Project description:The goal of this project was to characterize changes in gene expression in response to the anti-cancer agent sapphyrin PCI-2050. Cultured A549 human lung cancer cells were treated with sapphyrin PCI-2050 or actinomycin D.
Project description:The goal of this project was to characterize changes in gene expression in response to the anti-cancer agent sapphyrin PCI-2050. Cultured A549 human lung cancer cells were treated with sapphyrin PCI-2050 or actinomycin D, a known transcripitonal inhibitor. The gene expression profiles of drug-treated and control A549 cultures were determined using Human Genome U133 Plus 2.0 Arrays (Affymetrix, Santa Clara, CA). Further details are provided in our published manuscript: <http://www.molecular-cancer.com/content/6/1/9>. Keywords: responses to treatments with anti-cancer agents
Project description:We have shown that water solubilized versions of a zinc ionophore increase intracellular concentrations of free zinc and have antiproliferative activity in exponential phase A549 lung cancer cultures. The gene expression profiles of A549 lung cancer cultures treated with the lead compound PCI-5002 reveal the activation of stress response pathways. Medium supplementation with zinc (25 μM) led to activation of additional oxidative stress response as well as apoptotic pathways. We propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Keywords: Dose response
Project description:Transcription profiling of human A549 lung cancer cells treated with actinomycin D and sapphyrin PCI-2050 a new class of tumor-selective inhibitors of gene expression.
Project description:We have shown that water solubilized versions of a zinc ionophore increase intracellular concentrations of free zinc and have antiproliferative activity in exponential phase A549 lung cancer cultures. The gene expression profiles of A549 lung cancer cultures treated with the lead compound PCI-5002 reveal the activation of stress response pathways. Medium supplementation with zinc (25 μM) led to activation of additional oxidative stress response as well as apoptotic pathways. We propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Experiment Overall Design: A549 human lung cancer cells (1 x 105 cells per T-25 flask in 7 mL complete RPMI 1640 medium) were seeded 8 days prior to treatment of non-cycling plateau phase cultures with drug. At 4 hours prior to RNA isolation, sapphyrin PCI-5002 (10 μM final concentration), ZnOAc2 (25 μM final concentration), the combination, or control (5% mannitol) solution was added to the cultures. Each experiment was performed in triplicate. After incubation, all cultures were washed twice with HBSS supplemented with 0.5% BSA and total RNA was isolated and subjected to analysis on Human Genome U133 Plus 2.0 Arrays (Affymetrix, Santa Clara, CA), as described. ArrayAssist software (Stratagene/Affymetrix) and the RMA (Robust Microarray Analysis) algorithm were used to generate scaled gene expression values.
Project description:41 lung adenocarcinoma from never-smokers hybridized on Illumina SNP arrays on 13 HumanCNV370-Quadv3 chips. High-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in 41 never smokers for identification of new minimal common regions (MCR) of gain or loss. The SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity.The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers. A 'Cartes d'Identite des Tumeurs' (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net) 41 samples hybridized on Illumina SNP arrays. Submitter : Fabien PETEL petelf@ligue-cancer.net . Project leader : Pr Pierre FOURET pierre.fouret@psl.aphp.fr