative Stress;Phytotherapy;Pilot Projects;Precancerous Conditions;prevention & control;Public Health;Research;Rosaceae;therapy;urine;
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