TRIAD Burden of Illness Mucositis Study
Ontology highlight
ABSTRACT:
DISEASE(S): Mucositis,Gastrointestinal Mucositis (defined As Mucositis Involving The Mouth, Esophagus, Or Small Intestine)
PROVIDER: 2029722 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:To reveal the molecular mechanisms underlying oral ulcerative mucositis-induced pain, we investigated putative pain-associated mediators, pain-related behaviors and gene modulation in a rat oral mucositis model. On day 1 after acetic acid treatment, the mucosal area showed slight redness and swelling but no evidence of ulceration or pain induction. On day 2, oral ulcers were obvious, as was the induction of spontaneous and mechanical pain. In the treated mucosal area, bacterial loading and prostaglandin E2 increased beginning on day 2; no significant changes were observed on day 1. DNA microarray analysis of trigeminal ganglion tissue collected on day 2 identified 32 significantly regulated genes (>1.5-fold change in expression). The up-regulation of the top 3 genes, Hamp (hepcidin antimicrobial peptide), Reg3b (regenerating islet-derived 3β) and Serpina3n (serine peptidase inhibitor A3N), was validated through quantitative RT-PCR. Systemic antibiotic pre-treatment did not increase the mRNA levels. Therefore, we conclude that the oral ulcerative mucositis-induced pain is caused by infectious inflammation of the ulcerative area and stimulates anti-bacterial and anti-peptidase gene expressions in sensory neurons. Oral ulcerative mucositis-induced gene expression in trigeminal ganglion tissue was measured. Ten Wistar rats were divided into the following two groups, control, oral ulcerative mucositis (stomatitis). Five rats were anesthetized with sodium pentobarbital. A piece of filter paper was soaked in 50% acetic acid diluted with water and placed in the labial fornix region of the inferior incisors of rats for 30 sec. Other five rats received only anesthesia without any treatment were used as a control. On day 2 after acetic acid treatment, oral ulcerative mucositis was obvious and trigeminal ganglion tissues in two groups were collected for DNA microarray analysis.
2016-06-15 | E-GEOD-83349 | biostudies-arrayexpress
Project description:Objective: Head and neck cancer (HNC) accounts for almost 850,000 new cases per year. Radiotherapy (RT) is used to treat the majority of these patients. A common side-effect of RT-treatment is onset of oral mucositis: a painful irritation and swelling in mouth, which decreases the quality of life and is the major dose-limiting factor in RT. To understand the origin of oral mucositis, the biological mechanisms post-ionizing radiation (IR) need to be understood. This knowledge can be used to develop new treatment targets for oral mucositis and markers for the early identification of “at risk” patients. Results: Mass spectrometry-based proteomics identified 5879 proteins in primary keratinocytes and 4597 proteins in OKF6 cells. Amongst them, 212 proteins in primary keratinocytes and 169 proteins in OKF6 cells were significantly differentially abundant 96 h after 6 Gy irradiation compared to sham-irradiated controls. Protein-protein in silico enrichment predicted interferon (IFN) response and DNA strand elongation pathways as mostly affected pathways in both cell systems. Both pathways were confirmed in OKF6 cells. Immunoblot validations showed a decrease in minichromosome maintenance (MCM) complex proteins 2-7 and an increase in IFN associated proteins STAT1 and ISG15. In line with affected IFN signalling, mRNA levels of IFNβ and interleukin 6 (IL-6) increased significantly following irradiation and also levels of secreted IL-1β IL-6, IP-10, and ISG15 were elevated. Conclusion: This study has investigated biological mechanisms in keratinocytes post-in vitro ionizing radiation. A common radiation signature in keratinocytes was identified. A role of IFN response in keratinocytes along with increased levels of pro-inflammatory cytokines and proteins could hint towards a possible mechanism for oral mucositis.
