Project description:Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer (CRC). Colitis-associated dysplasia (flat or polypoid) continues to be a reliable marker for CRC in these patients. However, flat lesions are often missed during endoscopy and can rapidly progress to high-grade dysplasia or cancer. microRNAs (miRs), small non-coding RNAs, have emerged as a valuable diagnostic biomarker of human cancer due to their ease of detection and stability. The goal of this study was to identify a miR signature that can serve as a reliable biomarker for the early detection of colitis-associated dysplasia in patients with long-standing colitis.
Project description:This pilot, randomized phase I/II trial studies how well inositol works in preventing colorectal cancer in patients with abnormal cells (dysplasia) associated with inflammation of the colon (colitis). Patients with colitis-associated dysplasia may have an increased risk of developing colorectal cancer. Inositol is a vitamin-like substance that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Project description:This study characterizes the inflammatory processes in left-sided colitis, pancolitis, and UC-associated dysplasia at the transcriptional level in colonics biopsies in order to identify potential biomarkers and transcripts of importance for the carcinogenic behaviour of chronic inflammation
Project description:The impact of the antiinflammatory agent 5-aminosalicylic acid (5-ASA) on the risk for colitis-associated colorectal cancer remains controversial. The chemopreventive activity of 5-ASA was evaluated in the Swiss Webster model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated neoplasia. Mice were injected with AOM (7.4 mg/kg i.p.) and randomized to receive either vehicle or 5-ASA (75mg/kg) for the remainder of the study. Only untreated animals were used in this array. DSS treatment began at 9 weeks of age and continued for 3 cycles. At the time of sacrifice (18 weeks of age), the entire colon and rectum were processed for histopathologic examination and microarray profiling. For information regarding the histopathological analysis, refer to Clapper ML, Gary MA, Coudry RA, Litwin S, Chang WC, Devarajan K, Lubet RA, Cooper HS. 5-aminosalicylic acid inhibits colitis-associated colorectal dysplasias in the mouse model of azoxymethane/dextran sulfate sodium-induced colitis. Inflamm Bowel Dis. 2008 Oct;14(10):1341-7. doi: 10.1002/ibd.20489. PMID: 18452197.
Project description:In humans with UC, low-grade dysplasia also develops predominantly in the distal colon, progresses more rapidly to neoplasia than proximal colon low-grade dysplasia and associates with worse patient prognosis. In a mouse model of colitis-associated carcinogenesis induced by administration of the mutagen AOM and the luminal toxin DSS, tumors also develop exclusively in the distal part of the large intestine. We monitored global changes in the transcriptome of mouse proximal and distal colon during exposure to AOM/DSS with the aim to define biological pathways and processes that characterize regional responses of the large intestine to colitis-associated carcinogenesis.
Project description:Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers. Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed “loss of gradient” reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 – 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients.
Project description:Nonresolving inflammation is correlated to carcinogenesis. Ulcerative colitis-associated colorectal cancer (UC-CRC), one of the typical carcinoma generated by inflammation that cannot be resolved properly, has been widely believed to involve a multistep process contains “inflammation-dysplasia-cancer” sequence. The exact molecular mechanisms underlying the step-wise development of UC-CRC is still not fully understood. Detecting the changes in gene expression profiles may help to reveal why and how does the prolonged inflammatory response lead to carcinogenesis, and to characterize potential diagnostic/prognostic markers or additional therapeutic targets for UC-CRC. There for, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis-associated cancer, based on an AOM/DSS induced mouse model of UC-CRC.
Project description:Samples were taken from either surgically resected specimens or during surveillance colonoscopic examination. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for molecular markers for predicting development of cancer and/or dysplasia in ulcerative colitis, and to characterize potential diagnostic markers in UC-associated neoplasm. Experiment Overall Design: 43 UC-NonCa, 10 UC-Ca, 60 sporadic-Ca and 6 UC-associated Ca were analyzed
Project description:We performed miRNA and mRNA profiling at postnatal day 14 and day 29 to compare hyperoxia-induced bronchopulmonary dysplasia and wild type. We built potential miRNA-mRNA interaction networks specific to brochopulmonary dysplasia.