Linked Life Data

19159435

Source:http://linkedlifedata.com/resource/pubmed/id/19159435

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-2-25
pubmed:abstractText
Imatinib mesylate (STI571, Gleevec) is a signal transduction inhibitor and novel anti-cancer agent. It selectively inhibits aberrantly activated tyrosine kinases in malignant cells, for example, bcr-abl in leukaemia, platelet-derived growth factor receptor and stem cell factor receptor (c-Kit) in solid cancers including malignant glioma. However, recently published clinical studies with imatinib monotherapy in patients with malignant glioma demonstrated only very modest anti-tumour activity. The aim of this study was to investigate the biological activity of imatinib, its cellular mechanisms of action and its synergism with other chemotherapeutic agents in human malignant glioma cells in culture. Expression of PDGF/R and c-Kit was analyzed by RT-PCR. Proliferation was measured by MTT assays and drug synergy was assessed by the Chou-Talalay method. Cell cycle and apoptosis were analyzed by flow cytometry and migration by monolayer migration assays. Multi-immunoblot was performed on imatinib-treated and control malignant glioma cells. Results indicate that imatinib is more effective in inhibiting cell colony formation and migration rather than proliferation. Imatinib treatment caused cell cycle arrest of glioma cells in G0-G1 or G2/M, with significant elevation of a few cyclin-dependent kinases. Furthermore, imatinib acted synergistically with chemotherapy agents, such as the DNA alkylating agent, temozolomide, and riboneucleotide reductase inhibitors, for example, hydroxyurea at varied effective dose levels. In conclusion, imatinib exerts varied biological effects on malignant glioma cells in culture. Synergistic interaction of imatinib with chemotherapy agents may be related to cell cycle control mechanisms and could be potentially important in a clinical setting.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1742-7843
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
241-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19159435-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:19159435-Apoptosis, pubmed-meshheading:19159435-Cell Cycle, pubmed-meshheading:19159435-Cell Line, Tumor, pubmed-meshheading:19159435-Cell Movement, pubmed-meshheading:19159435-Cell Proliferation, pubmed-meshheading:19159435-Drug Synergism, pubmed-meshheading:19159435-Flow Cytometry, pubmed-meshheading:19159435-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19159435-Glioma, pubmed-meshheading:19159435-Humans, pubmed-meshheading:19159435-Piperazines, pubmed-meshheading:19159435-Proto-Oncogene Proteins c-kit, pubmed-meshheading:19159435-Pyrimidines, pubmed-meshheading:19159435-Receptors, Platelet-Derived Growth Factor, pubmed-meshheading:19159435-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19159435-Signal Transduction
pubmed:year
2009
pubmed:articleTitle
Differential effect of imatinib and synergism of combination treatment with chemotherapeutic agents in malignant glioma cells.
pubmed:affiliation
Department of Immunology, Harbin Medical University, 150081 Harbin, China. huan_ren@hotmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't