Aspirin antitumoral effect on pituitary adenoma
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ABSTRACT:
ORGANISM(S): Rattus
PROVIDER: GSE202934 | GEO | 2022/06/19
REPOSITORIES: GEO
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Project description:Aspirin antitumoral effect on pituitary adenoma
| PRJNA837778 | ENA
Project description:Background & Aims: Aspirin (ASA) is a proven chemoprotective agent for colorectal cancer; yet, mechanisms underlying these effects are incompletely understood. Human organoids are an ideal system to study genomic and epigenomic host-environment interactions. Here, we utilize human colonic organoids to profile ASA responses on genome-wide gene expression and chromatin accessibility. Methods: Human colonic organoids from one individual were cultured and treated in triplicate with 3mM ASA or vehicle control (DMSO) for 24 hours. Gene expression and chromatin accessibility were measured using RNA- and ATAC-sequencing, respectively. Differentially expressed genes were analyzed using DESeq2. Gene set enrichment was performed by SetRank. Differentially accessible peaks were analyzed using DiffBind and EdgeR. Motif enrichment was determined using HOMER and diffTF. Results: The results yielded strong transcriptional responses to ASA treatment with significant enrichment for fatty acid oxidation and PPAR signaling in the normal colonic epithelium that were validated in independent organoid lines. A large number of differentially accessible chromatin regions were found in response to ASA treatment with significant enrichment for Fos, Jun and Hnf transcription factor motifs. Integrated analysis of epigenomic and genomic treatment responses highlighted genes and regulatory regions that could mediate ASA’s specific effects in the colon including those involved in chemoprotection and/or toxicity. Conclusions: Assessment of chromatin accessibility and transcriptional responses to ASA yielded new observations about genome-wide effects in the colon facilitated by application of human colonic organoids. This framework can be applied to study colonic ASA responses between individuals and populations in future.
2023-01-01 | GSE198434 | GEO
Project description:Chronic inflammation plays important role in lung cancer development. Recently, we found that anti-inflammation drugs aspirin and triptolide when combined showed synergistic effect in suppressing lung cancer development. In this study, we aim to use gene microarray to define the genes and pathways that are affected by aspirin, triptolide individually or in combination.
2017-06-01 | GSE99514 | GEO
Project description:A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blind, placebo controlled study in current heavy smokers to compare modulating effects of intermittent versus continuous low dose ASA on gene signatures of smoking and lung cancer from nasal brushings. Fifty-four participants were randomized to intermittent ASA (ASA 81 mg daily for one week alternating with placebo daily for one week) or continuous ASA (81 mg daily) for 12 weeks. The primary endpoint was modulation of a smoking gene signature in nasal brushings. Other [JB1] endpoints included modulation of nasal and bronchial gene signatures for smoking, lung cancer and chronic obstructive pulmonary disease (COPD) and changes in cyclooxygenase (COX)- and 5-lipoxygenase (LOX)-mediated arachidonic acid (ARA) metabolism. Low dose ASA intervention caused minimal changes in smoking and lung cancer gene signature scores in nasal epithelium of current heavy smokers. The small sample size of the intervention groups may have limited the ability to detect modulation of the gene signatures. Low dose ASA lowered urinary prostaglandin E metabolite, a marker of COX-mediated ARA metabolic pathway with no change in urinary leukotriene E4, a marker of 5-LOX-mediated pathway. Exploratory genomic analysis showed that ASA intervention induced wide-ranging genomic changes in the nasal epithelium, including modulation of the arachidonic acid pathway and wound healing. A companion study is underway using ASA plus zileuton to test dual suppression of COX- and 5-LOX-mediated pathways on these gene signature scores in current heavy smokers.
2019-12-24 | GSE124637 | GEO
Project description:Aspirin is a non-steroidal anti-inflammatory drug. Till date there is no information on the molecular mechanism of aspirin on oral cancer cells. In this study, treated oral cancer cells were compared with untreated ones for gene expression for finding the effect of aspirin on biological process and significant pathways involved. Aspirin plays an important role in inducing apoptotic effect by activating regulators and further inhibits cell cycle progression.
