title: Molecular Classification of AIDS-Related Lymphomas [including third-party data]

status: Public on Jul 18 2012

first: Karen

last: Deffenbacher

state: NE

address: 987660 Nebraska Medical Center

department: Pathology and Microbiology

summary:
Gene expression profiling (GEP) of ARL patient samples was done to determine whether gene expression signatures derived from HIV- lymphomas retained their ability to molecularly classify HIV+ lymphomas. The GEP-based predictors robustly classified ARL tumors, distinguishing molecular Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), as well as activated B-cell-like (ABC) and germinal center B-cell-like (GCB) molecular subtypes of DLBCL.
Gene expression profiles were used to identify coordinately regulated gene sets and pathways that differ between HIV+ and HIV- lymphomas of corresponding molecular subtype.

overall_design:
Frozen tumor biopsies were obtained from 20 HIV-positive patients with an AIDS-defining lymphoma. Cases were ascertained at the University of Nebraska Medical Center and through the NCI AIDS and Cancer Specimen Resource tumor bank. Sufficient RNA for hybridization to Affymetrix U133 plus 2 arrays was obtained on 17 ARL cases.  Details of all 20 HIV-positive patients can be found in the supplementary file below.

Third party array data from HIV- lymphomas of corresponding molecular subtype were used for the comparison and molecular classification of the HIV+ cases in this study.
The third party HIV- lymphoma samples include the following.
[1] HIV- lymphoma, BL cases: 84 samples profiled on the Affymetrix HG U133 Plus 2 array. The data are publicly available on the website companion to Dave et al. NEJM 2006; Volume 354:13-24 (http://llmpp.nih.gov/BL/) and were used 'as is' (ie, not reanalyzed).
[2] HIV- lymphoma, DLBCL cases: 200 of the 414 cases in Series GSE10846 (listed in the supplementary file below). These included all R-CHOP treated cases of either ABC or GCB subtype. These data were also used as is. These data were published in Lenz et al. NEJM 2008; Volume 359: 2313-2323.

first: Wing

last: Chan


title: Expression data from skin biopsy samples from patients with moderate-to-severe psoriasis

status: Public on Jul 26 2012

city: Spring House

first: K

last: Li

state: PA

address: 1400 McKean Road

country: USA

institute: Janssen R&D

summary: A gene expression profiling sub-study was conducted in which skin biopsy samples were collected from 85 patients with moderate-to-severe psoriasis who were participating in ACCEPT, an IRB-approved Phase 3, multicenter, randomized trial. This analysis identified 4,175 probe-sets as being significantly modulated in psoriasis lesions (LS) compared with matched biopsies of non-lesional (NL) skin.

overall_design: Skin biopsy samples (n=170) were collected at baseline for RNA extraction and microarray analysis from 85 patients with moderate-to-severe psoriasis without receiving active psoriasis therapy.  The sample title is concatenated as <sample collection site ID>_<subject ID>_<skin type>.

first: Mayte

last: Suárez-Fariñas

first: Katherine

first: Judilyn

last: Fuentes-Duculan

last: Hayden

first: Carrie

last: Brodmerkel

first: James

middle: G

last: Krueger


title: Time-course effect of estradiol and ERa17p on Early Gene expression in T47D cells

status: Public on Jul 31 2012

city: Heraklion

first: George

last: Notas

address: PO BOX 2208

department: Medicine

country: Greece

institute: University of Crete

summary: ERα17p is a synthetic peptide corresponding to the sequence P295LMIKRSKKNSLALSLT311 of the estrogen receptor alpha (ERα) and initially synthesized to mimic its calmodulin binding site. ERα17p was subsequently found to elicit estrogenic responses in E2-deprived ERα-positive breast cancer cells, increasing proliferation and E2-dependent gene transcription.  Surprisingly, in E2-supplemented media, ERα17p induced apoptosis and modified the actin network, influencing thereby cell motility. Here, we report that ERα17p induces a massive early (3h) transcriptional activity in breast cancer cell line T47D.

overall_design: Cells after a 4h incubation with medium containing 10% charcoal stripped FBS were incubated with or without E2 (10-6M) or ERa17p in RPMI 1640 supplemented with 10% charcoal stripped FBS, for 3 hours. Total RNA was isolated using Nucleospin II columns (Macheray-Nagel, Dttren, Germany), according to the manufacturer’s instructions. RNA was labeled and hybridized according to the Affymetrix protocol (Affymetrix Gene-Chip Expression Analysis Technical Manual), using the HGU133A plus 2 chip, analyzing a total of 54675 transcripts. Signals were detected by an Affymetrix microarray chip reader.

first: Marilena

last: Kampa

first: Elias

last: Castanas


title: Identification of genes responsive to mild hyperthermia in human skin normal fibroblast Hs68 cells

status: Public on Jul 13 2012

city: Toyama

first: Yoshiaki

last: Tabuchi

state: Toyama

address: 2630 Sugitani

department: Life Science Research Center

country: Japan

institute: University of Toyama

summary: Hyperthermia is widely used to treat patients with various cancers. Here, the effects of heat stress at 41°C for 30 min (mild hyperthermia) on the gene expression in Hs68 human skin normal fibroblast cells were investigated using an Affymetrix GeneChip system. The cells were treated with mild hyperthermia, followed by incubation for 0, 1, or 3 h at 37°C. No cell death was observed in the mild hyperthermia-treated cells. On the other hand, many genes that were differentially expressed by a factor 1.5 or greater were identified in the cells treated with the mild hyperthermia.

overall_design: Hs68 human skin normal fibroblast cells were treated with heat stress (41°C for 30 min), followed by incubation for 0, 1, or 3 h at 37°C. Non-treated cells served as the control. Total RNA samples were prepared from the cells, and quality of the RNA was analyzed using a Bioanalyzer 2100. Gene expression was monitored by an Affymetrix GeneChip® system with a Human Genome U133-plus 2.0 array. Sample preparation for array hybridization was carried out as described in the manufacturer's instructions.

first: Ayako

last: Kariya

first: Yukihiro

last: Furusawa


title: Escherichia coli glutathionylspermidine: Phylogeny and regulation of gene expression

status: Public on Jul 12 2012

city: Bethesda

first: WeiPing

last: Chen

state: MD

address: Bldg 8, Room 1A11, NIDDK/NIH

department: GCL

institute: NIDDK/NIH

summary: Glutathionylspermdine synthetase/amidase (Gss) and the encoding gene (gss) have only been described in two widely separated species; namely Escherichia coli and several members of the Kinetoplastida phyla. In the present paper we have studied the species distribution more extensively. It is striking that all of the 75 Enterobacteria species that has been sequenced contain sequences with very high degree of homology to the E. coli Gss protein. Although homologous sequences are also present in various other bacteria, in contrast to Enterobacteria they are not present in all species of a given phyla. As previously reported homologous sequences were found in all five species of   Kinetoplastids tested (including Trypansosma cruzi), but it is striking that comparable sequences are not found in a variety of invertebrate and vertebrate species, Archea and plants. Studies in E. coli show that the highest accumulation of glutathionylspermidine is found in stationary phase cultures where most of the intracellular spermidine is converted to glutathionylspermidine. However, even in log phase cells there is some formation of glutathionylspermidine, and isotope exchange experiments show that there is a rapid exchange between glutathionylspermidine and intracellular spermidine. We have not been able to define a specific physiologic function for glutathionylspermidine, but microarray studies comparing gss+ and -gss strains of E. coli show that a large number of genes are either upregulated or downregulated by the loss of the gss gene.

overall_design: Comparison of gss mutant of E. coli and wild type cells, with triplicate samples from each.

first: Manas

middle: K

last: Chattopadhyay

first: Herbert

last: Tabor


title: Identification of genes responsive to mild hyperthermia in human normal fibroblast OUMS-36 cells

summary: Hyperthermia is widely used to treat patients with various cancers. Here, the effects of heat stress at 41°C for 30 min (mild hyperthermia) on the gene expression in OUMS-36 human normal fibroblast cells were investigated using an Affymetrix GeneChip system. The cells were treated with mild hyperthermia, followed by incubation for 0, 1, or 3 h at 37°C. No cell death was observed in the mild hyperthermia-treated cells. On the other hand, many genes that were differentially expressed by a factor 1.5 or greater were identified in the cells treated with the mild hyperthermia.

overall_design: OUMS-36 human normal fibroblast cells were treated with heat stress (41°C for 30 min), followed by incubation for 0, 1, or 3 h at 37°C. Non-treated cells served as the control. Total RNA samples were prepared from the cells, and quality of the RNA was analyzed using a Bioanalyzer 2100. Gene expression was monitored by an Affymetrix GeneChip® system with a Human Genome U133-plus 2.0 array. Sample preparation for array hybridization was carried out as described in the manufacturer's instructions.


title: Gene Expression Profiles of human primary alveolar type II (ATII) cells and macrophages (AMs) after influenza virus infection

city: Aurora

first: Tzu Lip

last: Phang

state: CO

address: 12700 East 19th Avenue

institute: University of Colorado, Denver

summary:
Abnormal function of genes is at the root of most cancers, but heritable cancer syndromes account for a very small minority of all tumors in humans and domestic animals. The majority of cancers are “sporadic,” that is, they are not heritable in the strictest sense. Instead, sporadic cancers occur due to interactions of unknown intrinsic (heritable) and environmental factors that lead to malignant transformation and uncontrolled growth. Identification of heritable risk factors in sporadic human cancers is difficult because individual genetic backgrounds are very heterogeneous. To this end, individual genetic backgrounds of purebred dogs are more homogeneous, and dog breeds show different predilection to develop specific cancers. Here, we used genomic screens based on gene expression profiling to identify sets of genes that may contribute to the development of canine hemangiosarcoma, a relatively common endothelial sarcoma. Specific genes in a single breed (Golden Retrievers) are modulated by (or with) heritable risk traits, showing functional features that appear to modulate tumor behavior. Our results suggest these methods are suitable to identify genes that will enhance our understanding of how these cancers happen, as well as possible treatment targets that will improve outcomes of both human and canine cancer patients.
24 samples were analysed.  12 samples with ATII cells with without influenza virus infection at 4h and 24h; 12 samples with AMs with without influenza virus infection at 4h and 24h

overall_design: primary cultured cells were infected with or without influenza virus PR/8 at moi of 0.5. At 4h and 24h, total RNA were isolated for microarray experiments

first: Jeiru

last: Wang

first: Tzu

middle: L

first: Bifeng

last: Gao

first: Robert

last: Mason


title: Expression data of IL-18 generated murine NK cells

status: Public on Jul 11 2012

city: Duesseldorf

first: Karl

last: Koehrer

address: Universitaetsstr. 1

department: BMFZ

country: Germany

institute: University of Duesseldorf

summary:
We analyzed gene expression profiles of IL-18 generated murine NK cells in comparison to unstimulated, freshly isolated splenic NK cells.
We identified a set of 1414 Affymetrix probe sets showing significant misregulation (Welch's T-test, p<0.05; Benjamini-Hochberg FDR corrected).

overall_design: IL-18 generated as well as unstimulated NK cells were isolated in three independent preparations and used for RNA extraction and hybridization on Affymetrix microarrays.

