MLH1 Promotor Hypermethylation in Colorectal and Endometrial Carcinomas from Patients with Lynch Syndrome.

Screening for Lynch syndrome (LS) in colorectal cancer (CRC) and endometrial cancer patients generally involves immunohistochemical staining of the mismatch repair (MMR) proteins. In case of MLH1 protein loss, MLH1 promotor hypermethylation (MLH1-PM) testing is performed to indirectly distinguish the constitutional MLH1 variants from somatic epimutations. Recently, multiple studies have reported that MLH1-PM and pathogenic constitutional MMR variants are not mutually exclusive.

Fully automated fluorescent in situ hybridization (FISH) staining and digital analysis of HER2 in breast cancer: a validation study.

HER2 assessment is routinely used to select patients with invasive breast cancer that might benefit from HER2-targeted therapy. The aim of this study was to validate a fully automated in situ hybridization (ISH) procedure that combines the automated Leica HER2 fluorescent ISH system for Bond with supervised automated analysis with the Visia imaging D-Sight digital imaging platform. HER2 assessment was performed on 328 formalin-fixed/paraffin-embedded invasive breast cancer tumors on tissue microarrays (TMA) and 100 (50 selected IHC 2+ and 50 random IHC scores) full-sized slides of resections/biopsies obtained for diagnostic purposes previously.

Westernized high-fat diet accelerates weight loss in dextran sulfate sodium-induced colitis in mice, which is further aggravated by supplementation of heme.

The Western diet, rich in fat and red meat, predisposes for inflammatory bowel disease (IBD); however, little is known about mechanisms involved. Red meat contains high levels of heme, a well-known inducer of the cytoprotective enzyme heme oxygenase-1 (HO-1). Pharmacological induction of HO-1 ameliorates experimental colitis.

COX-2 polymorphisms -765G-->C and -1195A-->G and colorectal cancer risk.

Aim: To determine the possible modulating effect of the COX-2 polymorphisms, -765G-->C and -1195A-->G, on the risk of colorectal cancer (CRC) in a Dutch population.

Methods: This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -765G-->C and -1195A-->G were determined by polymerase chain reaction-based restriction fragment length polymorphism.

Effects of active and passive smoking on disease course of Crohn's disease and ulcerative colitis.

Background: Smoking is a remarkable risk factor for inflammatory bowel disease (IBD), aggravating Crohn's disease (CD) while having beneficial effects on ulcerative colitis (UC). We studied the effects of active and passive smoking in Dutch IBD patients.

Methods: A questionnaire focusing on cigarette smoke exposure was sent to 820 IBD patients.

Role of epoxide hydrolase, NAD(P)H:quinone oxidoreductase, cytochrome P450 2E1 or alcohol dehydrogenase genotypes in susceptibility to colorectal cancer.

Colorectal cancer (CRC) is one of the most common forms of cancer in Western countries. CRC has been associated with genetic and lifestyle factors. Individual susceptibility to CRC may be due partly to variations in detoxification capacity in the gastrointestinal tract.

High oxygen radical production in patients with sporadic colorectal cancer.

It is hypothesized that excessive generation of reactive oxygen species (ROS) by phagocytes or leakage from mitochondria may harm key genes or proteins responsible for intestinal cell homeostasis. This may initiate the multistage process of colon cancer development. The present study investigates whether ROS production by whole blood may contribute to the etiology of colorectal cancer (CRC).

Glibenclamide depletes ATP in renal proximal tubular cells by interfering with mitochondrial metabolism.

Sulfonylurea drugs, like glibenclamide, stimulate insulin secretion by blocking ATP-sensitive potassium channels on pancreatic beta cells. Renal tubular epithelial cells possess a different class of K(ATP) channels with much lower affinities for sulfonylurea drugs, necessitating the use of micromolar glibenclamide concentrations to study these channels. Here, we describe the toxic effects of these concentrations on mitochondrial energy metabolism in freshly isolated renal proximal tubular cells.

No association between genetic polymorphisms in NAD(P)H oxidase p22phox and paraoxonase 1 and colorectal cancer risk.

Background: Impaired metabolism of ingested toxic or carcinogenic compounds is a postulated mechanism underlying colorectal cancer (CRC). Furthermore, it is suggested that reactive oxygen species (ROS) may play a role in human cancer development. Polymorphic variations in NAD(P)H oxidase p22phox and paraoxonase 1 (PON1) enzyme activities may alter superoxide production or the rate of chemical metabolism, respectively, and this may influence the risk for CRC.

Effects of dietary anticarcinogens and nonsteroidal anti-inflammatory drugs on rat gastrointestinal UDP-glucuronosyltransferases.

Background: Dietary compounds or nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce cancer rates. Elevation of phase II detoxification enzymes might be one of the mechanisms leading to cancer prevention. We investigated the effects of dietary anticarcinogens and NSAIDs on rat gastrointestinal UDP-glucuronosyltransferases (UGT).