title: Expression data from 34 Synovial Sarcomas

status: Public on Aug 09 2014

city: Bordeaux

first: céline

last: brulard

address: 229 cours de l'argonne

institute: Institut Bergonié

summary:
Background: Synovial sarcoma (SS) occur in children as well as in adults, although metastatic events are much more common in the latter. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC) and genomic (GI) prognostic signatures related to chromosome integrity in sarcomas and gastrointestinal stromal tumors (GISTs). Here we investigate whether these signatures can also predict outcomes in SS.
Methods: One hundred primary untreated SS were selected for expression and genomic profiling in a training/validation approach.
Results: CINSARC and GI have strong, independent and validated prognostic values (p<0.0001). Comparing expression profiles of tumors with or without metastasis, 14 genes common with the CINSARC signature were identified and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult vs. pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis.
Conclusions: Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and GI are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. GI is potentially the best overall biomarker, and clearly the most clinically relevant, considering that genome profiling from formalin fixed samples is already used in pathology.

overall_design: 34 Synovial Sarcomas hybridized to Agilent-026652 Whole Human Genome Microarray 4x44K

first: Frederic

last: Chibon

first: Maria

last: Debiec-Rychter


title: Metastatic potential is determined early in synovial sarcoma development and reflected by tumor molecular features

status: Public on Jul 31 2014

city: Stanford

first: Joanna

last: Przybyl

address: 300 Pasteur Drive

department: Department of Pathology

country: USA

institute: Stanford University

type: Genome variation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Gene expressions in pancreatic cancer cells

status: Public on Aug 06 2014

city: Seoul

first: Jung Min

last: Kim

address: Gangnam-gu Teheran-ro 216

department: Department of Health Genomics

country: South Korea

institute: NAR Center, Inc. & Genoplan, Inc.

summary:
We used time-dependent spheroidal cultures of pancreatic cancer cells to investigate how spatiotemporal regulation in spheroids induces epithelial-mesenchymal plasticity (EMP).
We generated a round bottom spheroidal model using β3 integrin-negative pancreatic cancer cells in 2D conventional monolayer cultures, and compared the expression of integrin signaling-related genes that induce spheroidal geometry to determine if spheroidal geometry induces integrin switching.

overall_design: To identify the potential genes whose expression changed in response to culture conditions, we performed microarray analysis of gene expression in human MIA PaCa-2 cells grown under monolayer and spheroid culture conditions for 6 days and 13 days.

first: Jung-Hoo

last: Hwang

first: Jung

middle: M

first: Byoungjae


title: Marine omega-3 phospholipids suppress hepatic steatosis by a complex inhibition of biosynthetic pathways in dietary obese mice

status: Public on Jul 30 2014

city: Wageningen

first: Evert

middle: M.

last: van Schothorst

address: De Elst 1

country: Netherlands

institute: Wageningen University

summary:
Background & Aims: Non-alcoholic fatty liver disease accompanies obesity and is independently associated with cardiovascular disease. Omega-3 fatty acids, such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid, reduce the risk of cardiovascular disease due to their anti-inflammatory and hypolipidemic effects. Recent data suggested that metabolic effects of EPA/DHA as marine phospholipids could be stronger than triglycerides (fish oil). We characterised the mechanisms underlying beneficial effects of EPA/DHA phospholipids alone or in combination with antidiabetic drugs on hepatosteatosis in dietary obese mice. Methods: Male C57BL/6N mice were fed for 7 weeks a corn oil-based high-fat diet (cHF) or subjected to cHF-based interventions: (i) cHF with DHA/EPA as phosphatidylcholine-rich concentrate replacing ~10 % of dietary lipids (PC); ii) cHF with a low-dose of thiazolidinedione rosiglitazone (10 mg/kg diet), which retains some of the beneficial effects but also potentiates hepatic lipid accumulation (R); and iii) PC+R. Metabolic profiling together with hepatic gene expression and lipidomic analyses were performed.
Results: PC and PC+R prevented weight gain and glucose intolerance induced by cHF, while all interventions reduced abdominal fat and plasma triglycerides. In contrast to R, PC and PC+R lowered hepatic and plasma cholesterol and eliminated hepatosteatosis. Hepatic microarray analysis primarily revealed a complex downregulation of lipogenic and cholesterol biosynthesis pathways by PC. Lipidomic analysis identified arachidonic acid, DHA and EPA in hepatic phosphatidylcholine and phosphatidylethanolamine fractions as the most important variables. Importantly, down-regulation of genes within these pathways was enlarged by phospholipid versus triglyceride forms of EPA/DHA in an independent experiment. Conclusions: Obesity-associated hepatosteatosis and hypercholesterolemia were ameliorated by marine phospholipids in association with a complex inhibition of biosynthetic pathways in liver. Stronger effects of phospholipids versus triglyceride form of EPA/DHA suggest their preferential use in the prevention and possible treatment of obesity-associated metabolic hepatic dysfunctions.

