Gene expression profiling during adhesion formation induced by cecum cauterization
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE123413 | GEO | 2018/12/07
REPOSITORIES: GEO
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Project description:Adhesions are fibrotic scars that form between abdominal organs following surgery or infection, and may cause bowel obstruction, chronic pain, or infertility. Adhesions occur post-operatively in 50-90% of all open abdominal operations and as such, represent an enormous clinical problem impacting hundreds of millions of patients worldwide. Our understanding of the biology of adhesion formation is very limited, which explains why there are essentially no available treatments that prevent adhesions. In this study, we systemically analyzed abdominal adhesions in mouse and human tissues gene expression using bulk- and sc-RNA-seq technologies to characterize the fibroblasts responsible for this devastating pathology.
2020-07-08 | GSE153929 | GEO
Project description:Abdominal surgeries are lifesaving procedures but can be complicated by the formation of peritoneal adhesions, intra-abdominal scars that cause intestinal obstruction, pain, infertility, and significant health costs. Despite this burden, the mechanisms underlying adhesion formation remain unclear and no cure exists. Here, we show that contamination of gut microbes increases post-surgical adhesion formation. Using genetic lineage tracing we show that adhesion myofibroblasts arose from the mesothelium. This transformation was driven by epidermal growth factor receptor (EGFR) signaling. The EGFR ligands Amphiregulin and Heparin-binding Epidermal Growth Factor, were sufficient to induce these changes. Correspondingly, EGFR inhibition led to a significant reduction of adhesion formation in mice. Adhesions isolated from human patients were enriched in EGFR positive cells of mesothelial origin and human mesothelium showed an increase of mesothelial EGFR expression during bacterial peritonitis. In conclusion, bacterial contamination drives adhesion formation through mesothelial EGFR signaling. This mechanism may represent a therapeutic target for the prevention of adhesions after intra-abdominal surgery.
2021-11-08 | GSE186658 | GEO
Project description:The aim was to investigate the effect of postoperative intra-abdominal infection on the gene expression patterns of peripheral blood leukocytes (PBL) after surgery for colorectal cancer
2017-06-12 | GSE77167 | GEO
Project description:Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. Overexpression of several genes may be a result of surgical trauma or preoperative manipulation, and may not reflect any biological impact of the disease. This study compares the expression profiles in preoperative tissue while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery.
2011-03-01 | E-MTAB-469 | biostudies-arrayexpress
Project description:Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. Overexpression of several genes may be a result of surgical trauma or preoperative manipulation, and may not reflect any biological impact of the disease. This study compares the expression profiles in preoperative tissue while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery.
2011-03-01 | E-MTAB-470 | biostudies-arrayexpress
Project description:Background: Adhesion formation in the peritoneal cavity is the most-common cause of intestinal obstruction. The aim of this study was to analyze the dynamic gene expression patterns in the small bowel of mice featuring surgically-induced intra-abdominal adhesion. Methods: In an experimental study, mRNA was extracted from the small bowels of sham control mice and small bowel-scraping mice following surgically-induced intra-abdominal adhesion at 1, 3, 7, and 14 days post surgery. The mouse cDNA microarray was used to monitor the dynamic changes of the tested genes. Results: We identified 520 genes with a greater than 1.5 fold change across all studied mice groups. Quantitative RT-PCR and immunohistochemical staining certified, respectively, the expression of certain selected genes. The number of apoptotic cells contained within the adhesion tissue increased in a time-dependent manner. The serum concentration of neuropeptide Y was significantly greater for the test mice compared to the controls. Conclusions: Surgical intervention to the small bowel induces an adaptive response of damaged tissue in order to eliminate excessive complement-mediated lysis, prevent oxidative injuries, and enhance cell proliferation. These findings may provide insights into the pathogenesis of complications following adhesion formation and might also help to identify some new target genes for specific diagnostic tools and novel therapeutic strategies. Keywords: Time course study
2006-05-24 | GSE4715 | GEO
Project description:Rationale: Adhesion formation is a frequent complication after abdominal surgery. Adhesion formation might be reduced by laparoscopic surgery, however sound evidence is lacking. Colorectal surgery would be a good clinical model to investigate adhesion formation between open and laparoscopic surgery because of the adhesion formation propensity of colorectal surgery. However, a randomized controlled study to provide direct evidence is unlikely because of large numbers of patients needed for such a trial and the difficulty to check for adhesion formation at second surgery. Therefore we investigate adhesion formation after laparoscopic and open colorectal surgery for malignancy at liver surgery for metastases.