first: Margret

last: Ehlers

first: Claudia

last: Papewalis

first: Benedikt

last: Jacobs

first: Klaus

last: Meyer

first: René

last: Deenen

first: Holger

middle: S

last: Willenberg

first: Sven

last: Schinner

first: Annette

last: Thiel

first: Werner

middle: A

last: Scherbaum

first: Evelyn

last: Ullrich

first: Laurence

last: Zitvogel

first: Matthias

last: Schott


title: Expression data from liver tissue from Npc1 mouse model

city: BETHESDA

first: Celine

last: Cluzeau

address: 10 Center Drive - room 9D41

department: PDEGEN

institute: NICHD/NIH

summary: We used microarrays to detail the global programme of gene expression underlying the disease progression in the mutant mice compared to their control littermates.

overall_design: We collected liver tissue from 1-, 3-, 5-, 7-, 9-, and 11-week-old Npc1+/+ and Npc1-/- mice (N=4), and some additional controls.

middle: V

first: Dawn

middle: E

last: Watkins-Chow

first: Rao

last: Fu

first: Bhavesh

last: Borate

first: Nicole

last: Yanjanin

first: Michelle

last: Dail

first: Cristin

middle: D

last: Davidson

first: Steven

middle: U

last: Walkley

first: Daniel

last: Ory

first: Christopher

last: Wassif

first: William

middle: J

last: Pavan

first: Forbes

last: Porter

first: Laura

last: Baxter

first: Art

last: Incao

last: Liscum

first: Rohini

last: Sidhu

first: Sally

last: Firnkes

first: Mark

last: Graham


title: Expression profiling of mouse B1a cells with high expression of PC1 vs. those with low expression of PC1.

status: Public on Jul 09 2012

city: Seoul

first: Dong-Mi

last: Shin

address: 1 gwanak-ro

country: South Korea

institute: seoul national university

summary:
Mouse peritoneal B1a cells were classified into two groups based upon the expression level of PC1. One is PC1 high group and the other is PC1 low.
To evaluate gene expression patterns that distinguished PC1 high expressing B1a cells from PC1 low expressing B1a cells, we used Affymetrix GeneChip® Mouse gene 1.0 ST Array.

overall_design: FACS-sorted PC1 high and low cells from individual mouse were used for RNA extraction and Affyarray hybridization. There were six independent biological replications in each group - six cases of PC1 high cells and six cases of PC1 low cells.

first: Hongsheng

last: Wang

first: Herbert

middle: C

last: Morse


title: Gene expression analysis of rectal mucosa in chronic irritable bowel syndrome (IBS) compared to healthy volunteers (HV)

city: Stevenage

first: Fiona

middle: M

last: Kelly

state: HERTS

address: GunnelsWood Road

department: Biopharm R&D

country: United Kingdom

institute: GlaxoSmithKline

summary: An investigation of gene expression changes in rectal biopsies from donors with IBS compared to controls to begin to understand this complex syndrome. To further investigate differences between IBS groups (constipation and diarrhoea predominant) (part1) and how IBS relates to bacterial infection (part2) with biopsies taken 6 months after Campylobacter jejuni infection.

overall_design:
Part1: 18 Constipation predominant IBS subjects (IBS-C) and 27 diarrhoea predominant IBS subjects (IBS-D) compared to 21 healthy volunteers (HV).
Part2: 21 Campylobacter jejuni infection (PIBD, PIBS, PINIBS) compared to 19 healthy volunteers (HV).
PIBD = post Campylobacter infection with IBS (within 6 months)
PIBS = post infection IBS (unknown time point and organism)
PINIBS = post Campylobacter infection with no resulting IBS

first: Robin

last: Spiller

first: Jonathan

middle: I

last: Wilde

first: Joanne

last: Cox

last: Lennon

first: George

last: Dukes


title: Gene expression profile of human iPS cell-derived mesoangioblasts (HIDEMs)

city: Modena

first: Enrico

last: Tagliafico

state: MO

address: Via Campi 287

department: Center for Genome Research

country: Italy

institute: University of Modena and Reggio Emilia

summary: Mesoangioblasts are stem/progenitor cells derived from a subset of pericytes expressing alkaline phosphatase. They have been shown to ameliorate muscular dystrophies (currently incurable diseases) in different animal models and are now undergoing clinical experimentation for Duchenne muscular dystrophy. We show here that patients affected by limb-girdle muscular dystrophy 2D (LGMD2D, characterized by α-sarcoglycan deficit) have a reduction of this subset of pericytes and hence mesoangioblast could not be derived  for cell therapy. Therefore, we reprogrammed LGMD2D fibroblasts and myoblasts to induced pluripotent stem cells (iPSCs) and developed a protocol for the derivation of mesoangioblast-like cells from them. These cells can be expanded and genetically corrected with a muscle-specific lentiviral vector expressing human α-sarcoglycan. Upon transplantation into ad hoc generated α-sarcoglycan-null immunodeficient mice, they generate myofibers expressing α-sarcoglycan. This approach may be useful for muscular dystrophies that show a reduction of resident progenitors and provides evidence of pre-clinical safety and efficacy of disease-specific iPSCs.

overall_design: 9 samples analyzed: 3 WT HIDEMs, 3 Limb-girdle muscular dystrophy 2D (LGMD2D) HIDEMs and 3 WT adult skeletal muscle derived mesoangioblasts (controls).

first: Francesco

last: Saverio Tedesco

first: Mattia

last: Gerli

first: Valentina

last: Artusi

last: Perani

first: Sara

last: Benedetti

first: Giulio

last: Cossu


title: A mouse model of deregulation of the malt1 oncogene recapitulates the pathogenesis of human malt lymphoma [MALT dataset]

status: Public on Jul 10 2012

city: Pamplona

first: Victor

last: Segura

state: Navarra

address: Avda. Pío XII, 55

department: Unit of Proteomics, Genomics and Bioinformatics

country: Spain

institute: FIMA

summary:
Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NF-kappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies.

Keywords: lymphoma profiling, MALT lymphoma

overall_design: 97 samples were analized of which 13 were normal B-cell purified subpopulations and 84 lymphoma samples (31 MALT lymphomas, 26 DLBCL, 15 FCL and 12 SMZL)

first: Carolina

last: Vicente-Dueñas

first: Lorena

last: Fontán

first: Ines

last: Gonzalez-Herrero

first: Angela

last: Aznar

first: Esther

last: Alonso-Escudero

first: Jose

last: Martinez-Ferrandis

first: Fernando

last: Abollo-Jimenez

first: Cristina

last: Bertolo

first: Francisco

last: Garcia-Criado

first: María

middle: B

last: García-Cenador

first: Federico

last: Garcia-Bragado

first: Ellen

last: Remstein

first: Reiner

last: Siebert

first: Ming

middle: Q

last: Du

first: Xabier

last: Sagaert

first: Izidore

last: Lossos

first: Teresa

last: Flores

first: Cesar

last: Cobaleda

first: Isidro

last: Sanchez-Garcia

last: Martinez-Climent


title: Novel mutations target distinct subgroups of medulloblastoma.

status: Public on Jul 06 2012

city: Memphis

first: David

last: Finkelstein

state: TN

address: 332 N. Lauderdale St.

department: Computational Biology

institute: St Jude Children's Research Hospital

summary: Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. To identify  mutations that drive medulloblastoma we sequenced the entire genomes of 37 tumours and matched  normal blood. One hundred and thirty-six genes harbouring somatic mutations in this discovery set were  sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet  implicated in medulloblastoma: several target distinct components of the epigenetic machinery in different  disease subgroups, e.g., regulators of H3K27 and H3K4 trimethylation in subgroup-3 and 4 (e.g., KDM6A  and ZMYM3), and CTNNB1-associated chromatin remodellers in WNT-subgroup tumours (e.g.,  SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate  WNT-subgroup tumours, identified genes that maintain this cell lineage (DDX3X) as well as mutated  genes that initiate (CDH1) or cooperate (PIK3CA) in tumourigenesis. These data provide important new  insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic  development.

overall_design: A total of 76 pediatric medulloblastoma samples were analyzed, representing 4 expression classes

first: Giles

last: Robinson

first: Matthew

last: Parker

first: Tanya

last: Kranenburg

first: Charles

last: Lu

first: Xiang

last: Chen

first: Li

last: Ding

first: Timothy

middle: N

last: Phoenix

first: Erin

last: Hedlund

first: Lei

last: Wei

first: Xiaoyan

last: Zhu

first: Nader

last: Chalhoub

first: Suzanne

last: Baker

first: Robert

last: Huether

first: Richard

last: Kriwacki

first: Natasha

last: Curley

first: Radhika

last: Thiruvenkatam

first: Jianmin

last: Wang

first: Gang

last: Wu

first: Michael

last: Rusch

first: Xin

last: Hong

first: Jared

last: Beckford

first: Pankaj

last: Gupta

first: Jing

last: Ma

first: John

last: Easton

first: Bhavin

last: Vadodaria

first: Arzu

last: Onar-Thomas

first: Tong

last: Lin

first: Shaoyi

last: Li

first: Stanley

last: Pounds

first: Steven

last: Paugh

last: Zhao

first: Daisuke

last: Kawauchi

first: Martine

middle: F

last: Roussel

middle: W

last: Ellison

first: Ching

last: Lau

first: Eric

last: Bouffet

first: Tim

last: Hassall

first: Sridharan

last: Gururangan

last: Cohn

first: Lucinda

last: Fulton


title: A mouse model of deregulation of the malt1 oncogene recapitulates the pathogenesis of human malt lymphoma

first: Victor

last: Segura

summary: This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: E.coli MG1655Δ6/pCA24N-dinJ treated with erythromycin vs. MG1655Δ6/pCA24N

city: State College

first: Thomas

middle: K.

last: Wood

address: Room 161 Fenske Laboratory, University Park

department: Chemical Engineering & Biochemistry and Molecular Biology

institute: Pennsylvania State University

summary: Antitoxins are becoming recognized as proteins that regulate more than their own synthesis; for example, we found previously that antitoxin MqsA represses the gene encoding the stationary phase sigma factor RpoS. Here, we investigated the physiological role of antitoxin DinJ of the DinJ/YafQ toxin/antitoxin system and found DinJ also affects the general stress response by decreasing RpoS levels. Corroborating the reduced RpoS levels upon producing DinJ, catalase activity, cell adhesins, and cyclic diguanylate decreased while swimming increased. Using a transcriptome search and DNA-binding assays, we determined that the mechanism by which DinJ reduces RpoS is by repressing cspE which encodes cold-shock protein CspE that inhibits translation of rpoS mRNA. Hence, DinJ influences the general stress response indirectly by regulating cspE.