overall_design: C57BL/6N wildtype male mice, aged 3 months and fed chow, received for 7 weeks a control corn oil-based high-fat diet (cHF), or one of the cHF supplementations: 1) ~7 % of dietary lipids was replaced by the EPA and DHA concentrate in the form of omega-3 phospholipids rich in phosphatidylcholine (PC); 2) low dose rosiglitazone (R); and 3) both PC and rosiglitazone (PC+R). After sacrification, liver was immediately dissected and snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 4x44K microarrays. Based on raw MA-plots, we excluded one HF and one R array sample before normalization.

first: E

first: D

last: Mandrikova

first: M

last: Rossmeisl

first: J

last: Keijer

last: Kopecky


title: Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma [expression]

status: Public on Jul 14 2014

city: San Francisco

first: Rintaro

last: Hashizume

address: 1450 3rd street

department: Neurosurgery

institute: UCSF

summary: Transcriptional profiling of two pediatric human DIPG cell lines, harboring the K27M mutation. DIPG cell lines were treated with GSKJ4 for 24 and 72 h. The untreated cell lines served as baseline, and expression fold changes in each treated cell line were determined relative to the baseline. Goal was to determine the effects of GSKJ4 treatment on global gene expression in DIPG cells harboring the K27M mutation.

overall_design: Three-condition experiment: 72 h GSKJ4 treated cells vs. 24 h GSKJ4 treated cells vs. untreated cells. Biological replicates: 1 cell line, with 2 technical replicates per condition.

first: Noemi

last: Andor

first: Yuichiro

last: Ihara

first: Robin

last: Lerner

first: Haiyun

last: Gan

first: Xiaoyue

last: Chen

first: Dong

last: Fang

first: Xi

last: Huang

first: Maxwell

middle: W

last: Tom

first: Vy

last: Ngo

first: David

last: Solomon

first: Sabine

last: Mueller

first: Pamela

last: Paris

first: Zhiguo

last: Zhang

first: Claudia

last: Petritsch

first: Nalin

last: Gupta

first: Todd

last: Waldman

first: C

middle: D

last: James


title: Metastatic potential is determined early in synovial sarcoma development and reflected by tumor molecular features  [transcriptome]

