ONTOLOGY SOURCE REFERENCE
Term Source Name	"ArrayExpress"	"EFO"	"BAO"	"http://www.owl-ontologies.com/Ontology1298855822.owl#"	"NPO"	"OBI"	"MSH"	"BTO"	"CHEBI"	"XCO"	"UO"	
Term Source File	"http://www.ebi.ac.uk/arrayexpress/"	"http://www.ebi.ac.uk/efo/efo.owl"	""	""	""	""	"http://bioportal.bioontology.org/ontologies/46836"	"http://bioportal.bioontology.org/ontologies/50231"	"http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=CHEBI"	"http://bioportal.bioontology.org/ontologies/50409"	"http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=UO"	
Term Source Version	""	""	""	""	""	""	"46836"	"50231"	"Jun 2010"	"50409"	"Jun 2010"	
Term Source Description	""	""	""	""	""	""	"Medical Subject Headings"	"BRENDA Tissue and Enzyme Source Ontology"	"Chemical Entities of Biological Interest"	"Experimental Conditions Ontology"	"Unit Ontology"	
INVESTIGATION
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INVESTIGATION PUBLICATIONS
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INVESTIGATION CONTACTS
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STUDY
Study Identifier	"E-GEOD-28185"
Study Title	"2 AML (acute myeloid leukemia) cell lines treated with the NSAID diclofenac, vs. control. [original title: The non-steroidal anti-inflammatory drugs Sulindac sulfide and Diclofenac induce apoptosis and differentiation in human acute myeloid leukemia cells through an AP-1 dependent pathway]"
Study Description	"Acute myeloid leukemia is a heterogeneous disease with regard to the underlying genetic and molecular pathophysiology. Non-steroidal anti-inflammatory drugs (NSAIDs) exert significant anti-proliferative effects in various malignant cells in vitro and in vivo. Hence, these agents can be utilized to study potential disease specific anti-proliferative pathways. In this study, a total number of 42 bone marrow derived CD34+ cells from de novo AML patients and the AML cell lines THP-1 and HL-60 were treated with the NSAIDs Sulindac sulfide and Diclofenac. We examined viability, apoptosis, differentiation and addressed the molecular mechanisms involved. We found a consistent induction of apoptosis and to some extent myeloid differentiation in NSAID treated AML cells. Comprehensive protein and gene expression profiling of Diclofenac treated AML cells revealed transcriptional activation of GADD45alpha and its downstream MAPK/JNK pathway as well as increased protein levels of the Caspase-3 precursor. This points towards a role of the c-Jun NH2-terminal kinase (JNK) in NSAID mediated apoptosis. This was dependent on JNK activity as addition of a specific JNK-inhibitor abrogated apoptosis. Furthermore, the AP-1 transcription factor family members c-Jun, JunB and Fra-2 were transcriptionally activated in NSAID treated AML cells. Re-expression of these transcription factors led to activation of GADD45alpha with induction of apoptosis. Mechanistically, we demonstrate that NSAIDs induce apoptosis in AML through a novel pathway involving increased expression of AP-1 heterodimers, which by itself is sufficient to induce GADD45alpha expression with consecutive activation of JNK and induction of apoptosis. HL-60 and THP-1 AML cells were treated with 100 µM Diclofenac or DMSO as control for 48 hours. Each experiment was performed in duplicate. After this treatment total RNA of the cells was harvested and analysed by means of gene expression profiling with the Affymetrix HU-133A array."
Comment[Study Grant Number]	""
Comment[Study Funding Agency]	""
Study Submission Date	""
Study Public Release Date	"26/03/2011"
Study File Name	"s_E-GEOD-28185_study_samples.txt"
STUDY DESIGN DESCRIPTORS
Study Design Type	"transcription profiling by array"
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STUDY PUBLICATIONS
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STUDY FACTORS
Study Factor Name	"cell line"	"disease state"	"treatment"
Study Factor Type	"cell line"	"disease state"	"treatment"
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STUDY ASSAYS
Study Assay File Name	"a_E-GEOD-28185_GeneChip_assay.txt"
Study Assay Measurement Type	"transcription profiling"
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Study Assay Technology Type	"DNA microarray"
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STUDY PROTOCOLS
Study Protocol Name	"P-GSE28185-1"	"P-GSE28185-6"	"P-GSE28185-3"	"P-GSE28185-8"	"P-GSE28185-7"	"P-GSE28185-2"	"P-GSE28185-4"	"P-GSE28185-5"
Study Protocol Type	"bioassay_data_transformation"	"hybridization"	"grow"	"feature_extraction"	"image_aquisition"	"specified_biomaterial_action"	"nucleic_acid_extraction"	"labeling"
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Study Protocol Description	"ID_REF =  VALUE = Model-based expression values were calculated using dChiP"	"Following fragmentation, 10 µg of cRNA were hybridized for 16 hr at 45¡C on HG-U133A Gene Expression Arrays. GeneChips were washed and stained in the Affymetrix Fluidics Station 400."	"Cells were cultured in RPMI-1640 supplemented with 10% fetal bovine serum"	"CEL files were analyed using dChip after smooth spline normalization"	"GeneChips were scanned using GeneChip Scanner 3000 7G"	"Cells were treated with 100 µM Diclofenac or DMSO (control) for 48 hours"	"Total RNA was harvested using the RNeasy Mini Kit from Qiagen"	"Biotinylated cRNA were prepared according to the standard Affymetrix protocol from 10 µg total RNA"
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STUDY CONTACTS
Study Person Last Name	"Bruns"	"Singh"	"Koch"
Study Person First Name	"Ingmar"	"Raminder"	"Annemarie"
Study Person Mid Initials	""	""	""
Study Person Email	"BrunsIn@med.uni-duesseldorf.de"	""	""
Study Person Phone	"-17979"	""	""
Study Person Fax	"-19096"	""	""
Study Person Address	"Hematology, Oncology and Clinical Immunology, University of Dusseldorf, Moorenstr. 5, Dusseldorf, NRW, Germany"	""	""
Study Person Affiliation	"University of DÌ_sseldorf"	""	""
Study Person Roles	"submitter"	""	""
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