Objective: The aim of our study is to compare the incidence of adhesions after laparoscopic versus open surgery for colorectal malignancies during liver resection for colorectal metastases.
Study design: The study is designed as a prospective observational cohort study.
Study population: All consecutive, adult patients undergoing laparotomy or laparoscopy for intended liver resection or radio frequency ablation for liver metastases of a colorectal malignancy in whom inspection of the middle and lower abdomen is possible to map adhesions.
Main study parameters/endpoints:
* Primary endpoint is incidence of adhesions to the ventral abdominal wall around the site of the original incision.
* Secondary endpoints are episodes of bowel obstruction between index surgery and liver surgery; total incidence of adhesions; extent of adhesions; Zühlke classification of adhesions; performance of adhesiolysis; duration of adhesiolysis; peroperative complications: enterotomy, seromuscular injury, inadvertent organ injury during adhesiolysis; postoperative complications: delayed diagnosed perforation, SAE’s.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This study is an observational study. The existence of adhesions will be assessed during laparotomy or laparoscopy for the treatment of liver metastases. The laparotomy is indicated for medical treatment and should not be enlarged solely for the assessment of adhesions nor will the operating time be influenced for this purpose.
Adhesions and peroperative complications have to be scored by the operating surgeon during or directly after surgery. The postoperative complications have to be scored during the postoperative course by the doctors on the ward. These assessments do not interfere with the treatment of the patients.
| 2134661 | ecrin-mdr-crc
Project description:Rationale
Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major-abdominal surgery, with postoperative pneumonia associated with an almost five-fold increase in 30-day mortality.
Objectives
To describe immune-pathways and gene-networks altered following major-abdominal surgery and identify transcriptomic patterns associated with postoperative pneumonia.
Methods and Measurements
From a prospective consecutive cohort (n=150) undergoing major-abdominal surgery whole-blood RNA was collected preoperatively and at three time-points postoperatively (2-6, 24 and 48hrs). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing.
Main Results
Compared to preoperative sampling, 3,639 genes were upregulated and 5,043 downregulated at 2-6hrs. Pathway-analysis demonstrated innate-immune activation with neutrophil-degranulation and Toll-like-receptor signalling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil-degranulation was associated with postoperative pneumonia acquisition (P=0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil-dysfunction and a more dysregulated host response, at 48hrs postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free (P=0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major-abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection.
Conclusions
Major-abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil-degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.
| EGAS00001007229 | EGA
Project description:The molecular mechanisms underlying postoperative pericardial adhesions are poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis. Using a previously established murine model, we successfully visualized the cell-based tissue dynamics during pericardial adhesion and discovered a unique angiogenic process for the induction of fibrosis. Masson’s trichrome staining revealed that collagen production was promoted from the fourth day after cardiac injury inflicted by talc injection into the pericardial cavity. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analysis demonstrated that arterioles excessively sprouted from pericardial tissues in mice as well as in humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial cells and myofibroblasts appeared in cytokine-exposed sprouting vessels and adhesion tissues, but not in quiescent vessels in the heart. Additionally, vascular smooth muscle cells were dedifferentiated from the contractile to the synthetic phenotype in heart tissue, and matrix metalloproteinase-dependent tissue remodeling in the pre-angiogenic stage potentially contributed to neovascularization and fibrosis in the pericardial cavity. Our findings will assist in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues.
2022-01-10 | GSE182735 | GEO