Characterization of the Menin-MLL Interaction as Therapeutic Cancer Target.

Inhibiting the interaction of menin with the histone methyltransferase MLL1 (KMT2A) has recently emerged as a novel therapeutic strategy. Beneficial therapeutic effects have been postulated in leukemia, prostate, breast, liver and in synovial sarcoma models. In those indications, MLL1 recruitment by menin was described to critically regulate the expression of disease associated genes.

N-glycosylation of ABC transporters is associated with functional activity in sandwich-cultured rat hepatocytes.

Hepatobiliary elimination via canalicular efflux transport proteins plays a key role in the clearance of endo- and xenobiotics. Correct membrane localization and coordinated action of the transport systems are essential for vectorial transport of drugs from blood into the bile. While basolaterally localized uptake transporters are responsible for the inward transport of substances from the blood into the hepatocyte, apically expressed ATP-dependent transport proteins such as P-glycoprotein (P-gp), multidrug resistance-associated protein (Mrp2) and breast cancer resistance protein (Bcrp) mediate the outward efflux into the bile canaliculus.

Development of a fluorescence-based assay for drug interactions with human Multidrug Resistance Related Protein (MRP2; ABCC2) in MDCKII-MRP2 membrane vesicles.

Purpose: To establish a fluorescence-based assay for drug interactions with the ABC-export-protein MRP2 (ABCC2).

Methods: Apical membrane vesicles were isolated by differential centrifugation from polarized MDCKII cells and MDCKII cells transfected with human MRP2. Vesicle fractions were characterized by electron microscopy, determination of the marker enzyme alkaline phosphatase and Western blot analysis of MRP2.

Characterization of cytochrome P450 protein expression along the entire length of the intestine of male and female rats.

Intestinal cytochrome P450 (P450) proteins play an important role in the biotransformation of drugs and may significantly limit their oral absorption and bioavailability. Therefore, we have investigated the amount of P450 proteins via Western blot analysis along the entire intestine of male and female rats. Despite of the use of an inbred rat strain, controlled housing conditions for the animals, and a timed sample preparation, high interindividual differences in the expression of all P450 proteins was observed.

Progress in the identification of stroke-related genes: emerging new possibilities to develop concepts in stroke therapy.

Stroke is a very complex disease influenced by many risk factors: genetic, environmental and comorbidities, such as hypertension, diabetes mellitus, obesity and having had a previous stroke. Neuroprotective therapies that have been found to be successful in laboratory animals have failed to produce the same benefits in clinical trials. Currently, a re-analysis of the clinical trial failures is underway and new therapeutic approaches using the growing knowledge from neurogenesis and neuroinflammation studies, combined with the information from gene expression studies, are taking place.

CCR1 is an early and specific marker of Alzheimer's disease.

Chemokines are a diverse group of small proteins that effect cell signaling by binding to G-protein-coupled, seven-trans-membrane receptors. Our group had found previously that the chemokine receptor CCR1 was present in neurons and dystrophic processes in a small sample of Alzheimer's disease cases. This expanded immunohistochemical study shows that the number of CCR1-positive plaque-like structures in the hippocampus and entorhinal cortex is highly correlated to dementia state as measured by the clinical dementia rating score.