1α,25-Dihydroxyvitamin D 3 [1α,25(OH) 2 D 3 ] is a steroid hormone derived from circulating 25(OH) vitamin D [25(OH)D] with chemopreventive effects in colorectal cancer. 1α,25(OH) 2 D 3 acts through transcriptional mechanisms; however, our understanding of vitamin D transcriptional responses in the colon is derived from studies in transformed cancer cell lines which may not represent responses in normal healthy tissue. Here, we describe the optimization of an ex vivo culture model using primary colonic biopsy samples for studying short-term transcriptional response induced by 1α,25(OH) 2 D 3 and 25(OH)D treatment. Colon biopsy samples from healthy subjects were maintained in primary culture and treated in parallel with 100 nM 1α,25(OH) 2 D 3 or 62.5 nM 25(OH)D and vehicle control (ethanol). Viability was assessed using histology and enzymatic assays. Genome-wide transcriptional responses to 1α,25(OH) 2 D 3 were assessed and expression of 25(OH)D targets CYP27B1 and CYP24A1 were measured by real time PCR. We show that ex vivo culture of colonic tissue remains viable for up to 8 h. The largest number of differentially expressed genes in response to 1α,25(OH) 2 D 3 was noted after 6 h ( n = 120). As proof of concept, the top upregulated gene was CYP24A1, a well-established vitamin D-responsive gene. With 25(OH)D treatment, mRNA expression of CYP27B1 was significantly increased after 1 h, while expression of CYP24A1 was greatest at 8 h. Ex vivo culture can be used to assess short-term transcriptional responses to 1α,25(OH) 2 D 3 and 25(OH)D in primary tissue from human colon. Future studies will address interindividual differences in transcriptional responses.

were associated with a significant suppression of proliferative biomarkers of cancer risk (reduced Ki67 expression, p<0.0001).Conclusion: The results of this study show that supervised acute dietary change has dramatic effects on specific colonic microbes and their metabolites that have been shown experimentally to modify colonic carcinogenesis, and that were shown here to be associated with decreased mucosal biomarkers of cancer risk.These results support the recommendations for reducing meat and fat and increasing fiber to suppress colon cancer in westernized populations.

Introduction: Screening for celiac disease (CD) is advocated in high-risk groups such as patients with type 1 diabetes mellitus (T1D) who carry similar genetic risk factors. However, little is known about screening and serological positivity in African Americans (AAs) with T1D. The aim of this study was to compare the rates of CD screening and antibody positivity in pediatric African American (AA) and Caucasian (Ca) patients with T1D at a single tertiary care center. Methods: A retrospective chart review was performed for patients seen between February 1999 and June 2013. Medical records were abstracted according to ICD-9 codes for T1D. Patients aged 18 years and younger were included, and self-identified race was recorded. Results for tissue transglutaminase (TTG) IgA, endomysial (EMA) IgA, and deaminated gliadin peptide (DGP) IgA and IgG serologies were obtained. Demographic data, screening frequency, and serological positivity were compared between AA and Ca patients by Student’s t test, Fischer’s exact test, and Chi-squared analysis with a significance level of p<0.05. Results: A total of 935 patients with T1D aged 18 years and younger were identified. Of the 798 patients with data on race, there were 380 AA and 405 Ca patients with T1D. There were no differences in mean age between AA and Ca, though AA patients were more commonly female (58.7% vs. 49.9%, p=0.015). The overall screening rate with any antibody test was 23.1%. Testing rates for TTG IgA (45/380 in AA vs. 180/405 in Ca, p<0.0001), EMA IgA (7/380 vs. 36/405, p<0.0001), DPG IgA (4/380 vs. 36/405, p<0.0001), and DGP IgG (4/380 vs. 34/405, p<0.0001) were all significantly lower in AA versus Ca. Positivity rates for TTG IgA (3/45 vs. 30/180, p=0.10), EMA IgA (0/7 vs. 13/36, p=0.08), DGP IgA (0/4 vs. 7/36, p=1.0), and DGP IgG (1/4 vs. 13/34, p=1.0) were not significantly different between the 2 groups. Conclusion: Despite recommendations to screen patients with T1D for CD, we found low screening rates in a pediatric T1D population overall. AA patients with T1D were significantly less likely to be screened than Ca patients. Interestingly, there were no differences in rates of serological positivity between AA and Ca, though this may be limited by a small sample size. Reasons for lower screening in AA T1D patients are not known but might be due to differences in perception of disease risk, symptomatology, lack of knowledge about screening recommendations, or referral bias. This study suggests the need for improvement in CD screening for pediatric patients with T1D and better estimates of CD prevalence in AA patients with T1D.