2023-06-09 | PXD040398 | Pride
Project description:Chemotherapy may cause DNA damage within the oral mucosa of cancer patients leading to mucositis, a dose-limiting side effect for effective cancer treatment. We used whole genome gene expression analysis to identify cellular damage to the mucosal tissue occuring two days post induction chemotherapy and identified gene expression patterns that may or may not be predictive of oral mucositis. Keywords: Treatment effect
2009-01-01 | GSE10746 | GEO
Project description:To reveal the molecular mechanisms underlying oral ulcerative mucositis-induced pain, we investigated putative pain-associated mediators, pain-related behaviors and gene modulation in a rat oral mucositis model. On day 1 after acetic acid treatment, the mucosal area showed slight redness and swelling but no evidence of ulceration or pain induction. On day 2, oral ulcers were obvious, as was the induction of spontaneous and mechanical pain. In the treated mucosal area, bacterial loading and prostaglandin E2 increased beginning on day 2; no significant changes were observed on day 1. DNA microarray analysis of trigeminal ganglion tissue collected on day 2 identified 32 significantly regulated genes (>1.5-fold change in expression). The up-regulation of the top 3 genes, Hamp (hepcidin antimicrobial peptide), Reg3b (regenerating islet-derived 3β) and Serpina3n (serine peptidase inhibitor A3N), was validated through quantitative RT-PCR. Systemic antibiotic pre-treatment did not increase the mRNA levels. Therefore, we conclude that the oral ulcerative mucositis-induced pain is caused by infectious inflammation of the ulcerative area and stimulates anti-bacterial and anti-peptidase gene expressions in sensory neurons.
2016-06-15 | GSE83349 | GEO
Project description:5-Fluorouracil (5-FU) is a commonly used drug for the treatment of malignant cancers. However, approximately 80% of patients undergoing 5-FU treatment suffer from gastrointestinal mucositis. The aim of this report was to identify the critical molecule involved in 5-FU-induced intestinal mucositis. Our data showed that 5-FU induced inflammation in the small intestine, characterized by the increased intestinal wall thickness and crypt length and the decreased villus height. Network analysis of 5-FU-affected genes by transcriptomic tool showed that the expression of genes was regulated by nuclear factor-κB (NF-κB), and NF-κB was the central molecule in the 5-FU-regulated biological network. NF-κB activity was activated by 5-FU in the intestine, which was judged by bioluminescence imaging and immunohistochemical staining. However, 5-aminosalicylic acid (5-ASA) inhibited 5-FU-induced NF-κB activation and proinflammatory cytokine production. Moreover, 5-FU-induced histological changes were improved by 5-ASA. In conclusion, our findings suggested that NF-κB was the critical molecule associated with the pathogenesis of 5-FU-induced mucositis, and inhibition of NF-κB activity ameliorated the mucosal damage caused by 5-FU.
2017-02-09 | GSE28873 | GEO
Project description:Background Toxicity of the oral and gastrointestinal mucosa induced by high-dose melphalan is a clinical challenge with no documented prophylactic interventions or predictive tests. The aim of this study was to describe molecular changes in human oral mucosa and to identify biomarkers correlated with the grade of clinical mucositis. Methods and Findings Ten patients with multiple myeloma (MM) were included. For each patient, we acquired three buccal biopsies, one before, one at 2 days, and one at 20 days after high-dose melphalan administration. We also acquired buccal biopsies from 10 healthy individuals that served as controls. We analyzed the biopsies for global gene expression and performed an immunohistochemical analysis to determine HLA-DRB5 expression. We evaluated associations between clinical mucositis and gene expression profiles. Compared to gene expression levels before and 20 days after therapy, at two days after melphalan treatment, we found gene regulation in the p53 and TNF pathways (MDM2, INPPD5, TIGAR), which favored anti-apoptotic defense, and upregulation of immunoregulatory genes (TREM2, LAMP3) in mucosal dendritic cells. This upregulation was independent of clinical mucositis. HLA-DRB1 and HLA-DRB5 (surface receptors on dendritic cells) were expressed at low levels in all patients with MM, in the subgroup of patients with ulcerative mucositis (UM), and in controls; in contrast, the subgroup with low-grade mucositis (NM) displayed 5–6 fold increases in HLA-DRB1 and HLA-DRB5 expression in the first two biopsies, independent of melphalan treatment. Moreover, different splice variants of HLA-DRB1 were expressed in the UM and NM subgroups. Conclusions Our results revealed that, among patients with MM, immunoregulatory genes and genes involved in defense against apoptosis were affected immediately after melphalan administration, independent of the presence of clinical mucositis. Furthermore, our results suggested that the expression levels of HLA-DRB1 and HLA-DRB5 may serve as potential predictive biomarkers for mucositis severity
