title: RAD51 Interconnects Between DNA Replication, DNA Repair and Immunity

status: Public on Feb 18 2017

city: Dallas

first: Souparno

last: Bhattacharya

state: TEXAS

address: NC7.126  2201 Inwood Rd

department: Radiation Oncology

country: USA

institute: UT southwestern medical center

summary:
RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage.
Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity.

overall_design: Gene expression analysis of WT and sh RAD51 HT1080 cells was carried out before and after 1 Gy of high LET Fe particle radiation.

first: Kalayarasan

last: Srinivasan

first: Salim

last: Abdisalaam

first: Fengtao

last: Su

first: Prithvi

last: Raj

first: Igor

last: Dozmorov

first: Ritu

last: Mishra

first: Edward

last: Wakeland

first: Subroto

last: Ghose

first: Aroumougame

last: Asaithamby


title: Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival

status: Public on Feb 16 2017

city: Berlin

first: Theresa

middle: Maria

last: Thole

address: Augustenburger Platz 1

department: Klinik für Pädiatrie mit Schwerpunkt Onkologie, Hämatologie und STZ

country: Germany

institute: Charite Universitätsmedizin Berlin

summary: The number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment. Delineating and deciphering specific functions of single histone deacetylases in neuroblastoma may support development of targeted acetylome-modifying therapeutics for patients with molecularly defined high-risk neuroblastoma profiles. We show here that HDAC11 depletion in MYCN-driven neuroblastoma cell lines strongly induces cell death, mostly mediated by apoptotic programs. Genes necessary for mitotic cell cycle progression and cell division were most prominently enriched in at least two of three time points in whole-genome expression data combined from two cell systems, and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by HDAC11 depletion. High-level expression of all nine genes in primary neuroblastomas signiﬁcantly correlated with unfavorable overall and event-free survival in patients, suggesting a role in mediating the more aggressive biological and clinical phenotype of these tumors. Our study identiﬁed a group of cell cycle-promoting genes regulated by HDAC11, being both predictors of unfavorable patient outcome and essential for tumor cell viability. The data indicates a signiﬁcant role of HDAC11 for mitotic cell cycle progression and survival of MYCN-amplified neuroblastoma cells, and suggests that HDAC11 could be a valuable drug target.

overall_design: A knockdown of HDAC11 was performed in BE(2)-C and IMR-32 cells using two different siRNAs separately in a time kinetic (42, 48 and 54h). One siRNA negative control was used. Two biological replicates were performed for every condition.

middle: M

first: Marco

last: Lodrini

first: Johannes

last: Fabian

first: Jasmin

last: Wuenschel

first: Sebastian

last: Pfeil

first: Thomas

last: Hielscher

first: Annette

last: Kopp-Schneider

first: Ulrike

last: Heinicke

first: Simone

last: Fulda

first: Olaf

last: Witt

first: Angelika

last: Eggert

first: Matthias

last: Fischer

first: Hedwig

middle: E

last: Deubzer


title: Expression data from colorectal cancer cell lines transfected with CDKL1-shRNA

status: Public on Feb 15 2017

city: Shanghai

first: Chunzhi

last: Qin

state: Shanghai

address: 180 Fenglin Road

department: General surgery

country: China

institute: Zhongshan Hospital

summary:
CDKL1 protein was overexpressed in colorectal cancer tissues compared with paired normal tissue. Knockdown of CDKL1 in HCT116 and Caco2 significantly inhibited cell growth, colony formation ability, tumor invasion, and G1-S phase transition of the cell cycle.
We used microarrays to detail the gene expression of colorectal cells after CDKL1 knockdown by shRNA.

overall_design: CDKL1-shRNA-expressing and control-shRNA-expressing lentivirus were constructed and infected into colorectal cancer cells DLD1. Then total RNA was prepared for RNA extraction and hybridization on Affymetrix microarrays. Three independent samples were collected for each group.

first: Li

last: Ren


title: Polycomb-mediated deactivation of AR-feedback loop leads to castration-resistant prostate cancer [gene expression]

status: Public on Feb 19 2017

city: Atlanta

first: Jindan

last: Yu

state: GA

address: E330, 1760 Haygood Dr NE

department: Urology

institute: Emory University

summary: Castration-resistant prostate cancer (CRPC) is a lethal disease, often characterized by aberrant  androgen receptor (AR) activation independently of androgen. We have previously reported that  AR can directly repress the expression of many target genes, one of which is NOV/CCN3. Here  we show that NOV, primarily localized in the cytoplasm, physically interacts with AR at its Nterminus  and sequesters AR and AR variants in the cytoplasm, thereby reducing AR chromatintargeting.  This negative feedback loop, however, is disrupted in CRPC due to epigenetic silencing of NOV by the   Polycomb group protein EZH2, rendering AR transcriptional activities and drug-resistant prostate cancer   progression. Our findings thus suggest a working model wherein AR-repressed genes critically prevent   CRPC through negative feedback loops inhibiting AR signaling.

overall_design: genetic_modification_design; gene expression of LNCaP or C42B cells

first: Ka-wing

last: Fong

first: Jonathan

last: Zhao


title: Role of HER2 in breast cancer stem cells

city: Columbia

first: Hexin

last: Chen

state: SC

address: 715 Sumter Street,PSC621

department: Biological sciences

institute: University of South Carolina

summary: HER2 overexpression results in expansion of breast cancer stem cells (CSCs). However, the underlying mechanism remains elusive. We performed microarray analysis to obtain HER2-induced gene expression profiles in MCF10A breast epithelial cells and found that an array of inflammatory cytokine genes, including IL-1 and IL-6, are activated.  Our study indicates that targeting the HER2-IL-1α-IL-6 axis provides an effective approach for eliminating of CSCs and treating HER2-positive breast cancer.

overall_design: MCF10A cells were stably transduced with human HER2-cDNA overexpressing and empty control pRABE retroviruses.  RNA was extracted and hybridized to Illumina microarrays.

first: Shou

last: Liu


title: Whole-transcriptome gene expression profiling in TRPC1-silenced hepatocellular carcinoma cells.

status: Public on Feb 14 2017

city: Edinburgh

first: Cigdem

last: Selli

address: Little France Crescent

department: Centre for Reproductive Health

country: United Kingdom

institute: Queen's Medical Research Institute

summary: Effects of TRPC1 silencing on whole-transcriptome gene expression were determined in Huh7 hepatocellular carcinoma cells using whole-transcriptome gene expression profiling.

overall_design: Gene expression profile in TRPC1-silencing vector transfected Huh7 cells was compared to control cells transfected with empty vector.

first: Metiner

last: Tosun


title: Pathogenic Implications for Autoimmune Mechanisms Derived by Comparative eQTL Analysis of CD4+ Versus CD8+ T cells

status: Public on Feb 23 2017

city: Tartu

first: Pärt

last: Peterson

address: Ravila 19

country: Estonia

institute: University of Tartu

summary: Inappropriate activation or inadequate regulation of CD4+ and CD8+ T cells may contribute to the initiation and progression of multiple autoimmune and inflammatory diseases. Studies on disease-associated genetic polymorphisms have highlighted the importance of biological context for many regulatory variants, which is particularly relevant in understanding the genetic regulation of the immune system and its cellular phenotypes. Here we show cell type-specific regulation of transcript levels of genes associated with several autoimmune diseases in CD4+ and CD8+ T cells including a trans-acting regulatory locus at chr12q13.2 containing the rs1131017 SNP in the RPS26 gene. Most remarkably, we identify a common missense variant in IL27, associated with type 1 diabetes that results in decreased functional activity of the protein and reduced expression levels of downstream IRF1 and STAT1 in CD4+ T cells only. Altogether, our results indicate that eQTL mapping in purified T cells provides novel functional insights into polymorphisms and pathways associated with autoimmune diseases.

overall_design:
The study includes 304 individuals, no replicates. From each individual there are CD4+ and CD8+ T cell and peripheral blood samples extracted. The total number of good quality samples is 653, of which 293 have CD4+ T cell, 283 have CD8+ T cell and 77 have peripheral blood data.
GSE59065 contains the DNA methylation data for samples with the same names.

first: Lili

last: Milani


title: Ultrasonic surgical aspirate is a reliable source for culturing glioblastoma stem cells

status: Public on Feb 10 2017

city: Oslo

first: Biljana

last: Stangeland

address: Sognsvannsveien 20

department: Institute of Surgical Research

country: Norway

institute: Oslo University Hospital

summary: Glioblastoma stem cells (GSCs) are thought to be the source of tumor growth and therapy resistance. Core biosies that are used to generate GSC cultures are ususally taken from one part of the tumor and are thus unlikely to represent intra-tumoral heterogeneity. This study shows that the ultrasonic aspirates (UA), that are usually considered as a biological waste, can be used as a reliable source of GSCs. Furthermore the UA aspirates seem to be capturing the tumorigenic signature better than the traditional biopsies.

overall_design: Total RNA isolated from the core tumor tissues (Fr-Co) was compared to that from the ultrasonic aspirates (Fr-UA). Total RNA isolated from the tumorspheres generated from core tumor tissues (Sp-Co) was compared to the total RNA isolated from tumorspheres generated from ultrasonic aspirates (Sp-UA).


title: Analysis of differentially expressed genes between trastuzumab-sensitive and -resistant gastric cancer cells

status: Public on Feb 13 2017

city: Verona

first: Carmine

last: Carbone

state: Select a State or Province

address: p.zza L.A. Scuro 10

country: Italy

institute: Policlinico Universitario GB Rossi

summary: We compared gene expression profiles in trastuzumab-sensitive NCI-N87 cell line versus four trastuzumab-resistant cell lines (N87-TR1, N87-TR2, N87-TR3, N87-TR4) by microarray analysis in order to identify groups of genes associated with a specific signaling pathway or biological process.

overall_design: One trastuzumab-sensitive cell line (NCI-N87) and four trastuzumab-resistant cell lines (N87-TR1, N87-TR2, N87-TR3, N87-TR4). Total RNA was obtained from subconfluent cells using Trizol reagent.

first: Federica

last: di Nicolantonio


title: Comparison of gene expression in megakaryocytes derived from primary myelofibrosis or healthy individuals

city: Chicago

first: John

last: Crispino

state: IL

address: 303 E Superior

department: Medicine-Hematology/Oncology

institute: Northwestern University

summary: CD34+ cells from healthy individuals or those with primary myelofibrosis were cultured ex vivo under conditions to derive megakaryocytes. Following culture, megakaryocytes were purified by flow cytometry. The gene expression in these cells was determined by Illumina microarray analysis. Note that samples JC1-12 were run at a different time than JC13-24. Investigators may wish to perform the analysis of the two sets independently.

