8 research outputs found
S1726 Circulating Levels of MD-2 Are Elevated in Patients with Inflammatory Bowel Disease: Relevance to Loss of Tolerance of the Intestinal Epithelium to Commensal Bacteria and to the Related Risk of Cancer Development
A Cell-Penetrant Manganese SOD-Mimic Is Able To Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases
International audienceInorganic complexes are increasingly used for biological and medicinal applications and the question of the cell-penetration and of the cell-distribution of metal-lodrugs is key to understand their biological activity. Oxi-dative stress is known to be involved in inflammation and in Inflammatory Bowel Diseases for which antioxidative defenses are weakened. We report here the study of a Mn-complex Mn1 mimicking superoxide dismutase, a protein involved in the cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining investigation of Mn1 intracellular speciation using mass spectrometry, of its quantification and distribution using electron paramagnetic resonance and spatially-resolved X-ray fluorescence with evaluation of its biological activity. More precisely, we have looked for and find the MS-signature of Mn1 in cell lysates and quantified the overall Mn-content. Intestinal epithelial cells activated by bacterial lipopolysaccharide were taken as a cellular model of oxidative stress and inflammation. Mn1 exerts an intra-cellular anti-inflammatory activity, remains at least partially coordinated, with a diffuse distribution over the whole cell and functionally complements mitochondrial MnSOD
Sera from patients with Crohnâs disease break bacterial lipopolysaccharide tolerance of human intestinal epithelial cells via MD-2 activity
Current smoking differentially affects blood mononuclear cells from patients with crohnÊŒs disease and ulcerative colitis: Relevance to its adverse role in the disease
Diffusion Tensor and Volumetric Magnetic Resonance Measures as Biomarkers of Brain Damage in a Small Animal Model of HIV
High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohnâs Disease
International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohnâs disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohnâs perianal disease followed up in the Cancers Et Surrisque AssociĂ© aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohnâs disease. Subjects were followed up for a median time of 35 months (interquartile range, 29â40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohnâs lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistulaârelated adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistulaârelated adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohnâs disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohnâs disease have a high risk of anal cancer, including perianal fistulaârelated cancer, and a high risk of rectal cancer