overall_design:
strain: E.coli MG1655Δ6/pCA24N-dinJ vs MG1655Δ6/pCA24N
treatment:erythromycin
Medium:LB low salt
Time:10 min
Temp: 37°C

first: Ying

last: HU

first: Michael

last: Benedik

middle: K


title: Indole-3-Acetaldehyde Inhibits Escherichia coli O157:H7 Biofilm Formation by Reducing Curli Formation

status: Public on Jul 05 2012

city: Gyeongsan-Si

first: Jintae

last: Lee

state: Gyeongsangbuk-Do

address: 214-1 Daedong

department: Chemical engineering

institute: Yeungnam University

summary: Pathogenic biofilms have been associated with persistent infections due to their high resistance to antimicrobial agents. To identify non-toxic biofilm inhibitors for enterohemorrhagic Escherichia coli O157:H7, indole-3-acetaldehyde was used and reduced E. coli O157:H7 biofilm formation. Global transcriptome analyses revealed that indole-3-acetaldehyde most repressed two curli operons, csgBAC and csgDEFG, and induced tryptophanase (tnaAB) in E. coli O157:H7 biofilm cells. Electron microscopy showed that indole-3-acetaldehyde reduced curli production in E. coli O157:H7. Together, this study shows that Actinomycetales are an important resource of biofilm inhibitors as well as antibiotics.

overall_design: For the microarray experiments, E. coli O157:H7 EDL933 was inoculated in 100 ml of LB in 250 ml flasks with overnight cultures that were diluted at 1:100. Cells were shaken with 10g of glass wool at 250 rpm and 37°C for 7 hrs.  Cells were immediately chilled with dry ice and 95% ethanol (to prevent RNA degradation) for 30 sec before centrifugation in 50 ml centrifuge tubes at 13,000 g for 2 min; cell pellets were frozen immediately with dry ice and stored -80°C.  RNA was isolated using Qiagen RNeasy mini Kit (Valencia, CA, USA). To eliminate DNA contamination, Qiagen RNase-free DNase I was used to digest DNA. RNA quality was assessed by Agilent 2100 bioanalyser using the RNA 6000 Nano Chip (Agilent Technologies, Amstelveen, The Netherlands), and quantity was determined by ND-1000 Spectrophotometer (NanoDrop Technologies, Inc., DE, USA).

first: Jin-Hyung

last: LEE

first: Yong-Guy

last: KIM

first: Chang-Jin

first: Moo

middle: H

last: CHO


title: HDAC3 requirement for the inflammatory gene expression program in macrophages [gene expression]

city: Vienna

first: Iros

last: Barozzi

address: Borschkegasse 8a

country: Austria

institute: Medical University Vienna

summary: Pan-Hdac inhibitors (HDACi) are endowed with a potent anti-inflammatory activity, but the relative role of each of the eleven Hdac proteins sensitive to HDACi to the inflammatory gene expression program is unknown. Using an integrated genomic approach we found that Hdac3-deficient macrophages are unable to activate almost half of the inflammatory gene expression program when stimulated with lipopolysaccharide (LPS). A large part of the activation defect is due to loss of basal and LPS-inducible expression of IFNb, which in basal cells maintains Stat1 protein levels, and after stimulation acts in an autocrine/paracrine manner to promote a secondary wave of Stat1-dependent gene expression. We show that loss of Hdac3-mediated repression of nuclear receptors leads to hyperacetylation of thousands of genomic sites and associated gene derepression. The upregulation of the constitutively expressed prostaglandin endoperoxide synthase, Ptgs1 (Cox-1), has a causative role in the phenotype, since its chemical inhibition reverts the Ifnb activation defect. These data may have relevance for the use of selective Hdac inhibitors as anti-inflammatory agents.

overall_design: Gene expression profiles for bone marrow-derived macrophages from either HDAC3 +/- (wt) or HDAC3 -/- (KO). Cells were left untreated or challenged with lipopolysaccharide (LPS) for 4hrs. Each genotype-treatment combination was performed in triplicate.

first: Xuefen

last: Chen

first: Alberto

last: Termanini

first: Elena

last: Prosperini

first: Flore

last: Mietton

first: Gianluca

last: Matteoli

first: Scott

last: Hiebert

first: Gioacchino

last: Natoli


title: Comparison of the transcriptome of day 3 human embryo with that of the trophectoderm

city: Montpellier

first: Said

last: Assou

address: 80, Av. Augustin Flich

country: France

institute: INSERM

type:
Expression profiling by array
Third-party reanalysis

summary: In humans, the embryonic genome activation (EGA) program is functional by day 3 after fertilization. The 6-8 cell stage embryo (day 3 post-fertilization) starts the process of “compaction” that leads to the generation of the tightly organized cell mass of the morula and is followed by differentiation of the morula into a blastocyst. The transition from day 3 embryos to day 5 blastocysts is likely to be controlled by many and specific changes in the expression of different genes. We used mRNA amplification technique and compared the transcriptomes of day 3 human embryos and trophectoderm (TE) cells from day 5 human blastocysts to identify transcripts that are differentially expressed during the embryo-to-TE transition and involved in the TE specification.

overall_design:
These six embryo samples were compared to our five human trophectoderm samples that are available in GEO under the following accession numbers:
GSM706168
GSM706169
GSM706170
GSM706171
GSM706172

first: SAID

last: ASSOU

first: JOHN

last: DE VOS

first: SAMIR

last: HAMAMAH


title: Gastric Cancer Subtyping (Australian Patient Cohort)

city: Singapore

first: Zhengdeng

last: Lei

address: 8 College Road

country: Singapore

institute: Duke-NUS graduate medical school

summary:
Genome-wide mRNA expression profiles of 70 primary gastric tumors from the Australian patient cohort. Like many cancers, gastric adenocarcinomas (gastric cancers) show considerable heterogeneity between patients. Thus, there is intense interest in using gene expression profiles to discover subtypes of gastric cancers with particular biological properties or therapeutic vulnerabilities.
Identification of such subtypes could generate insights into the mechanisms of cancer progression or lay the foundation for personalized treatments. Here we report a robust gene-xpression-based clustering of a large collection of gastric adenocarcinomas from Singaporean patients [GSE34942 and GSE15459]. We developed and validated a classifier for the three subtypes in Australian patient cohort.

overall_design: Profiling of 70 primary gastric tumors on Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. All tumors were collected with approvals from Peter MacCallum Cancer Center, Australia; the Research Ethics Review Committee; and signed patient informed consent.

first: Steve

last: Rozen

first: Patrick

last: Tan

first: Alex

last: Boussioutas


title: Nucleosome dynamics specifies genome-wide binding of the male germ cell gene regulator CTCFL and of CTCF [MoGene-1_0 Expression]

status: Public on Jul 25 2012

city: Rotterdam

first: frank

last: sleutels

address: Dr Molewaterplein 50

department: cell biology and genetics

country: Netherlands

institute: ErasmusMC

summary: CTCFL binding to DNA and the effect of CTCFL expression  in ES cells

overall_design: RNA extracted from CTCFL induced and non-induced ES cells was hybridized on Affymetrix Mouse Gene 1.0ST arrays

first: Frank

last: Sleutels

first: Widia

last: Soochit

first: Marek

last: Bartkuhn

first: Helen

last: Heath

first: Sven

last: Dienstbach

first: Philipp

last: Bergmaier

first: Vedran

last: Franke

first: Manuel

last: Rosa-Garrido

first: Suzanne

last: van de Nobelen

first: Lisa

last: Caesar

first: Michael

last: van der Reijden

first: Jan

last: Christian Bryne

first: Wilfred

last: van Ijcken

first: J

middle: A

last: Grootegoed

first: M

last: Delgado

first: Boris

last: Lenhard

first: Rainer

last: Renkawitz

last: Grosveld

first: Niels

last: Galjart


title: Expression data from MDA-MB-231 cells exposed to hypoxia and/or paclitaxel or epirubicin

status: Public on Jul 03 2012

city: Namur

first: Bertrand

last: De Meulder

state: Namur

address: Rue de Bruxelles, 61

department: Biology

country: Belgium

institute: FUNDP

summary:
Hypoxia protects cancer cells from chemotherapeutic drug-induced cell death.
We used microarrays to detail the changes in gene expression underlying hypoxia-induced chemoresistance in cancer cells.

overall_design: MDA-MB-231 were exposed to paclitaxel or epirubicin under normoxia or hypoxia for 16hours, then RNA was extracted and analyzed by Affymetrix arrays

first: Lionel

last: Flamant

first: Carine

last: Michiels


title: A novel five-gene signature predicts overall and recurrence-free survival in NSCLC

status: Public on Jul 01 2012

city: Tampa

first: Jonathan

last: Nguyen

state: FL

department: Tumor Biology

institute: Moffitt Cancer Centre & Research Institute

summary: Earlier studies had shown that side population cells isolated from established non-small cell lung cancer (NSCLC) cell lines exhibit cancer stem cell properties. Microarray data from side population (SP) and main population (MP) cells isolated from 4 NSCLC lines (A549, H1650, H460, H1975) were used to examine gene expression profiles associated with stemness. Total RNA extracted from SP and MP samples were used to generate cRNA targets, which were hybridized to Human Genome U133 Plus 2.0 probe arrays. Raw data was processed and the mean center expression level for each gene was determined.

overall_design: Four cell lines (A549, H1650, H460, H1975), each having 1 SP and 1 MP sample.

first: Deepak

last: Perumal

first: Sandeep

last: Singh

first: Sean

last: Yoder

first: Gregory

last: Bloom

first: Srikumar

middle: P

last: Chellappan


title: OTX2 drives medulloblastoma proliferation via direct regulation of cell cycle genes and inhibits differentiation

status: Public on Jul 04 2012

city: Amsterdam

first: Richard

last: Volckmann

state: Noord-Holland

address: van der Boechorststraat 6a

department: Laboratory of Experimental Oncology and Radiobiology

institute: msterdam UMC and University of Amsterdam

summary:
The transcription factor OTX2 has been implicated as an oncogene in medulloblastoma, which is the most common malignant brain tumor in children. It is highly expressed in most medulloblastomas and amplified in a subset of them. The role of OTX2 in medulloblastoma and its downstream targets are unclear. Therefore, we generated D425 medulloblastoma cells in which we can silence endogenous OTX2 by inducible shRNA. Silencing of OTX2 strongly inhibited cell proliferation and resulted in a neuronal-like differentiation. Expression profiling of time courses after silencing showed a progressive change in gene expression for many cellular processes. Down regulated genes were highly enriched for cell cycle and visual perception genes, while up regulated genes were enriched for genes involved in development and differentiation. This shift in expression profiles is reminiscent to changes described to occur during normal cerebellum development. OTX2 is expressed in proliferating granular progenitor cells, but the expression diminishes when these cells exit the cell cycle and start differentiating. ChIP-on-chip analyses of OTX2 in D425 cells showed that cell cycle and perception genes were direct OTX2 targets, while regulation of most differentiation genes appears to be indirect. These analyses provide the first insight in the molecular network of OTX2, demonstrating that OTX2 is essential in medulloblastoma and directly drives proliferation by regulating the expression of cell cycle genes. Since many of these genes also correlate in expression with OTX2 in primary tumors, they might be potential targets for therapy in medulloblastoma patients.
Keywords: OTX2, medulloblastoma, mRNA profiling

overall_design:
*** This Series represents the gene expression component of the study.