first: Laure

last: Gilles

first: Ayalew

last: Tefferi


title: Expression profile after stable HIF-1a inhibition in gastric cancer cells under normoxic conditions

status: Public on Feb 11 2017

first: Nadine

last: Rohwer

institute: Charité

summary:
Based on the results of numerous clinical and preclinical analyses, the transcription factor HIF-1a has been identified as an important tumor-promoting factor and is considered to be an attractive target for cancer therapy. To further deconstruct the molecular nature of HIF-1a’s role in tumorigenesis, we have applied lentiviral shRNA transduction to establish HIF-1a-deficient gastric cancer cells. Interestingly, functional analyses failed to show a significant growth defect of HIF-1a-deficient gastric cancer cells in vitro and in vivo. These observations led us to propose that stable inactivation of HIF-1a resulted in efficient compensation enabling cell growth and, ultimately, tumor progression in a HIF-1a-independent manner. To better understand the mechanisms that control this compensation, we performed transcriptomics of control (“scrambled” (SCR)) and HIF-1a-deficient (HIF) gastric cancer cells.
Analysis of hypoxia-inducible factor-1alpha (HIF-1a)-deficient gastric cancer cells under normoxia. The transcription factor HIF-1a is a key regulator of oxygen homeostasis and has been identified as an important tumor-promoting factor. Results provide insight into the role of HIF-1a in gastric carcinogenesis.

overall_design: Gastric cancer AGS cells were lentiviral and stably transduced with a small hairpin RNA targeting human HIF-1a or a control shRNA. RNA was extracted from control and HIF-1a-deficient cells. Each cell line was analyzed in triplicate for a total of six samples.

first: Fabian

last: Bindel

first: Christina

last: Grimm

first: Hans

last: Lehrach

first: Bertram

last: Klinger

first: Nils

last: Blüthgen

first: Ilona

last: Du Bois

first: Bernd

last: Schmeck

first: Marjo

last: de Graauw

first: Alessandro

last: Prigione

first: Stefan

last: Kempa

first: Thorsten

last: Cramer


title: Remyelination is correlated with regulatory T cell induction following human EBNPC transplantation

city: San Diego

first: Ronald

middle: L

last: Coleman

state: California

address: 3215 Merryfield Row

department: Chemical Physiology

institute: The Scripps Research Institute

summary:
We have recently described sustained clinical recovery associated with dampened neuroinflammation and remyelination following transplantation of neural precursor cells (NPCs) derived from human embryonic stem cells (hESCs) in a viral model of the human demyelinating disease multiple sclerosis. In order to test the general applicability of NPC transplantation, we developed a new method for the differentiation and purification of NPCs from pluripotent stem cells (PSCs). Herein, we investigated the therapeutic potential of NPCs generated from human induced pluripotent stem cells (iPSCs) in mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) that induces an immune-mediated demyelinating disease sharing clinical and histologic similarities to the human demyelinating disease multiple sclerosis (MS). JHMV-infected mice intraspinally transplanted with EB (embryoid body)-derived NPCs (EB-NPCs) exhibited decreased accumulation of CD4+ T cells in the central nervous system that was concomitant with reduced demyelination at the site of injection. Dampened neuroinflammation and remyelination was correlated with a transient increase in CD4+FOXP3+ regulatory T cells (Tregs) concentrated within the peripheral lymphatics. Importantly, pathological improvements were limited in comparison to our previous report on hESC-derived NPCs and did not result in significant clinical recovery. Further examination of EB-NPCs by whole genome expression analysis showed them to be significantly different than our previously published cells. These findings highlight an intrinsic disparity in the therapeutic potential of NPCs generated from pluripotent stem cells.
Pluripotent stem cells were differentiated to neural precursor cells (NPCs) by two separate methods to study the differences in final cell type. The first method was a 4 factor 9 day directed differentiation. This was applied to WA09 embryonic stem cells (ESCs)  as well as two lines of induced pluripotent stem cells (iPSCs) that were developed in our lab HDF51iPSC and HDF69iPSC. The other method was a multistep process that included transition through an embryoid body (EB) stage.  This was done with the used on the HDF51iPCS line. For controls we used the original pluripotent stem cell lines (WA09, HDF51iPSC and HDF69iPSC) as well as HDF417 which is a human dermal fibroblast line collected by our lab.

overall_design: 17 Samples were analyzed in this study. This included 4 pluripotent cell lines, 1 Fibroblast line and 12 NPC lines.

first: R


title: The role of vitamin D in the transcriptional program of human pregnancy.

status: Public on Feb 09 2017

city: Boston

first: Alvin

middle: T.

last: Kho

state: MA

address: 320 Longwood Avenue

department: Informatics Program

institute: Boston Children's Hospital

summary:
Peripheral whole blood transcriptome profiles of pregnant women enrolled in the “Vitamin D Antenatal Asthma Reduction Trial” (VDAART) at enrollment during early pregnancy, and again at 32-38 weeks of gestation. Mothers were enrolled in 2 treatment groups: Intervention group with 4400 IU vitamin D supplementation and Control group with 400 IU vitamin D supplementation.
Comparing the whole blood (PAXgene) transcriptome profile of 30 mothers at enrollment during early pregnancy versus their matching individual profile at 32-38 weeks of gestation.

overall_design: Whole blood transcriptome, dose response, time course, matched pair analysis

first: Amal

last: Al-Garawi

first: Vincent

middle: J

last: Carey

first: Divya

last: Chhabra

first: Hooman

last: Mirzakhani

first: Jarrett

last: Morrow

first: Jessica

last: Lasky-Su

first: Weiliang

last: Qiu

first: Nancy

last: Laranjo

first: Augusto

middle: A

last: Litonjua

first: Scott

middle: T

last: Weiss


title: Expression data from human microvascular endothelial cells

first: Qing

last: Li

address: 600 YiShan Road

institute: Institute of Microsurgery on Extremities

summary:
Exosomes can serve as a vehicle to transfer membrane receptors, proteins, mRNAs, and microRNAs to recipient cells and thereby alter the gene expression of the recipient cells.
We used microarray to analyze the gene expression of human microvascular endothelial cells (HMECs) treated with EPCs-derived exosomes (EPC-Exos) or an equal volume of PBS, and identified the significantly altered genes during the process.

overall_design: HMECs were treated with EPC-Exos or an equal volume of PBS for 24 hours.Total RNA from HMECs was extracted for hybridization on Affymetrix microarrays.The differentially expressed genes (DEGs; absolute fold change ≥1.5, p value <0.05) were biologically interpreted and their involved regulatory signaling pathways were further explored.

first: Yang

last: Wang


title: AMP18 Dual Effects

city: SYRACUSE

first: Mira

last: Krendel

state: New York

address: 505 Irving Ave

institute: Upstate Medical University

summary:
AMP-18 inhibits growth of cancer cells, but stimulates growth of normal cell lines. Microarray assay was performed to identify gene expression profiles between a head/neck cancer.
Cell line (SCC61) and a normal cell line  (HaCaT) with and without AMP-18 treatment at 2 and 24 hour.

overall_design:
Total RNA obtained from triplicated groups of SCC61 and HaCaT cells  treated with and without AMP-18 from 2 and 24 hour was subjected to microarry assay.
Please note that Detection pvalues are provided as a supplementary file (Detection-pvalues.txt).

first: Peili

last: Chen

first: Gary

middle: F

last: Toback

first: Chunling

last: Zhang


title: Genome-wide analysis of gene expression in response to leptin and IL-1β in gingival fibroblasts

city: Newcastle Upon Tyne

first: John

last: Taylor

state: Tyne and Wear

address: Framlington Place

department: Molecular Immunology

institute: Newcastle University Medical School

summary: Analysis of response to leptin and IL-1β in gingival fibroblasts at the gene expression level. The hypothesis tested in the present study was that leptin and IL-1β synergistically effect the phenotype of gingival fibroblasts. Results provide important information regarding the response of gingival fibroblasts to leptin and IL-1β, such as specific inflammatory genes that were up- or down-regulated.

overall_design: Total RNA isolated from gingival fibroblasts extracted from 3 human donors, stimulated in vitro for 24 h with leptin, IL-1β, leptin+IL-1β, or unstimulated as a control.

first: Rachel

middle: C

last: Williams

first: Andrew

last: Skelton

middle: D

last: Rowan

first: Philip

last: Preshaw


title: Gene expression profiles of endothelial cell colony forming unit cells derived from malignant breast disease patients and healthy controls

city: Miaoli County

first: Ya-Wen

address: 35, Keyan Rd, Zhunan Town

department: National Institute of Cancer Research

country: Taiwan

institute: National Health Research Institutes

summary: Microarray analysis was performed to understand the difference of endothelial cell colony forming unit cells from malignant breast disease patients and healthy controls.

overall_design: Endothelial cell colony forming unit cells form 6 healthy control and 10 malignant breast disease patients

first: C

middle: P

last: Chou

first: Y

middle: W


title: Substantia nigra (SN) and basal ganglia (BG) gene expression in neurodegenertion with brain iron accumulation (NBIA) cases vs normal controls

city: Callaghan

first: Adrienne

last: Milward

state: NSW

address: Medical Science Building MSB

department: School of Biomedical Sciences and Pharmacy

country: Australia

institute: University of Newcastle

summary: Differential gene expression is assessed in substantia nigra and basal ganglia of  neurodegenertion with brain iron accumulation cases (BIA)  compared to matched normal controls (c).

overall_design: Post-mortem substantia nigra and basal ganglia of two clinicopathologically confirmed NBIA cases of unknown genetic subtype from the Canadian Brain Tissue Bank, University of Toronto, compared to two age- and gender-matched adults with no diagnosed neurological conditions from the Newcastle Brain Tissue Resource, University of Newcastle, UK.  Tissue was obtained with fully informed consent and the study approved by the Human Research Ethics Committee of the University of Newcastle, Australia (H-2010-1219).

first: Elizabeth

first: Daniel

last: Johnstone

first: Moones

last: Heidari


title: Gene expression in human or mouse brain with iron loading

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: Expression data from intravaginal Chlamydia-infected mouse T lymphocytes

city: Badalona

first: Lauro

last: Sumoy

state: Barcelona

address: Ctra. Can Ruti, Camí de les escoles s/n

department: High Content Genomics and Bioinformatics

country: Spain

institute: IGTP

summary:
Intravaginal infection of C57BL/6 mice with Chlamydia muridarum promotes activation and migration of effector lymphocytes to the genital tract mucosa. Among up regulated genes related to the specific immune response 7 days after infection we aimed to detect adhesion molecules associated with migration to this mucosa.
We used microarrays to determine the global gene expression changes underlying homing to genital tract mucosa and identified distinct classes of up-regulated genes during effector T lymphocyte migration to this tissue.

overall_design: Circulating TEM cells were sorted from three 7d Chlamydia-infected mice (VAG group) and three contemporary sham-treated mice (controls). Blood samples (≈500µl) were immediately lysed using a RBC lysis buffer. T cells were identified as CD3+ and finally sorted as CD3+ CD62L- CD44+ activated T effector memory cells. Total RNA from each of the six samples was analyzed with an individual Affymetrix  HT MG-430 PM Strip Array.

