The effect of 5-ASA on colitis-associated carcinogenesis
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PROVIDER: PRJNA769946 | ENA |
REPOSITORIES: ENA
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Project description:The effect of 5-ASA on colitis-associated carcinogenesis
| PRJNA769946 | ENA
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. 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.
2021-10-10 | GSE185599 | GEO
Project description:Objective The risk of ulcerative colitis (UC)-associated colorectal cancer (CRC) increases with the duration of UC. Oral 5-aminosalicylic acid (5-ASA) formulations are the first-line treatment for mild-to-moderate UC; nevertheless, preventive effect of oral 5-aminosalicylic acid (5-ASA) formulations on UC-associated CRC remains unsolved. We investigated the impact of 5-ASA to colitis-associated neoplasia in C57BL/6J-ApcMin heterozygous (ApcMin/+) mice. Design ApcMin/+ mice exposed to 1.5 w/v% dextran sulfate sodium (DSS) ad libitum for 3 days followed by 25 days of tap water to develop colitis-associated neoplasia. Mice were intracolorectally administrated with 5-ASA to evaluate the effects on the number of tumors. The mechanism of action was presumed by microarray analysis using in vivo samples and was confirmed by in vitro culture of HT-29, a human colorectal adenocarcinoma cell line with supernatant of human primary neutrophils. Results A remission between acute and recurrent episodes of diarrhea, which were ameliorated by 5-ASA treatment were observed in this model. The number of tumors was reduced by continuous 5-ASA administration in this model. This reduction was abolished by withdrawal of 5-ASA in remission period compared to continuous 5-ASA administration. Microarray analysis revealed that neutrophils were involved in the protective mechanism of 5-ASA against proliferation of tumors. Additionally, calprotectin production from human primary neutrophil as activation marker was strongly correlated with proliferation of HT-29.
2019-06-26 | GSE83749 | GEO
Project description:Colorectal cancer (CRC) remains the leading cause of cancer-related death in the world. Aspirin (ASA) and curcumin (CUR) are widely investigated chemopreventive candidates for CRC. However, the precise mechanisms of their action and their combinatorial effects have not been evaluated. The purpose of the present study was to determine the effect of ASA, CUR, and their combination in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-accelerated colorectal cancer (CAC). We also aimed to characterize the differential gene expression profiles in AOM/DSS-induced tumors as well as in tumors modulated by ASA and CUR using RNA-seq. Diets supplemented with 0.02% ASA, 2% CUR or 0.01% ASA + 1% CUR were given to mice from 1 week prior to the AOM injection until the experiment was terminated 22 weeks after AOM initiation. Our results showed that CUR had a superior inhibitory effect in colon tumorigenesis compared to that of ASA. The combination of ASA and CUR at a lower dose exhibited similar efficacy to that of a higher dose of CUR at 2%. RNA isolated from colonic tissue from the control group and from tumor samples from the experimental groups was subjected to RNA-seq. Transcriptomic analysis suggested that the low-dose combination of ASA and CUR modulated larger gene sets than the single treatment. These differentially expressed genes were situated in several canonical pathways important in the inflammatory network and liver metastasis in CAC. We identified a small subset of genes as potential molecular targets involved in the preventive action of the combination of ASA and CUR. Taken together, the current results provide the first evidence in support of the chemopreventive effect of a low-dose combination of ASA and CUR in CAC. Moreover, the transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from normal colonic tissue to tumor development as well as the cancer inhibitory effects and potential molecular targets of ASA and CUR.
2017-03-24 | GSE97013 | GEO
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.
2021-10-09 | GSE185504 | GEO
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.
2015-06-01 | GSE64658 | GEO
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.
2012-08-02 | GSE31106 | GEO
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 M-bM-^@M-^\inflammation-dysplasia-cancerM-bM-^@M-^] 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. 6-week-old male ICR mice were given a single intraperitoneal injection of AOM (10mg/kg) at Day 1, followed by three cycles of DSS administration (cycle 1: 2%, Day 8~14; cycle 2: 1.5%, Day 29~33; cycle 3: 1.5%, Day 50~54) in the drinking water. Instead, control group of mice were given a single intraperitoneal injection of saline (10mg/kg) at Day 1 and distilled water drinking from the beginning to the end without DSS. Colorectal tissues were collected at days 14, 28, 42, 56 and 140 (at the end of the 2nd, 4th, 6th, 8th and 20th week) from the AOM/DSS group and at day 14 from the control group. Pathological changes of each sample were identified under microscope. Samples collected at the end of the 2nd week were inflamed mucosae, the 4th week were low grade dysplasias, the 6th week were high grade dysplasias, the 8th week were high grade dysplasias with active inflammation, the 20th week were carcinomas, and the control sample were normal mucosae. Total RNA were extracted and detected by Affymerix GeneChip Mouse Genome 430 2.0 Array.
2012-08-01 | E-GEOD-31106 | biostudies-arrayexpress
Project description:To seek effects of inflammatory status and 5-aminosalicylic acid (5-ASA, mesalazine) exposure ex vivo on mRNA levels within rectal mucosal biopsies from patients with ulcerative colitis. A total of 12 biopsies were analysed, 3 biological replicates in each of 4 categories (inflamed with or without 5-ASA, non-inflamed with or without 5-ASA).
2013-12-12 | E-GEOD-46451 | biostudies-arrayexpress
Project description:A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. Zileuton, a 5-LOX inhibitor has single agent activity and adds to the activity of NSAIDs in preclinical models of tobacco carcinogenesis We hypothesized that COX inhibitor + 5-LOX inhibitor may be more effective than placebo in modulating nasal epithelium gene signatures of tobacco exposure and lung cancer. We conducted a randomized, double-blinded study of low dose ASA plus zileuton vs. double placebo in current smokers to compare modulating effects on nasal epithelium gene expression and arachidonic acid (AA) metabolism. Sixty-three participants were randomized to combined treatment of ASA (81 mg QD) and zileuton (Zyflo CR) two 600 mg extended release tablets BID or placebo pills for 12 weeks. Combined ASA plus zileuton had minimal effects on nasal gene expression of nasal or bronchial gene expression signatures associated with smoking, lung cancer and chronic obstructive pulmonary disease but did favorably modulate a bronchial gene signature of squamous dysplasia. Combined ASA plus zileuton suppressed urinary leukotriene (LTE4) (change of 89.867±68.35 from baseline to 32.25±23.25, p <0.001), a surrogate of 5-LOX mediated AA metabolism but did not suppress urinary prostaglandin E2 metabolite (PGEM), a surrogate of cyclooxygenase-mediated AA metabolism. In conclusion, combined COX and 5-LOX inhibition by combined low dose ASA with zileuton in smokers favorably modulated a bronchial squamous dysplasia gene expression signature in the nasal epithelium of current smokers but had minimal effects on other carcinogenesis gene signatures. This combination decreased 5-LOX but not COX-2 mediated AA metabolism. Nasal gene expression signature determination is a novel approach to biomarker analysis, giving an approximation of the pulmonary milieu without having to perform invasive tissue sampling.
2022-06-29 | GSE175616 | GEO