2014-11-22 | GSE58162 | 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:Oral aspirin challenge may induce different global CpG methylation patterns between aspirin-exacerbated respiratory disease (AERD) and aspirin-tolerant asthma (ATA), which may affect gene expression several hours later. Therefore, in the present study, we compared global CpG methylation profiles before and after an oral aspirin challenge in patients with asthma. In addition, we compared differences in methylation profiles between AERD and ATA using an Illumina 860K Infinium Methylation EPIC BeadChip array platform, which had greater coverage than in the previous study (26,485 CpGs) to discover new methylated CpGs in PBLs associated with aspirin-induced bronchospasm.
2023-06-27 | GSE235569 | GEO
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
Project description:Aspirin is a widely prescribed non-steroidal anti-inflammatory drug used as an effective analgesic and at low doses as anti-platelet drug for the prevention of cardiovascular diseases. However, aspirin is associated with a significant incidence of upper gastrointestinal (GI) complications, notably peptic ulceration. This study aims to identify genetic risk factors associated with the pathogenesis of aspirin-induced upper GI ulceration.A cohort of 248 patients with aspirin-induced, endoscopiclly confirmed GI ulceration and 491 controls (ulcer, without aspirin or aspirin without ulcer) were genotyped for 1.524,956 SNPs using the Illumina Omni 2.5 SNP array. A replication cohort (206 NSAID-induced ulcer cases [of which 87 were aspirin] and 309 controls) was subsequently genotyped for identified SNP association signals using Sequenom iPLEX Massarry. Logistic regression analysis of identified two SNP signal with suggestive association with aspirin-induced GI ulceration. A SNP within the EYA1 locus (rs12678747) was found to be associated with aspirin GI ulceration in both the discovery cohort (p=3.79x10-7, OR=2.06 ([1.55-2.73]) and, to a lesser extent, in the replication cohort (p=.0005, OR=1.71[1.17-2.50]. Combined analysis of both cohorts yielded a genome wide significant association (p=1.46x10-8). The rs12678747 genotype was found to be associated with significantly higher EYA1 transcript in ulcer biopsy tissue (p<0.05).Data suggest that EYA1 may represent a risk locus for aspirin-induced GI ulceration. Though it is thought that EYA1 may play a key role in mediating cell death/ survival
| EGAS00001002052 | EGA
Project description:Theoretically, the differentiation of mesenchymal stem cells (MSCs) into either adipocytic or osteoblastic phenotype can be deemed as a seesaw, where induction of one lineage comes at the expense of the other. Previously, researchers, including our team, found that aspirin promoted osteoblast differentiation of bone mesenchymal stem cells (BMSCs) whereas inhibiting adipogenic differentiation. However, the precise mechanisms, that is, which pathways, what biological process or key genes involved during this process, had not been systematically studied. In the present study, we tend to analyze the whole transcriptome of the anti-adipogenic and promote-osteoblastic effects of aspirin in BMSCs. Our results showed that aspirin’s presence restored or further strengthened the expression of an important part of the gene population repressed during adipogenesis or increased during osteogenesis. Besides, classical pathways related to osteogenic differentiation (p53 signaling pathway, focal adhesion, osteoclast differentiation, PI3K-Akt signaling pathway, MAPK signaling pathway, and Wnt signaling pathway) and the fat metabolism were also disturbed during the promote-osteoblastic and anti-adipogenic effects of aspirin. Therefore, our whole-genome transcriptomic results shed new light and open the door to more specific “omics” studies. Our results allow a better understanding of the anti-adipogenic and promote-osteoblastic effects of aspirin and pave the way to aspirin clinical use for the prevention and treatment of diseases like tissue defect and osteoporosis.
2022-01-01 | GSE186026 | GEO