first: Jamal

last: Qualai

first: Lin-Xi

first: Jose

last: Carrascosa

first: Eduard

last: Cabré

first: Gemma

last: Falguera

first: Stephen

last: McSorley

first: Meritxell

last: Genesca


title: KLF12 overexpression effect in colorectal cancer cells

city: Seoul

first: YUNYONG

last: PARK

address: 84 Heukseok-ro

country: South Korea

institute: ChuangAng University

summary: The Krüppel-like factor (KLF) family is transcription factors that play diverse biological roles in cell differentiation, proliferation, and apoptosis.  KLF12 is frequently elevated in esophageal adenocarcinoma and has been reported to promote gastric cancer progression. To identify the downstream target of KLF12 in colorectal cancer cells, we carried out microarray.

overall_design: KLF12 was over-expressed in LS174T colorectal cancer cells. Eath group is trplicate sample (Contro=3, KLF12 Over-expression=3)

first: Sun-Hee

last: Kim

first: Yun-Yong

last: Park

first: Raymond

middle: N

last: DuBois


title: A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness (expression)

city: Montreal

first: David

last: Cheishvili

state: Quebec

address: 3655 Sir William Osler

country: Canada

institute: McGill

summary:
Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from noninvasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion.  Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness.
Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins.

overall_design: Total RNA obrtained from MCF7, MDA-MB-231, HepG2, SKHep1, LNCaP and PC3 cancer cell lines

first: Moshe

last: Szyf


title: Regulation of matrix metalloproteinases (MMPs) expression and secretion by LIM and SH3 protein (LASP1)

status: Public on Feb 03 2017

city: Wuerzburg

first: Susanne

middle: Elma

last: Kneitz

address: Biozentrum, Am Hubland

department: Physiologigcal Chemistry

institute: University of Wuerzburg

summary:
The process of tumor invasion requires degradation of extracellular matrix by proteolytic enzymes. Cancer cells form protrusive invadopodia, which produce and release matrix metalloproteinases (MMPs) to degrade the basement membrane and thereby allowing metastasis. We investigated the effect of LASP1, a newly identified protein in invadopodia, on expression, secretion and activation of MMPs in invasive breast tumor cells.
By analyzing and verifying microarray data sets and performing reporter assays, we demonstrate that LASP1 positively modulates the expression of c-Fos and AP-1 activity, and thereby up-regulates expression of MMP1, -3 and -9 in breast cancer cells. Furthermore, zymography assays and Western blot analysis revealed cytosolic LASP1 promotion of MMP vesicle secretion into the extracellular matrix, thus altering the microenvironment during cancer progression.
The newly identified role of LASP1 in regulating matrix degradation by affecting MMP transcription and secretion elucidated the migratory potential observed in studies that investigated the upregulation of LASP1 in aggressive cancers.

overall_design: total samples analysed are 4

first: Elke

last: Butt

first: Marcel

last: Endres

first: Ruwan

middle: K

last: Perera


title: Genotype and gene expression data from induced Pluripotent Stem cells from OPA1 Haploinsufficiency patients

city: Oxford

first: Sally

last: Cowley

address: South Parks Road

department: Sir William Dunn School of Pathology

institute: University of Oxford

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


title: Identification of genes modulate by MLS000408882-01 and MLS000573813-01 in lung cancer cells

city: Dallas

first: Elisabeth

last: Martinez

state: TX

address: 6000 Harry Hines Blvd

department: Department of Pharmacology

institute: UT Southwestern Medical Center

summary:
MLS000408882-01 and MLS000573813-01 were identified through a cell based screen that measures the reactivation of an epigenetically silenced transgene.
MLS000408882-01 and MLS000573813-01 shows selectivity for cancer vs. normal cells affecting both transcriptional patterns and cell viability in a cancer specific manner.

overall_design: the patient matched HCC4017 (cancer) vs. HBEC30KT (immortalized normal) lung cell pair were treated with DMSO vehicle or MLS000408882-01 and MLS000573813-01 for 4 h or 24 h and RNA extracted.

first: Tram

last: Tran


title: Gene expression data from induced Pluripotent Stem cells from OPA1 Haploinsufficiency patients

summary:
We have generated human induced Pluripotent Stem cells (hiPSc) from two individuals with OPA1 haploinsufficiency, and one control donor, using Sendai virus-mediated delivery of reprogramming factors. hiPSc lines have been screened using SNP array to assess chromosomal stability (alongside the fibroblast lines from which they derived), and validation of the pluripotency of the hiPSc lines is provided by Pluritest assessment of transcriptome datasets, prior to differentiation to dopaminergic neuronal clutures and downstream functional assays.
Mitochondrial fragmentation in iPSC-derived dopaminergic neurons with OPA1 haploinsufficiency underpins increased apoptosis   and syndromic Parkinsonism.

overall_design: human iPSc lines were derived from human dermal fibroblasts from 2 related individuals with heterozygous OPA1 mutations, one of whom had syndromic Parkinsonism,  and 1 control donor.

first: M

last: Jonikas

first: T

last: Zekoll

first: S

last: Wigfield

first: A

last: Mathy

last: Kurzawa-Akanbi

first: C

last: Browne

first: D

last: Sims

first: P

last: Chinnery

first: G

last: Tofaris


title: Suppression of B-cell development genes is key to glucocorticoid efficacy in treatment of acute lymphoblastic leukemia

status: Public on Feb 02 2017

city: Iowa City

first: Miles

last: Pufall

state: IA

address: 51 Newton Rd., BSB Rm 4-430

department: Biochemistry

institute: University of Iowa

summary:
Glucocorticoids (GCs) are a central component of combination chemotherapy for childhood B-cell precursor acute lymphoblastic leukemia (B-ALL). GCs work by activating the glucocorticoid receptor (GR), a ligand induced transcription factor, which in turn regulates genes that induce leukemic cell death.  Which GR-regulated genes are required for GC cytotoxicity, the pathways that affect their regulation, and how resistance arises are not well understood. Here we systematically integrate the transcriptional response of B-ALL to GCs with a next-generation shRNA screen to identify GC-regulated “effector” genes that contribute to cell death as well as genes that affect the sensitivity of B-ALL cells to dex. This analysis reveals a pervasive role for GCs in suppression of B-cell development genes that is linked to therapeutic response. Inhibition of PI3Kδ, a lynchpin in the pre-B-cell receptor and IL7R signaling pathways critical to B-cell development, with CAL-101 (idelalisib), interrupts a double-negative feedback loop, enhancing GC-regulated transcription to synergistically kill even highly resistant B-ALL with diverse genetic backgrounds. This work not only identifies numerous opportunities for enhanced lymphoid-specific combination chemotherapy that have the potential to overcome treatment resistance, but is also a valuable resource for understanding GC biology and the mechanistic details of GR-regulated transcription.
Please note that the cell lines and primary samples were processed and normalized separately.

overall_design:
The data submitted include the gene expression profiles for 11 cell lines and three primary patient samples.  The cells were all treated in the same way: grown in RPMI plus 10% FBS @ 37˚C with 5% CO2; treated for 4 hours with either 1µM dexamethasone, or 0.1% ethanol as a control; RNA was harvested then run on Illumina HT12 v 4 arrays.  There are at least three reapeats for each treatment and control.
Control repeats have the suffix U* whereas the treated have either I* or D* as a suffix.

first: Joseph

last: DeYoung


title: Genome-wide transcriptome profile of CYTOR (LINC00152)-silenced MDA-MB-231 breast cancer cell line

city: Gosselies

first: Martin

last: Bizet

address: Rue Adrienne Bolland, 8

country: Belgium

institute: Université Libre de Bruxelles

summary: The transcriptional profile of MDA-MB-231 cells silenced for CYTOR (LINC00152, long intergenic non-protein coding RNA 152) was compared to LNA-control-treated MDA-MB-231 cells to identify potential CYTOR targets.

overall_design: MDA-MB-231 cells were treated with LNA targeting CYTOR or with LNA control (from Exiqon), and total RNA was obtained.


title: P/CAF mediates Pax3-FKHR dependent oncogenesis in alveolar rhabdomyosarcoma

city: Bangalore

first: madavan

last: vasudevan

state: Karnataka

address: Kasturi Nagar

country: India

institute: Theomics International Private Limited

summary: Analysing the differential expression of various genes upon knockdown of acetyltransferase P/CAF in Rh31 to identify its targets

overall_design: Total RNA was isolated from three scarmble control siRNA and siP/CAF 72 hours post-transfection from Rh30 cells and analysed for the differential expression of genes involved in regulation of proliferation, grwoth, apoptosis and muscle development

first: Narendra

last: Bharathy

first: Sudha

last: Suriyamurthy

first: Vinay

last: Rao

first: Huey

last: Lim

first: Madavan

last: Vasudevan

first: Payal

last: Chakraborty

first: Chetan

last: Dhamne

first: Victor

last: Min

first: Tapas

last: Kundu

first: Reshma

last: Taneja


title: Personalized genome sequencing coupled with iPSC technology identifies GTDC1 as a gene involved in Neurodevelopmental Disorders

status: Public on Feb 01 2017

city: Lyon

first: Irene

last: Aksoy

address: 18 avenue du Doyen Lepine

country: France

institute: Stem Cell and Brain Research Institute

summary: The cellular and molecular mechanisms underlying neurodevelopmental conditions such as autism spectrum disorders have been studied intensively for decades. The ability to generate patient-specific induced pluripotent stem cells (iPSCs) now offers a novel strategy for modeling human disease. Recent studies have reported the derivation of iPSCs from patients with neurological disorders. The key challenge remains the demonstration of disease-related phenotypes and the ability to model the disease. Here we report a case study with signs of neurodevelopmental disorders (NDDs) harbouring chromosomal rearrangements that were sequenced using long-insert DNA paired-end tag (DNA-PET) sequencing approach. We identified the disruption of a specific gene, GTDC1. By deriving iPSCs from this patient and differentiating them into neural progenitor cells (NPCs) and neurons we dissected the disease process at the cellular level and observed defects in both NPCs and neuronal cells. We also showed that disruption of GTDC1 expression in wild type human NPCs and neurons showed similar phenotype as patient’s iPSCs. Finally, we utilized a zebrafish model to demonstrate a role for GTDC in development of the central nervous system. Our findings highlight the importance of combining sequencing technolgies with the iPSC technology for NDDs modelling that could be applied for personalized medicine.

overall_design: Total RNA obtained from neurons derived from CD6 patient's iPSCs and shGTDC1 hESCs were compared to Control hiPSCs and shControl hESCs respectively.

first: Lawrence

last: s Stanton


title: mRNA expression profile in DLD-1 and MOLT-4 cancer cell lines cultured under Microgravity

status: Public on Feb 07 2017

city: Chennai

first: Rama

middle: Shanker

last: Verma

state: Tamilnadu

address: Bhupat and Jyoti Mehta School of Biosciences IITM

department: Biotechnology

institute: Indian Institute of Technology Madras

summary:
DLD-1 and MOLT-4 cell lines were cultured in a Rotating cell culture system to simulate microgravity and mRNA expression profile was observed in comparison to Static controls
Simulated microgravity affected the solid tumor cell line DLD-1 markedly which showed a higher percentage of dysregulated genes compared to the hematological tumor cell line, MOLT-4. Microgravity affects the cell cycle of DLD-1 cells and disturbs expression of cell cycle regulatory gene networks. Multiple microRNA host genes were dysregulated and significantly, mir-22, tumor suppressor microRNA, is highly upregulated in DLD-1.

