plitidepsin and Weight-Loss

plitidepsin has been researched along with Weight-Loss* in 1 studies

Other Studies

1 other study(ies) available for plitidepsin and Weight-Loss

ArticleYear
CXCR4-independent rescue of the myeloproliferative defect of the Gata1low myelofibrosis mouse model by Aplidin.
    Journal of cellular physiology, 2010, Volume: 225, Issue:2

    The discovery of JAK2 mutations in Philadelphia-negative myeloproliferative neoplasms has prompted investigators to evaluate mutation-targeted treatments to restore hematopoietic cell functions in these diseases. However, the results of the first clinical trials with JAK2 inhibitors are not as promising as expected, prompting a search for additional drugable targets to treat these disorders. In this paper, we used the hypomorphic Gata1(low) mouse model of primary myelofibrosis (PMF), the most severe of these neoplasms, to test the hypothesis that defective marrow hemopoiesis and development of extramedullary hematopoiesis in myelofibrosis is due to insufficient p27(Kip1) activity and is treatable by Aplidin, a cyclic depsipeptide that activates p27(Kip1) in several cancer cells. Aplidin restored expression of Gata1 and p27(Kip1) in Gata1(low) hematopoietic cells, proliferation of marrow progenitor cells in vitro and maturation of megakaryocytes in vivo (reducing TGF-beta/VEGF levels released in the microenvironment by immature Gata1(low) megakaryocytes). Microvessel density, fibrosis, bone growth, and marrow cellularity were normal in Aplidin-treated mice and extramedullary hematopoiesis did not develop in liver although CXCR4 expression in Gata1(low) progenitor cells remained low. These results indicate that Aplidin effectively alters the natural history of myelofibrosis in Gata1(low) mice and suggest this drug as candidate for clinical evaluation in PMF.

    Topics: Age Distribution; Animals; Antineoplastic Agents; Bone Marrow Cells; Cyclin-Dependent Kinase Inhibitor p27; Depsipeptides; Dose-Response Relationship, Drug; Drug Administration Schedule; GATA1 Transcription Factor; Gene Expression Regulation; Male; Mice; Mutation; Peptides, Cyclic; Primary Myelofibrosis; Receptors, CXCR4; Stem Cells; Weight Loss

2010