scholarly journals Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia

2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Karen Kleberg ◽  
Gerda Majgaard Jensen ◽  
Dan Ploug Christensen ◽  
Morten Lundh ◽  
Lars Groth Grunnet ◽  
...  
Author(s):  
A. L. Latner ◽  
G. A. Turner ◽  
D. Tregoning

Cyclic adenosine 3′, 5′ monophosphate (cyclic-AMP) has been estimated in mucosal biopsy samples removed from the descending colon and rectum at endoscopy to investigate the possibility of using this substance for monitoring pre-malignant changes in the large bowel. Four groups of patients have been studied: those with normal large bowel and rectal mucosa; those with non-malignant inflammatory bowel disease; those with an adenomatous polyp in the descending colon or sigmoid colon; and those with a rectal adenocarcinoma. No difference was found in the cyclic-AMP content of ‘normal’ rectal mucosa, ‘normal’ colonic mucosa, ‘diseased’ colonic mucosa, carcinomas, and uninvolved mucosa adjacent to the polyps. Less cyclic-AMP was found in the polyps than in adjacent uninvolved mucosa. Conversely, more cyclic-AMP was found in the carcinomas than in adjacent uninvolved mucosa. It is concluded that although cyclic-AMP may be a very useful parameter for delineating the extent of the disease in individual patients, it is not a suitable biochemical marker for the screening of neoplastic changes in the large bowel in the population as a whole.


2021 ◽  
Author(s):  
Ulrike Ries Feddersen ◽  
Sebastian Kjærgaard Hendel ◽  
Mark Alexander Berner-Hansen ◽  
Thomas Andrew Jepps ◽  
Niels Bindslev ◽  
...  

Abstract BackgroundAberrations in cyclooxygenase and lipoxygenase (LOX) pathways in non-neoplastic, normal appearing mucosa from patients with colorectal neoplasia (CRN), could hypothetically qualify as predisposing CRN-markers. To test this hypothesis, biopsies were obtained during colonoscopy from macroscopically normal colonic mucosa from patients with and without CRN. Prostaglandin E2 (PGE2) receptors, EP1-4, were examined in Ussing-chambers by exposing biopsies to selective EP receptor agonists, antagonists and PGE2. Furthermore, mRNA expression of EP receptors, prostanoid synthases and LOX enzymes were evaluated using qPCR technology.Results Data suggest that PGE2 binds to high and low affinity EP receptors. In particular, PGE2 demonstrated EP4 receptor potency in the low nanomolar range. Similar results were detected using EP2 and EP4 agonists. In CRN patients, mRNA-levels were higher for EP1 and EP2 receptors and for enzymes prostaglandin-I synthase, 5-LOX, 12-LOX and 15-LOX. ConclusionIn conclusion, normal appearing colonic mucosa from CRN patients demonstrates deviating expression in eicosanoid pathways, indicating a likely predisposition for early CRN development. Moreover, PGE2 potency activates high affinity EP4 receptor subtypes, supporting relevance of testing EP4 antagonists in colorectal cancer management.


2009 ◽  
Vol 27 (2) ◽  
pp. 186-192 ◽  
Author(s):  
Paul Salama ◽  
Michael Phillips ◽  
Fabienne Grieu ◽  
Melinda Morris ◽  
Nik Zeps ◽  
...  

Purpose To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3+ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer.


2021 ◽  
Vol 30 (1) ◽  
pp. 59-65
Author(s):  
Anca Loredana Udristoiu ◽  
Daniela Stefanescu ◽  
Gabriel Gruionu ◽  
Lucian Gheorghe Gruionu ◽  
Andreea Valentina Iacob ◽  
...  

Background and Aims: Mucosal healing (MH) is associated with a stable course of Crohn’s disease (CD) which can be assessed by confocal laser endomicroscopy (CLE). To minimize the operator’s errors and automate assessment of CLE images, we used a deep learning (DL) model for image analysis. We hypothesized that DL combined with convolutional neural networks (CNNs) and long short-term memory (LSTM) can distinguish between normal and inflamed colonic mucosa from CLE images. Methods: The study included 54 patients, 32 with known active CD, and 22 control patients (18 CD patients with MH and four normal mucosa patients with no history of inflammatory bowel diseases). We designed and trained a deep convolutional neural network to detect active CD using 6,205 endomicroscopy images classified as active CD inflammation (3,672 images) and control mucosal healing or no inflammation (2,533 images). CLE imaging was performed on four colorectal areas and the terminal ileum. Gold standard was represented by the histopathological evaluation. The dataset was randomly split in two distinct training and testing datasets: 80% data from each patient were used for training and the remaining 20% for testing. The training dataset consists of 2,892 images with inflammation and 2,189 control images. The testing dataset consists of 780 images with inflammation and 344 control images of the colon. We used a CNN-LSTM model with four convolution layers and one LSTM layer for automatic detection of MH and CD diagnosis from CLE images. Results: CLE investigation reveals normal colonic mucosa with round crypts and inflamed mucosa with irregular crypts and tortuous and dilated blood vessels. Our method obtained a 95.3% test accuracy with a specificity of 92.78% and a sensitivity of 94.6%, with an area under each receiver operating characteristic curves of 0.98. Conclusions: Using machine learning algorithms on CLE images can successfully differentiate between inflammation and normal ileocolonic mucosa and can be used as a computer aided diagnosis for CD. Future clinical studies with a larger patient spectrum will validate our results and improve the CNN-SSTM model.


2010 ◽  
Vol 103 (6) ◽  
pp. 595-596 ◽  
Author(s):  
Divey Manocha ◽  
Savio John ◽  
Philip Holtzapple

1996 ◽  
Vol 82 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Giuseppe Pappalardo ◽  
Antonio Guadalaxara ◽  
Giuseppe Maiani ◽  
Giovanni Illomei ◽  
Mauro Trifero ◽  
...  

In consideration of findings reported in the literature and of our study, we examined the correlation between antioxidants (β-carotene, vitamin C, vitamin E) and colorectal carcinogenesis. Although diagnostic progress has been made in the last decades, no significant improvements in death rates have been achieved in the western world. Exogenous factors might be responsible for a complex alteration process of normal colonic mucosa into adenoma and carcinoma. Free radicals and reactive oxygen metabolites, due to increased production or to reduced inactivation, following a decrease in the antioxidant burden in the mucosa, might cause damage to DNA, thereby resulting in genetic alterations. This might represent the cause of the transformation process: normal mucosa→ adenoma→ carcinoma. In a prospective study, we observed a reduction of β-carotene levels in normal colonic mucosa in patients with polyps and colorectal cancer. We also showed that β-carotene supplementation raises levels of this micronutrient in the colonic mucosa of these patients. Findings from the literature and our trials show a significant decrease in the antioxidant capacity of colorectal mucosa in patients affected by colorectal cancer, although there is a significant interindividual variability. Such results suggest a possible chemopreventive role of antioxidant agents in colorectal cancer.


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