Aim
To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-cateninS552 as a biomarker of recurrent dysplasia.
Conclusion
Enumerating crypts with increased numbers of pβ-cateninS552 - positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.
Methods
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.
Results
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.