overall_design: Cells were grown in 10mL rotating vessels in an RCCS and in 60mm Petri dishes (test, control respectively).Two replicates of test (Microgravity) and control (static), each from DLD-1 and MOLT-4  were analyzed by microarray.

first: Prasanna

last: Vidyasekar

first: Pavithra

last: Shyamsunder

middle: S


title: JQ1 treatment of germ cell cancer cells induces differentiation, apoptosis and cell cycle arrest

city: Bonn

first: Sina

last: Jostes

address: Venusberg Campus 1

department: Department of Developmental Pathology

institute: Institute of Pathology

summary: Type II testicular germ cell cancers (GCC) are the most frequently diagnosed tumors in young men (20 - 40 years) and are classified as seminoma or non-seminoma. GCCs are commonly treated by orchiectomy and chemo- or radiotherapy. However, a subset of metastatic non-seminomas display only incomplete remission or relapse and require novel treatment options. Recent studies have shown effective application of the small-molecule inhibitor JQ1 in tumor therapy, which interferes with the function of bromodomain and extra-terminal (BET)-proteins. Here, we demonstrate that upon JQ1 doses ≥ 250 nM GCC cell lines and Sertoli cells display compromised survival and induction of cell cycle arrest. JQ1 treated GCC cell lines display upregulation of genes indicative for DNA damage and a cellular stress response. Additionally, downregulation of pluripotency factors and induction of mesodermal differentiation was detected. GCCs xenografted in vivo showed a reduction in tumor size, proliferation and angiogenesis when subjected to JQ1 treatment. The combination of JQ1 and the histone deacetylase inhibitor romidepsin further enhanced the apoptotic effect in vitro and in vivo. Thus, we propose that JQ1 alone, or in combination with romidepsin may serve as a novel therapeutic option for GCCs.

overall_design: TCam-2 (seminoma), NCCIT (embryonal carcinoma), FS1 (Sertoli) and MPAF (fibroblast) cells were treated with 100 nM JQ1 or DMSO as solvent control. Samples were taken after 24h and 72h

first: Daniel

last: Nettersheim

first: Hubert

last: Schorle


title: Characterization of primary isolated villous CTB and proximal column EVT from first trimester human placenta.

city: La Jolla

first: Mana

last: Parast

address: 9500 Gilman drive #0695

department: Pathology

institute: University of California San Diego

summary: The goal of this study was to identify the gene expression signatures of two closely related types of trophoblast in human placentas: villous cytotrophoblasts (vCTB) and proximal column extravillous trophoblasts (pcEVT). The two populations were isolated from first trimester placentas and identified using the specific surface markers, EGFR (vCTB) and HLA-G (pcEVT).

overall_design: First trimester trophoblasts were isolated from 6-9 week gestational age placentas and sorted into EGFR+/HLAG- vCTB and EGFR-/HLAG+ pcEVT. Whole genome expression analysis was performed on purified RNA of the two sorted populations.

first: Anna

last: Wakeland

first: Matteo

last: Moretto-Zita

first: Francesca

last: Soncin

first: Mariko

last: Horii

first: Katharine

last: Nelson

first: Donald

last: Pizzo

first: Louise

last: Laurent

middle: M


title: Cytoplasmic Localization of Proline, Glutamic Acid, Leucine-rich Protein 1 (PELP1) Induces Breast Epithelial Cell Migration through Up-regulation of Inhibitor of κB Kinase ϵ and Inflammatory Cross-talk with Macrophages

status: Public on Jan 31 2017

city: Minneapolis

first: Todd

last: Knutson

state: MN

address: 117 Pleasant St SE

department: Minnesota Supercomputing Institute

institute: University of Minnesota

summary: Cytoplasmic localization of proline, glutamic acid, leucine-rich protein 1 (PELP1) is observed in ∼40% of women with invasive breast cancer. In mouse models, PELP1 overexpression in the mammary gland leads to premalignant lesions and eventually mammary tumors. In preliminary clinical studies, cytoplasmic localization of PELP1 was seen in 36% of women at high risk of developing breast cancer. Here, we investigated whether cytoplasmic PELP1 signaling promotes breast cancer initiation in models of immortalized human mammary epithelial cells (HMECs). Global gene expression analysis was performed on HMEC lines expressing vector control, PELP1-wt, or mutant PELP1 in which the nuclear localization sequence was altered, resulting in cytoplasmic localization of PELP1 (PELP1-cyto). Global gene expression analysis identified that PELP1-cyto expression in HMECs induced NF-κB signaling pathways. Western blotting analysis of PELP1-cyto HMECs showed up-regulation of inhibitor of κB kinase ϵ (IKKϵ) and increased phosphorylation of the NF-κB subunit RelB. To determine whether secreted factors produced by PELP1-cyto HMECs promote macrophage activation, THP-1 macrophages were treated with HMEC-conditioned medium (CM). PELP1-cyto CM induced changes in THP-1 gene expression as compared with control cell CM. Double conditioned medium (DCM) from the activated THP-1 cells was then applied to HMECs to determine whether paracrine signaling from PELP1-cyto-activated macrophages could in turn promote migration of HMECs. PELP1-cyto DCM induced robust HMEC migration, which was reduced in DCM from PELP1-cyto HMECs expressing IKKϵ shRNA. Our findings suggest that cytoplasmic localization of PELP1 up-regulates pro-tumorigenic IKKϵ and secreted inflammatory signals, which through paracrine macrophage activation regulates the migratory phenotype associated with breast cancer initiation.

overall_design: The study contains 3 different sample groups measured in duplicate for a total of 6 individual samples (6 arrays). In HMEC-hTERT cell lines (human mammary epithelial cells, immortalized with hTERT expression), we created three stable clones expressing either (1) vector control LXSN, or (2) the wild type form of PELP1, or (3) a cytoplasmic-only version of PELP1 (via mutation of the NLS). These three cell lines were cultured in HuMEC Ready Media supplemented with epidermal growth factor, hydrocortisone, isoproterenol, transferrin, insulin, and 25 mg of bovine pituitary extract before total RNA harvest. Thus, the experiment contains three cell lines, analyzed in duplicate. Standard Illumina HT-12v4 chip controls were used during hybridization.

first: Brian

last: Girard

first: Bethanie

last: Kuker

first: Laura

last: McDowell

first: Kathryn

last: Schwertfeger

first: Julie

middle: H

last: Ostrander


title: Hypoxia directs human villous CTB differentiation towards the EVT lineage in a HIF-dependent manner.

summary: We showed that hypoxia directs first trimester primary villous cytotrophoblast (vCTB) differentiation preferentially towards HLAG+ extravillous trophoblast (EVT). Infection of primary vCTB with ARNT-specific shRNA attenuates this effect, suggesting a role of the intact HIF-complex in hypoxia-directed CTB differentiation into EVT.

overall_design: First trimester cytotrophoblast were isolated from five 8-10 week gestational age placentas and plated on fibronectin-coated plates. To assess the role of the HIF-complex in CTB differentiation, we targeted the beta subunit of this complex, ARNT. Cells were infected with either Scramble (control) or ARNT-specific shRNA lentivirus to induce specific ARNT knockdown. Both shScramble and shARNT infected cells were incubated either in 20% oxygen (normoxia) or 2% oxygen (hypoxia) for 4 days. Gene expression profiles were obtained for cultured cells as well as freshly isolated CTB.


title: Identification of SOX11 target genes in myxoid liposarcoma

city: Heidelberg

first: Marcus

last: Renner

address: Im Neuenheimer Feld 224

department: General Pathology

summary: To identify potential SOX11 target genes in myxoid liposarcoma (MLS) we stably transfected codon optimized full-length human SOX11 into the SOX11 negative MLS cell line MLS-1765. An emtpy vector (EV) was used as control. Potential SOX11 target genes were correlated with data set GSE52390.

overall_design: Two biological replicates (rep1 and rep2) with different cell passage numbers (early and late) were used for MLS-1765 overexpressing SOX11 or emtpy vector.

first: Sadaf

last: Mughal

first: Gunhild

last: Mechtersheimer


title: Expression data of K562 cells with KLF3 deficiency and shRNA vector control

status: Public on Jan 25 2017

city: Beijing

first: yadong

last: yang

address: No.1-104 Beichen West Road, Chaoyang

institute: Beijing Institute of Genomics

summary:
KLF3, a member of the Krüppel-like factor (KLF) family, is expressed in a wide range of cell types. It is involved in hematopoiesis of several blood cell lineages including erythrocyte and B lymphocyte. However, the research of regulatory roles on hematopoiesis of KLF3 in K562 cells has been still largely limited. To comprehensively assess the regulatory roles of KLF3 on hematopoiesis in K562 cells, a microarray analysis was performed in KLF3-deficient K562 cells. The differentially expressed genes were applied to IPA analysis to observe the perturbed hematopoiesis-associated functions, networks, and molecular pathways. This study will extensively assess the regulatory roles of KLF3 on hematopoiesis in K562 cells.
We used microarrays to study the genome-wide expression profiles of KLF3-deficient K562 cells.

overall_design: The stable K562 cell lines with KLF3-deficiecy and shRNA control were established in laboratory. Total RNA was extracted from each cell culture dish and used for microarray assay using illumine Total Prep RNA Amplification Kit. Two mRNA-chip libraries of K562 Ctrl and KLF3 KD cells were generated in parallel and the expression profiles of each sample was determined in duplicates.

first: Xiangdong

last: Fang


title: OCT4 controls mitotic spindle function and inactivates the RB tumor suppressor pathway to enhance high-grade serous ovarian cancer aggressiveness

city: Trieste

first: Silvano

last: Piazza

address: localita' Padriciano 99

institute: ICGEB

summary: The transcription factor OCT4 orchestrates self-renewal gene expression signatures in embryonic stem cells and cancer cells. We show that OCT4 enhances HG-SOC aggressiveness by promoting the inactivation of the Retinoblastoma pathway and mediating mitotic stability by driving the expression of Chromosomal Passenger Complex in HG-SOC. Our data show that OCT4 has an unprecedented role in enforcing mitotic stability and controlling the RB tumorsuppressor pathway in human cancer cells.

overall_design: Ovcar3 cell lines were transfected with control or Oct4 siRNA, Rb1 siRNA, or Ccnf siRNA + Nipp1 siRNA. The study comprises three experimental conditions and the control cell lines, each in triplicate.