first: Joanna

last: Przybyl

summary: Synovial sarcoma (SynSa) is an aggressive mesenchymal tumor, comprising approximately 10% of all soft tissue sarcomas. Over half of SynSa patients develop metastasis or local recurrence, but the underlying molecular mechanisms of the aggressive clinical behavior remain poorly characterized.  Sixty four frozen tumor specimens from 54 SynSa patients were subjected to array comparative genomic hybridization (aCGH) and gene expression profiling. The examined set of tumor specimens included 16 primary tumors from untreated patients who did not develop metastasis/local recurrence (SynSa1 group), 26 primary tumors from untreated patients who developed metastases or local recurrence during follow-up (SynSa2 group), and 22 metachronous metastatic/recurrent SynSa tumors (SynSa3 group).    AURKA and KIF18A, which play important roles in various mitotic events, were the two most up-regulated genes in SynSa2 and SynSa3 groups compared to the SynSa1 group. Expression profiles of SynSa2 and SynSa3 tumors did not show any significant differences. Analysis of genomic index (GI) based on aCGH profiles demonstrated that the SynSa1 group consisted of tumors with significantly less complex genomes compared to SynSa2 and SynSa3 groups. There was no significant difference in genome complexity between SynSa2 and SynSa3 tumors.  Primary SynSa tumors from patients who develop metastases or local recurrence share common molecular features with metastatic/recurrent tumors. Presented data suggest that the aggressive clinical SynSa behavior is determined early in tumorigenesis and might be related to impaired regulation of mitotic mechanisms.  Introduction: Synovial sarcoma (SynSa) is an aggressive mesenchymal tumor, comprising approximately 10% of all soft tissue sarcomas. Over half of SynSa patients develop metastasis or local recurrence, but the underlying molecular mechanisms of the aggressive clinical behavior remain poorly characterized.  Materials and methods: Sixty four frozen tumor specimens from 54 SynSa patients were subjected to array comparative genomic hybridization (aCGH) and gene expression profiling. The examined set of tumor specimens included 16 primary tumors from untreated patients who did not develop metastasis/local recurrence (SynSa1 group), 26 primary tumors from untreated patients who developed metastases or local recurrence during follow-up (SynSa2 group), and 22 metachronous metastatic/recurrent SynSa tumors (SynSa3 group).   Results: AURKA and KIF18A, which play important roles in various mitotic events, were the two most up-regulated genes in SynSa2 and SynSa3 groups compared to the SynSa1 group. Expression profiles of SynSa2 and SynSa3 tumors did not show any significant differences. Analysis of genomic index (GI) based on aCGH profiles demonstrated that the SynSa1 group consisted of tumors with significantly less complex genomes compared to SynSa2 and SynSa3 groups. There was no significant difference in genome complexity between SynSa2 and SynSa3 tumors.  Conclusions: Primary SynSa tumors from patients who develop metastases or local recurrence share common molecular features with metastatic/recurrent tumors. Presented data suggest that the aggressive clinical SynSa behavior is determined early in tumorigenesis and might be related to impaired regulation of mitotic mechanisms.

overall_design: Gene expression profiling of 15 primary tumors from untreated patients who did not develop metastasis/local recurrence (SynSa1 group), 21 primary tumors from untreated patients who developed metastases or local recurrence during follow-up (SynSa2 group), and 21 metachronous metastatic/recurrent SynSa tumors (SynSa3 group); Agilent One-Color technology.

first: Raf

last: Sciot

first: Agnieszka

last: Wozniak

first: Patrick

last: Schöffski

first: Vanessa

last: Vanspauwen

first: Ignace

last: Samson

first: Janusz

middle: A

last: Siedlecki

first: Piotr

last: Rutkowski

first: Maria

last: Debiec-Rychter


title: Expression profile of HCT116 cells transfected with miR-204-5p

city: WUXI

first: zhaohui

last: Huang

state: Jiangsu

address: 200 Huihe Road

department: Wuxi Oncology Institute

country: China

institute: the Affiliated Hospital of Jiangnan University

summary: We have employed whole genome microarray expression profiling as a discovery platform to screen potential target genes of miR-204-5p in colorectal cancer cell HCT116.  HCT116 cells were seeded in 6-cm2 tissue culture plates and transfected with the miR-204-5p mimic or negative control (NC) using Lipofectamine 2000 (Invitrogen, USA). After propagation for 48 hours, total RNA was extracted using TRIzol reagent (Invitrogen, USA). Expression profiling was performed using an Agilent human whole genome oligo microarray chip (4×44K) (Agilent, USA)

overall_design: Expression profiling in HCT116 cells was measured at 48 hours after transfection with miR-204-5p or negative control. Experiments were performed using the two samples without repeat experiment.

