Abstract
Background: To estimate the effects of ginger on apoptosis,
proliferation, and
differentiation in the normal human colorectal mucosa, we measured
the expression of cell
cycle markers in the normal-appearing colon mucosa of patients at
increased for CRC in a
pilot, randomized, double-blinded, placebo-controlled, clinical
trial.
Methods: A total of 20 patients were treated with either 2.0 g
(eight 250 mg capsules) of
encapsulated ginger (standardized to 5%-gingerols) or placebo daily
for 28 days. Overall
expression and distributions of Bax, Bcl-2, p21, hTERT and MIB-1 in
colorectal crypts in
biopsies of normal-appearing colon mucosa were detected and
measured using automated
immunohistochemistry and quantitative image analysis. Percent
changes in biomarker
expression over the treatment period were calculated, categorized,
assigned a score and then
summed to construct a "cell-cycle score."
Results: Image analysis measurement intra-rater reliability was
≥ 0.90 for all biomarkers. In
the ginger group relative to the placebo group, Bax expression
decreased 15.6% (p = 0.81)
along the full length of the crypts, 6.6% (p = 0.38) in the upper
40% (differentiation zone) of
the crypts, and 21.7% (p = 0.77) in the lower 60% (proliferative
zone) of the crypts;
however, there was a 19% increase (p = 0.80) in the proportion of
the expression of Bax in
the upper 40% relative to the whole crypt. While p21 and Bcl-2
expression remained
relatively unchanged, hTERT expression along the full length of
crypts decreased by 41.2%
(p = 0.05); the estimated treatment effect on hTERT expression was
slightly more
pronounced in the canonical differentiation zone of crypts (-47.9%;
p = 0.04). In the ginger
group relative to the placebo group, MIB-1 expression decreased
along the entire crypt,
upper 40% of crypts, and lower 60% of crypts by 16.9% (p = 0.39),
46.8% (p = 0.39), and
15.3% (p = 0.41), respectively.
Conclusions: These preliminary results 1) suggest that ginger may
reduce proliferation in the
normal-appearing colorectal epithelium and increase apoptosis and
differentiation relative to
proliferation-especially in the proliferative zone of the crypts,
and 2) support a full-scale
clinical trial to further investigate these results.
Table of Contents
BACKGROUND
................................................................................................................................
1
INTRODUCTION
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8
METHODS
........................................................................................................................................
10
RESULTS
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17
DISCUSSION
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19
TABLES AND FIGURES
...............................................................................................................
25
CONCLUSIONS AND PUBLIC HEALTH IMPLICATIONS
.............................................. 33
REFERENCES
..................................................................................................................................
35
APPENDICES
...................................................................................................................................
48
About this Master's Thesis
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