first: Elisa

last: Comisso

first: Michele

last: Scarola

first: Yari

last: Ciani

first: Claudio

last: Schneider

first: Stefan

last: Schoeftner

first: Roberta

last: Benetti


title: Expression data from CACS15-New-Transcript 1(CASC15-NT1 or CANT1) lncRNA overexpressed UM cells

status: Public on Jan 16 2017

city: Shanghai

first: Yue

last: Xing

state: Shanghai

address: Zhizaoju Road No.639, Huangpu District

department: Department of Ophthalmology

institute: Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine

summary: The function and mechanism of lncRNA in human uveal melanoma (UM)  is not clearly studied. We used microarrays to identify the downstream target genes of CANT1 lncRNA in UM cells to explain the mechanism of lncRNA in UM tumorigenesis

overall_design:
CANT1 lncRNA was overexpressed in two human uveal melanoma cell lines MUM2B and OCM1 (MUM2B- CANT1 and OCM1- CANT1). The wild type uveal melanoma cell lines MUM2B and OCM1 were used as controls.RNA extraction from the four cell lines was used to be hybridized on Affymetrix microarrays.
Microarray replicates 2 and 3 are also included.

first: Xianqun

last: Fan

first: He

last: Zhang


title: Transcriptional analysis of HD and control iPSCs and derived NPCs

status: Public on Jan 19 2017

city: Singapore

first: Mahmoud

last: Pouladi

address: 8A Biomedical Grove, L5 Immunos

department: BMSI

country: Singapore

institute: A*STAR

summary: Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in HTT. In this study, we corrected HD human induced pluripotent stem cells (hiPSC) using a CRISPR-Cas9 and piggyBac transposon-based approach. To explore transcriptional differences amongst the HD, the corrected lines and the non-related healthy control lines, we performed genome-wide microarray gene expression analysis on the hiPSCs and neural progenitor cells derived from them.

overall_design: Total of 24 samples were used for the analysis, with 3 replicates per line per cell type

first: Xiaohong

last: Xu

first: Yilin

last: Tay


title: Gene expression and response to psychological therapy

city: London

first: Thalia

last: Eley

address: DeCrespigny Park, Denmark Hill

department: SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience

institute: King's College London

summary: This study represents the first investigation of genome-wide expression profiles with respect to psychological treatment outcome. Participants (n=102) with panic disorder or specific phobia received exposure-based CBT. Treatment outcome was defined as percentage reduction from baseline in clinician-rated severity of their primary anxiety diagnosis at post-treatment and six month follow-up. Gene expression was determined from whole blood samples at 3 time-points using the Illumina HT-12v4 BeadChip microarray. No changes in gene expression were significantly associated with treatment outcomes when correcting for multiple testing (q<0.05), although a small number of genes showed a suggestive association with treatment outcome (q<0.5, n=20). Study reports suggestive evidence for the role of a small number of genes in treatment outcome. Although preliminary, the findings contribute to a growing body of research suggesting that response to psychological therapies may be associated with changes at a biological level.

overall_design: Whole blood RNA was collected from patients (n=102) receiving exposure-based CBT at pre- and post-treatment and at follow-up, for investigation of association with therapy outcome. Includes 9 technical replicates.

first: Susanna

last: Roberts

first: Kathryn

last: Lester


title: Expression array analysis of MEC1, MEC2 and JeKo-1 cells 3h and 10h after overexpression of KLF4

status: Public on Jan 23 2017

first: Katharina

last: Filarsky

address: Im Neuenheimer Feld 580

institute: German Cancer Research Center

summary: In a recent study we identified the transcription factor KLF4 as deregulated by DNA methylation in chronic lymphocytic leukemia (CLL) cells in comparison to healthy B-cells. To analyze the function of KLF4 in leukemia cells and to identify downstream targets of the transcription factor we overexpressed KLF4 in 3 different cell lines: the CLL cell lines MEC1 and MEC2 and in the mantel cell lymphoma cell line JeKo-1.

overall_design: Cell lines MEC1, MEC2 and JeKo-1 were transfected with pcDNA3.1V5/HIS-KLF4 and pcDNA3.1V5/HIS-ctrl using the Amaxa nucleofector II device (Lonza), nucleofection solution V and program X-001. RNA was isolated from samples taken 3h and 10h after nucleofection using the DNA/RNA allprep Kit (Qiagen).


title: Dietary and protein-restriction protect against renal ischemia-reperfusion injury in mice

status: Public on Jan 20 2017

city: Bilthoven

first: Jeroen

last: Pennings

address: A. van Leeuwenhoeklaan 9

country: Netherlands

institute: Natl. Inst. Public Health & Environment

summary: During kidney transplantation, ischemia reperfusion injury (IRI) is inevitable and leads to oxidative stress and inflammation. We investigated the role of macronutrients in the effects of dietary restriction on both a phenotypical and transcriptional level, thereby comparing protective and nonprotective diets in search for pathways and regulators involved in the protection against IRI.

overall_design:
36 samples, each from individual mice
Upon arrival, mice were allowed free ad libitum (AL) access to the SDS chow for 7 days. The fasting experiment was done separately, during which mice were randomly divided into a control group or 3 days of fasting. In a subsequent experiment, mice were randomly divided into the following groups: control group SDS or two weeks 30% dietary restriction, control type I, or  ad libitum access to  control type I, 3 days of a protein-free, fat-free or  carbohydrate-free diet.
The SDS control diet is the standard chow given in our laboratory faculties. SDS is the control food for the fasting and dietary restriction groups. In these groups the composition of the diets does not change, but only the amount given.
Control type I is a specific control diet for the diets lacking one  nutrient (carbohydrate, fat or protein). Because the food in these diets is changed in composition, the control type I diet is specially made to function as control diet for these groups.

first: Franny

last: Jongbloed


title: Genome-wide analysis of LPS-responsive gene expression in human macrophages

status: Public on Jan 12 2017

city: Silver Spring

first: BIJU

last: ISSAC

state: MD

address: 503 Robert Grant Ave, Rm 2W123

department: Military HIV Research Program

country: USA

institute: Walter Reed Army Institute of Research

summary: Analysis of gene expression changes in human macrophages in response to LPS in the absence or presence of a CD11b agonist LA1. The hypothesis being tested in the present study was that LA1 mediated CD11b activation suppresses TLR signaling.

overall_design: Total RNA obtained from human macrophages subjected to LPS for 8 hours in vitro in the absence or presence of LA1. Control cells were treated with either vehicle (DMSO) or with LA1 alone. Cells were treated with vehicle DMSO (1% DMSO), LA1 (20 μM), LPS (50 ng/mL), or LPS (50ng/mL) and LA1 (20 μM) for 4h.

first: Vineet

last: Gupta

first: Mohd

last: Faridi

first: Biju

last: Isaac


title: Dissecting tumor/stroma pretreatment endoscopic biopsies and posttreatment surgical specimen in rectal cancer

status: Public on Jan 11 2017

city: L'HOSPITALET DE LLOBREGAT

first: DAVID

middle: G

last: MOLLEVI

address: Gran Via 197-203

department: PROCURE

institute: ICO

summary: Although preoperative chemoradiotherapy (CRT) and surgical mesorectal resection is the standard of care for locally advanced rectal carcinomas, it is still difficult to predict which patients will respond to treatment.   We explored how differential stromal transcriptomic profiles from microdissected pretreatment rectal biopsies can be used to define an immunohistochemical score based on two CAF-specific proteins for predicting neoadjuvant treatment response.  The analysis of differentially expressed genes (DEGs) of stroma and tumour glands from responder and non-responder patients shows that most changes were associated with the stromal compartment. Gene ontology analysis revealed that the DEGs codify mainly for extracellular matrix and ribosomal components.   We built a CAF-specific classifier with genes showing monotonic changes in expression according to the tumour regression grade (coefficient >1; FN1, COL3A1, COL1A1, MMP2 and IGFBP5). These are the genes that display the biggest a priori differences in expression between non-responder and responder stroma. We translated these five genes at the protein level by means of immunohistochemical staining in a cohort of 38 patients. For predictive purposes we used a leave-one-out cross-validated (LOOCV) model with a positive predictive value (PPV) of 80%. Classifier optimisation with Random Forest identified FN1 and COL3A1 as the best predictors. Rebuilding the LOOCV regression model improved the classification performance with a PPV of 89.5% and a negative predictive value (NPV) of 73.7%. An independent cohort of 36 patients was used to validate the classifier performance, which had a PPV of 84.2% and an NPV of 70.6%. In a multivariate analysis the two-protein classifier proved to be the only independent predictor of response (HR=2.58; P=0.003). We also explored a pharmacogenomic approach to gather information about possible therapeutic strategies for non-responder patients.  In conclusion, we developed a two-protein immunohistochemical classifier that performs well at predicting the absence of response to neoadjuvant treatment in rectal cancer.

overall_design: This study involves microdissected samples (tumor and stroma) of patients with rectal cancer that were analysed by Primeview microarray (Affymetrix). Biopsies were taken at two different timepoints: before neoadjuvant treatment (tumor and stroma) and after neoadjuvant treatment (surgical specimen; tumor and stroma). Microarrays were run in one batch. Fresh samples were embedded in OCT compound, sectioned in a cryotome, and stained using an Arcturus Histogene LCM Frozen Section kit. Stromal and tumour compartments were microdissected using an Arcturus XT microdissection system. After preoperative treatment we assessed the pathological response, using Mandard’s classification: TRG1 (pathologically complete response, pCR), TRG2 (scattered tumour cells), TRG3 (partial response with preponderance of fibrosis), TRG4 (partial response with preponderance of tumour cells) and TRG5 (no changes of regression). TRG1 and TRG2 were considered to be responders and TRG3, TRG4 and TRG5 were classified as non-responders.

first: Samuel

last: Gonçalves-Ribeiro

first: David

last: Mollevi


title: Expression and methylation array analysis of CD19+ B-cells from Chronic lymhocytic leukemia (CLL) patients and age matched healthy donor samples [Expression]

country: Germany

summary: Whole genome sequencing revealed CLL as a disease of the genome and epigenome defined by somatic mutations and aberrant DNA-methylation. To uncover the impact of aberrant methylation on transcription, gene expression and methylation array profiling was performed in CLL and B-cells.  RNA from 13 CLL patients and 6 healthy donor samples was analyzed on expression arrays.

overall_design: Total RNA was obtained from CD19+ sorted B-cells and CLL cells using the DNA/RNA all prep Kit (Qiagen). Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood by density centrifugation using Biocoll. CD19+ PBMCs were purified using CD19 Micro Beads for magnetic positive selection.

first: Angela

last: Garding

first: Manuela

last: Zucknick

first: Natalia

last: Becker


title: Inherited human IRAK-1 deficiency selectively abolishes TLR signaling in fibroblasts

status: Public on Jan 29 2017

city: Doha

first: Nico

last: Marr

address: Education City

country: Qatar

institute: Hamad Bin Khalifa University

summary: We describe here a male infant with a 100 kb de novo Xq28 deletion encompassing parts of the TMEM187 and MECP2 protein-coding genes and the IRAK1 protein-coding gene, as well as the MIR3202-1, MIR3202-2, and MIR718 RNA-coding genes. We analyzed the impact of human IRAK-1 deficiency on a genome-wide gene expression in human fibroblasts in response to TLR2/6, TLR4 agonists as well as to IL-1β and TNF-α, using primary fibroblasts from healthy controls and IRAK-4-, MyD88- and MECP2-deficient patients for comparison.

