showing 5 related works from this author
Mitochondrial BAX Determines the Predisposition to Apoptosis in Human AML
2017
Abstract Purpose: Cell-to-cell variability in apoptosis signaling contributes to heterogenic responses to cytotoxic stress in clinically heterogeneous neoplasia, such as acute myeloid leukemia (AML). The BCL-2 proteins BAX and BAK can commit mammalian cells to apoptosis and are inhibited by retrotranslocation from the mitochondria into the cytosol. The subcellular localization of BAX and BAK could determine the cellular predisposition to apoptotic death. Experimental Design: The relative localization of BAX and BAK was determined by fractionation of AML cell lines and patient samples of a test cohort and a validation cohort. Results: This study shows that relative BAX localization determine…
The kinase inhibitor LS104 induces apoptosis, enhances cytotoxic effects of chemotherapeutic drugs and is targeting the receptor tyrosine kinase FLT3…
2008
Activating mutations of FLT3 are found in approximately one-third of acute myeloid leukemia (AML)-cases and are considered to represent an attractive therapeutic target. In this study, we report that the hydroxystyryl-acrylonitrile compound LS104 inhibits proliferation and induces potent cytotoxic effects in FLT3 expressing leukemic cells in vitro. Immunoblot and phosphoprotein-FACS analysis demonstrated inhibiton of phosphorylation of FLT3-ITD and of its downstream targets. In pharmacokinetic studies, a rapid and dose dependent cellular uptake of LS104 lasting up to 11h could be demonstrated. Combination of LS104 with chemotherapeutic agents markedly enhanced cytotoxic effects. Recently, a…
Addition of rituximab to standard therapy improves response rate and progression-free survival in relapsed or refractory thrombotic thrombocytopenic …
2007
SummaryTreatment of relapsed or refractory autoimmune mediated haemolytic syndromes, such as autoimmune haemolytic anaemia (AIHA) and thrombotic thrombocytopenic purpura (TTP), represents a therapeutic challenge. Here we report on our experience with the monoclonal anti-CD20 antibody rituximab (R) compared to standard treatment in these diseases. Patients with non-familialTTP orAIHA and no underlying malignancy were included in our analysis. Safety and efficacy of R-treatment were compared to results obtained in standard treatment approaches. Altogether, 27 patients were analyzed, comprising 15 patients withTTP and 12 patients with AIHA. The patients’ average age at the time of diagnosis wa…
Intracellular retention of ABL kinase inhibitors determines commitment to apoptosis in CML cells
2012
PLoS one 7(7), e40853 (2012). doi:10.1371/journal.pone.0040853
A Phase 1b, Dose-Finding Study Of Ruxolitinib Plus Panobinostat In Patients With Primary Myelofibrosis (PMF), Post–Polycythemia Vera MF (PPV-MF), Or …
2013
Abstract Background Myelofibrosis (MF) is a myeloproliferative neoplasm associated with progressive, debilitating symptoms that impact patient quality of life (QoL) and reduce survival. Ruxolitinib (RUX), a potent dual JAK1/JAK2 inhibitor, demonstrated superiority in spleen volume and symptom reduction, improved health-related QoL measures, and prolonged survival compared with traditional therapies or placebo in the phase 3 COMFORT studies. Panobinostat (PAN) is a potent oral pan-deacetylase inhibitor (DACi) that inhibits JAK pathway signaling through increased acetylation of the JAK2 protein chaperone HSP90. In phase 1/2 studies in MF, PAN has shown reduction in splenomegaly and JAK2 V617F…