Three independent time course experiments of OTX2 silencing, and 1 control experiment in D425 medulloblastoma cells.

first: Jens

last: Bunt

first: Nancy

last: Hasselt

first: Danny

last: Zwijnenburg

first: Mohamed

last: Hamdi

last: Koster

first: Rogier

last: Versteeg

first: Marcel

last: Kool


title: Expression data of A375 melanoma cells after DMSO or MLN4924 +/- Nutlin treatment for 26 hours

city: Cambridge

first: Hugues

last: Bernard

state: MA

address: 35 Landsdowne St.

department: Molecular Pathology

institute: Millennium: The Takeda Oncology company

summary:
Microarrays were used to determine the change in gene expression of genes involved in the p53 pathway after siRNA knock down of p53, CDT1 or BRCA1
A375 cells were grown, transfected with siRNA, incubated for 48hrs, then incubated for another 26hrs in the presence of either 0.065% DMSO as control, 650nM MLN4924, 5uM Nutlin or 100nM Daunorubicin. RNA extraction and hybridization on Affymetrix HG-U133Plus 2.0 arrays were performed.

overall_design: 12 conditions in triplicate for a total of 42 samples

first: Eric

middle: S

last: Lightcap

last: Blank


title: Gene expression profiling in BCR-ABL expressing LSCs and BCR-ABL-BLK expressing LSCs

city: Worcester

first: shaoguang

last: li

address: 364 Plantation street

department: medicine

institute: Umass medical school

summary: Using BCR-ABL-induced chronic myeloid leukemia (CML) as a disease model for leukemia stem cells (LSCs), we showed that BCR-ABL down-regulates the B lymphoid kinase (Blk) gene in leukemia stem cells in CML mice and that Blk functions as a tumor suppressor in LSCs and suppresses LSC function. Inhibition of this Blk pathway accelerates CML development, whereas increased activity of the Blk pathway delays CML development. To identify the pathways in which Blk regulates function of LSCs, we performed a comparative DNA microarray analysis using total RNA isolated from non-BCR-ABL-expressing Lin-Sca-1+c-Kit+, BCR-ABL- and BCR-ABL-Blk expressing LSCs. This analysis revealed a large group of candidate genes that exhibited changes in the levels of transcription in the Blk expressing LSCs, and uncovered the molecular mechanisms by which Blk suppresses LSCs and CML development.

overall_design: Bone marrow cells were transduced with GFP, BCR-ABL-GFP or BCR-ABL-Blk-GFP, followed by transplantation into recipient mice. Fourteen days after transplantation, bone marrow cells were isolated and LSCs were sorted by FACS for isolation of total RNA for DNA microarray analysis.

first: Shaoguang

last: Li

first: Haojian

last: Zhang


title: HCT116 colon cancer CRC in high and low glucose

city: Stanford

last: Sweet-Cordero

state: CA

address: CCSR-1215B, 269 Campus Dr

department: Pediatrics

institute: Stanford University

summary: HCT116 Kras WT and Kras G13D isogenic pair cell lines were cultured in either 25 mM or 1 mM for one week.

overall_design: Two independent replicate samples for each cell line and for each treatment were profiled using Affymetrix HG U133 plus 2.0 arrays

first: Alejandro


title: A new classification of chromosome instability (CIN) phenotype, CIN-high and CIN-low

city: Bunkyo-ku

first: Toshiaki

last: Watanabe

state: Tokyo

department: Department of Surgical Oncology

institute: University of Tokyo

summary: Samples were taken from colorectal cancers in surgically resected specimens in 35 colorectal cancer patients. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for molecular markers for CIN phynotype.

overall_design:
Specimens from 35 consecutive stage II and stage III patients who had undergone surgical resection of CRC were studied. Patients with familial adenomatous polyposis and HNPCC were excluded from the study. Specimens from tumors and corresponding normal tissues in surgically resected specimens were snap-frozen in liquid nitrogen and stored at -80 ºC until use. Parallel tumor specimens were formalin fixed and paraffin embedded for histological examination. DNA and RNA was extracted from paired tumor and normal tissue using frozen samples. The patients provided written, informed consent to the collection of specimens, and the local Ethics Committee approved the study protocol. MSI and LOH phenotype analysis were done as follows;
Using DNA, we performed the polymerase chain reaction (PCR) and determined the MSI status. In addition to five microsatellite markers recommended by the National Cancer Institute workshop, we also used TP53, D18S46, D18S363 and D18S474.9  We determined LOH status in non–MSI-high tumors, because LOH is rare in MSI-high tumors and also interpretation of LOH is difficult in MSI-high tumors. We defined LOH at each locus as a 50% reduction in the height of one of two allele peaks in tumor DNA relative to non-neoplastic control DNA. LOH was defined as present if any of the markers on the same chromosome show LOH. In order to evaluate the severity of chromosomal instability based on the actual frequency of LOH among evaluable loci, we defined the LOH Ratio (%) as:
LOH Ratio (%) = Total number of chromosomes with LOH / Total number of chromosomes that could be evaluated for LOH × 100. Depending on the LOH Ratio, we classified tumors as having high levels of chromosomal instability (CIN-high) (33%  < LOH Ratio < 100%) or low levels of chromosomal instability (CIN-low) (0% < LOH Ratio <33%). Furthermore, CIN-high tumors were divided into two subgroups; CIN-high (mild type) (33% < LOH Ratio < 75%) and CIN-high (severe type) (75% < LOH Ratio <100%).

first: Takashi

last: Kobunai

first: Eriko

last: Hashimoto


title: Gene expression profile of phagocyticially challenged human trabecular meshwork cells under physiolgical and oxidative stress conditions

status: Public on Jun 30 2012

city: Durham

first: Paloma

last: Liton

state: NC

address: PO Box 3802

department: Ophthalmology

institute: Duke University

summary: In theses experimetns we have analized the differential gene expression profile in human trabecular meshwork cells phagocytically challenged to E. coli and pigment under physiological and oxidative stress conditions using affymetrix microarrays

overall_design: HTM cells grown for two weeks either at 5% oxygen concentration or 40% oxygen concentration were phagocytically challenged to either E.coli or pigment. Changes in gene profile were analyzed at day 2.

first: Kristine

last: Porter


title: Comparison of gene expression alterations induced by distinct PI3K inhibitors

city: Basel

first: Saskia

middle: Maria

last: Brachmann

address: Klybeckstrasse 141

department: Oncology Basel

country: Switzerland

institute: NIBR

summary:
The goal is the characterization of the off-target activity of BKM120 observed in A2058 human melanoma cell line at IC90 concentration (3.606 µM) but not at lower concentrations. Controls are BEZ235, GDC0941, showing no off-target activity.
A secondary objective is the characterizations of drug effects on transcript expression with respect to a control treatment (DMSO) of those PI3K inhibitors.

overall_design: 3 compounds, 3 concentrations per compound treatment, DMSO control treatement, 4 biological replicates

first: Swann

last: Gaulis


title: Expression data from hESCs expressing RB7LP or T121

status: Public on Jun 29 2012

first: Julien

last: Sage

address: 265 Campus Drive, SIM1 G2078

summary:
We used microarray analysis to study the expression differences between controls and hESCs expressing RB7LP for 3 days, and controls and hESCs expressing T121 for 3 days. RB7LP is the large pocket fragment of the retinoblastoma protein (RB) fused to GFP,
in which seven phosphorylation sites for Cdk have been mutated (Angus, SP et al. Mol Cell Biol 23, 8172 (Nov, 2003). T121 is a truncated form of the SV40 Large T (LT) viral oncoprotein that inactivates the function of the three members of the retinoblastoma (RB) protein family (RB, p107, p130).

overall_design: We plated hESCs that had been infected with inducible lentiviruses to express either RB7LP or T121. The day after plating, one well from each virus was treated with doxycyline to induce expression of either RB7LP or T121 and after 3 days were harvested for microrarray analysis.

first: Jamie

last: Conklin


title: Nanomolar treatment with epigenetic drug combination induces genome-wide methylation and expression alterations in neuro-ectodermal cell lines [mRNA]

first: Floor

last: Duijkers

address: Dr. Molewaterplein 50-60 Ee15-02

department: Pediatric Oncology-Hematology

institute: Erasmus MC

summary: Abstract: Epigenetic alterations are a fundamental aspect of cancer cells, and epigenetic drugs are currently used in clinical practice for hematological malignancies. Pediatric neuro-ectodermal tumors originate from neural crest cells and show epigenetic defects of apoptotic pathways, which makes the introduction of epigenetic drugs in this patient category logical. However, the young age of these patients is accompanied by ongoing developmental processes which are regulated epigenetic mechanisms, and prompted us to study molecular effects of nanomolar dosage epigenetic drugs in neuro-ectodermal tumor cell lines.   Combination treatment of 5-aza-2`-deoxicytidine (DAC) and Trichostatin A (TSA) at nanomolar dosages resulted in wide-spread demethylating effects in 17 NBL and 5 PNET cell lines in vitro. This widespread demethylation had large effects on gene-expression profiles. In NBL cell lines, almost every cellular pathway (193/200) investigated demonstrated altered expression upon treatment, and resulted in upregulation of known epigenetically regulated genes such as X-chromosomal, tissue-specific, and a few imprinted genes. Integration analysis of CpG island methylation array data and whole genome gene expression data identified 30 genes potentially upregulated by gene promoter demethylation. Homeobox genes frequently showed demethylation in both short term (72 hours) and long term cultures (3 months) of NBL lines. Continuous treatment with epigenetic drugs resulted in low rates of proliferation. The low rate of proliferation that might explain limited consecutive demethylation upon prolonged exposure.  In conclusion, genome-wide methylation and gene expression changes are induced DAC and TSA treatment at nanomolar dosages. These effects affected more than 97% of cellular pathways investigated. Further studies towards the effects of epigenetic drug combinations are advised before being applied in clinical trials for pediatric patients.

overall_design: Comparison of gene expression profiles of neuro-ectodermal cell lines with and without DAC and TSA


title: Expression Data from siRae1 and siNT infected with VSV or mock infected

city: Winston-Salem

first: Jeff

last: Chou

address: Medical Center Blvd

institute: Atrium Health Wake Forest Baptist

summary: To test the effect of silencing Rae1 on expression on RNA polymerase II transcripts, host mRNAs were analysed by cDNA microarrays. We hypothesized that if silencing Rae1 expression increases cellular resistance to inhibition of transcription in VSV infected cells, mRNA characteristic of host antiviral response would be increased than compared to cells transfected with control siRNA.

overall_design: HeLa cells transfected with siRNA targeted against Rae1 (siRae1) or against non-targeting siRNA (siNT). The sequence of nontargeting (NT) siRNA is scrambled and does not match any sequence on the human genome. Transfected cells were either infected with VSV or mock infected. Six hours later RNA was extracted from the cells. Two separate experiments of such were analyzed by microarrays

first: Karishma

last: Rajani

first: Douglas

last: Lyles


title: Immune Clearance of Attenuated Rabies Virus Results in Neuronal Survival with Altered Gene Expression

status: Public on Jun 28 2012

city: Philadelphia

first: Sankar

last: Addya

address: 233 South 10th Street

department: Kimmel Cancer Center

institute: Thomas Jefferson University Hospital

summary: Rabies virus (RABV) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre) to switch neurons constitutively expressing tdTomato (red) to expression of a Cre-inducible EGFP (green), permanently marking neurons that had been infected in vivo. We were able to isolate these previously infected neurons (“infected”) by flow cytometry and assayed their gene expression profiles compared to uninfected cells (“uninfected”) from the same mice.

