In vitro study of gene expression and response to chemotherapy across 50 human-melanoma derived cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE10916 | GEO | 2009/01/29
SECONDARY ACCESSION(S): PRJNA107215
REPOSITORIES: GEO
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Project description:To identify patterns of gene expression that correlate with response to treatment with either melphalan or temozolomide we measured both gene expression using microarray genechips and response to drug using a standard in vitro cell proliferation assay. Senstivity to melphalan was measured 48hrs after drug treatment while sensitivity to temozolomide was measured 12 days after drug treatment. Experiment Overall Design: For each of the 50 melanoma-derived cell lines, 1 flask of cells was grown to 80% confluence and harvested for RNA isolation. Cells were lysed in buffer with 1% β-mercaptoethanol and RNA isolated using Qiagen RNeasy-plus RNA isolation kit which included a step to eliminate genomic DNA. RNA concentration was measured and quality assessed using the NanoDrop ND100 spectrophotometer. RNA was reverse transcribed and biotin-labeled cRNA synthesized. The product was hybridized to the Affymetrix human genechip HU133 Plus2 according to manufacturer's instructions. Data was initially assessed for quality and a relative value for expression was calculated as the difference between the perfect match and the mismatch signal intensities using the Affymetrix GeneChip Operating System (GCOS). A detection call (present, absent or marginal) as well as a detection p-value was also calculated. Data was normalized by multiplying each signal by a scaling factor such that the mean signal intensity for each GeneChip was equal to 500. Scaling factors were all under 10.
2009-02-09 | E-GEOD-10916 | biostudies-arrayexpress
Project description:To identify patterns of change in gene expression that correlated with drug treatment (saline control, ADH-1 alone, melphalan alone and ADH-1 plus melphalan) in our animal model of regional therapy for extremity melanoma we evaluated gene expression using microarray genechips and a Pearson correlation analysis. Genes were ranked according to the degree to which expression correlated with systemic ADH-1 treatment alone or in combination with regional melphalan. Tissue samples were harvested at 4, 24 and 48 hours after treatment with melphalan. Specific cellular pathways associated with drug treatment were identified using gene set enrichment analysis (GSEA). Keywords: time course; chemotherapy; melanoma; melphalan; N-cadherin; ADH-1
2008-10-30 | GSE8615 | GEO
Project description:To identify patterns of change in gene expression that correlated with drug treatment (saline control, ADH-1 alone, melphalan alone and ADH-1 plus melphalan) in our animal model of regional therapy for extremity melanoma we evaluated gene expression using microarray genechips and a Pearson correlation analysis. Genes were ranked according to the degree to which expression correlated with systemic ADH-1 treatment alone or in combination with regional melphalan. Tissue samples were harvested at 4, 24 and 48 hours after treatment with melphalan. Specific cellular pathways associated with drug treatment were identified using gene set enrichment analysis (GSEA). Experiment Overall Design: Sample size was 2 rats for each drug treatment group at both the 4 and 24 hour time points. At the 48 hour time point sample size was 1 rat for each drug treatment group. ADH-1 treatment preceded melphalan by 1 hour. ADH-1 treatment was repeated at 24 and 48 hrs. Tissue was harvested for RNA analysis at 4, 24 and 48 hours after completion of isolated limb infusion with melphalan (and 1 hour after an ADH-1 dose).
2008-11-07 | E-GEOD-8615 | biostudies-arrayexpress
Project description:Multiple myeloma is an incurable hematological malignancy that impacts tens of thousands of people every year in the U.S. Treatment for eligible patients includes three stages: induction, consolidation with stem cell rescue, and maintenance. High dose therapy with the DNA alkylating agent, melphalan, remains the primary drug for consolidation therapy in conjunction with autologous stem cell transplant. As a result, melphalan resistance remains a clinical challenge. Here, we use proteometabolomics to examine mechanisms of melphalan resistance in two cell line models. Drug metabolism, steady-state metabolomics, activity-based protein profiling (ABPP), acute treatment metabolomics, and immunoblotting analyses have allowed us to further elucidate metabolic processes contributing to melphalan resistance. Proteometabolomics data indicate that both drug resistant cells have higher levels of pentose phosphate pathway metabolites than their naïve counterparts. Interestingly, we also observed cell line specific changes in purine, pyrimidine and glutathione metabolism that are linked to the differences in steady state metabolism of naïve cells and highlight the heterogeneity of melphalan resistance in these models. Because of the diversity of metabolic changes, our data suggest that omics approaches will be needed to fully examine melphalan resistance in patient specimens and define personalized strategies to optimize the delivery of this therapy.