overall_design: Primary fibroblasts were derived from a boy with a large de novo Xq28 chromosomal deletion encompassing both MECP2 and IRAK1 (herein referred to as “P”), and for comparison, previously described patients with deficiencies for IRAK-4 (n=1), MyD88 (n=1) and MECP2 (n=1) as well as healthy controls (n=3). Fibroblasts were used to seed culture plates which were incubated overnight and then either left unstimulated or stimulated for 6 hours with PAM-2 (10 μg/ml), FSL-1 (1 μg/ml), LPS (10 μg/ml), MPLA (1 μg/ml), IL-1β (10 ng/ml) or TNF-α (20 ng/ml).

first: Erika

last: Della-Mina

first: Alessandro

last: Borghesi

first: Hao

last: Zhou

first: Salim

last: Bougarn

first: Sabri

last: Boughorbel

first: Laura

last: Israel

first: Ilaria

last: Melonig

first: Maya

last: Chrabieh

first: Yun

last: Ling

first: Yuval

last: Itan

first: Alessandra

last: Renieri

first: Iolanda

last: Mazzucchelli

first: Sabrina

last: Basso

first: Piero

last: Pavone

first: Raffaele

last: Falsaperla

first: Roberto

last: Ciccone

first: Rosamaria

last: Cerbo

first: Mauro

last: Stronati

first: Capucine

last: Picard

first: Orsetta

last: Zuffardi

first: Laurent

last: Abel

first: Damien

last: Chaussabel

first: Xiaoxia

last: Li

first: Jean-Laurent

last: Casanova

first: Anne

last: Puel


title: Expression and methylation array analysis of CD19+ B-cells from Chronic lymhocytic leukemia (CLL) patients and age matched healthy donor samples

first: Katharina

last: Filarsky

type: Methylation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: IFN-γ and IL-4 regulate epigenetic modifiers in macrophages

status: Public on Jan 15 2017

city: Bristol

first: Andrew

last: Newby

state: International/Other

address: Level 7 Bristol Royal Infirmary, Upper Maudlin Street

country: United Kingdom

institute: University of Bristol

summary: Interferon-γ (IFN-γ) or interleukin-4 (IL-4) prime macrophages towards classical (M1) or alternative (M2) activation, respectively. How IFN-γ and IL-4 prime epigenetic responses by altering expression of histone modifying enzymes and how this affects M1/M2 polarization is incompletely understood.

overall_design: We performed a microarray study of transcripts upregulated by IFN-γ or IL-4 in the presence and absence of the combined KDM6A and B inhibitor GSK-J4

first: Gökçe

last: Yıldırım-Buharalıoğlu

first: Mark

last: Bond

first: Graciela

middle: B

last: Sala-Newby

first: Charles

last: Hindmarch


title: CHANGES IN THE HUMAN TRANSCRIPTOME UPON VITAMIN D SUPPLEMENTATION

status: Public on Jan 28 2017

city: Tromso

first: Christopher

last: Fenton

state: Norge

address: MH bygget

department: GSCT

institute: Universiry of Tromso

summary: Subjects of a randomized controlled trial (RCT) received either vitamin D3 (n = 47) in a weekly dose of 20,000 IU or placebo (n = 47) for a period of three to five years

overall_design: Blood samples for preparation of RNA were drawn from the subjects and mRNA gene expression in blood was determined using microarray analyses.

first: Yvonne

last: Pasing

first: Rolf

last: Jorde

first: Ruth

last: Paulssen


title: Gene expression profile of T-DM1 resistant and parental cell lines

city: Lyon

first: Juliette

last: Sauveur

state: Rhone-Alpes

address: 8 Avenue Rockefeller, Faculté Rockefeller

department: Immunité, Virus, Inflammation

institute: Cancer Research Center of Lyon

type: Expression profiling by high throughput sequencing

summary: The esophageal cancer cell line OE-19 was used to select resistant cells to T-DM1. They were selected by prolonged exposure to increasing concentrations of T-DM1 in the absence or presence of ciclosporin A (CsA). Two cell lines resulted from these experimental conditions: OE-19 TR in the absence of CsA and OE-19 TCR in the presence of CsA. The parental cell line was named OE-19 S. The present study aims to detect the transcriptomic changes between OE-19 S, OE-19 TR and OE-19 TCR cell lines to identify the deregulated pathways involved in acquired resistance to T-DM1.

overall_design: OE-19 S, TR and TCR were recovered without previous drug exposure. Total RNA was extracted and analyzed. The experiment was performed in triplicate.

first: Kamel

last: Chettab

first: Severine

last: Croze

first: Elody

last: Orcel

last: Dumontet


title: OTX015 (MK-8628), a novel BET inhibitor, exhibits antitumor activity in non-small cell and small cell lung cancer models harboring different oncogenic mutations

status: Public on Jan 03 2017

city: Bellinzona

first: Francesco

last: Bertoni

state: Ticino

address: Via V. Vela 6

department: Lymphoma & Genomics Research Program

country: Switzerland

institute: IOR

summary: Assess the efficacy of OTX015 (MK-8628) BET inhibitor,  with respect to various lung carcinomas tumors, and to characterize its mechanism of action

overall_design: GEP analysis of 7 lung carcinomas cell lines with and without treatment

first: Maria

middle: E

last: Riveiro

first: Lucile

last: Astorgues-Xerri

first: Andrea

last: Rinaldi


title: A locus at 6p21.33 shows differential expression in peripheral mononuclear cells

status: Public on Jan 09 2017

city: Granada

first: Jose

middle: Antonio

last: Lopez-Escamez

state: Granada

address: Av. Ilustracion 114

department: Genomics of vestibular disorders

institute: Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO)

summary: Analysis of PBMC gene expression levels according to homozygous haplotype rs9380217- rs4947296. The hypothesis tested in the present study was that the haplotype rs9380217- rs4947296 at locus 6p21.33 influence gene expression of the immune response. Results provide important information involving class II HLA genes and TWEAK/Fn14 pathway

overall_design: Total RNA obtained from three peripheral mononuclear cells homozygous haplotype rs9380217/rs4947296 (CC/TT_1; CC/TT_2; CC/TT_3) compared to three homozygous haplotype rs9380217/rs4947296 (TT/CC_1; TT/CC_2; TT/CC_3).

middle: A


title: Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methlation inhibitor guadecitabine

status: Public on Jan 01 2017

city: Urbana

first: Michael

last: Spinella

state: IL

address: 2001 South Lincoln Ave

department: Comparative Biosciences

institute: University of Illinois

summary: Comparison of gene expression in cisplatin resistant testicular germ cell tumor xenografts treated with vehicle (PBS) or the DNA methylation inhibitor guadecitabine

overall_design: Total RNA was isolated from flank xenograft tumors treated once per day for 4 days with 1.5 mg/kg guadecitabine or PBS.  Drug was subcutaneous injection.  Both control and guadecitabine treatments were in biological triplicates.


title: Genome-wide analysis of B and T cell gene expression during a six-week gluten challenge in patients with celiac disease

status: Public on Jan 27 2017

city: Stanford

first: Mitchell

last: Garber

state: CA

address: 333 Campus Drive

department: Chemistry

institute: Stanford University

summary: Dietary gluten proteins (prolamins) from wheat, rye, and barley are the driving forces behind celiac disease, an organ-specific autoimmune disorder that targets both the small intestine and organs outside the gut. In the small intestine, gluten induces inflammation and a typical morphological change of villous atrophy and crypt hyperplasia. Gut lesions improve and heal when gluten is excluded from the diet and the disease relapses when patients consume gluten. Oral immune tolerance towards gluten may be kept for years or decades before breaking tolerance in genetically susceptible individuals. Celiac disease provides a unique opportunity to study autoimmunity and the transition in immune cells as gluten breaks oral tolerance. Seventy-three celiac disease patients on a long-term gluten-free diet ingested a known amount of gluten daily for six weeks. A peripheral blood sample and intestinal biopsies were taken before and six weeks after initiating the gluten challenge. Biopsy results were reported on a continuous numeric scale that measured the villus height to crypt depth ratio to quantify gluten-induced gut mucosal injury. Pooled B and T cells were isolated from whole blood, and RNA was analyzed by DNA microarray looking for changes in peripheral B- and T-cell gene expression that correlated with changes in villus height to crypt depth, as patients maintained or broke oral tolerance in the face of a gluten challenge.

overall_design: Whole blood sample were taken before and six weeks after a gluten challenge in 73 patients with celiac disease. B and T cells were purified from whole blood using anti-CD3 and anti-CD19 conjugated magnetic beads. Total RNA obtained from the purified pool of B and T cells was used for DNA microarray analysis using the Illumina platform.


title: Tonic B-Cell-Receptor Signaling in the Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma

city: Houston

first: R. Eric

last: Davis

state: Texas

address: 1515 Holcombe Blvd, Unit 0903

department: Lymphoma and Myeloma

institute: The UT MD Anderson Cancer Center

summary: Multiple types of B-cell lymphoma respond clinically to BTK inhibition, reflecting their dependence on B-cell receptor signaling. The germinal center B-cell subtype of diffuse large B-cell lymphoma resists BTK inhibition, but we found that B-cell receptor elimination in cell lines of this lymphoma type reduced their size and proliferation. Their B-cell receptor signals in a “tonic”, antigen-independent manner, requiring SYK, CD19, and phosphorylation of a specific tyrosine residue in the CD79A immunoreceptor tyrosine-based activation motif domain. The effect of B-cell receptor elimination or inhibition in these lines is proportional to their B-cell receptor surface density and its relative contribution to AKT activity, on which these lines uniformly depend, and is rescued by spontaneous or induced loss of PTEN protein. Biomarker-guided targeting of tonic B-cell receptor signaling may improve treatment of germinal center B-cell lymphoma.

overall_design: Total RNA was extracted from BCR KO cells isolated by FACS sorting 4-7 days after electroporation with chimeric Cas9/gRNA plasmids targeting Ig Heavy hypervariable or constant regions. 2-4 differennt KO replicates were compared to 1-2 replicates of GFP+ FACS sorted cells that had been electroporated in parallel with empty px458 plasmid.