overall_design: Two cre reporter mice were infected intranasally with RABV-Cre, allowed to resolve the acute infection, and then sacrificed at 3 months post-infection. EGFP+ cells from the brains of these mice were collected by FACS and represent those infected with RABV (“Infected-1” and “Infected-2”); tdTomato+ cells collected from these same mice represent uninfected cells (“Uninfected-1” and “Uninfected-2”). RNA was collected from these samples for microarray analysis.

first: Emily

last: Gomme

first: Christoph

last: Wirblich

first: Glenn

last: Rall

first: Matthias

last: Schnell


title: Expression data from murine colon tissue after exposure to 4% DSS for 6 days DSS followed by 4 days of water or 1% L-arginine

status: Public on Jun 27 2012

city: Nashville

first: Keith

last: Wilson

address: 2215B Garland Ave.

institute: Vanderbilt University School of Medicine

summary: L-Arginine (L-Arg) is the substrate for both inducible nitric oxide synthase and arginase, which are upregulated in human IBD and in mouse colitis models. We have found that L-Arg supplementation enhances wound restitution in vitro, and improves the clinical parameters of weight loss, survival, and colon weight/length, in dextran sulfate sodium (DSS) induced murine colitis. Our aim was to further identify the potential mechanisms underlying the clinical benefit of L-Arg supplementation.

overall_design: 12 Total samples were analyzed, 3 samples from each of 4 groups. We generated the following pairwise comparisons: Ctrl vs Ctrl + L-Arg; Ctrl vs DSS; DSS vs DSS + L-Arg; Ctrl + L-Arg vs DSS, Ctrl + L-Arg vs DSS + L-Arg. Genes with a p-value < 0.01 and a fold-change ≥2 were selected. To identify genes that were altered in response to L-Arg, we performed the following multiple sample comparisons using a p-value < 0.01 and a fold-change ≥2: Ctrl vs DSS vs DSS + L-Arg

middle: T

first: Lori

last: Coburn

first: Zhongming

last: Zhao

first: Xue

last: Gong


title: Expression data for UPEC and GBS cystitis in female C57BL/6 mice

city: Gold Coast

first: Glen

last: Ulett

state: QLD

address: Parklands Drive

department: School of Medical Science

country: Australia

institute: Griffith University

summary:
Data defines for the first time a whole bladder transcriptome of UPEC cystitis in female C57BL/6 mice using genome-wide expression profiling and temporal analysis to map early host response pathways stemming from UPEC colonization
We used microarrays to detail the global programme of gene expression in GBS UTI in mice over time and in UPEC UTI in mice at 24h

overall_design:
Whole mouse bladder collected at 2h and 24h following transurethral infection for RNA extraction and hybridization on Affymetrix microarrays. Non-pooled samples were used, with one array per mouse to expand power of expression profiles. Control mice for each time point received only PBS as a mock infection. Group sizes were five mice per group, and therefore five arrays were used per group.
Whole mouse bladder collected at 24h following transurethral infection for RNA extraction and hybridization on Affymetrix microarrays. Non-pooled samples were used, with one array per mouse to expand power of expression profiles. Control mice for each time point received only PBS as a mock infection. Group sizes were five mice per group, and therefore five arrays were used per group.

first: Tan

last: Tan

first: Alison

middle: J

last: Carey


title: THP-1 cell study: RA and TNF Treatments; RA time course

city: University Park

first: A.

middle: Catharine

last: Ross

state: PA

address: 110 Chandlee Laboratory

department: Nutritional Sciences

institute: Penn State

summary: The study consisted of two experiments. The hypothesis tested was that RA and tumor necrosis factor (TNF)-alpha would independently and synergistically regulate the expression of genes in THP-1 human myeloid cells, and that RA alone would be a significant modulator, as tested in a kinetic experiment.

overall_design: Experiment 1 included 21 arrays from 4 groups of THP-1 cells. Biological replicates (n) equalled 6, 5, 5, and 5 samples/arrays, each representing an independent well of cultured cells: control (0.1% ethanol only); 20 nM RA for 16 h, followed by re-treatment after 24 h for a total time of 40 h; TNFalpha, 5 ng/ml for 24 h; RA, 20 nM for 16 h followed by treatment with RA and TNFalpha for 24 h, respectively. All cells were harvested at the 40 h time point. Experiment 2 was an RA time course study, without TNFalpha, which included 17 arrays from THP-1 cells treated with RA, 20 nM, at time 0 and cells were harvested at times of 0 (ethanol control), 2 hr, 6 hr, and 16 hr. After 16 hr, RA was added again to the remaining 2 wells, which were harvested at 40 h. The number of biological replicates was n=8, 2, 2, 3, and 2, respectively.


status: Public on Jun 25 2012

city: Bronx

first: Boris

last: Bartholdy

state: NY

address: 1300 Morris Park Ave

department: Cell Biology

institute: Albert Einstein College of Medicine

summary: Identification of differentially expressed genes upon treatment with Eltrombopag in HL60 cells. HL60 cells were untreated, or treated with 3ug/ml of Eltrombopag for 36 hrs in RPMI with 10% FBS

first: Britta

last: Will

first: Constantine

last: Mitsiades

first: Michael

last: Roth

first: Ulrich

middle: G

last: Steidl


title: Establishment of objective criteria for selecting relevant intestinal cell-based models

status: Public on Jun 24 2012

city: Berne

first: Pascale

last: Anderle

state: BE

address: Buehlstrasse 28

department: Institute of Biochemistry and Molecular Medicine

institute: University of Berne

summary: The objective of this study was to make use of gene expression signatures and functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium to assess their appropriateness as a tumor model or for drug absorption studies.

overall_design:
[Cell lines] Total RNA of biological replicate samples (i.e.different passages) from a  panel of cell lines was collected and resulting amplified cRNA hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays. Samples are labeled as follows: SampleNumber_CellLine.

[Laser dissected tumor cells (LDM)] Total RNA of three different samples laser dissected tumor cells, normal colonocytes, and enterocytes of ileum and two samples of jejunum was collected and resulting amplified cRNA hybridized to Affymetrix Human Genome U133 Plus 2.0 arrays. Samples are labeled as follows: SampleNumber_TissueType_Origin.

first: Jon

last: Christensen

first: Sara

last: El-Gebali

first: Manuela

last: Natoli

first: Thierry

last: Sengstag

first: Mauro

last: Delorenzi

first: Susanne

last: Bentz

first: Hanifa

last: Bouzourene

first: Martin

last: Rumbo

first: Armando

last: Felsani

first: Sanna

last: Siissalo

first: Jouni

last: Hirvonen

first: Maya

middle: R

last: Vila

first: Piercarlo

last: Saletti

first: Michel

last: Aguet


title: Nanomolar treatment with epigenetic drug combination induces genome-wide methylation and expression alterations in neuro-ectodermal cell lines

city: Rotterdam

first: Floor

last: Duijkers

type: Methylation profiling by genome tiling array

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Molecular profiles for GTL16 cell lines

status: Public on Jun 22 2012

city: San Diego

first: Keith

last: Ching

address: 10777 Science Center Dr.

department: Computational Sciences

institute: Pfizer, Inc.

type:
Genome variation profiling by SNP array
Expression profiling by array

summary: Gene expression and copy number variation arrays for parental GTL16 and GTL16 clones resistant to c-Met inhibitor.

overall_design: Affymetrix U133 Plus 2.0 and SNP 6.0 chips were used to assess gene expression and copy number variation, respectively, of GTL16 and resistant GTL16 clones.

first: Nathan

middle: V

last: Lee

first: Maruja

middle: E

last: Lira

first: Adam

last: Pavlicek

first: Jingjing

last: Ye

first: Dana

last: Buckman

first: Shubha

last: Bagrodia

first: Sreesha

last: Srinivasa

first: Yongjun

last: Zhao

first: Samuel

last: Aparicio

first: Paul

last: Rejto

first: James


title: Janus-Like Opposing Roles of CD47 in Autoimmune Brain Inflammation in Human and Mice

first: May

last: Han

address: 1201 Welch Road

summary: Gene transcripts and proteins expressed during disease pathogenesis identify targets for therapy. We performed microarray analysis of histologically characterized multiple sclerosis (MS) brain lesions in comparison with control brain samples to identify differentially expressed molecules. We identified CD47 as a target of interest and studied its biology in MS and EAE.

overall_design: We isolated total RNA from acute plaque (AP), chronic active plaque (CAP) and chronic plaque (CP) from MS brains and white matter from healthy controls and performed microarray studies.

first: Deborah

last: Lundgren

first: Siddhartha

last: Jaiswal

first: Mark

last: Chao

first: Kareem

last: Graham

first: Robert

middle: C

last: Axtell

first: Peggy

last: Ho

first: Christopher

middle: B

last: Lock

first: Joslyn

middle: I

last: Woodward

first: Sara

last: Brownell

first: Maria

last: Zondilova

first: Jack

last: Hunt

first: Servio

last: Baranzini

first: Eugene

last: Butcher

first: Cedric

last: Raine

first: Raymond

last: Sobel

first: David

first: Irving

last: Weissman

first: Lawrence

last: Steinman


title: Severe acute respiratory syndrome coronavirus envelope protein regulates cell stress responses and apoptosis

status: Public on Jun 21 2012

city: Cantoblanco

first: Juan

middle: Carlos

last: Oliveros

state: Madrid

address: Darwin 3

institute: CNB, CSIC

summary: Severe acute respiratory syndrome virus (SARS-CoV) that lacks the envelope (E) gene (rSARS-CoV-ΔE) is attenuated in vivo [1,2]. To identify factors that contribute to rSARS-CoV-ΔE attenuation, gene expression in cells infected by SARS-CoV with or without E gene was compared. Twenty-five stress response genes were preferentially upregulated during infection in the absence of the E gene. In addition, genes involved in signal transduction, transcription, cell metabolism, immunoregulation, inflammation, apoptosis and cell cycle and differentiation were differentially regulated in cells infected with rSARS-CoV with or without the E gene. Administration of E protein in trans reduced the stress response in cells infected with rSARS-CoV-ΔE, with respiratory syncytial virus, or treated with drugs, such as tunicamycin and thapsigarcin that elicit cell stress by different mechanisms. In addition, SARS-CoV E protein down-regulated the signaling pathway inositol-requiring enzyme 1 (IRE-1) of the unfolded protein response, but not the PKR-like ER kinase (PERK) or activating transcription factor 6 (ATF-6) pathways, and reduced cell apoptosis. Overall, the activation of the IRE-1 pathway was not able to restore cell homeostasis, and apoptosis was induced probably as a meassure to  protect the host by limiting virus production and dissemination. The expression of proinflammatory cytokines was reduced in rSARS-CoV-ΔE-infected cells compared to rSARS-CoV-infected cells, suggesting that the increase in stress responses and the reduction of inflammation in the absence of the E gene contributed to the attenuation of rSARS-CoV-ΔE.

overall_design: We used Affymetrix microarrays (Human Genome U133 plus 2.0) to compare global gene expression between SARS-CoV-infected, mock-infected and SARS-CoV-ΔE-infected cells. For ech type of sample three hybridizations were carried-out (independent biological replicates).

