Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-9-12
pubmed:abstractText
We have studied the actions of autologous plasma on both basal and DNA damage-induced apoptosis in B-chronic lymphocytic leukaemia (B-CLL) cells. Apoptosis was quantified using morphological criteria and Western blot analysis for the apoptosis-specific p85 fragment of poly(ADP ribose) polymerase. Cell viability was estimated using the methyl thiazol tetrazolium bromide dye reduction assay. Plasma cultures showed lower rates of basal apoptosis as well as a decreased cytotoxic response to chlorambucil and gamma-radiation compared with cultures in fetal calf serum. Experiments using neutralizing antibodies suggested that the protective actions of plasma could not be accounted for by interleukin 4, the interferons alpha or gamma or stromal cell-derived factor 1, each of which have been shown to protect B-CLL cells from apoptosis in vitro. Plasma addition to B-CLL cells resulted in rapid activation of the Akt protein kinase, a key signalling enzyme that has been implicated in anti-apoptotic signalling. LY294002, an inhibitor of phosphatidylinositol 3'-kinase, blocked Akt activation by plasma. To the best of our knowledge, this is the first report to show that factors present in plasma promote basal survival of B-CLL cells and resistance to cytotoxic drugs via stimulation of the Akt cytoprotective-signalling pathway. Pharmacological blockade of this pathway may have potential in the development of novel therapeutic strategies for B-CLL treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz..., http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Alkylating, http://linkedlifedata.com/resource/pubmed/chemical/Chlorambucil, http://linkedlifedata.com/resource/pubmed/chemical/Chromones, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4, http://linkedlifedata.com/resource/pubmed/chemical/Morpholines, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0007-1048
pubmed:author
pubmed:issnType
Print
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
608-15
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11552986-Antineoplastic Agents, Alkylating, pubmed-meshheading:11552986-Apoptosis, pubmed-meshheading:11552986-Blotting, Western, pubmed-meshheading:11552986-Chlorambucil, pubmed-meshheading:11552986-Chromones, pubmed-meshheading:11552986-Drug Resistance, pubmed-meshheading:11552986-Enzyme Activation, pubmed-meshheading:11552986-Enzyme Inhibitors, pubmed-meshheading:11552986-Female, pubmed-meshheading:11552986-Humans, pubmed-meshheading:11552986-Interleukin-4, pubmed-meshheading:11552986-Leukemia, Lymphocytic, Chronic, B-Cell, pubmed-meshheading:11552986-Male, pubmed-meshheading:11552986-Morpholines, pubmed-meshheading:11552986-Phosphatidylinositol 3-Kinases, pubmed-meshheading:11552986-Plasma, pubmed-meshheading:11552986-Protein-Serine-Threonine Kinases, pubmed-meshheading:11552986-Proto-Oncogene Proteins, pubmed-meshheading:11552986-Proto-Oncogene Proteins c-akt, pubmed-meshheading:11552986-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Autologous plasma activates Akt/protein kinase B and enhances basal survival and resistance to DNA damage-induced apoptosis in B-chronic lymphocytic leukaemia cells.
pubmed:affiliation
Department of Haematology, Royal Free and University College School of Medicine, London, UK. r.wickremasinghe@rfc.ucl.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't