ABSTRACT: Transcription profiling by array of three human cancer cell lines (H295R, HeLa and MCF-7her2) with and without treatment with histone deacetylase inhibitor LBH589 (panobinostat)
Project description:To identify the targets of LBH589 treatment, we compared gene expression profiles in three different types of human cancer cell lines (H295R, HeLa and MCF-7her2) with and without LBH589 treatment. Affymetrix microarray analysis was performed to determine changes in gene expression that are unique to LBH treatment.
Project description:To identify the targets of LBH589 treatment, we compared gene expression profiles in three different types of human cancer cell lines (H295R, HeLa and MCF-7her2) with and without LBH589 treatment. Affymetrix microarray analysis was performed to determine changes in gene expression that are unique to LBH treatment. LBH-treated cell lines received 50 nM of LBH589 for 24 hours. DMSO and LBH treatments are in triplicate.
Project description:Histone deacetylase (HDAC) inhibitors are part of a new generation of epigenetic drugs for cancer treatment. It is known that histone acetylation plays a key role in controlling essential chromosome functions, including gene regulation, and this process has been linked with cancer development and progression. Better understanding of molecular mechanisms involving HDAC inhibitors is needed for the design of new targeted drugs, and also to evaluate the effectiveness of current treatments. In this study, an untargeted metabolomics approach was used to identify intracellular metabolite deregulation after treating cancer cell lines with the HDAC inhibitor HC-Toxin. Metabolomics analysis was performed using high resolution mass spectrometry, in combination with univariate and multivariate statistics and pathway analysis. HDAC inhibition showed highly specific metabolic changes in cancer cell lines compared to non-cancerous cells. In particular, N-acetyl-L-cysteine, N-acetylmethionine, and N-acetyl-L-carnitine showed a dose dependent change. Moreover, pathways controlling protein biosynthesis, as well as tryptophan, cysteine and methionine metabolism were significantly altered by HDAC inhibition. This study illustrates that HDAC inhibition has multiple effects on different metabolic pathways and our results can be extrapolated to inform on the molecular transitions in human cells.
Project description:<p>Diffuse Intrinsic Pontine Glioma (DIPG) is a universally fatal childhood cancer. Here, we performed a chemical screen in patient-derived DIPG cell cultures along with RNAseq expression analysis and integrated computational modeling to identify potentially effective therapeutic strategies. Panobinostat, among the more promising agents identified, demonstrated efficacy in pontine orthotopic xenograft models of both H3K27M and histone WT DIPG. These data suggest the potential utility of specific drug combinations and provides evidence of in vivo treatment efficacy of the multi-histone deacetylase inhibitor panobinostat. We are depositing to dbGaP deep sequencing whole exome data for 22 patient tumor samples and 13 matched normals, along with RNAseq data for 12 patient tumor samples and 6 normal pediatric brain tissue samples. In addition, we are depositing 22 RNAseq samples from DIPG cell lines before and after panobinostat treatment.</p>
Project description:The human steroid receptor RNA activator (SRA) gene encodes both non-coding RNAs (ncRNAs) and protein-generating isoforms. However, the breadth of endogenous target genes that might be regulated by SRA RNAs remains largely unknown. To address this, we depleted SRA RNA in two human cancer cell lines (HeLa and MCF-7) with small interfering RNAs, then assayed for changes in gene expression by microarray analyses using Affymetrix HGU133+2 arrays. We also tested if SRA depletion affects estradiol-regulated genes in MCF-7 breast cancer cells. We transiently transfected HeLa or MCF-7 human cancer cell lines with with non-targeting (NT) or SRA-targeting siRNAs. Six total HeLa RNA samples were analyzed on an Affymetrix HGU133+2 array, representing three biological triplicates. Likewise, 12 total MCF-7 RNA samples were analyzed on Affymetrix HGU133+2 arrays, representing biological trilplicates for both NT and siSRA transfected cells and with/without 10 nM estradiol (E2) for 6 hours.
Project description:Gene expression analysis of three sets of patient-derived T-ALL xenografted murine lines treated or not treated with Givinostat, to investigate the immediate anti-leukemic effects after 6 hours of in vivo treatment with this histone deacetylase inhibitor.
Project description:The aim of this study is to determine the efficacy of combining the histone deacetylase (HDAC) inhibitor sodium valproate (VPA) with anti-EGFR monoclonal antibody (panitumumab or cetuximab) maintenance in the first-line treatment of patients with RAS wild type metastatic CRC.
Project description:Reversing gene expression signatures in relapsed patient may restore chemosensitivity. We demonstrate that the histone deacetylase inhibitor vorinostat not only reprograms the aberrant gene expression profile of relapsed blasts but is synergistic when applied prior to chemotherapy in primary patient samples and leukemia cell lines Primary patient samples were collected from patients treated at the New York University Medical Center and from the Childrenâs Oncology Group (COG) cell bank,RNA was isolated from three primary patient samples and three B-lineage leukemia cell lines with or without treatment with vorinostat for 24 hours.
Project description:Treatment with the histone deacetylase inhibitor trichostatin a (TSA) changes the radial positioning of the CFTR gene in HeLa S3 cells. The gene relocates from the nuclear periphery to the nuclear interior. In Calu-3 cells the gene is located in the nuclear interior. To identifiy potential regulatory elements for the positioning of CFTR, the histone h3 and h4 acetylation patterns of untreated and TSA-treated HeLa S3 and untreated Calu-3 cells were determined by ChIP-chip. A CTCF site close to the CFTR promoter displayed consistent histone H3 hyperacetylation in TSA treated HeLa S3 cells and Calu-3 cells.
Project description:Analysis of gene expression change after 8hr's treatment with 5μM SAHA, which is a histone deacetylase inhibitor, in MDA-MB-231 cell lines.