Targeting the epigenome: effects of epigenetic treatment strategies on genomic stability in healthy human cells

Epigenetic treatment concepts have long been ascribed as being tumour-selective. Over the last decade, it has become evident that epigenetic mechanisms are essential for a wide range of intracellular functions in healthy cells as well. Evaluation of possible side-effects and their underlying mechanisms in healthy human cells is necessary in order to improve not only patient safety, but also to support future drug development. Since epigenetic regulation directly interacts with genomic and chromosomal packaging density, increasing genomic instability may be a result subsequent to drug-induced epigenetic modifications. This review highlights past and current research efforts on the influence of epigenetic modification on genomic stability in healthy human cells

Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells

Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza) and the growth factors (GF) granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy

The good, the bad and the persuasive : Normative quality and actual persuasiveness of arguments from authority, arguments from cause to effect and arguments from example

Contains fulltext : 74866.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 23 februari 2010Promotores : Hoeken, H., Schellens, P.J.292 p

De redelijkheid en overtuigingskracht van normatief sterke en normatief zwakke argumenten

Contains fulltext : 67793.pdf (publisher's version ) (Open Access)15 p

The perceived quality and the actual persuasiveness of normatively strong and normatively weak arguments

Item does not contain fulltextEtmaal van de communicatiewetenschap, 7 februari 200

Arguing about the likelihood of consequences: Laypeople’s criteria to distinguish strong arguments from weak ones

Contains fulltext : 121654.pdf (publisher's version ) (Closed access)27 juni 201

Determining laymen criteria: evaluating methods

Item does not contain fulltex