Enhancing therapeutic efficacy by targeting non-oncogene addicted cells with combinations of signal transduction inhibitors and chemotherapy. (Articolo in rivista)

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  • Enhancing therapeutic efficacy by targeting non-oncogene addicted cells with combinations of signal transduction inhibitors and chemotherapy. (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Abrams SL, Steelman LS, Shelton JG, Chappell W, Bäsecke J, Stivala F, Donia M, Nicoletti F, Libra M, Martelli AM, McCubrey JA. (2010)
    Enhancing therapeutic efficacy by targeting non-oncogene addicted cells with combinations of signal transduction inhibitors and chemotherapy.
    in Cell cycle (Georget. Tex.)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Abrams SL, Steelman LS, Shelton JG, Chappell W, Bäsecke J, Stivala F, Donia M, Nicoletti F, Libra M, Martelli AM, McCubrey JA. (literal)
Pagina inizio
  • 1839 (literal)
Pagina fine
  • 1846 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 9 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Microbiology and Immunology; Brody School of Medicine at East Carolina University; Greenville, NC USA; Division of Hematology and Oncology; Department of Medicine; University of Göttingen; Göttingen, Germany; Department of Biomedical Sciences; University of Catania; Catania, Italy; Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell’Apparato Locomotore; Sezione di Anatomia Umana; Cell Signalling Laboratory; Università di Bologna; Bologna, Italy; IGM-CNR; Sezione di Bologna; C/o IOR; Bologna, Italy (literal)
Titolo
  • Enhancing therapeutic efficacy by targeting non-oncogene addicted cells with combinations of signal transduction inhibitors and chemotherapy. (literal)
Abstract
  • The effects of inhibition of the Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways and chemotherapeutic drugs on cell cycle progression and drug sensitivity were examined in cytokine-dependent FL5.12 hematopoietic cells. We examined their effects, as these cells resemble normal hematopoietic precursor cells as they do not exhibit \"oncogene-addicted\" growth, while they do display \"cytokine-addicted\" proliferation as cytokine removal resulted in apoptosis in greater than 80% of the cells within 48 hrs. When cytokine-dependent FL5.12 cells were cultured in the presence of IL-3, which stimulated multiple proliferation and anti-apoptotic cascades, MEK, PI3K and mTOR inhibitors transiently suppressed but did not totally inhibit cell cycle progression or induce apoptosis while chemotherapeutic drugs such as doxorubicin and paclitaxel were more effective in inducing cell cycle arrest and apoptosis. Doxorubicin induced a G(1) block, while paclitaxel triggered a G(2)/M block. Doxorubicin was more effective in inducing cell death than paclitaxel. Furthermore the effects of doxorubicin could be enhanced by addition of MEK, PI3K or mTOR inhibitors. Cytokine-dependent cells which proliferate in vitro and are not \"oncogene-addicted\" may represent a pre-malignant stage, more refractory to treatment with targeted therapy. However, these cells are sensitive to chemotherapeutic drugs. It is important to develop methods to inhibit the growth of such cytokine-dependent cells as they may resemble the leukemia stem cell and other cancer initiating cells. These results demonstrate the enhanced effectiveness of targeting early hematopoietic progenitor cells with combinations of chemotherapeutic drugs and signal transduction inhibitors. (literal)
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