Comprehensive comparison between azacytidine and decitabine treatment in an acute myeloid leukemia cell line

Azacytidine (AzaC) and decitabine (AzadC) are cytosine analogs that covalently trap DNA methyltransferases, which place the important epigenetic mark 5-methyl-2’-deoxycytidine by methylating 2’-deoxycytidine (dC) at the C5 position. AzaC and AzadC are used in the clinic as antimetabolites to treat myelodysplastic syndrome and acute myeloid leukemia and are explored against other types of cancer. Although their principal mechanism of action is known, the downstream effects of AzaC and AzadC treatment are not well understood and the cellular prerequisites that determine sensitivity toward AzaC and AzadC remain elusive. Here, we investigated the effects and phenotype of AzaC and AzadC exposure on the acute myeloid leukemia cell line MOLM-13. We found that while AzaC and AzadC share many effects on the cellular level, including decreased global DNA methylation, increased formation of DNA double-strand breaks, transcriptional downregulation of important oncogenes and similar changes on the proteome level, AzaC failed in contrast to AzadC to induce apoptosis efficiently in MOLM-13. The only cellular marker that correlated with this clear phenotypical outcome was the level of hydroxy-methyl-dC, an additional epigenetic mark that is placed by TET enzymes and repressed in cancer cells. Whereas AzadC increased hmdC substantially in MOLM-13, AzaC treatment did not result in any increase at all. This suggests that hmdC levels in cancer cells should be monitored as a response toward AzaC and AzadC and considered as a biomarker to judge whether AzaC or AzadC treatment leads to cell death in leukemic cells

CNMA - A european initiative for OSI network management

Computer networks are in widespread use in industrial, technical and administrative environments for many different applications nowadays. Users already rely heavily on networks and networks are expected to become even more important in the future. Therefore it is quite natural that network management has become an important matter in networking. This article describes the concepts, developments and achievements of the European Strategic Programme for Research and Development in Information Technology (ESPRIT) project, Communications Network for Manufacturing Applications (CNMA) in the field of OSI network management

Unusual vascular focal high-grade arterial stenoses in a young woman with systemic lupus erythematosus and secondary antiphospholipid syndrome

We report the case of a 28-year old woman with an unusual presentation of peripheral arterial occlusive disease clinically characterized by intermittent claudication and bilateral, focal stenoses of the iliac arteries without signs of atherosclerosis in other vascular beds. The successful percutaneous intervention is described in detail and pathogenetic aspects of the disease are discussed