scholarly journals Specific detection of cell-free DNA derived from intestinal epithelial cells using methylation patterns

2018 ◽  
Author(s):  
Roni Lehmann-Werman ◽  
Aviad Zick ◽  
Cloud Paweletz ◽  
Marisa Welch ◽  
Ayala Hubert ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Ductal Adenocarcinoma ◽  
Intestinal Epithelial ◽  
Specific Detection ◽  
Cell Free Dna ◽  
Free Dna ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Methylation Patterns

AbstractEpithelial cells of the intestine undergo rapid turnover and are thought to be cleared via stool. Disruption of tissue architecture, as occurs in colorectal cancer (CRC), results in the release of material from dying intestinal epithelial cells to blood. This phenomenon could be utilized for diagnosis and monitoring of intestinal diseases, if circulating cell-free DNA (cfDNA) derived from intestinal cells could be specifically identified. Here we describe two genomic loci that are unmethylated specifically in intestinal epithelial cells, allowing for sensitive and specific detection of DNA derived from such cells. As expected, intestinal DNA is found in stool, but not in plasma, of healthy individuals. Patients with inflammatory bowel disease (IBD) have minimal amounts of intestinal cfDNA in the plasma, whereas patients with advanced CRC show a strong signal. The intestinal markers are not elevated in plasma samples from patients with pancreatic ductal adenocarcinoma (PDAC), and a combination of intestine- and pancreas-specific markers allowed for robust differentiation between plasma cfDNA derived from CRC and PDAC patients. Intestinal DNA markers provide a mutation-independent tool for monitoring intestinal dynamics in health and disease.

Proteomic response of inflammatory stimulated intestinal epithelial cells to in vitro digested plums and cabbages rich in carotenoids and polyphenols

2016 ◽  
Vol 7 (10) ◽  
pp. 4388-4399 ◽  
Author(s):  
Anouk Kaulmann ◽  
Sébastien Planchon ◽  
Jenny Renaut ◽  
Yves-Jacques Schneider ◽  
Lucien Hoffmann ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Epithelial Cells ◽  
Intestinal Cells ◽  
Intestinal Epithelial ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Proteomic Response

Proteomic response of intestinal cells as a model of inflammatory bowel diseases to digested plum and cabbage rich in polyphenols and carotenoids.

Potassium Channels in Intestinal Epithelial Cells and their Pharmacological Modulation: A Systematic Review

2020 ◽  
Author(s):  
Dina Cosme ◽  
Maria Manuela Estevinho ◽  
Florian Rieder ◽  
Fernando Magro
Keyword(s):  
Epithelial Cells ◽  
Potassium Channels ◽  
Intestinal Epithelial Cells ◽  
Strong Association ◽  
Physiological Role ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Pharmacological Modulation ◽  
Inflammatory Bowel

Background: Several potassium channels (KCs) have been described throughout the gastrointestinal tract. Notwithstanding, their contribution to both physiologic and pathophysiologic conditions, as inflammatory bowel disease (IBD), remains underexplored. Therefore, we aim to systematically review, for the first time, the evidence on the characteristics and modulation of KCs in intestinal epithelial cells (IECs). Methods: PubMed, Scopus and Web of Science were searched to identify studies focusing on KCs and their modulation in IECs. The included studies were assessed using a reporting inclusiveness checklist. Results: From the 745 identified records, 73 met the inclusion criteria; their reporting inclusiveness was moderate-high. Some studies described the physiological role of KCs, while others explored their importance in pathological settings. Globally, in IBD animal models, apical KCa1.1 channels, responsible for luminal secretion, were upregulated. In human colonocytes, basolateral KCa3.1 channels were downregulated. The pharmacological inhibition of K2P and Kv influenced intestinal barrier function, promoting inflammation. Conclusion: Evidence suggests a strong association between KCs expression and secretory mechanisms in human and animal IECs. Further research is warranted to explore the usefulness of KC pharmacological modulation as a therapeutic target.

Signaling pathway via TNF-α/NF-κB in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis

2009 ◽  
Vol 296 (4) ◽  
pp. G850-G859 ◽  
Author(s):  
Michio Onizawa ◽  
Takashi Nagaishi ◽  
Takanori Kanai ◽  
Ken-ichi Nagano ◽  
Shigeru Oshima ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Maintenance Therapy ◽  
Intestinal Epithelial Cells ◽  
Immunoblot Analysis ◽  
Intestinal Epithelial ◽  
Tnf Receptor ◽  
Tnf Α ◽  
Sequential Administration ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Treatment with anti-TNF-α MAb has been accepted as a successful maintenance therapy for patients with inflammatory bowel diseases (IBD). Moreover, it has been recently reported that blockade of TNF receptor (TNFR) 1 signaling in infiltrating hematopoietic cells may prevent the development of colitis-associated cancer (CAC). However, it remains unclear whether the TNF-α signaling in epithelial cells is involved in the development of CAC. To investigate this, we studied the effects of anti-TNF-α MAb in an animal model of CAC by administration of azoxymethane (AOM) followed by sequential dextran sodium sulfate (DSS) ingestion. We observed that the NF-κB pathway is activated in colonic epithelia from DSS-administered mice in association with upregulation of TNFR2 rather than TNFR1. Immunoblot analysis also revealed that the TNFR2 upregulation accompanied by the NF-κB activation is further complicated in CAC tissues induced in AOM/DSS-administered mice compared with the nontumor area. Such NF-κB activity in the epithelial cells is significantly suppressed by the treatment of MP6-XT22, an anti-TNF-α MAb. Despite inability to reduce the severity of colitis, sequential administration of MP6-XT22 reduced the numbers and size of tumors in association with the NF-κB inactivation. Taken together, present studies suggest that the TNFR2 signaling in intestinal epithelial cells may be directly involved in the development of CAC with persistent colitis and imply that the maintenance therapy with anti-TNF-α MAb may prevent the development of CAC in patients with long-standing IBD.

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