first: Ondrej

last: Havranek

first: Jingda

last: Xu

first: Stefan

last: Köhrer

first: Zhiqiang

last: Wang

first: Lisa

last: Becker

first: Justin

last: Comer

first: Wencai

last: Ma

first: Jason

middle: R

last: Westin

first: Dipanjan

last: Ghosh

first: Nicholas

last: Shinners

first: Luhong

last: Sun

first: Anusha

last: Karry

first: Jan

last: Burger

first: Tomasz

last: Zal

first: R


title: Plasmablast response to influenza vaccines - 2012

city: palo alto

first: weiqi

last: wang

state: ca

address: 1291 welch road

institute: stanford

summary:
To study the plasmablast response to influenza vaccines
We want to test and see that LAIV, TIV and ID TIV induced different plasmablast response

overall_design: We take peripheral plasmablast and test its response to influenza vaccines at day 7 after vaccination. This array data is for day 0 (before vaccines)

first: Harry

last: Greenberg


title: Altered global gene profile in KSHV-infected primary oral fibroblasts

city: New Orleans

last: Qin

state: LA

address: 1700 Tulane Ave

institute: LSUHSC-NO

summary: The Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), the most common HIV/AIDS-associated tumor worldwide. Involvement of the oral cavity portends a poor prognosis for patients with KS, but mechanisms for KSHV regulation of the oral tumor microenvironment are largely unknown. Infiltrating fibroblasts are found with KS lesions, and KSHV establishes latent infection within human primary fibroblasts in vitro, but contributions for KSHV-infected fibroblasts to the KS microenvironment have not been previously characterized. In the present study, we used Illumina microarray to detect the global gene profile altered in KSHV-infected primary human fibroblasts (PDLF and HGF) isolated from the oral cavity.

overall_design: PDLF and HGF cells were infected by KSHV and the gene expression signature was compared to respective mock cells

first: Lu

last: Dai

first: Lihua

last: Bai

first: Zeng

last: Lin

first: Jovanny

last: Zabaleta


title: Pigment epithelium derived factor (PEDF): a novel trophoblast derived factor limiting feto-placental angiogenesis in late pregnancy

city: Graz

first: Silvija

last: Tokic

address: Auenbruggerplatz 14

country: Austria

institute: Medical University of Graz

summary:
We hypothesized that the trophoblast secretes anti-angiogenic factors, which increase in late pregnancy to limit angiogenesis. Therefore, we determined the paracrine effect of primary human trophoblasts from early versus late pregnancy on the angiogenic potential of isolated feto-placental endothelial cells.
We found that the expression and secretion of anti-angiogenic factors differs in early vs late pregnancy, and differentially affects feto-placental angiogenesis.

overall_design: Trophoblasts were isolated from third trimester placenta. A pool of 5 preparations from different cell types was used for each microarray.

first: Jelena

last: Loegl

first: Erika

last: Nussbaumer

first: Ursula

last: Hiden

first: Alejandro

last: Majali-Martinez

first: Nassim

last: Tabrizi-Wiszy

last: Cvitic

first: Ingrid

last: Lang

first: Gernot

last: Desoye

first: Berthold

last: Huppertz


title: Gene expression analysis of multiple myeloma cell lines treated with novel PIM2 inhibitor JP11646

city: Bethesda

first: Jayakumar

last: Nair

address: 10 center drive

department: Women malignancies Branch

institute: National Cancer Institute

summary: The PIM kinase family (PIM1, 2 and 3) play a central role in integrating growth and survival signals, and are expressed in a wide range of solid and hematological malignancies. We now confirm that PIM2 is overexpressed in multiple myeloma (MM) patients, and within MM group it is overexpressed in the high-risk MF subset (activation of proto-oncogenes MAF/MAFB). This is consistent with our finding of PIM2’s role in key signaling pathways (IL-6, CD28 activation) that confer chemotherapy resistance in MM cells. These studies have identified a novel PIM2-selective non-ATP competitive inhibitor (JP11646) that has a 4 to 760-fold greater suppression of MM proliferation and viability than ATP-competitive PIM inhibitors. This increased efficacy is due not only to the inhibition of PIM2 kinase activity, but also to a novel mechanism involving specific downregulation of PIM2 mRNA and protein expression not seen with the ATP competitive inhibitors.  To better understand Off target effects of JP11646 and specific genes that have been directly or indirectly affected by JP11646, MM cell lines MM.1S and U266 were treated with JP11646 and then gene expression was analyzed.

overall_design: The chemotherapeutic sensitive multiple myeloma cell line MM1.S and the more resistant U266 were treated with the ATP non-competitive PIM2 specific novel inhibitor JP11646 (Jasco Pharmaceuticals LLC) for over 24 hours or left untreated and then analyzed for gene expression levels.  Cells (5 million per replicate) were treated in triplicate with 20 nM or 200 nM JP11646 (sublethal concentrations that was predetermined to induce 50% cell death over 48 hr and >80% viability over 24 hrs) for 24 hours, or treated in plain media (RPMI1640+10%FBS).  Cells were isolated, washed in cold PBS and the RNA isolated was used for gene expression analysis on a Illumina Human HT12 V4 gene chip at the Genomics facility at Roswell Park Cancer Institute, Buffalo, NY.  Gene expression values for each gene (average of all the probesets) was normalized, quantile transformed and background corrected and is provided in this submission.

first: Kelvin

last: Lee

first: Justin

last: Caserta

first: Carmen

last: Baldino


title: Long-term Antiretroviral Treatment Initiated in Primary HIV-1 Infection Affects the Size, Composition and Decay Kinetics of the Reservoir of HIV-1 Infected CD4 T Cells

city: Cambridge

first: Xu

last: Yu

state: Massachusetts

address: 400 Technology sqr

institute: Ragon Institute of MGH, MIT and Harvard

summary: Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy in primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of therapy in chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed exclusively during the initial 3-4 years of treatment; however, in patients who started antiretroviral therapy in acute infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. Moreover, gene transcripts in CD4 T cells associated with the total viral CD4 T cell reservoir size frequently correlated with the relative proportion of these long-lived CD4 T cell subsets, suggesting shared gene expression signatures for maintaining HIV-1 persistence and preservation of long-lasting CD4 T cell subsets. Despite effective suppression of viral antigens for >10 years, HIV-1-specific T cell responses remained continuously detectable in both study groups. Together, these data suggest that although early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients attractive candidates for future interventional studies aiming at HIV-1 eradication and cure.

overall_design: We used Dynabeads Untouched Human CD4 T Cells kit (Invitrogen) for CD4 isolation from a median of 10 million PBMCs. RNA was extracted from CD4+ T cells using the mirVana miRNA Isolation Kit, Ambion. whole genome transcriptional profiling was performed using WG-DASL microarrays (Illumina) according to standard protocols. We included an cohort of elite controllers (n =10 ), patients long term HAART treated after the chronic phase of the infection (n=10) and patients long term HAART treated after the acute phase of the infection (n=8).

first: Maria

middle: J

last: Buzon

first: Forencia

last: Pareyra

first: Enrique

last: Martin-Gayo

first: Zhengyu

last: Ouyang

first: Hong

last: Sun

first: Jon

middle: Z

last: Li

first: Michel

last: Piovoso

first: Amy

last: Shaw

first: Judith

last: Dalmau

first: Nadine

last: Zangger

first: Javier

last: Martinez-Picado

first: Ryan

last: Zurakowski

first: Amalio

last: Telenti

first: Bruce

last: Walker

first: Eric

last: Rosenberg

first: Mathias

last: Lichterfeld


title: Reproductive activity triggers accelerated male mortality and decreases lifespan: genetic and gene expression determinants in Drosophila.

status: Public on Dec 31 2016

city: Boston

first: Alan

last: Branco

address: 665 Huntington Ave.

department: Environmental Health

institute: Harvard School of Public Health

summary: Fly strain y[1]; bw[1]; e[4]; ci[1] ey[R] was obtained from the Bloomington Stock Center. Flies were reared in incubators at 25°C, 65% of relative humidity, and photoperiod of 12 hours. For gene expression analyses virgin male flies were aged for 33 days, and allowed to mate for 48h with young virgin female flies. After exposure, they were flash-frozen in liquid nitrogen. Four replicas of each sample were collected and stored at -80°C. Total RNA was extracted from whole flies using TRIzol (Life Technologies). The synthesis of cDNA and its labeling with fluorescent dyes (Cy3 and Cy5) as well as hybridization reactions were carried out using 3DNA protocols and reagents (Genisphere). Slides were scanned using Axon 400B scanner (Axon Instruments) and GenePix Pro 6.0 software. Foreground fluorescence of dye intensities was normalized by the Loess method in Bioconductor / Limma.

overall_design: Dye "swaps," loop design.

middle: T

first: Bernardo

last: Lemos


title: The BET-bromodomain inhibitor OTX015 (MK-8628) exerts in vitro and in vivo anti-tumor activity in triple-negative breast cancer models as single agent and in combination with everolimus

first: Francesco

last: Bertoni

summary: assess the efficacy of OTX015 (MK-8628) BET inhibitor in vitro and in vivo triple negative breast cancer models

overall_design: GEP analysis of 2 breast cancer cell lines with and without treatment at different timepoints

first: Ramiro

last: Vázquez

first: María

last: Riveiro

first: Andrea

last: Rinaldi


title: Molecular determinants of tumor response to hyperthermia

first: Sangbae

last: Kim

state: TX

address: 1 Baylor plaza

department: HGSC

institute: Baylor Colleage of Medicine

summary: A deeper mechanistic understanding of response to hyperthermia in cancer cells in comparison between hyperthermia sensitive and resistant ovarian cancer cell lines

overall_design: Four groups of samples are included: 1,2 A2780 cells treated with control (37C) or hyperthermia (46C) . 3,4. SKOV3 cells treated with control (37C) or hyperthermia (46C).

first: Hiroto

last: Hatakeyama

first: Anil

last: Sood

first: Ju-Seog

last: Lee


title: Expression data for peripheral human blood leukocytes gene expression

city: New York

first: Hua

last: Zhou

state: NY

address: 550 First Avenue, Smilow 1307

department: PATHOLOGY

institute: NYU SCHOOL OF MEDICINE

summary:
Gene expression level in PBLs (peripheral blood leukocytes) could serve as biomarkers for symptomatic knee osteroarthritis (OA).
We used microarrays to detail the significant genes that are down/up regulated in OA PBLs by studying both the control and OA groups.
We would like to acknowledge NIAMS support through (AR052873 & AR054817) and U01-AR050911.

overall_design: For patiens with or without OA, blood samples were collected. Total RNA isolated and were used for hybridization against the Human Genome U133A microarray.

first: Mukundan

last: Attur

first: Steven

last: Abramson


title: Epithelial Splicing Regulatory protein 1 promotes human colorectal cancer cell growth and metastasis

city: Turin

first: Fiorella

last: Altruda

address: Via Nizza 52

country: Italy

institute: University of Turin

summary: Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific RBP and splicing factor. Both a tumor suppressor role and a pro-metastatic function of ESRP1 have been reported.Our aim was to clarify the role of ESRP1 in colorectal cancer  setting.We employed both loss-of-function and gain-of-function approaches to study the role of ESRP1 in human colorectal tumorigenesis in vitro and in vivo, as well as in the metastatic process in vivo.

overall_design: RNA from 4 conditions was analyzed. Every condition is represented by a duplicate.

first: Enzo

last: Medico

first: Enrico

last: Moiso

first: Sharmila

last: Fagoonee


title: Phase I/Ii study of mTOR inhibitor everolimus and Hyper-CVAD plus RAD001 (Everolimus) chemotherapy in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia

city: Westmead

first: Linda

last: Bendall

state: NSW

address: 176 Hawkesbury ave

department: Center for Cancer Research

institute: Westmead Millennium Institute

summary: Analysis of the effects of everolimus on gene expression and if this correlates to drug and/or clinical response.