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Project description:An evaluation of biopsies from patients with in-transit extremity melanoma who have been treated with ADH-1 followed by melphalan in the setting of isolated limb infusion Gene expression profiles were obtained from 28 lesions across 15 patients and evaluated for expression values that correlated with ADH-1 treatment given 4-8hrs prior to melphalan isolated limb infusion Chemotherapy response analysis: complete response - CR; partial response - PR; stable disease - SD; progressive disease - PD; lost to follow-up - LTU/F ADH-1 treatment classification: 'pre' - lesions obtained prior to any treatment with ADH-1; 'post' - lesions obtained just prior to ILI with melphalan after 1 treatment with ADH-1; '2nd' - lesions obtained after a 2nd dose of ADH-1 given 8 days after melphalan ILI
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Project description:To determine which genes are affected by NG25 and melphalan, we performed an RNA-seq on INA-6 cells treated with NG25, melphalan or a combination of the two. GSEA focusing on the hallmark pathways showed that melphalan-treatment upregulated genes involved in UV-response, DNA-repair, p53-pathway and TNF-signaling via NF-kB. NG25 induced expression of genes involved in cholesterol homeostasis and mTORC1-signaling and down-regulated MYC- and E2F-targets. MYC is a central driver of MM pathology, and regulate survival as well as cell cycle control through E2F. NG25 reversed the melphalan-induced UV-response.
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Project description:Super-selective intra-ophthalmic artery chemotherapy (SSIOAC) is an organ-specific drug-delivery strategy to treat retinoblastoma, the most common primary ocular malignancy in children. Unfortunately, recent clinical reports associate adverse vascular toxicities with SSIOAC using melphalan, the most commonly used chemotherapeutic. To explore the reason for the unexpected vascular toxicities, we have developed in vitro studies with human retinal endothelial cells to test the effects of the chemotherapeutics and a non-human primate model to monitor the SSIOAC treatment in real-time and post-treatment. Melphalan and carboplatin (another chemotherapeutic used to treat retinoblastoma via SSIOAC) triggered migration, proliferation, and apoptosis when used to treat human retinal endothelial cells. Melphalan was associated with increased adhesion of leukocytes to human retinal endothelial cells, and tended to increase with increased cell expression of adhesion proteins (ICAM-1) and soluble chemotactic factors (IL-8). Histopathology post-SSIOAC indicated vessel wall sloughing, leukostasis, and vessel occlusion. We have established an in vitro human cell culture model and a non-human primate model to evaluate strategies designed to obviate vascular side effects, and optimize the efficacy of SSIAOC and the drug preparations used in SSIOAC. 4 non-treated (MNT) vs. 4 melphalan-treated primary human retinal endothelial cells (RECs).
2011-12-13 | E-GEOD-34381 | biostudies-arrayexpress
Project description:Melphalan-induced modulation of miR-221/222 levels in MM cells. Melphalan-resistant U266/LR7 cells showed the highest induction of miR-221/222 after drug exposure. To study the transcriptome perturbation induced in MM cells following the combination of miR-221/222 inhibitors plus melphalan we used the whole gene expression data
2015-09-08 | GSE66618 | GEO
Project description:To understand the mechanistic basis of ILF2’s regulation of mRNA splicing in response to DNA damage in Multiple Myeloma, we performed RNA immunoprecipitation (RIP) and sequencing of ILF2-bound transcripts under both physiological and DNA damage (melphalan treatment) conditions. Cells were treated with melphalan for 10 hours. RNA immunopreciptation (RIP) and sequencing of ILF2-bound RNAs was performed in the JJN3 and H929 cell lines (two biological replicates/condition). Cells were treated with melphalan for 10 hours.
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