2016-12-19 | GSE81979 | GEO
Project description:Objectives: In patients with tonsil squamous cell cancer (TSCC), radiation-therapy (RT) induce mucositis, which is clinically challenging with limited prophylactic interventions and no predictive tests. In a pilot study set-up, we performed global gene-expression analysis on human oral mucosa tissue and blood cells to identify differential expressed genes involved in mucositis pathogenesis. Materials and Methods: Eight patients with TSCC had consecutive buccal biopsies and blood samples taken before, after 7 days of RT, and 20 days following RT. We monitored clinical mucositis and applied gene-expression analysis to the tissues. Single biopsies and blood tests from 9 healthy individuals served as controls (CON). Results: In response to RT, we did not register changes in the blood cells, but we found upregulation of both apoptosis inducers and inhibitors in the mucosa: EDA2R and MDM2; and POLH, encoding a polymerase that replicates UV-damaged DNA. Six members of the histone cluster family, e.g., HIST1H3B, involved in nucleosome structure, were downregulated. Genes related to proliferation were also altered: MKI67 (downregulated), encoding Ki-67-proliferation; and KRT16 (upregulated), encoding keratin16, characteristic in early differentiated epithelial cells. None of these alterations were associated to mucositis severity. However, before treatment, LY6G6C, which encodes a surface immunoregulatory protein, was upregulated in NM compared to UM, although not significantly. Conclusion: RT caused divergent changes in genes expression related to DNA damage and proliferation, all independently altered of mucositis severity. LY6G6C may be a potential predictive biomarker for UM following RT. Based on these result, we will design a prospective clinical validation trial, including more patients.
2017-12-22 | GSE103412 | GEO
Project description:Chemotherapy may cause DNA damage within the oral mucosa of cancer patients leading to mucositis, a dose-limiting side effect for effective cancer treatment. We used whole genome gene expression analysis to identify cellular damage to the mucosal tissue occuring two days post induction chemotherapy and identified gene expression patterns that may or may not be predictive of oral mucositis. Experiment Overall Design: Punch buccal biopsies from healthy controls (HC, samples BRENC1, BRENC2, BRENC3, n=3) and five AML patients pre-chemotherapy (Pre-C, samples BREN11, BREN21, BREN41, BREN51, n=4) and (Post-C, samples BREN22, BREN32, BREN42, BREN52, n=4)(Ntotal=11) gave suitable RNA integrity to perform microarray analysis. Samples Pre-C:BREN31 and post-C:BREN12 were not suitable for microarray analysis. Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA) was used to conduct gene expression profiling.
2009-01-14 | E-GEOD-10746 | biostudies-arrayexpress
Project description:Dynamic shifts in oral microbiota in patients with mucositis during radiotherapy.
| PRJEB15392 | ENA
Project description:ObjectivesTo evaluate the association and risk factors of healthcare-associated infection (HAI) and burden of illness among chemotherapy-induced ulcerative mucositis (UM) patients.MethodsFor this research, US National Inpatient Sample database 2017 was utilized to study UM patients. The association of healthcare-associated infection-related burden of illness among UM patients was assessed on the outcome--length of hospital stays (LOS), total charges, in-hospital mortality, and discharge disposition.ResultIn 2017, there were 11,350 adult (> 18 years of age) UM patients, among them there were 415 (3.5%) HAI. After adjusting for patient and clinical characteristics, UM patients with HAI were most likely to have higher total charges and longer LOS (1.91; 95% CIs: 1.51-2.41; P < 0.001; 1.84; 95% CIs: 1.53-2.21; P < 0.001) than those without HAI. Further, mortality was not significantly different. UM patients with HAI were less likely to have higher burden of illness who were younger, females, those living in non-metropolitan or micropolitan counties, and those with lower co-morbidity score. Additionally, UM patients with HAI were more likely to discharge to skilled nursing facility (SNF), intermediate care facility (ICF), and another type of facility (ATF), (aOR = 2.58 (1.16-5.76), P = 0.02), than they were to discharge to self-care or home care.ConclusionUM patients with HAI were more likely to have higher burden of illness and more likely to discharged to the SNF, ICF, and ATF rather than to home or self-care. Clinical relevance UM patients when associated with HAI have higher burden of illness; a tailored approach to oral care might prevent HAIs and burden of illness among UM.
| S-EPMC8342036 | biostudies-literature