losartan-potassium and tofacitinib

losartan-potassium has been researched along with tofacitinib* in 1 studies

Other Studies

1 other study(ies) available for losartan-potassium and tofacitinib

Article	Year
The JAK kinase inhibitor CP-690,550 suppresses the growth of human polycythemia vera cells carrying the JAK2V617F mutation. Cancer science, 2008, Volume: 99, Issue:6 The somatic activating janus kinase 2 mutation (JAK2)(V617F) is detectable in most patients with polycythemia vera (PV). Here we report that CP-690,550 exerts greater antiproliferative and pro-apoptotic activity against cells harboring JAK2(V617F) compared with JAK2(WT). CP-690,550 treatment of murine factor-dependent cell Patersen-erythropoietin receptor (FDCP-EpoR) cells harboring human wild-type or V617F JAK2 resulted in inhibition of cell proliferation with a 50% inhibitory concentration (IC(50)) of 2.1 microM and 0.25 microM, respectively. Moreover, CP-690,550 induced a significant pro-apoptotic effect on murine FDCP-EpoR cells carrying JAK2(V617F), whereas a lesser effect was observed for cells carrying wild-type JAK2. This activity was coupled with inhibition of phosphorylation of the key JAK2(V617F)-dependent downstream signaling effectors signal transducer and activator of transcription (STAT)3, STAT5, and v-akt murine thymoma viral oncogene homolog (AKT). Furthermore, CP-690,550 treatment of ex-vivo-expanded erythroid progenitors from JAK2(V617F)-positive PV patients resulted in specific, antiproliferative (IC(50) = 0.2 microM) and pro-apoptotic activity. In contrast, expanded progenitors from healthy controls were less sensitive to CP-690,550 in proliferation (IC(50) > 1.0 microM), and apoptosis assays. The antiproliferative effect on expanded patient progenitors was paralleled by a decrease in JAK2(V617F) mutant allele frequency, particularly in a patient homozygous for JAK2(V617F). Flow cytometric analysis of expanded PV progenitor cells treated with CP-690,550 suggests a possible transition towards a pattern of erythroid differentiation resembling expanded cells from normal healthy controls. Topics: Animals; Apoptosis; Blotting, Western; Bone Marrow; Cell Cycle; Cell Nucleus; Cell Proliferation; Cells, Cultured; Erythroid Precursor Cells; Erythropoietin; Flow Cytometry; Humans; Immunoprecipitation; Janus Kinase 2; Membrane Potential, Mitochondrial; Mice; Mutation; Phosphorylation; Piperidines; Polycythemia Vera; Protein Kinase Inhibitors; Protein Transport; Pyrimidines; Pyrroles; Receptors, Erythropoietin; Signal Transduction; STAT3 Transcription Factor	2008

Article

Year

The JAK kinase inhibitor CP-690,550 suppresses the growth of human polycythemia vera cells carrying the JAK2V617F mutation.

Cancer science, 2008, Volume: 99, Issue:6

The somatic activating janus kinase 2 mutation (JAK2)(V617F) is detectable in most patients with polycythemia vera (PV). Here we report that CP-690,550 exerts greater antiproliferative and pro-apoptotic activity against cells harboring JAK2(V617F) compared with JAK2(WT). CP-690,550 treatment of murine factor-dependent cell Patersen-erythropoietin receptor (FDCP-EpoR) cells harboring human wild-type or V617F JAK2 resulted in inhibition of cell proliferation with a 50% inhibitory concentration (IC(50)) of 2.1 microM and 0.25 microM, respectively. Moreover, CP-690,550 induced a significant pro-apoptotic effect on murine FDCP-EpoR cells carrying JAK2(V617F), whereas a lesser effect was observed for cells carrying wild-type JAK2. This activity was coupled with inhibition of phosphorylation of the key JAK2(V617F)-dependent downstream signaling effectors signal transducer and activator of transcription (STAT)3, STAT5, and v-akt murine thymoma viral oncogene homolog (AKT). Furthermore, CP-690,550 treatment of ex-vivo-expanded erythroid progenitors from JAK2(V617F)-positive PV patients resulted in specific, antiproliferative (IC(50) = 0.2 microM) and pro-apoptotic activity. In contrast, expanded progenitors from healthy controls were less sensitive to CP-690,550 in proliferation (IC(50) > 1.0 microM), and apoptosis assays. The antiproliferative effect on expanded patient progenitors was paralleled by a decrease in JAK2(V617F) mutant allele frequency, particularly in a patient homozygous for JAK2(V617F). Flow cytometric analysis of expanded PV progenitor cells treated with CP-690,550 suggests a possible transition towards a pattern of erythroid differentiation resembling expanded cells from normal healthy controls.

Topics: Animals; Apoptosis; Blotting, Western; Bone Marrow; Cell Cycle; Cell Nucleus; Cell Proliferation; Cells, Cultured; Erythroid Precursor Cells; Erythropoietin; Flow Cytometry; Humans; Immunoprecipitation; Janus Kinase 2; Membrane Potential, Mitochondrial; Mice; Mutation; Phosphorylation; Piperidines; Polycythemia Vera; Protein Kinase Inhibitors; Protein Transport; Pyrimidines; Pyrroles; Receptors, Erythropoietin; Signal Transduction; STAT3 Transcription Factor

2008