AIM To assess dietary myo-inositol in reducing stem cell activation in colitis,and validate pβ-cateninS^(552) as a biomarker of recurrent dysplasia.METHODS We examined the effects of dietary myo-inositol treatment on...AIM To assess dietary myo-inositol in reducing stem cell activation in colitis,and validate pβ-cateninS^(552) as a biomarker of recurrent dysplasia.METHODS We examined the effects of dietary myo-inositol treatment on inflammation,pβ-cateninS^(552) and p Akt levels by histology and western blot in IL-10-/-and dextran sodium sulfate-treated colitic mice. Additionally,we assessed nuclear pβ-cateninS^(552) 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-cateninS^(552) 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-cateninS^(552) staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease.CONCLUSION Enumerating crypts with increased numbers of pβ-cateninS^(552)-positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.展开更多
基金Supported by Veterans Affairs Merit Award,No.IO1CX001353(to Barrett TA)National Institutes of Health,No.2R01DK095662-06A1(to Barrett TA)+3 种基金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 P20GM103527-05American Physiological Society STEP-UP Fellowship(to Thompson CA)
文摘AIM To assess dietary myo-inositol in reducing stem cell activation in colitis,and validate pβ-cateninS^(552) as a biomarker of recurrent dysplasia.METHODS We examined the effects of dietary myo-inositol treatment on inflammation,pβ-cateninS^(552) and p Akt levels by histology and western blot in IL-10-/-and dextran sodium sulfate-treated colitic mice. Additionally,we assessed nuclear pβ-cateninS^(552) 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-cateninS^(552) 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-cateninS^(552) staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease.CONCLUSION Enumerating crypts with increased numbers of pβ-cateninS^(552)-positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.