overall_design: RNA exracted from peripheral blood before and 24 hours after treatment with everolimus.

first: Jordan

last: Basnett

first: Marina

last: Konopleva


title: Expression data from sodium butyrate treated A549 cells

status: Public on Dec 29 2016

city: Wenzhou

first: xiaoqiang

last: xiao

state: zhejiang

address: No 270.Xueyuan road

country: China

institute: Wenzhou Medical University

summary: As a histone deacetylase inhibitor, sodium butyrate involves in cellular events such as proliferation, differentiation,apoptosis and cell cycle control via reprogramming gene expression. However, the target genes associated with the cell cycle control and molecular signaling triggering cell apopotosis and death are not well elucidated.

overall_design: Here, we treated A549 cells, a cell line belong to the non-small cells lung cancer, with high concentration of sodium butyrate and then used microarray detail the global reprogramme of gene expression and identified differentially-expressed genes during this process.

first: Xiaoqiang

last: Xiao


title: Epigenetically regulated Fibronectin leucine rich transmembrane protein 2 (FLRT2) shows tumor suppressor activity in breast cancer cells

status: Public on Dec 30 2016

city: goyang

first: seungyeon

last: lee

address: dongguk-ro 32

department: life science

institute: dongguk unversity

summary: To investigate the role of FLRT2 in breast cancer, its expression was knocked down and upregulated in mammary cell lines. Our results show that FLRT2 has tumor suppressor activity in breast cancer.

overall_design: Total RNA is obtained from MCF-10A and 7 where FLRT2 is knocked down and upregulated using lipofectamine 2000

first: Byungtak

first: Sunjung


title: Differentiation of human induced pluripotent stem cells to mammary-like organoids

status: Public on Dec 22 2016

city: Los Angeles

first: Xiaojiang

last: Cui

state: California

address: 8700 Beverly blvd

department: Surgery

institute: Cedars-Sinai medical center

summary:
Analysis of the different expression genes between iPSCs and differentiated mEBs. The purpose of this experiment is to test which stage of mEBs enrich the stem cells that pre-committed to mammary lineage
experiment is to test which stage of mEBs enrich the stem cells that pre-committed to mammary lineage.

overall_design: Total RNA was obtained from iPSCs, 5-d mEBs, and 10-d mEBs for cDNA microarray.

first: Ying

last: Qu


title: Targeting Taxane-Platin Resistant Lung Cancers with JumonjiC Lysine Demethylase Inhibitors

city: Dallas

first: Luc

last: Girard

address: 5323 Harry Hines Blvd

department: Hamon Center for Therapeutic Oncology Research

institute: UT Southwestern Medical Center

summary: While taxane-platin standard chemotherapy provides benefit in advanced and localized non-small cell lung cancer (NSCLC), the majority of patients relapse with drug resistant tumors. Mechanisms underlying NSCLC resistance to this standard doublet chemotherapy are still not fully understood, and treatment options for chemoresistant lung tumors are limited. The goals of this work were to establish new preclinical NSCLC models of resistance to taxane-platin doublet chemotherapy, identify mechanisms of resistance, and develop new rational pharmacologic approaches to target drug resistant NSCLCs.

overall_design: Isogenic drug resistant cell lines were established by long-term treatment of chemosensitive, parental NSCLC cell lines (NCI-H1299 and NCI-H1355) with drug on/drug off cycles of paclitaxel + carboplatin doublet chemotherapy given in a clinically relevant 2:3 paclitaxel-to-carboplatin ratio. Total RNA was extracted and microarrays were performed on parental cell lines (used as control) and all developed resistant cell line variants (denoted as T followed by number of chemotherapy cycles). Samples included biological replicates (5 for parental,  2 for each intermediate resistance variant, 3 for the most resistant variant). Subcutaneous xenografts of H1299 parental cell line and the resistant H1299 T18 variant were also profiled by microarrays (3 tumors per group). 35-gene resistance signature was derived from cell lines and xenografts, and evaluated in neoadjuvant treated NSCLC patients to identify a clinically relevant, druggable target. Pharmacological targeting using JumonjiC histone lysine demethylase inhibitors, JIB-04 and GSK-J4, resulted in selective killing of chemoresistant cells over parental cell lines. To reveal mechanistic insights into JumonjiC inhibitor sensitization, H1299 Parental and H1299 T18 resistant cells were each treated with either DMSO, 0.2 µM JIB-04 or 1 µM GSK-J4 for 24 h, and studied by microarrays (2 biological replicates per treatment).

first: Maithili

middle: P

last: Dalvi

first: Elisabeth

middle: D

last: Martinez

first: John

last: Minna


title: Whole transcriptome microarray analysis of human cells treated with the endosomolytic D-amino acid CPP, D-dfTAT

city: College Station

first: Jean-Philippe

last: Pellois

address: 300 Olsen Blvd

department: Biochemistry and Biophysics

institute: Texas A&M university

summary: Analysis of the impact of D-dTAT treatment on primary human dermal flibroblast (HDF) and immortalized fibroblast cells (MCH58) at the transcriptome level. Results show that D-dTAT cytosolic penetration dysregulation of mRNA expression compared to dfTAT treated and untreated cells.

overall_design: HDF and MCH58 cells were treated with dfTAT or D-dTAT (5µM) for 1h. Total RNA was harvested from cells 24hrs after treatment.

first: Kristina

last: Najjar


title: High-dimensional assessment of B cell responses to quadrivalent meningococcal conjugate and plain polysaccharide vaccine

status: Public on Dec 26 2016

city: Oxford

first: Daniel

last: O'Connor

state: Oxfordshire

address: Churchill Hospital

department: Paediatrics

institute: University of Oxford

summary: Twenty adults were randomly assigned to receive either a meningococcal plain-polysaccharide or conjugate vaccine; one month later all received the conjugate vaccine. Blood samples were taken pre-vaccination, and 7, 21, and 28 days after vaccination; B-cell responses were assessed by ELISpot, serum bactericidal assay, flow cytometry and gene expression microarray.

first: Andrew

last: Pollard


title: Expression data from 4T1 tumors treated with everolimus

city: Barcelona

first: Miguel Angel

last: Pujana

address: Gran Via 199

institute: Institut Catala d'Oncologia IDIBELL

summary: Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

overall_design: 4T1 cells were injected subcutaneously in syngeneic mice and subsequently were treated with RAD001 (5 mg/kg) or DMSO daily by intraperitoneal injection. Tumors were excised at day 23 and processed for gene expression microarray analysis.

first: Helena

last: Aguilar

first: Mary-Helen

last: Barcellos-Hoff

first: Miguel


title: Combinatorial treatments targeting MAPK and PI3K/mTOR pathways in metastatic melanoma

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

institute: IRCSS Istituto Nazionale Tumori

summary: Therapeutic targeting of BRAFV600E has shown a significant impact on progression-free and overall survival in advanced melanoma, but only a fraction of patients benefit from these treatments, suggesting that additional signaling pathways involved in melanoma growth/survival need to be identified. In fact MAPK and PI3K/mTOR signaling pathways are constituively activated in most cancers, including melanoma, to sustain the melanoma growth/survival. A large panel of melanoma were characterized for resistance/susceptibility to different inhibitors targeting MAPK and PI3K/mTOR signaling pathways and  the synergistic effect of combinatorial treatments affecting both pathways. These effects were evaluated in terms of cell viability (MTT), apoptosis (Annexin V-PI), caspase 3/7 activity and subG1 cell fraction, highlighting a hierarchy in the combination effects. Further, a smaller panel of melanoma cell lines, were treated with inhibitors singularly and in combination to test the effects on the expression of principal proteins involved in these two pathways. Gene expression profile was performed to analyse the gene modulation induced by inhibitors to identify new strategies to fight melanoma resistance.

overall_design: The human melanoma cell line Me13 was established in our laboratory from a surgical specimen. Cells were routinely maintained in RPMI medium 1640 supplemented with 8% FBS and 2 mM glutamine. Cells were maintained at 37°C in a water-saturated atmosphere of 7% CO2 in air. 4.5x10^6 cells were seeded in 75 cm^2 flasks in RPMI medium 1640 supplemented with 8% FBS; after 24h, cells were untreated or treated with MAPK and or PI3K/mTOR inhibitors at different concentrations for 8 hours in RPMI medium 1640 supplemented with 4% FBS. Each treatment or combination was performed in triplicate. The cells were collected and RNA extracted.

first: L

first: A

last: Anichini


title: caArray_trich-00099: Identification of a PAX-FKHR gene expression signature that defines molecular classes and determines the prognosis of alveolar rhabdomyosarcomas

city: Rockville

first: Mervi

last: Heiskanen

state: MD

address: 9609 Medical Center Drive, 1W378

department: CBIIT

institute: NCI

summary:
Alveolar rhabdomyosarcomas (ARMS) are aggressive soft-tissue sarcomas affecting children and young adults. Most ARMS tumors express the PAX3-FKHR or PAX7-FKHR (PAX-FKHR) fusion genes resulting from the t(2;13) or t(1;13) chromosomal translocations, respectively. However, up to 25% of ARMS tumors are fusion negative, making it unclear whether ARMS represent a single disease or multiple clinical and biological entities with a common phenotype. To test to what extent PAX-FKHR determine class and behavior of ARMS, we used oligonucleotide microarray expression profiling on 139 primary rhabdomyosarcoma tumors and an in vitro model. We found that ARMS tumors expressing either PAX-FKHR gene share a common expression profile distinct from fusion-negative ARMS and from the other rhabdomyosarcoma variants. We also observed that PAX-FKHR expression above a minimum level is necessary for the detection of this expression profile. Using an ectopic PAX3-FKHR and PAX7-FKHR expression model, we identified an expression signature regulated by PAX-FKHR that is specific to PAX-FKHR-positive ARMS tumors. Data mining for functional annotations of signature genes suggested a role for PAX-FKHR in regulating ARMS proliferation and differentiation. Cox regression modeling identified a subset of genes within the PAX-FKHR expression signature that segregated ARMS patients into three risk groups with 5-year overall survival estimates of 7%, 48%, and 93%. These prognostic classes were independent of conventional clinical risk factors. Our results show that PAX-FKHR dictate a specific expression signature that helps define the molecular phenotype of PAX-FKHR-positive ARMS tumors and, because it is linked with disease outcome in ARMS patients, determine tumor behavior.
NOTE: Migrated from caArray 1.x, identifier='gov.nih.nci.ncicb.caarray:Experiment:1015897589792480:1'

overall_design:
trich-00099
Assay Type: Gene Expression
Provider: Affymetrix
Array Designs: HG-U133A
Organism: Homo sapiens (ncbitax)
Material Types: synthetic_RNA, organism_part, whole_organism, total_RNA
Disease States: Dead, Alive
Experiment Filename: caArray_trich-00099.zip
MAGE-TAB (IDF and SDRF) files: trich-00099_magetab_export.zip