Medical University of Graz

About: Medical University of Graz is a education organization based out in Graz, Steiermark, Austria. It is known for research contribution in the topics: Population & Medicine. The organization has 5684 authors who have published 12349 publications receiving 417282 citations.

Epigenetic control of epithelial-mesenchymal-transition in human cancer (Review)

Abstract: Development and tissue homeostasis as well as carcinogenesis share the evolutionary conserved process of epithelial-mesenchymal transition (EMT). EMT enables differentiated epithelial cells to trans-differentiate to a mesenchymal phenotype which is associated with diverse cellular properties including altered morphology, migration and invasion and stemness. In physiological development and tissue homeostasis, EMT exerts beneficial functions for structured tissue formation and maintenance. Under pathological conditions, EMT causes uncontrolled tissue repair and organ fibrosis, as well as the induction of tumor growth, angiogenesis and metastasis in the context of cancer progression. Particularly, the metastatic process is essentially linked to diverse EMT-driven functions which give the mesenchymal differentiated tumor cells the capacity to migrate and form micrometastases in distant organs. Recent analyses of the mechanisms controlling EMT revealed a significant epigenetic regulatory impact reflecting the reversible nature of EMTs. As several approaches of epigenetic therapy are already under clinical evaluation, including inhibitors of DNA methyl transferase and histone deacetylase, targeting the epigenetic regulation of EMT may represent a promising therapeutic option in the future. Therefore, we undertook this review to reassess the current knowledge on the roles of epigenetic control in the regulation of EMT in human cancer. These recent findings are discussed in view of their implications on future diagnostic and therapeutic strategies.

Signaling through RAS-RAF-MEK-ERK: from basics to bedside.

Abstract: Aberrant signaling caused by mutations in the RAS-RAF-MEK-ERK pathway and its upstream activators critically contributes to human tumor development. Strategies, which aim at inhibiting hyperactive signaling molecules, appear conceptually straight forward, but their translation into clinical practice has been hampered by many setbacks. Understanding structure, function and regulation of this intracellular pathway as well as its crosstalk with other signaling activities in the cell will be essential to ensure reasonable usage of new therapeutic possibilities. This review provides an understanding of this signaling cascade as revealed by genetic and biochemical approaches and discusses the existing or arising possibilities to interfere with unphysiological activation in cancer. Signaling aberrations and signal transduction therapies will be discussed exemplary for two types of hematological neoplasia, acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS). In the future understanding the role of tumor stem cells, both as a source of tumor recurrence and tumor heterogeneity, the signals controlling their fate as well as epigenetic changes in cancer will be the next critical steps to further advance the applicability of these novel therapeutic strategies.

Prednisolone vs. ciclosporin for severe adult eczema. An investigator‐initiated double‐blind placebo‐controlled multicentre trial

Abstract: Background Patients with severe eczema frequently receive systemic glucocorticosteroids. The efficacy of prednisolone and other steroids, however, has never been evaluated appropriately. A meta-analysis indicated that ciclosporin is the best evaluated systemic treatment for eczema. Objectives To investigate the comparative efficacy of prednisolone and ciclosporin for severe eczema. Methods In an investigator-initiated double-blind randomized multicentre trial, adults with severe eczema (objective SCORAD > or = 40 and Dermatology Life Quality Index > or = 10) were randomly allocated to receive prednisolone (initial dose 0.5-0.8 mg kg(-1) daily) for 2 weeks followed by placebo for 4 weeks or ciclosporin (2.7-4.0 mg kg(-1) daily) for 6 weeks and followed for another 12 weeks. Concomitant treatment included a moderately potent topical steroid, emollients, and continuation of antihistamines. Primary endpoint was the proportion of patients with stable remission, i.e. > or = 50% SCORAD improvement under active treatment and no flare (> or = 75% of baseline SCORAD) during follow-up. Sample size calculation indicated that 66 patients were needed to see clinically relevant differences between groups. Analysis was by intention-to-treat (ClinicalTrials.gov Identifier: NCT00445081). Results Because of unexpectedly high numbers of withdrawals due to significant exacerbations of eczema (n = 15/38) an independent data monitoring and safety board proposed early study termination. Thirty-eight patients were randomized and analysed. Stable remission was achieved in one of 21 patients receiving prednisolone compared with six of 17 patients treated with ciclosporin (P = 0.031). Conclusions Ciclosporin is significantly more efficacious than prednisolone for severe adult eczema. Despite its frequent use in daily practice, prednisolone is not recommended to induce stable remission of eczema.