first: Marta

middle: L

last: DeDiego

first: José

last: Nieto-Torres

middle: M

last: Jiménez-Guardeño

last: Regla-Nava

first: Enrique

last: Álvarez

first: Jincun

last: Zhao

first: Craig

last: Fett

first: Stanley

last: Perlman

first: Luis

last: Enjuanes


title: Changes in Global Gene Expression Associated with 3D Structure of Tumors: an ex vivo Matrix-Free Mesothelioma Spheroid Model

city: Bethesda

first: Mitchell

last: Ho

state: MD

address: 37 Convent Drive, MSC 4264

department: Laboratory of Molecular Biology

institute: National Cancer Institute, NIH

summary: Tumor microenvironments present significant barriers to anti-tumor agents. Molecules involved in multicellular tumor microenvironments, however, are difficult to study ex vivo. Here, we generated a matrix-free tumor spheroid model using the NCI-H226 mesothelioma cell line and compared the gene expression profiles of spheroids and monolayers using microarray analysis. Microarray analysis revealed that 142 probe sets were differentially expressed between tumor spheroids and monolayers. Gene ontology analysis revealed that upregulated genes were primarily related to immune response, wound response, lymphocyte stimulation and response to cytokine stimulation, whereas downregulated genes were primarily associated with apoptosis. Among the 142 genes, 27 are located in the membrane and related to biologic processes of cellular movement, cell-to-cell signaling, cellular growth and proliferation and morphology. Western blot analysis validated elevation of MMP2, BAFF/BLyS/TNFSF13B, RANTES/CCL5 and TNFAIP6/TSG-6 protein expression in spheroids as compared to monolayers. Thus, we have reported the first large scale comparison of the transcriptional profiles using an ex vivo matrix-free spheroid model to identify genes specific to the three-dimensional biological structure of tumors. The method described here can be used for gene expression profiling of tumors other than mesothelioma.

overall_design: We generated a matrix-free tumor spheroid model using the NCI-H226 mesothelioma cell line and compared the gene expression profiles of spheroids and monolayers using microarray analysis. Microarray analysis experiments were performed in triplicates. A total of six samples (three for monolayers and three for spheroids) were analyzed.

first: Heungnam

last: Kim

first: Yen

last: Phung


title: Patterns of cancer development and progression in the protein-protein interaction network

city: Barcelona

first: Miguel Angel

last: Pujana

address: Gran Via 199

institute: Institut Catala d'Oncologia IDIBELL

summary: For this study we selected a gene, α-synuclein (SNCA), that is consistently under-expressed in MCF7 cells and breast tumors. Following transfection with an SNCA expression construct, two stable MCF7 clones (named MCF7-SNCA #1 and 2) were selected and examined for expression differences relative to the parental MCF7 cells.

overall_design: MCF7 cells were transfected with an expression vector containing the full-length SNCA sequence. After selection with blasticidin, two different clones were isolated and examined for expression differences relative to the parental MCF7 cells.

first: Helena

last: Aguilar

first: Miguel

middle: A


title: smallRNA profiling of THP1 cell line

city: New York

first: Brian

last: Brown

address: 1470 Madison Avenue

department: Genetics and Genomic Sciences

institute: Icahn School of Medicine at Mount Sinai

type: Non-coding RNA profiling by high throughput sequencing

summary: Analysis of smallRNA in THP1 (human monocytic leukemia) cell line in order to correlate miRNA activity with target abundance.

overall_design: THP1 smallRNA profiles were generated in triplicates by deep-sequencing in Illumina HiSeq2000.

middle: D

first: Ravi

last: Sachidanandam


title: Transcription profiling of human colon Caco-2 cells treated with hydroxytyrosol (HTy) and hydroxytyrosyl ethyl ether (HTy-Et)

status: Public on Jun 20 2012

city: Jaén

first: Gema

last: Pereira-Caro

state: Jaén

address: Ctra. Bailén Motril, km 18.5

institute: IFAPA

summary:
The anticarcinogenic activity of hydroxytyrosyl ethyl ether (HTy-Et) compared to its precursor hydroxytyrosol (HTy) has been studied in human Caco-2 colon adenocarcinoma cells.
Changes in global gene expression in Caco-2 cells exposed to HTy and HTy-Et for 24 h were evaluated using Affymetrix array.
Microarray analysis showed that after exposure to HTy and HTy-Et, 451 and 977 genes respectively were differentially expressed compared with untreated cells (P < 0.005; FDR=0). Results show that HTy and its lipophilic ether derivative alter genes related with cancer prevention, which includes inducing cell cycle arrest, promoting apoptosis and enhancing xenobiotic metabolism.

overall_design: Caco-2 cells were treated with 10 μM of HTy and HTy-Et for 24 h, and total RNA from 3 biological replicates of each treatment together with the control cells, were isolated using a QIAGEN® RNeasy Mini Kit according to the manufacturer’s instructions (Qiagen). RNA samples of each of the replicates were processed using Affymetrix Human HG-U133 Plus 2.0 microarrays (Affymetrix).

first: Raquel

last: Mateos

first: Maria

middle: H

last: Traka

first: James

last: Bacon

first: Roy

last: Bongaerts

first: Beatriz

last: Sarriá

first: Laura

last: Bravo

first: Paul

last: Kroon


title: Ethanolamine gene regulation in EHEC

status: Public on Jun 18 2012

city: Dallas

first: Melissa

last: Kendall

state: TX

address: 5323 Harry Hines Blvd.

department: Microbiology

institute: U.T. Southwestern Medical Center at Dallas

summary: Bacterial pathogens must be able to both recognize suitable niches within the host for colonization and successfully compete with commensal flora for nutrients in order to establish infection. Ethanolamine (EA) is a major component of mammalian and bacterial membranes and may be used by pathogens as a carbon and/or nitrogen source in the gastrointestinal tract. We examined how EA influences gene expression in the human pathogen enterohemorrhagic Escherichia coli O157:H7 (EHEC).  Our results indicate EA is not only important for nitrogen metabolism, but that EA is used in cell-to-cell signaling to activate virulence gene expression. Genes encoding for the global regulatory proteins QseC, QseE, and QseA, as well as for attaching and effacement (AE) lesion formation and Shiga toxin are differentially regulated when EHEC is grown with micromolar concentrations of EA. We also constructed a deletion of eutR that encodes the regulator of the eut (EA utilization) operon and examined virulence gene expression. These results suggest that EutR is important in regulating gene expression in response to EA, but that EA signaling does not occur solely through EutR. This is the first report linking EA to cell-to-cell signaling and pathogenesis.

overall_design: Design of the study was to compare the transcriptional response of WT cells grown with ethanolamine to that of wild type cells grown without ethanolamine.

first: M

first: C

last: Gruber

first: V

last: Sperandio


title: Expression data from 2C::tomato+ vs 2C::tomato - ES cells

city: La Jolla

first: Todd

last: Macfarlan

address: 10010 North Torrey Pines

institute: The Salk Institute

summary:
We compared gene expression from 2C::tomato+/- ES cells from Kdm1a wt and mutant ES cultures
2C::tomato-   samples  1, 5, 9
2C::tomato+  samples  2, 6, 10

overall_design: We collecteded 3 replicates of RNA from  2C::tomato+ and - ES cells


title: Modulation of gene expression in cultured human intestinal colon explants by probiotic bacteria

city: Burjassot (Valencia)

first: Gaspar

last: Perez Martinez

state: Valencia

address: P.O. Box 73

department: Food Biotechnology

institute: Institute of Agrochemistry and Food Technology (CSIC)

summary: Background: In the last decade, much attention has been drawn to probiotic bacteria in the context of inflammatory bowel disease (IBD), since the potential of certain strains to attenuate inflammation was demonstrated in several animal experiments and clinical studies. Data in humans elucidating the molecular mechanism of probiotic action are still scarce. To this end, we used an organ culture system of human colon mucosa and investigated the gene expression profiles after treatment with different probiotic bacteria in phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO)) stimulated samples using whole genome microarrays. Moreover, we analyzed changes occurring in the intestinal explants cultured for 8 hours when compared to fresh, directly frozen mucosa, in order to infer the suitability of the system to study an inflammatory stimulus and likely antiinflammatory responses. Results: Culturing intestinal colon fragments during 8 hours elicited differential gene expression in 283 genes, 229 upregulated and 54 downregulated. Upregulated genes were predominantly related to apoptosis, whereas downregulated genes encoded mitochondrial proteins. No specific enrichment of genes related to inflammation or immune response could be detected, confirming the suitability of the system to further study the inmunomodulatory/anti-inflammatory properties of Lactobacillus casei BL23 (BL23), L.plantarum 299v (LP299v) and L.plantarum 299v (A-) (LP299v (A-)), a mutant strain with reduced adhesive properties to enterocytes. Intestinal explants were stimulated with PMA/IO for 3 hours and subsequently incubated with probiotic bacteria for 4 h. ANOVA analysis (p ≤ 0,01) revealed 205 differentially expressed genes between Control, PMA/IO (Inflamed), and the 3 bacterial treatments. Most importantly, a number of PMA/IO induced genes related to immune response and immune system process such as IL-2, IFN-γ, IL17A and pro-inflammatory cytokines CXCL9 and CXCL11 were downregulated by BL23, LP299v and LP299v (A-). The behaviour of the three Lactobacillus strains was quite similar, although their presence induced differential expression of a small number of genes in a strain dependent manner. Conclusion: The human colon organ culture was found to be a suitable model for the study of inflammatory/anti-inflammatory stimuli, and therefore it constitutes a valuable tool to determine the inmunomodulatory effect of probiotic bacteria. The global transcriptional profile evoked by strains BL23, LP299v and LP299v (A-) in artificially inflamed tissue indicated a clear homeostasis restoring effect, including a decrease of the signals produced by activated T cells.

overall_design: Macroscopically healthy colonic intestinal tissue was obtained at surgery from 3 patients. Intestinal explants were treated with PMA and ionomycin for 3 h to induce pro-inflammatory conditions. Then, culture medium was changed and replaced with either medium or medium containing either Lactobacillus casei BL23, Lactobacillus plantarum 299v, or a nonadherent mutant of L. plantarum 299v (A-) and incubated for further 4 hours. In parallel, control intestinal explants were cultured without any treatment of PMA/ionomycin or probiotic bacteria and compared to directly frozen tissue in order to evaluate changes in gene expression which are due solely to the culture conditions.

first: Christine

last: Bäuerl

first: Marta

last: Llopis

first: María

last: Antolín

first: Vicente

last: Monedero

first: Manuel

last: Zúñiga

last: Mata

first: Francisco

last: Guarner

last: Pérez Martínez


title: Cooperative and antagonistic roles for Irx3 and Irx5 in cardiac morphogenesis and postnatal physiology

city: San Francisco

first: Nathalie

last: Gaborit

address: 1650 Owens Street

institute: the J. David Gladstone Institute

summary: Analysis of the roles of Irx3 and Irx5 transcription factors in mouse heart development and postnatal heart function. Results show that show that Irx3 and Irx5 have redundant function in the in the endocardium to regulate atrioventricular canal morphogenesis and outflow tract formation. A postnatal deletion of Irx3 and Irx5 surprisingly results in a restoration of the repolarization gradient that is altered in Irx5 mutant hearts, suggesting a model whereby postnatal Irx3 activity is normally repressed by Irx5.

