Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma cells
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ABSTRACT: 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:Copy number and Gene expression profiling of HT-29 wild-type and bortezomib resistant cell lines Identification of mechanisms of bortezomib resistance Copy number differences between HT-29 cell line variants and a HapMap control population of 9 female samples were identified using the Agilent 1M Human CGH microarray
Project description:Copy number and Gene expression profiling of HT-29 wild-type and bortezomib resistant cell lines Identification of mechanisms of bortezomib resistance Gene expression differences between HT-29 cell line variants
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: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: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: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: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.
Project description:Ribosome profiling is a widespread tool for studying translational dynamics in human cells. Its central assumption is that ribosome footprint density on a transcript quantitatively reflects protein synthesis. Here, we test this assumption using pulsed-SILAC (pSILAC) high-accuracy targeted proteomics. We focus on multiple myeloma cells exposed to bortezomib, a first-line chemotherapy and proteasome inhibitor. In the absence of drug effects, we found that direct measurement of protein synthesis by pSILAC correlated well with indirect measurement of synthesis from ribosome footprint density. This correlation, however, broke down under bortezomib-induced stress. By developing a statistical model integrating longitudinal proteomic and mRNA-seq measurements, we found that proteomics could directly detect global alterations in translational rate caused by bortezomib; these changes are not detectable by ribosomal profiling alone. Further, by incorporating pSILAC data into a gene expression model, we predict cell-stress specific proteome remodeling events. These results demonstrate that pSILAC provides an important complement to ribosome profiling in measuring proteome dynamics. Timecourse experiment with six points over 48hr after bortezomib exposure in MM.1S myeloma cells. mRNA-seq and ribosome profiling data at each time point.
Project description:This experiment is designed to evaluate gene expression alterations following treatment with gambogic acid and bortezomib in human HepG2 cells. We find gambogic acid yielded a similar gene expression profile as did bortezomib. Total RNA were extracted from human HepG2 cancer cells treated with gambogic acid (0.25μM, 0.5μM, 0.75μM) or bortezomib (50nM) for 9hr. HepG2 cells treated with vehicle alone was used as a control.
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. 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.