first: Zhaohui


title: Modeling Luminal breast cancer heterogeneity: Combination therapy to suppress hormone receptor negative cells in Luminal disease

city: los Angeles

first: Hany

last: Abdel-Hafiz

state: California

address: 110 N George Burns RD, DRoom 3057

department: Medicine/ Medical Oncology

institute: Cedars-Sinai Medical Center

summary: Many Luminal breast cancers are heterogeneous, containing substantial numbers of estrogen (ER-) and progesterone (PR-) receptor-negative cells among the ER+PR+ ones. Currently, the Basal-like ER-PR- Luminobasal subpopulation in Luminal disease is not targeted for treatment. To address the relationships between ER+PR+ and ER-PR- cells in Luminal cancers and tightly control their ratios, we have generated isogenic pure Luminal (pLUM) and pure Luminobasal (pLB) cells from the same parental Luminal human breast cancer cell line. We show that pLUM suppress proliferation of pLB cells in mixed-cell 3D colonies in vitro and in pLUM:pLB mixed-cell xenografts in mice. High-throughput screening of FDA-approved oncology drugs reveal pLB cells are sensitive to the EGFR inhibitors Gefitinib and Erlotinib. In mixed-cell 3D colonies and mixed-cell solid mouse tumors, combination therapy with the antiestrogen Fulvestrant and the EGFRi Gefitinib constitutes a robust treatment strategy. We propose that response to combination endocrine/EGFRi therapies in heterogeneous Luminal cancers will improve long-term survival in patients whose primary tumors have been preselected for the appropriate biomarkers.

overall_design: The study contains 2 different sample groups measured in triplicate, for a total of 6 individual samples (6 arrays). To generate pLUM, cells from an E tumor were propagated in vitro ~2 months in 1nM E. Live cells were FACS-sorted (Moflo XDP 100, BeckmanCoulter) using CLD3 (mouse Anti-human CLD3-FITC, R&D Systems) and CD49f (PE-Cy5 Rat Anti-Human CD49f, BD Pharmingen) to separate Luminal (CLD3+CD49f-) from Luminobasal (CLD3-CD49f+) cells. Cells were re-plated, cultured another ~2 months in E, then resorted twice to generate pure pLUM (CLD3+CD49f-). They are maintained in E-containing medium and remain Luminobasal-free. To generate pLB, cells from an E+P tumor were plated in vitro ~2.5 months under EWD conditions. They were FACS sorted and the CLD3-CD49f+ subpopulation was re-cultured an additional ~2 months under EWD conditions then resorted twice to yield pure pLB (CLD3-CD49f+). They are maintained in EWD media and remain Luminal-free. Thus, the experiment contains two cell lines and analyzed in triplicate (6 microarrays). RNA from triplicate sorts was profiled using Agilent 4x44K chips. Labeling, hybridization and initial analyses were performed at MOgene LC (www.mogene.com).

first: Kathryn

middle: B

last: Horwitz

first: Mauricio

middle: P

last: Pinto


title: Analysis of biological characterization and metastasis-related genes in cell lines derived from the Primary lesion and lymph node metastasis of a squamous cell carcinoma arising in the mandibular gingiva

status: Public on Jun 30 2014

city: Fukuoka

first: Takahiro

last: Fujinaga

state: Fukuoka

address: 3-1-1 Maidashi Higashi-ku

department: Faculty of Dental Science

country: Japan

institute: Kyushu University

summary: Controlling metastatic lesions is an important part of improving cancer prognosis, in addition to controlling the primary lesion. There have been many histological examinations of primary and metastatic lesions, but little basic research using cell strains from primary and metastatic lesions belonging to the same patient. In this study, we successfully established a cell strain derived from lower gingival carcinoma (WK2) and a strain derived from secondary cervical lymph node metastasis (WK3F) through primary cultures of tissue from a patient with oral squamous cell carcinoma. We then investigated the biological characteristics of the cancer cell strains from these primary and metastatic lesions, and analyzed metastasis-related genes.  Comparing the biological characteristics in vitro showed WK3F to have higher cell proliferation ability and shorter cell doubling time than WK2. It also showed increased cell migratory ability, and high invasive and self-replication abilities. Heterotransplantation into nude mice resulted in high tumor formation rates in the tongue and high metastasis rates in the cervical lymph nodes.  Changes in WK2 and WK3F gene expression were comprehensively analyzed with the microarray method. Genes with increased expression in WK3F compared to WK2 were extracted when Z-score ≥ 2.0 and ratio ≥ 5.0, while genes with reduced expression in WK3F compared to WK2 were extracted when Z-score ≤ -2.0 and ratio ≤ 0.2. As a result, differences were found in 604 genes. From these, MAGEC1 (88.0 times), MMP-7 (18.6 times), SNAI1 (6.6 times), MACC1 (6.2 times), and HTRA1 (0.012 times) were selected as metastasis-related candidate genes. The results suggest that these molecules could be important to clarifying the mechanism of metastasis, and could become therapeutic targets.

