Mutational analysis of driver genes defines the colorectal adenoma: in situ carcinoma transition.

A large proportion of colorectal carcinomas (CRC) evolve from colorectal adenomas. However, not all individuals with colonic adenomas have a risk of CRC substantially higher than those of the general population. The aim of the study was to determine the differences or similarities of mutation profile among low- and high-grade adenomas and in situ carcinoma with detailed follow up.

A head-to-head comparison of 4-L polyethylene glycol and low-volume solutions before colonoscopy: which is the best? A multicentre, randomized trial.

Purpose: The purpose of this study is to compare the efficacy and tolerability of polyethylene glycol (PEG) to sodium picosulfate/magnesium citrate (SPMC) and low-volume polyethylene glycol/ascorbic acid (PEGA) in a single- or split-dose regimen for colonoscopy bowel preparation.

Methods: This was a prospective, randomized, endoscopist-blinded, multicentre study. Outpatients received either PEG or SPMC or PEGA in a single or a split dose before the colonoscopy.

Inflammation regulates 11β-hydroxysteroid dehydrogenase type 1 differentially in specific compartments of the gut mucosal immune system.

The bioavailability of glucocorticoids is modulated by enzyme 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), which catalyzes the conversion of inactive 11-oxo-glucocorticoids to active 11-hydroxy-glucocorticoids cortisol and corticosterone and is regulated by pro-inflammatory cytokines. Our aim was to assess the effect of colitis on the expression of 11HSD1 in specific microanatomical compartments of the mucosal immune system. Using qRT-PCR we quantified the expression of 11HSD1 and cytokines in the colon, mesenteric lymph nodes (MLN) and spleen of mice with colitis.

[Effective bowel preparation before coloscopy - low-volume PEG in the divided dose regimen].

Introduction: The good and safe bowel cleansing is key to the success of coloscopy. The standard preparation involves 4 l polyethylene glycol (PEG). Now the combination of PEG and ascorbic acid (PEGA) of half the volume is available.

Synchronous gastric and sebaceous cancers, a rare manifestation of MLH1-related Muir-Torre syndrome.

Muir-Torre syndrome (MTS), a rare variant of the hereditary non polyposis colorectal cancer syndrome, is an autosomal dominant genodermatosis characterised by coincidence of sebaceous gland neoplasms (sebaceous adenoma, epithelioma, or carcinoma) and at least one internal malignancy. The underlying cause of MTS is a germline mutation in DNA mismatch repair genes MSH2, MLH1 and MSH6. We report the case of a 52-year-old caucasian woman with the development of metachronous colon cancer at the age of 38 years, uterine cancer at the age of 43 years, and unique occurrence of synchronous gastric and sebaceous carcinomas related to germline point mutation c.

[Zdeněk Mařatka and his share in the founding of the Czech Gastroenterological Society and its journal. Gastroenterological Society in Czech and Slovac republics].

Zdeněk Mařatka (1914-2010) was a leading person in a Czech and Slovak gastroenterology in spite of the infavourable approach of the official communist policy to him.. He was one of the founders of gastroenterology in Czechoslovakia.

Expression of 11β-hydroxysteroid dehydrogenase type 2 is deregulated in colon carcinoma.

Although the effects of glucocorticoids on proliferation, differentiation and apoptosis are well known, and steroid hormones have been identified to play a role in pathogenesis and the development of various cancers, limited data are available regarding the relationship between the local metabolism of glucocorticoids and colorectal adenocarcinoma (CRC) formation. Glucocorticoid metabolism is determined by 11β-hydroxysteroid dehydrogenases type 1 and 2 (11HSD1, 11HSD2), which increase the local concentration of cortisol due to the reduction of cortisone, or decrease this concentration due to the oxidation of cortisol. The objective of this study was to evaluate the extent of 11HSD1 and 11HSD2 mRNA in pre-malignant colorectal polyps and in CRC.

Local metabolism of glucocorticoids and its role in rat adjuvant arthritis.

11beta-Hydroxysteroid dehydrogenase 1 (11HSD1) regulates local glucocorticoid activity and plays an important role in various diseases. Here, we studied whether arthritis modulates 11HSD1, what is the role of pro-inflammatory cytokines in this process and whether altered local metabolism of glucocorticoids may contribute to the feedback regulation of inflammation. Adjuvant arthritis increased synovial 11HSD1 mRNA and 11-reductase activity but treatments with tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) antagonists etanercept and anakinra reduced 11HSD1 upregulation.

Expression profiles of proliferative and antiapoptotic genes in sporadic and colitis-related mouse colon cancer models.

Elevated levels of survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) and the regulatory factors c-MYB and Tcf-4 are often found in human cancers including colorectal cancer (CRC) and have been implicated in the development and progression of tumorigenesis. The aim of this study was to determine the expression of these genes in mouse models of sporadic and colitis-associated CRC. To address these issues, we used qRT-PCR approach to determine changes in gene expression patterns of neoplastic cells (high-grade dysplasia/intramucosal carcinoma) and surrounding normal epithelial cells in A/J and ICR mouse strains using laser microdissection.

Enhanced expression of proproliferative and antiapoptotic genes in ulcerative colitis-associated neoplasia.

Background: Inflammatory bowel diseases including long-standing ulcerative colitis (UC) have an increased risk of evolving into colorectal cancer (CRC). The overexpression of some proproliferative and antiapoptotic genes, such as survivin, telomerase catalytic subunit (hTERT), integrin-linked kinase (ILK), and regulatory factors c-MYB and Tcf-4, has been implicated in the development and progression of several human malignancies including CRC.

Methods: In this study we analyzed the expression alterations of these markers and proinflammatory enzymes cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) during the transition of colonic mucosa from chronic inflammation to epithelial neoplasia in biopsies of UC patients using quantitative real-time polymerase chain reaction and immunohistochemistry; additionally, we compared the expression profiles of this gene panel in samples of patients with CRC after tumor resection and in human tumor xenografts of SW620 malignant colonic cells.

11beta-hydroxysteroid dehydrogenase 1 and 2 expression in colon from patients with ulcerative colitis.

Background And Aim: 11beta-hydroxysteroid dehydrogenase (11betaHSD) is an enzyme responsible for the interconversion of active 11beta-hydroxysteroids (cortisol) into biologically inactive 11-oxosteroids (cortisone). The isoform 11betaHSD1 operates predominantly as a reductase converting cortisone to cortisol, whereas 11betaHSD2 catalyzes oxidation of cortisol to cortisone. This mechanism of peripheral metabolism of glucocorticoids has been suggested to be involved in increasing the availability of anti- inflammatory glucocorticoids as a response to inflammatory stimuli.

Expression of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in colorectal cancer.

Glucocorticoid hormones have been reported to operate as regulators of cell proliferation and differentiation and to inhibit growth of several colon tumors and adenocarcinoma cell lines. The glucocorticoid action is regulated, in part, at the pre-receptor level through the expression of isoforms of 11beta-hydroxysteroid dehydrogenase (11betaHSD1, 11betaHSD2) which are responsible for the interconversion of hormonally active cortisol to cortisone. Since both of these isoforms are expressed in the mammalian colon, we examined whether 11betaHSD1 and 11betaHSD2 are expressed in human colorectal cancer and whether their expression differs between neoplastic and autologous non-neoplastic tissue.