To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-cateninS552 as a biomarker of recurrent dysplasia.
We examined the effects of dietary myo-inositol treatment on inflammation, pβ-cateninS552 and pAkt levels by histology and western blot in IL-10-/- and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-cateninS552 in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia.
In mice, pβ-cateninS552 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, pβ-cateninS552 staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease.
Enumerating crypts with increased numbers of pβ-cateninS552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.
Digital Object Identifier (DOI)
Supported by Veterans Affairs Merit Award, No. IO1CX001353 (to Barrett TA); National Institutes of Health, No. 2R01DK095662-06A1 (to Barrett TA); the National Cancer Institute at the National Institutes of Health, No. N01-CN-35157 (to Bergan R); the Training Program in Oncogenesis and Developmental Biology through the National Cancer Institute, No. NCI T32 CA080621 (to Bradford EM); an Institutional Development Award from the National Institute of General Medical Sciences of the National Institutes of Health, No. 8 P20GM103527-05; and American Physiological Society STEP-UP Fellowship (to Thompson CA).
Bradford, Emily M.; Thompson, Corey A.; Goretsky, Tatiana; Yang, Guang-Yu; Rodriguez, Luz M.; Li, Linheng; and Barrett, Terrence A., "Myo-Inositol Reduces β-Catenin Activation in Colitis" (2017). Internal Medicine Faculty Publications. 115.