overall_design: We successfully established a cell strain derived from lower gingival carcinoma (WK2) and a strain derived from secondary cervical lymph node metastasis (WK3F) through primary cultures of tissue from a patient with oral squamous cell carcinoma. Changes in WK2 and WK3F gene expression were comprehensively analyzed with the microarray method.

first: Fujinaga

last: Takahiro

first: Kumamaru

last: Wataru


title: CHD7 regulates gene networks involved in neural crest cell migration and axon guidance

status: Public on Jul 01 2014

city: Goettingen

first: Gabriela

last: Salinas

state: Lower-Saxony

address: Kreuzbergring 57

country: Germany

institute: Universitaetsmedizin Goettingen

summary: Heterozygous loss-of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, peripheral nerves and several organ systems like eyes, ears, nose and heart. Recently, it was demonstrated that CHD7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures. So far only few CHD7 target genes involved in neural crest cell development have been identified and the role of CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial transition is unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7Whi/+ and Chd7Whi/Whi) mouse embryos at day 9.5, the time point of neural crest cell migration. We identified 98 genes showing greater than two fold differences in expression (log2 fold-change) and a P-value to false discovery rate (FDR) < 0.05 between wild-type and Chd7Whi/Whi embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance like semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 and one of its target genes, namely semaphorin3a in Xenopus laevis embryos, we could show abnormalities in the migration of neural crest cells in vivo. Additionally, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7 negative CHARGE patients suggesting a role for SEMA3A in the pathogenesis of CHARGE syndrome.

overall_design: To identify genes that are affected by the absence of functional Chd7 at the time point of neural crest cell migration, the expression profiles of E9.5 wild-type, Chd7Whi/+ and Chd7Whi/Whi female mouse embryos were compared by whole-genome microarray analysis. Mouse embryos of the same sex were used to avoid sex-dependent gene expression effects. We performed microarray analysis by using the Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Agilent) on four biological replicates from each group.

first: Yvonne

last: Schulz

first: Peter

last: Wehner

first: Lennart

last: Opitz

last: Salinas-Riester

first: Ernie

last: Bongers

first: Conny

last: Ravenswaaij-Arts

first: Josephine

last: Wincent

first: Jacquline

last: Schoumans

first: Jürgen

last: Kohlhase

first: Annette

last: Borchers

first: Silke

last: Pauli


title: Establishment of trophoblast stem cells under defined culture conditions in mice

status: Public on Jul 08 2014

city: Kofu

first: Yasuhide

last: Ohinata

state: Yamanashi

address: 4-4-37 Kakeda

department: Faculty of Life and Environmental Science

institute: Yamanashi University

summary: The inner cell mass (ICM) and trophoblast cell lineages duet early embryonic development in mammals. After implantation, the ICM forms the embryo proper as well as some extraembryonic tissues, whereas the trophoectoderm (TE) exclusively forms the fetal portion of the placenta and the trophoblast giant cells. Although embryonic stem (ES) cells can be derived from ICM in cultures of mouse blastocysts in the presence of LIF and/or combinations of small-molecule chemical compounds, and the undifferentiated pluripotent state can be stably maintained without use of serum and feeder cells, defined culture conditions for derivation and maintenance of undifferentiated trophoblast stem (TS) cells have not been established. Here, we report that addition of FGF2, activin A, XAV939, and Y27632 are necessary and sufficient for derivation of TS cells from both of E3.5 blastocysts and E6.5 early postimplantation extraembryonic ectoderm. Moreover, the undifferentiated TS cell state can be stably maintained in chemically defined culture conditions. Cells derived in this manner expressed TS cell marker genes, including Eomes, Elf5, Cdx2, Klf5, Cdh1, Esrrb, Sox2, and Tcfap2c; differentiated into all trophoblast subtypes (trophoblast giant cells, spongiotrophoblast, and labyrinthine trophoblast) in vitro; and exclusively contributed to trophoblast lineages in chimeric animals. This delineation of minimal requirements for derivation and self-renewal provides a defined platform for precise description and dissection of the molecular state of TS cells.

