ABSTRACT: Bortezomib-based secondary induction therapy and mobilization could represent alternative strategies to reduce tumor burden. We used microarrays to investigate genome-wide expression changes between bortezomib and non-bortzomib mobilizaton strategies and identified distinct genes and pathways that were significantly differentially regulated. CD34+ stem cells were enriched from leukapheresis products from multiple myeloma patients treated with a bortezomib- or non-bortezomib-based mobilization. RNA extraction, amplification and hybridization on Affymetrix microarrays was performed. Post-induction stem cell collection was initiated when patients' ANC reached >1.0M-CM-^W10^9/L.
Project description:In this study we wanted to investigate the role of cIAP2 in drug resistance, the plausible mechanisms underlying this resistance and possible strategies to overcome this by combinatorial treatment in human MM cell lines containing a TRAF3 mutation Gene expression profiling of the human MM cell line LP-1 under 6 different experimental perturbations: untreated or treated with bortezomib (10nM), 2 different timepoints (6 and 24 hours) and cIAP2 overexpression or endogenous cIAP2 level.
Project description:The estrogen receptor-alpha (ERα) determines breast cancer cell phenotype and is a prognostic indicator. A better understanding of the mechanisms controlling ERα function may uncover improved strategies for the treatment of breast cancer. Proteasome inhibition was previously reported to regulate estrogen-induced transcription but the mechanisms by which it influences ERα function remain controversial. In this study we investigated the transcriptome-wide effects of the proteasome inhibitor Velcade on estrogen-regulated transcription in MCF7 human breast cancer cells and demonstrate a specific global decrease in estrogen-induced transcription. This set contains 12 microarray samples. 3 controls, 3 estrogen stimulated, 3 Bortezomib stimulated, 3 Bortezomib + estrogen stimulated
Project description:Bortezomib-based secondary induction therapy and mobilization could represent alternative strategies to reduce tumor burden. We used microarrays to investigate genome-wide expression changes between bortezomib and non-bortzomib mobilizaton strategies and identified distinct genes and pathways that were significantly differentially regulated.
Project description:Primary effusion lymphoma is an aggressive B-cell lymphoma most commonly diagnosed in HIV-positive patients and universally associated with Kaposi’s sarcoma-associated herpesvirus (KSHV). Chemotherapy treatment of PEL yields only short-term remissions in the vast majority of patients yet efforts to develop superior therapeutic approaches have been impeded by lack of animal models that more accurately mimic human disease. To address this issue we developed a direct xenograft model, UM-PEL-1, by transferring freshly-isolated human PEL cells into the peritoneal cavities of NOD/SCID mice without in vitro cell growth. We utilized this model to show that bortezomib induces PEL remission and extends overall survival of mice bearing lymphomatous effusions. Transcriptome analysis by genomic arrays revealed that bortezomib downregulated cell cycle progression, DNA replication, and Myc-target genes. The microarray analysis was conducted on mice bearing UM-PEL-1 xenografts after treatment for 24 hours with PBS or bortezomib. Both arms of the experiment had three mice and the RNA was pooled from the three treated mice for gene expression analysis.
Project description:Bortezomib is a proteasome inhibitor used in severel different hematological malignancies. Resistance to this drug is still poorly understood. In order get more insight in the resistance mechanism, we developed several bortezomib resistant subclones of the THP-1 monocytic/macrophage cell line. On these subclones expression arrays were performed. We performed expression array three different bortezomib resistant subclones of the THP-1 cell line. The resistant subclones were spotted against the parental THP-1 wildtype cell line.
Project description:The estrogen receptor-alpha (ERα) determines breast cancer cell phenotype and is a prognostic indicator. A better understanding of the mechanisms controlling ERα function may uncover improved strategies for the treatment of breast cancer. Proteasome inhibition was previously reported to regulate estrogen-induced transcription but the mechanisms by which it influences ERα function remain controversial. In this study we investigated the transcriptome-wide effects of the proteasome inhibitor Velcade on estrogen-regulated transcription in MCF7 human breast cancer cells and demonstrate a specific global decrease in estrogen-induced transcription. This set contains 21 microarray samples. 3 controls, 3 estrogen stimulated, 3 Bortezomib + estrogen stimulated, 2* 3 siRNA controls, 3 siRNA PSMB3 knockdowns, 3 siRNA PSMB5 knockdowns
Project description:Multiple Myeloma (MM) is cancer in the antibody-producing plasma cells. It comprises 1 percent of all hematological malignancies. MM is incurable and fatal. The proteasome inhibitor bortezomib has improved treatment significantly, but inherent and acquired resistance remains a problem. Glutathione (GSH) is an important red-ox buffer in eukaryotic cells. In this experiment we investigate how GSH affects bortezomib-induced gene expression changes
Project description:This SuperSeries is composed of the following subset Series: GSE29711: Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma cells [CGH data] GSE29712: Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma cells [GEP data] Refer to individual Series
Project description:Bortezomib is a proteasome inhibitor used in severel different hematological malignancies. Resistance to this drug is still poorly understood. In order get more insight in the resistance mechanism, we developed several bortezomib resistant subclones of the CCRF-CEM T-ALL cell line. On these subclones comparative Genome hybridization (arrayCGH) for DNA copy number analysis gene expression and micro-RNA expression arrays were performed. We performed gene expression microarray analysis on four different bortezomib resistant subclones of the CCRF-CEM cell line. The resistant subclones were compaired to treated and untreated the parental CCRF-CEM wildtype cell line.
Project description:Gene expression profile (GEP) was analyzed from cultured bone marrow (BM) samples from patients with bortezomib responsive versus bortezomib resistant myeloma after 6-8 hours incubation in vitro with bortezomib 2 µg/ml or with PBS. Case D also had a fresh BM sample taken 75 minutes after IV injection of bortezomib. Comparative gene expression profiling of cultured bone marrow samples from from patients with bortezomib responsive versus bortezomib resistant myeloma after 6-8 hours incubation in vitro with bortezomib 2 µg/ml or with PBS.