overall_design: 4 genotypes were analyzed: Irx5+/- (3 samples), Irx3-/-;Irx5+/- (4 samples), Irx5-/- (3 samples), Irx5-/-;Irx3-/- (4 samples). The Irx5+/- samples are the reference.

first: Rui

last: Sakuma

first: John

middle: N

last: Wylie

first: Kyoung-Han

last: Kim

first: Shan-Shan

last: Zhang

first: Chi-Chung

last: Hui

first: Benoit

last: Bruneau


title: Transcriptome Analysis Identifies Fn14, a TNF Superfamily Receptor Member, as a Therapeutic Target in Alcoholic Hepatitis

status: Public on Jun 15 2012

first: Juanjo

last: Lozano

address: C/ Rosselló 153

department: Plataforma de Bioinformatica

institute: CIBEREHD

summary: Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease and occurs in patients with excessive alcohol intake It is characterized by marked hepatocellular damage, steatosis and pericellular fibrosis. Patients with severe AH have a poor short-term prognosis. Unfortunately, current therapies (i.e. corticosteroids and pentoxyphylline) are not effective in many patients and novel targeted therapies are urgently needed. The development of such therapies is hampered by a poor knowledge of the underlying molecular mechanisms. Based on studies from animal models, TNF alfa was proposed to play a pivotal role in the mechanisms of AH.   Consequently, drugs interfering TNF alfa were tested in these patients. The results were disappointing due to an increased incidence of severe infections. Unluckily, there are not experimental models that mimic the main findings of AH in humans. To overcome this limitation, translational studies with human samples are required. We previously analyzed samples from patients with biopsy-proven AH. In these previous studies, we identified CXC chemokines as a potential therapeutic target for these patients. We expanded these previous observations by performing a high-throughout transcriptome analysis.

overall_design: Hepatic gene expression profiling was assessed by DNA microarray in patients with Alcoholic hepatitis (n=15) and normal livers (n=7).

first: S

last: Affo

first: M

last: Dominguez

first: J

first: P

last: Sancho-Bru

first: D

last: Rodrigo-Torres

first: O

last: Morales-Ibanez

last: Moreno

first: C

last: Millán

first: A

last: Loaeza

last: Altamirano

last: Garcia-Pagán

last: Arroyo

last: Ginès

last: Caballería

first: R

last: Bataller


title: Multilineage dysplasia does not influence prognosis in patients with CEBPA mutated AML supporting the WHO proposal to classify these patients as a unique entity

city: Munich

first: Andreas

last: Roller

address: Max-Lebsche-Platz 31

institute: Munich Leukemia Laboratory

summary: By WHO 2008, CEBPA-mutated AML became a provisional subentity, but it remains to be clarified how CEBPAmut AML with multilineage dysplasia (MLD; ≥50% dysplastic cells in 2-3 lineages) but no other MDS-related feature should be classified. We investigated 108 CEBPAmut AML (15.7-87.6 years) for the impact of MLD and genetic features. MLD-positive patients differed from MLD-negative only by lower mean WBC counts (p=0.004), but not by other blood values, biologic characteristics, cytogenetic risk profiles, or additional molecular markers (NPM1mut, FLT3-ITD/TKD, RUNX1, MLL-PTD, IDH1/2). Biallelic CEBPAmut differed from wild-type-cases by differential expression of 213 genes, but did not differ significantly between MLD-positive/-negative patients. Survival outcomes were improved for females and those <60 years, intermediate versus adverse karyotypes (p=0.021), and for  biallelic versus monoallelic/homozygous CEBPAmut (p=0.060) in case of FLT3-ITD-negativity. In contrast, 2-year OS (MLD+: 56.5%; MLD-: 65.5%) and 2-year EFS (MLD+: 13.8 months; MLD-: 16.3 months) did not differ significantly between MLD-positive/-negative patients. By univariable Cox regression analysis, gender, age, WBC count and MRC-cytogenetic risk category only were prognostically relevant for OS, while MLD was  irrelevant. Therefore, CEBPAmut AML patients should be characterized only according to mut-status, cytogenetic risk groups, or additional mutations, whereas dysplasia is not relevant for this subtype.

overall_design: The sample preparation assay for gene expression profiling using Affymetrix HG-U133 Plus 2.0 microarrays and subsequent data analysis were previously described. Only cases with biallelic CEBPA mutations were investigated by gene expression profiling due to previous reports that only double mutated cases conferred a specific gene expression signature, while monoallelic cases could not be discriminated from CEBPA wild-type cases. We performed comparison of gene expression profiles of 20 cases with biallelic CEBPA mutations and of 10 cases without CEBPA mutations.

first: Ulrike

last: Bacher

first: Susanne

last: Schnittger

first: Katja

last: Macijewski

first: Vera

last: Grossmann

first: Alexander

last: Kohlmann

first: Tamara

last: Alpermann

last: Kowarsch

first: Wolfgang

last: Kern

first: Claudia

last: Haferlach

first: Torsten


title: Identify the downstream targets of Stat3 by using an engineered mouse ES cell line treated with GCSF and LIF plus PD0325901

status: Public on Jun 14 2012

city: los angeles

first: Qilong

last: Ying

address: 1425 san pablo st BCC509b

institute: USC

summary: To identify downstream targets of Jak/Stat3 pathways without being distracted by differentiation signalings from MEK/ERK pathway, we exploited a engineered B6 cells, which stably stably expressing a chimeric receptor (GRgp-Y118F). The chimeric receptor can induce the phosphorylation of Stat3 by GCSF without activating the MEK/ERK pathway. To mimic the effect of GCSF, the chimeric B6 cells were also treated with LIF plus a selective MEK chemical inhibitor, PD0325901, to induce LIF/Jak/Stat3 but MEK/ERK pathways.

overall_design: mESCs starved in serum free growth medium for 6hrs were treated with GCSF or with LIF plus PD0325901 for 1hr, after which total RNA was extracted for analysis.

first: Chihi

last: Tai


title: Gene expression profiling of generated Erlotinib-resistant (ER) cell lines

status: Public on Jun 16 2012

first: Elton

last: Chan

state: California

address: 600 16th Street Rm N216R

department: Medicine

institute: UCSF

summary:
Targeted therapies have provided advantages to cancer patients, but these therapies are limited by differential responses and developed resistance.
To discover mechanisms of resistance, we developed drug-resistant cell lines and have their gene expressions profiled and compared.

overall_design: HCC827 cells, which were initially sensitive to Erlotinib treatment, are subjected to Erlotinib treatment. Two clonal populations that resistant to Erlotinib resulted.

first: Zhenfeng

last: Zhang

first: Jae

last: Lee

first: Valerie

last: Au

first: Thomas

last: LaFramboise

first: Mohamed

last: Abdel-Rahman

first: Xiaoqi

last: Wang

first: Alan

last: Levine

first: Jin

middle: K

last: Rho

first: Yun

last: Choi

first: Chang-Min

first: Sang-We

last: Kim

first: Se

last: Jang

first: Young

middle: S

last: Park

first: Vincent

last: Miller

first: Maria

last: Arcila

first: Marc

last: Ladany

first: Philicia

last: Moonsamy

first: Charles

last: Sawyers

first: Patrick

last: Ma

first: Carlota

last: Costa

first: Miquel

last: Taron

first: Rafael

last: Rosell

first: Balazs

last: Halmos

first: Trever

last: Bivona


title: Androgen regulated gene expression in human prostate

city: Oulu

first: Markku

last: Vaarala

address: Aapistie 5

department: Department of Surgery

country: Finland

institute: University of Oulu

summary:
Androgens are a prequisite for the development of human prostate and prostate cancer. Androgen action is mediated via androgen receptor. Androgen ablation therapy is used for the treatment of metastasized prostate cancer. The aim of the study was to identify genes differentially expressed in benign human prostate, prostate cancer and in prostate tissue three days after castration. These genes are potential diagnostic and therapeutic targets for prostate cancer and benign prostatic hyperplasia.
We used microarrays to examine the gene expression profiles in benign prostate adjacent to prostate cancer and prostate cancer in radical prostatectomy specimens and in prostate tissue samples taken 3 days after surgical castration performed for treatment of prostate cancer.

overall_design: Human prostate tissue was obtained from radical prostatectomy samples and from prostate biopsy samples (castrated samples). Benign and malignant tissues samples were microdissected from prostatectomy samples. Tissues were used for RNA isolation and were further processed as samples for microarray. Three prostatectomy samples were used as replicates (benign and malignant prostate). All prostate cancers were Gleason 3+3 pattern. Castrated tissue samples were taken from patients three days after surgical castration for the treatment of advanced or metastasized prostate cancer. Six biopsies were taken from each subject and individual subject samples were used as three replicates in microarray.

first: Pasi

last: Hirvikoski

first: Saila

last: Kauppila

first: Jussi

middle: T

last: Vuoristo

first: Timo

last: Paavonen


title: Gene expression profile of murine intestinal epithelial cells after RANKL treatment

status: Public on Jun 17 2012

city: Yokohama

first: Takashi

last: Kanaya

address: 1-7-22, Suehiro-cho, Tsurumi-ku

institute: RIKEN

summary:
RANKL (receptor acrivator of NFkB ligand) is a member of TNF superfamily cytokines. In the gastrointestinal tract, RANKL is expressed in the stromal cells of Peyer's patches, and involved in the development of the specialized intestinal epithelial cells, called M cells.
To identify the genes involved in M-cell development, we treated BALB/c mice with recombinant GST-RANKL. After RANKL-treatment, epithelial cells were isolated from small intestine, and used for microarray analysis.

overall_design: Total of 15 samples were analyzed. We generated the Excel sheet for comparing gene expression.

first: Ifor

last: Williams

first: Hiroshi

last: Ohno


title: Gene expression in human germinal center light zone and dark zone B cells

city: Cambridge

first: Gabriel

last: Victora

address: 9 Cambridge Center

institute: Whitehead Institute

summary:
Microarrays of gene expression in human germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4
We used microarray data to identify genes differentially expressed by B cells in the light and dark zones of germinal centers from human tonsil specimens.

overall_design: Germinal center B cells (CD19+CD38+IgD-) were sorted from pediatric tonsil discard specimens into light zone (CXCR4hi/CD83lo) and dark zone (CXCR4lo/CD83hi) populations, from which RNA was extracted

first: David

last: Dominiguez-Sola

first: Riccardo

last: Dalla-Favera

first: Michel

last: Nussenzweig


title: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (genomic SEQ)

status: Public on Jun 12 2012

city: Marseille

first: Romain

last: Fenouil

address: Parc Scientifique et Technologique de Luminy - Case 906

department: CIML

institute: CNRS

type: Genome binding/occupancy profiling by high throughput sequencing

summary: One clear hallmark of mammalian promoters is the presence of CpG islands (CGIs) at more than two thirds of genes whereas TATA boxes are only present at a minority of promoters. Using genome-wide approaches, we show that GC content and CGIs are major promoter elements in mammalian cells, able to govern open chromatin conformation and support paused transcription. First, we define three classes of promoters with distinct transcriptional directionality and pausing properties which correlate with their GC content. We further analyze the direct influence of GC content on nucleosome positioning and depletion, and show that CGIs correlate with nucleosome depletion both in vivo and in vitro. We also show that transcription is not essential for nucleosome exclusion but influences both a weak +1 and a well-positioned nucleosome at CGI borders. Altogether our data support the idea that CGIs have become an essential feature of promoter structure defining novel regulatory properties in mammals.