overall_design: Total RNA was purified by using RNeasy Mini kit (QIAGEN). Microarray targets from 200 ng total RNA were synthesized and labelled using the Low RNA Input Linear Amp Kit (Agilent) and hybridized to Mouse 4x44K Ver.2.0 arrays. Arrays were scanned on an Agilent Technologies Microarray scanner and signal intensities were calculated in Agilent Feature Extraction 10.7.3.1 software.


title: PADI4 acts as a coactivator of Tal1 by counteracting repressive histone arginine methylation at the IL6ST (gp130) promoter

status: Public on Jun 02 2014

summary: Analysis of common genes regulated by Tal1 and PADI4

overall_design:
2 controls + 2x3 knockdown samples
HEL cells were transduced with lentiviruses harboring shconstructs against the transcription factor Tal1 and PADI4 respectively, in biological triplicates. Two control samples with a control lentivirus with an shRNA against LacZ were included. RNA was prepared 6 days after transduction.

first: Joern

last: Lausen

first: Stephan

last: Kolodziej

first: Claudia

last: Pommerenke


title: Differential Expression of Stress and Immune Response Pathway Transcripts and miRNAs in Normal Human Endothelial Cells Subjected to Fractionated or Single-Dose Radiation [mRNA]

city: Northbrook

first: Michael

last: Falduto

state: IL

address: 1808 Janke, Unit M

institute: GenUs BioSystems, Inc.

summary: While modern radiotherapy technologies can precisely deliver higher doses of radiation to tumors; thus, reducing overall radiation exposure to normal tissues, moderate dose and normal tissue toxicity still remains a significant limitation. The present study profiled the global effects on transcript and miR expression in Human Coronary Artery Endothelial Cells (HCAECs) using single-dose irradiation (SD, 10Gy) or multi-fractionated irradiation (MF, 2Gy x 5) regimens. Longitudinal timepoints were collected after a SD or final dose of MF irradiation for analysis using Agilent Human Gene Expression and miRNA microarray platforms. Compared to SD, the exposure to MF resulted in robust transcript and miR expression changes in terms of the number and magnitude. For data analysis, statistically significant mRNAs (2-fold) and miRs (1.5-fold) were processed by Ingenuity Pathway Analysis (IPA) to uncover miRs associated with target transcripts from several cellular pathways post-irradiation. Interestingly, MF radiation induced a cohort of mRNAs and miRs that coordinate the induction of immune response pathway under tight regulation. Additionally, mRNAs and miRs associated with DNA replication, recombination and repair, apoptosis, cardiovascular events and angiogenesis were revealed.

overall_design: Human Coronary Artery Endothelial Cells (HCAECs) were irradiated in a PANTAK high frequency X-ray generator (Precision X-ray Inc., N. Bedford, CT), operated at 300kV and 10MA. The dose rate was 1.6 Gy per min. Cells were plated into T75cm2 flasks (1-1.5 x 10^6 for single dose radiation and 0.6-0.8 x 10^6 for fractionated radiation). After 24h, cells were exposed to a total of 10 Gy radiation administered either as a single-dose radiation (SD), or as multi-fractionated radiation of 2 Gy x 5 (MF). These non-isoeffective doses were selected to simulate clinical hypofractionated and conventionally fractionated radiotherapy regimens. For the MF protocol, cells were exposed to 2 Gy radiation twice a day, at 6h interval. The cells were approximately 90% confluent at the time of harvesting. For both protocols, radiation-induced changes were analyzed at 6h and 24h after a SD and 6h and 24h after the final dose of fractionated irradiation. Separate controls were maintained for SD and MF radiation protocols.

