Journal
WORLD JOURNAL OF GASTROENTEROLOGY
Volume 23, Issue 28, Pages 5115-5126Publisher
BAISHIDENG PUBLISHING GROUP INC
DOI: 10.3748/wjg.v23.i28.5115
Keywords
Chemoprevention; Dysplasia; Biomarker; Stem cell; Colitis-associated cancer
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Funding
- Veterans Affairs Merit Award [IO1CX001353]
- National Institutes of Health [2R01DK095662-06A1]
- National Cancer Institute at the National Institutes of Health [N01-CN-35157]
- Training Program in Oncogenesis and Developmental Biology through the National Cancer Institute [NCI T32 CA080621]
- National Institute of General Medical Sciences of the National Institutes of Health [8 P20GM103527-05]
- American Physiological Society STEP-UP Fellowship
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AIM To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate p beta-catenin(S552) as a biomarker of recurrent dysplasia. METHODS We examined the effects of dietary myo-inositol treatment on inflammation, p beta-catenin(S552) and pAkt levels by histology and western blot in IL-10(-/-) and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear p beta-catenin(S552) in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia. RESULTS In mice, p beta-catenin(S552) staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia (LGD), two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans, p beta-catenin(S552) staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease. CONCLUSION Enumerating crypts with increased numbers of p beta-catenin(S552) - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.
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