Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-4-21
pubmed:abstractText
Imatinib represents at present the most attractive therapy for BCR-ABL positive leukemias, even though a percentage of CML patients develop resistance to this compound. For these resistant patients a therapeutic approach based on a combination of drugs is more likely to be effective. In the last years, constitutive NF-kappaB/Rel activity has been demonstrated in several hematological malignancies. As a result, NFkB/Rel-blocking approaches have been proposed as antineoplastic strategies. Furthermore, the identification of specific kinases within the NF-kappaB activation pathway offers a selective target to address tailored therapies. In the current study, we show that the IKK inhibitor PS1145 is able to inhibit the proliferation of CML cell lines and primary BM cells. Moreover, the addition of Imatinib increases the effects of PS1145 in resistant cell lines and BM cells from resistant patients, with a further increase of apoptosis and inhibition of proliferation and colony growth. Our data provide the rational for a new therapeutic approach, which combines Imatinib and the IKK inhibitor PS1145 in CML resistant patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0887-6924
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
61-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16270044-Antineoplastic Agents, pubmed-meshheading:16270044-Apoptosis, pubmed-meshheading:16270044-Binding Sites, pubmed-meshheading:16270044-Blotting, Western, pubmed-meshheading:16270044-Bone Marrow Cells, pubmed-meshheading:16270044-Cell Proliferation, pubmed-meshheading:16270044-Cell Survival, pubmed-meshheading:16270044-Cells, Cultured, pubmed-meshheading:16270044-Combined Modality Therapy, pubmed-meshheading:16270044-DNA, pubmed-meshheading:16270044-Drug Resistance, Neoplasm, pubmed-meshheading:16270044-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:16270044-Heterocyclic Compounds, 3-Ring, pubmed-meshheading:16270044-Humans, pubmed-meshheading:16270044-I-kappa B Kinase, pubmed-meshheading:16270044-K562 Cells, pubmed-meshheading:16270044-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:16270044-NF-kappa B, pubmed-meshheading:16270044-Piperazines, pubmed-meshheading:16270044-Pyridines, pubmed-meshheading:16270044-Pyrimidines, pubmed-meshheading:16270044-Tumor Stem Cell Assay
pubmed:year
2006
pubmed:articleTitle
The NF-kappaB pathway blockade by the IKK inhibitor PS1145 can overcome imatinib resistance.
pubmed:affiliation
Division of Hematology and Internal Medicine, Department of Clinical and Biological Sciences of the University of Turin, Turin, Italy. daniela.cilloni@unito.it
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't