first: Sanjeewani

middle: T

last: Palayoor

first: Molykutty

last: John-Aryankalayil

first: Adeola

middle: Y

last: Makinde

first: Scott

middle: R

last: Magnuson

first: C

middle: N

last: Coleman


title: Differential Expression of Stress and Immune Response Pathway Transcripts and miRNAs in Normal Human Endothelial Cells Subjected to Fractionated or Single-Dose Radiation

type:
Non-coding RNA profiling by array
Expression profiling by array


title: Gene expression profiling in MCF-7 cells exposed to blackcurrant extract.

status: Public on Jun 10 2014

city: Aomori

first: Naoki

last: Nanashima

state: Aomori

address: 58-1 Mase, Hamadate

department: Department of Nutrition

institute: Aomori University of Health and Welfare

summary: Blackcurrants (Ribes nigrum L., Grossulariaceae) have a high content of anthocyanin polyphenols and these have been shown to have beneficial effects on health, owing to their antioxidant and anti-carcinogenic properties. This study analyzed the constituents of blackcurrant extract (BCE) and investigated its potential phytoestrogenic effects using a breast cancer cell line (MCF-7) overexpressing the estrogen receptor (ER) α.  Microarray and ingenuity pathway analysis showed that BCE activated upstream genes such as ERα and transforming growth factor beta 1, and upregulated the expression of many genes downstream of ERα.

overall_design: MCF-7 cells were seeded in culture dish and maintain to confluent. Then medium replace with phenol-red-serum-free DMEM medium with or without BCE (50μg/ml). After the cells were incubated for 24 h at 37 °C 5% CO2.


title: The effect of inhaled IFNbeta (SNG001) versus placebo on peripheral blood mononuclear cells during an upper respiratory tract infection

city: Southampton

first: Phillip

last: Monk

address: Tremona Road

department: Southampton General Hospital

country: United Kingdom

institute: Synairgen Research Ltd

summary:
Microarray analysis of whole blood samples (collected into PAXgene tubes from PreAnalytiX) during a phase II double-blind, randomized (1:1 ratio) clinical trial in which inhaled IFN-β (SNG001) or placebo treatment was initiated within 24 hours of asthmatics reporting cold symptoms.
Patients were dosed once a day for 14 days, with samples collected at day 1 (prior to first dose), day 4 and day 7.  Analysis of genome-wide gene expression (only conducted using samples from the BTS Step 4/5, mITT subgroup), showed a treatment-related enhancement of systemic innate immunity, thereby providing compelling evidence for exogenous IFN-β enhancing antiviral responses.

overall_design: Placebo versus SNG001 (IFNbeta). Day 4 (visit 3); Placebo 25 replicates, SNG001 18 replicates.  Day 7 (visit 4); Placebo 28 replicates, SNG001 20 replicates.


title: Maternal microRNAs secreted by the endometrium act as  transcriptomic regulators of the pre-implantation embryo (mouse)

city: Valencia

first: Juan

last: Moreno-Moya

address: Catedrático Agustín Escardino

country: Spain

institute: FIVI

summary: The developmental origins of adult disease are now recognized to reflect intrauterine conditions during embryonic and fetal life. Cell-cell communication between the maternal endometrium and the pre-implantation embryo can occur by several means. Here, we show that maternal miRNAs are secreted by the endometrial epithelium to the endometrial fluid. Microarray assessments revealed the presence of specific miRNAs that are associated with the window of implantation and therefore in direct contact with the human preimplantation embryo. These miRNAS are transported as free or exosome-associated molecules secreted to the endometrial fluid and then uptake into the pre-implantation embryo through the trophoectoderm. Finally, these maternal miRNAs were able to induce transcriptional and functional modifications of the embryo. Therefore, we propose an innovative model whereby endometrial maternal miRNAS may function as transcriptomic regulators during early embryo development offering a new perspective on the developmental origins of adult diseases such as obesity, type 2 diabetes, and others that are now recognized to reflect intrauterine conditions.