overall_design:
Nucleosome density and positioning were studied by high-throughput sequencing of DNA previously treated with Mnase. In parallel, chIPseq for PolII and H3K27ac  were performed in mouse and human with different conditions to assess a potential effect of transcription on nucleosomes properties.
Sonicated genomic DNA has been sequenced to quantify and exclude sequencing bias in the largest CGIs regions studied in this article.

first: Pierre

last: Cauchy

first: Frederic

last: Koch

first: Nicolas

last: Descostes

first: Joaquin

middle: Z

last: Cabeza

first: Charlène

last: Innocenti

last: Ferrier

first: Salvatore

last: Spicuglia

first: Marta

last: Gut

first: Ivo

first: Jean-Christophe

last: Andrau


title: Expression data from Ewing's sarcoma tumor samples

city: Paris

first: Loredana

last: Martignetti

address: 26, rue d'Ulm

institute: Insitut Curie/ INSERM U900 / Mines Paris Tech

summary:
Ewing sarcoma a rare pediatric tumor characterized by EWSR1-ETS fusions. We performed expression profiling of both miRNA and mRNA from the same Ewing's sarcoma tumors.  We propose a novel statistical measure of non-linear dependence between miRNA and mRNA expression, In order to infer miRNA-target interactions. This approach, That we name antagonism pattern detection, Is based on the statistical recognition of a triangular-shaped pattern in miRNA-target expression profiles. This pattern is observed in miRNA-target expression measurements since their simultaneously elevated expression is statistically under-represented in the case of miRNA silencing effect. The proposed method enables miRNA target prediction to strongly rely on cellular context and physiological conditions reflected by expression data.
Expression profiling of Ewing sarcoma samples in the frame of the CIT program from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net).

overall_design: Total RNAs issued of 39 Ewing tumors were used for mRNA and miRNA microarray analyses. The mRNA data were collected using the Affymetrix GeneChip HG-U133A and Affymetrix GeneChip HG-U133Plus2.

first: Olivier

last: Delattre

first: Karine

last: Laud-Duval

first: Franck

last: Tirode

first: Gaelle

last: Pierron

first: Stelly

last: Ballet


title: GAA deficiency (Pompe Disease) in infantile-onset patients

city: Framingham

first: Adam

last: Palermo

address: 49 New York Ave

department: Functional Genomics

institute: Genzyme

summary: Pompe disease is a genetic disorder resulting from a deficiency of lysosomal acid alpha-glucosidase (GAA) that manifests as a clinical spectrum with regard to symptom severity and rate of progression. In this study, we used microarrays to examine gene expression from the muscle of two cohorts of infantile-onset Pompe patients to identify transcriptional differences that may contribute to the disease phenotype. We found strong similarities among the gene expression profiles generated from biceps and quadriceps, and identified a number of signaling pathways altered in both cohorts. We also found that infantile-onset Pompe patient muscle had a gene expression pattern characteristic of immature or regenerating muscle, and exhibited many transcriptional markers of inflammation, despite having few overt signs of inflammatory infiltrate. Further, we identified genes exhibiting correlation between expression at baseline and response to therapy. This combined dataset can serve as a foundation for biological discovery and biomarker development to improve the treatment of Pompe disease.

overall_design: Biceps biopsies from 9 infantile-onset Pompe patients and 10 controls were compared.  In a separate experiment, quadriceps biopsies from 11 Pompe patients at either 0, 12, or 52 weeks after the initiation of treatment with rhGAA were compared to quadriceps biopsies from 7 controls.  No technical replicates were included.

first: Rachel

last: Palmer

first: Kathy

last: So

first: Sueli

last: Oba-Shinjo

first: Mindy

last: Zhang

first: Brenda

last: Richards

first: Shruti

last: Madhiwalla

first: Patrick

middle: F

last: Finn

first: Anna

last: Hasegawa

first: Kristina

last: Ciociola

first: Mario

last: Pescatori

first: Alison

middle: J

last: McVie-Wylie

first: Robert

last: Mattaliano

first: Stephen

last: Madden

last: Marie

first: Katherine

middle: W

last: Klinger

last: Pomponio


title: Molecular Profiling provides evidence of the existence of two functionally distinct classes of ovarian cancer stroma

first: Loukia

last: Lili

address: 770 Lexington Ave, 14-07 14th floor

department: Icahn School of Medicine at Mount Sinai

institute: The Institute for Next Generation Healthcare

summary: RNA microarray profiling of 45 tissue samples was carried out using the Affymetrix (U133) gene expression platform. Laser capture microdissection (LCM) was employed to isolate cancer cells from the tumors of 18 serous ovarian cancer patients (Cepi). For 7 of these patients, a matched set of surrounding cancer stroma (CS) was also collected. For controls, surface ovarian epithelial cells (OSE) were isolated from the normal (non-cancerous) ovaries of 12 individuals including matched sets of samples of OSE and normal stroma (NS) from 8 of these patients. Unsupervised hierarchical clustering of the microarray data resulted in the expected separation between the OSE and Cepi samples. Consistent with models of stromal activation, we also observed significant separation between the NS and CS samples. Unexpectedly, the CS samples sub-divided into two distinct groups. Analysis of expression patterns of genes encoding signaling molecules and compatible receptors in the CS and Cepi samples are consistent with the hypothesis that the two CS sub-groups differ significantly in their relative propensities to support tumor growth.The results indicate the existence of distinct categories of ovarian cancer stroma and suggest that functionally significant variability exists among ovarian cancer patients in the ability of the microenvironment to modulate cancer development.

overall_design: Gene expression analysis of 8 normal stroma (NS) and 8 matched normal ovarian surface epithelium (OSE) from 12 individuals, along with 7 cancer stroma and 7 matched cancer epithelium from 18 additional ovarian cancer patients

first: Lilya

middle: V

last: Matyunina

first: L

last: Walker

first: Benedict

last: Benigno

first: John

last: McDonald


title: Long-term proteasomal inhibition in transgenic mice  by UBB+1 expression results in  dysfunction of central respiration control reminiscent of  brainstem neuropathology in Alzheimer patients

status: Public on Jun 13 2012

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

institute: Helmholtz Zentrum Muenchen

summary: Aging and neurodegeneration are often accompanied by a functionally impaired ubiquitin-proteasome system (UPS). In tauopathies and polyglutamine diseases a mutant form of Ubiquitin B, UBB+1, accumulates in disease-specific aggregates. UBB+1 mRNA is generated at low levels in vivo during transcription from the Ubiquitin B locus by molecular misreading. The resulting mutant protein has been shown to inhibit proteasome function. To elucidate causative effects and neuropathological consequences of UBB+1 accumulation, we used a UBB+1 expressing transgenic mouse line, that models UPS inhibition in neurons and exhibits behavioral phenotypes reminiscent of Alzheimer’s disease (AD). In order to reveal affected organs and functions, young and aged UBB+1 transgenic mice were comprehensively phenotyped for more than 240 parameters. This revealed unexpected changes in spontaneous breathing patterns and an altered response to hypoxic conditions. Our findings point to a central dysfunction of respiratory regulation in transgenic mice in comparison to wildtype littermate mice. Accordingly, UBB+1 was strongly expressed in brainstem regions of transgenic mice controlling respiration. These regions included, for example, the medial part of the nucleus of the tractus solitarius and the lateral subdivisions of the parabrachial nuclei. In addition, UBB+1 was also strongly expressed in these anatomical structures of AD patients (Braak stage #6) and was not expressed in non-demented controls. We conclude that long-term UPS inhibition due to UBB+1 expression causes central breathing dysfunction in a transgenic mouse model of AD. The UBB+1 expression pattern in humans is consistent with the contribution of bronchopneumonia as a cause of death in AD patients.

overall_design: 12 animals were analysed (6 Ubb+1 transgenic animals, 6 wildtype animals) on MOE430A/B arrays (for MOE430A one wt was omitted).

first: Martin

last: Irmler

first: Christiane

last: Lach

first: Constanze

last: König

first: Fred

last: Van Leeuwen


title: The multifaceted balance of TNF-a and type I / II interferon responses in SLE and RA: how monocytes manage the impact of cytokines

city: Berlin

first: Pawel

last: Durek

address: Charitéplatz 1

institute: Deutsches Rheuma-Forschungszentrum

summary: Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as TNFα in RA and IFNα/γ in SLE. To relate the transcriptional imprinting of cytokines in a cell type-specific and disease-specific manner, we generated gene-expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNFα, IFNα2a and IFNγ. Monocytes from SLE and RA patients revealed disease-specific gene-expression profiles. In vitro-generated signatures induced by IFNα2a and IFNγ showed similar profiles that only partially overlapped with those induced by TNFα. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN-responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNFα-regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNFα that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene-expression profiles, which can be molecularly dissected when compared to in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention.

overall_design: Expression profiles of human peripheral blood monocytes activated in vivo and stimulated in vitro. Monocytes from patients with SLE and RA and from healthy donors were used for generating disease-specific gene-expression profiles, where these profiles represent in vivo activation of monocytes. In addition, monocytes from healthy donors were stimulated in vitro by cytokines: TNFα, IFNα2a and IFNγ. Cytokine-specific gene-expression profiles were generated by comparing stimulated monocytes with unstimulated ones. TNFα-, IFNα2a- and IFNγ as cytokine-specific gene-expression profiles were compared with RA and SLE, as disease-specific gene-expression profiles.

first: Biljana

last: Smiljanovic

first: Joachim

middle: R

last: Grün

last: Biesen

first: Ursula

last: Schulte-Wrede

first: Ria

last: Baumgrass

first: Bruno

last: Stuhlmüller

first: Wlodzimierz

last: Maslinski

first: Falk

last: Hiepe

first: Gerd-R

last: Burmester

first: Andreas

last: Radbruch

first: Thomas

last: Häupl

last: Grützkau


title: Mutations in IDH1 and IDH2 are associated with DNA hypermethylation in intrahepatic cholangiocarcinomas

status: Public on Jun 11 2012

city: Chapel Hill

first: Derek

last: Chiang

address: UNC Lineberger Cancer Center, 450 West Drive, CB #7295

department: Department of Genetics

institute: University of North Carolina

summary:
We compared the DNA methylation profiles of 12 intrahepatic cholangiocarcinomas harboring mutations in the genes encoding isocitrate dehydrogenase, IDH1 and IDH2, with 28 intrahepatic cholangiocarcinomas without these mutations.
We profiled these samples with the Illumina HumanMethylation450 BeadChip, and characterized over 2,000 genes that were hypermethylated in tumors with mutations in IDH1 or IDH2.

overall_design: Genomic DNA from fresh frozen tumors was bisulfite converted with the Zymo Research EZ DNA Methylation kit, then hybridized to the Illumina HumanMethylation450 Beadchip.

first: P

last: Wang

first: C

last: Zhang

last: Kuan

first: J

last: Kim

first: S

last: Yourstone

middle: Y