Reduced keratin expression in colorectal neoplasia and associated fields is reversible by diet and resection.

Background: Patients with adenomatous colonic polyps are at increased risk of developing further polyps suggesting field-wide alterations in cancer predisposition. The current study aimed to identify molecular alterations in the normal mucosa in the proximity of adenomatous polyps and to assess the modulating effect of butyrate, a chemopreventive compound produced by fermentation of dietary residues.

Methods: A cross-sectional study was undertaken in patients with adenomatous polyps: biopsy samples were taken from the adenoma, and from macroscopically normal mucosa on the contralateral wall to the adenoma and from the mid-sigmoid colon.

Production, Characterization and Potential Uses of a 3D Tissue-engineered Human Esophageal Mucosal Model.

The incidence of both esophageal adenocarcinoma and its precursor, Barrett's Metaplasia, are rising rapidly in the western world. Furthermore esophageal adenocarcinoma generally has a poor prognosis, with little improvement in survival rates in recent years. These are difficult conditions to study and there has been a lack of suitable experimental platforms to investigate disorders of the esophageal mucosa.

Pulsatile exposure to simulated reflux leads to changes in gene expression in a 3D model of oesophageal mucosa.

Oesophageal exposure to duodenogastroesophageal refluxate is implicated in the development of Barrett's metaplasia (BM), with increased risk of progression to oesophageal adenocarcinoma. The literature proposes that reflux exposure activates NF-κB, driving the aberrant expression of intestine-specific caudal-related homeobox (CDX) genes. However, early events in the pathogenesis of BM from normal epithelium are poorly understood.

Loss of dystroglycan function in oesophageal cancer.

Aims:  Oesophageal cancer is an increasingly common human malignancy, with its incidence in the West rapidly rising. It is associated with a very poor prognosis, and its exact pathogenesis is uncertain. Dystroglycan and E-cadherin are cell adhesion molecules, the loss of which is often related to tumour differentiation, aggressiveness and invasiveness.

NF-κB is activated in oesophageal fibroblasts in response to a paracrine signal generated by acid-exposed primary oesophageal squamous cells.

Oesophageal exposure to duodenogastro-oesophageal refluxate leads to reflux oesophagitis and is implicated in the development of Barrett's metaplasia (BM). NF-κB signalling in epithelial cells is associated with the activation of transcription factors believed to be central to BM development, whilst NF-κB activation in fibroblasts plays a critical role in matrix remodelling. Our aim was to study the effects of acid exposure on NF-κB activation in primary human oesophageal fibroblasts (HOFs) and primary and immortalized oesophageal squames and to investigate any epithelial/stromal interactions in the response of these cells to acid.

Short-chain fatty acid level and field cancerization show opposing associations with enteroendocrine cell number and neuropilin expression in patients with colorectal adenoma.

Background: Previous reports have suggested that the VEGF receptor neuropilin-1 (NRP-1) is expressed in a singly dispersed subpopulation of cells in the normal colonic epithelium, but that expression becomes dysregulated during colorectal carcinogenesis, with higher levels in tumour suggestive of a poor prognosis. We noted that the spatial distribution and morphology if NRP-1 expressing cells resembles that of enteroendocrine cells (EEC) which are altered in response to disease state including cancer and irritable bowel syndrome (IBS). We have shown that NRP-1 is down-regulated by butyrate in colon cancer cell lines in vitro and we hypothesized that butyrate produced in the lumen would have an analogous effect on the colon mucosa in vivo.

Keratin 8 expression in colon cancer associates with low faecal butyrate levels.

Background: Butyrate has been implicated in the mechanistic basis of the prevention of colorectal cancer by dietary fibre. Numerous in vitro studies have shown that butyrate regulates cell cycle and cell death. More recently we have shown that butyrate also regulates the integrity of the intermediate filament (IF) cytoskeleton in vitro.

Riboflavin depletion impairs cell proliferation in adult human duodenum: identification of potential effectors.

Background And Aims: Riboflavin (vitamin B2) is an essential dietary component with a known function in oxidative metabolism. Our previous data using a rat model of riboflavin deficiency suggested that riboflavin also functions as a luminal signaling molecule regulating crypt development and cell turnover. Riboflavin deficiency is prevalent in both high- and low-income countries across the globe.

The development and characterization of an organotypic tissue-engineered human esophageal mucosal model.

There is a demand for a reliable three-dimensional tissue-engineered model of the esophageal mucosa for use as an experimental platform for investigating esophageal epithelial biology and the pathogenesis of esophageal neoplasia and precursor lesions such as Barrett's metaplasia. A number of models have been described, but there has been little systematic assessment of the different approaches, making selection of a preferred platform difficult. This study assesses the properties of organotypic cultures using four different scaffolds (human esophageal matrix, porcine esophageal matrix, human dermal matrix, and collagen) and two different epithelial cell types (primary human esophageal squamous cells and the Het-1A esophageal squamous cell line).

A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study.

Background: A number of studies, notably EPIC, have shown a descrease in colorectal cancer risk associated with increased fibre consumption. Whilst the underlying mechanisms are likely to be multifactorial, production of the short-chain fatty-acid butyrate fro butyratye is frequently cited as a major potential contributor to the effect. Butyrate inhibits histone deacetylases, which work on a wide range of proteins over and above histones.

Commonly used bowel preparations have significant and different effects upon cell proliferation in the colon: a pilot study.

Background: Markers of crypt cell proliferation are frequently employed in studies of the impact of genetic and exogenous factors on human colonic physiology. Human studies often rely on the assessment of tissue acquired at endoscopy. Modulation of cell proliferation by bowel preparation with oral laxatives may confound the findings of such studies, but there is little data on the impact of commonly used bowel preparations on markers of cell proliferation.

Overexpression of cellular iron import proteins is associated with malignant progression of esophageal adenocarcinoma.

Purpose: There is growing evidence that iron is important in esophageal adenocarcinoma, a cancer whose incidence is rising faster than any other in the Western world. However, how iron mediates carcinogenesis at the molecular level remains unclear. In this study, we investigated the expression of iron transport proteins involved in cellular iron import, export, and storage in the premalignant lesion Barrett's metaplasia and esophageal adenocarcinoma.