Increased 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.
In the chronically inflamed ileum, unique mechanisms of alteration of transport processes suggest regulation by different immune-inflammatory mediator pathways. We previously demonstrated that Na+-glucose cotransport in the chronically inflamed ileum was inhibited by a decrease in cotransporter number without a change in glucose affinity. The aim of this study was to determine the alterations in Na+-amino acid cotransport in chronically inflamed ileum produced by coccidial infection in rabbits. [3H]alanine uptake was performed in cells and vesicles by rapid filtration. In villus cells from chronically inflamed ileum, Na+-K+-ATPase was reduced 50% and Na+-alanine cotransport was also reduced (5.8 ± 1.2 in normal and 1.4 ± 0.5 nmol/mg protein in inflamed; n = 6, P < 0.05). [3H]alanine uptake in brush-border membrane vesicles was reduced in chronically inflamed ileum (73.2 ± 1.2 in normal and 21.5 ± 3.2 pmol/mg protein in inflamed; n = 3, P < 0.05), suggesting a direct effect on the cotransporter itself. Na+-amino acid cotransport in chronically inflamed ileum was inhibited by a decrease in affinity without a change in the maximal rate of uptake, and unaltered steady-state mRNA levels also suggested that the number of cotransporters was unchanged. Thus the mechanisms of inhibition of Na+-amino acid cotransport and Na+-glucose cotransport in chronically inflamed ileum are different. These observations suggest that different immune-inflammatory mediators may regulate different transport pathways during chronic ileitis.
Contrast-enhanced MR cholangiography with IV mangafodipir trisodium can successfully detect the presence and location of bile duct leaks in patients suspected of having such leaks after undergoing cholecystectomy. More research is necessary before acceptance of this examination as routine in the workup of these patients.
Black raspberries inhibit a broad range of cancers in preclinical models which has led to clinical evaluations targeting premalignant lesions of the colon, oral cavity and esophagus. A phase I pilot study was conducted in twenty Barrett's esophagus (BE) patients to investigate the effect of lyophilized black raspberries (LBR) on urinary metabolites and markers of lipid peroxidation, DNA damage and tissue markers of cellular proliferation, detoxification, and inflammation. Surveys, biopsies, blood and urine samples were collected before and after 6 months of LBR treatment (32 or 45 g). LBR significantly reduced urinary excretion of 8-epi-prostaglandin F2α, a marker of lipid peroxidation linked to oxidative stress and free radical damage. Urinary levels of the ellagitannin metabolites, urolithin A-glucuronide, urolithin A-sulfate and dimethylellagic acid glucuronide were significantly increased following 12 and 26 weeks of LBR consumption and may prove useful as indicators of compliance in future clinical studies. Immunohistochemical staining of BE biopsies following LBR treatment showed significant increases in mean GST-pi levels, with 55.6% of subjects responding favorably. In summary, LBR significantly decreased urinary lipid peroxidation levels and significantly increased GST-pi, a marker of detoxification, in BE epithelium. Still, LBR may need to be formulated differently, administered at higher concentrations or multiple times a day to increase efficacy.
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