overall_design: The B6C3F1 mice strain was purchased. Female mice aged 6–8 weeks were primed to ovulate by administering 10 IU pregnant mare serum gonadotropin(Sigma-Aldrich, Irvine, UK), followed by administration of 10 IU hCG(Sigma-Aldrich, Irvine, UK),  48 hours later. Females were housed overnight with male breeders and examined the following morning for the presence of a vaginal plug (day 1 of pregnancy). On day 2 of pregnancy, mice were sacrificed by cervical dislocation, and embryos flushed with PBS from the oviduct using a blunt 30-gauge needle. Then, embryos were cultured in CCM-30 medium (Vitrolife, Lubeck, Germany) in presence or absence of 400nM of mir-30d MIMIC or Scramble-Alexa 488 for 72 hours. Then embryos are four times washed in fresh CCM. Experiment were carried out by triplicate and with 30 embryos/condition

first: Felipe

last: Vilella-Mitjana

first: Sebastián

last: Martínez-Escribano

first: Antonio

last: Marcilla

first: Carlos

last: Simón


title: Transcription profile of hearts extracted from zebrafish embryos treated with SU5402 at 48 hpf

status: Public on May 12 2014

city: La Jolla

first: Xin-Xin

middle: I.

last: Zeng

state: CA

address: 9500 Gilman Drive 0380

department: Division OF Biological Sciences

institute: UCSD

summary: Heart formation requires input from two populations of progenitor cells - the first and second heart fields - that differentiate at distinct times and create different cardiac components. The cardiac outflow tract (OFT) is built through recruitment of late-differentiating, second heart field (SHF) -derived cardiomyocytes to the arterial pole of the heart. Mechanisms responsible for selection of an appropriate number of OFT cells from the SHF remain unclear, although several lines of evidence emphasize the importance of FGF signaling in promoting this process.  Here, we examine the impact of inhibition of FGF signaling on cardiac transcription profiles in an effort to identify genes operating downstream of FGF during OFT development.

overall_design: We compared hearts from embryos treated with the FGFR inhibitor SU5402 to the hearts from sibling embryos treated with DMSO.  Two replicates were performed.

middle: I

first: Deborah

last: Yelon


title: Human cellular models for Herpes Simplex Virus, type 1 (HSV-1) using induced pluripotent stem cell derived neuronal lineages

status: Public on May 02 2014

city: Pittsburgh

first: Leonardo

last: D'Aiuto

state: PA

address: 3811 O’Hara Street

institute: UPMC

summary: Herpes simplex virus type 1 (HSV-1) is a 152 Kb double stranded DNA alpha-herpesvirus, which establishes long life latent infection in sensory neurons. Most of our knowledge regarding HSV-1 latency comes from in vivo studies using small animal models, mainly rodents and rabbits, which are not naturally infected by HSV-1. Furthermore, these animal models do not fully recapitulate the species specific effects of human HSV-1 infection. Human cellular models utilize trigeminal ganglia removed from cadavers or, alternatively, neuron-like cells derived from cancerous cell lines that do not fully reflect effects on normal human neurons. This limitation poses the need to develop an in vitro model to investigate molecular details of the mechanisms underlying latency and reactivation in human neurons. Induced pluripotent stem (iPS) cell technologies offer an unprecedented opportunity to generate unlimited supplies of neurons and the facility to manipulate such cells in vitro. In this study, we developed an in vitro HSV-1 infection model in human iPS-derived neural progenitor cells (NPCs) and neurons, which displays the main hallmarks of latency defined in animal models and in humans.

overall_design: Induced pluripotent stem (iPS) cells were generated from human skin biopsy samples

first: Vishwajit

last: Nimgaonkar

first: Jadranka

last: Milosevic

first: Luigi

last: Viggiano


title: Oncogenic role of TOX in CTCL

status: Public on Apr 29 2014

city: Vancouver

first: Youwen

last: Zhou

state: BC

address: Room 490, 828 West 10th Ave.

department: Dermatology and Skin Science

country: Canada

institute: UBC

summary: TOX is a nuclear factor essential for the development of CD4+ T cells in the thymus. TOX is found to be aberrantly up-regulated in the skin biopsies and in the blood CD4+ T cells of cutaneous T cell lymphoma. The goal of this study is to identify potential transcriptional targets of TOX in CTCL by comparison between TOX shRNA transfected CTCL cells (Hut78 and HH) and control CTCL cells.

overall_design: Two color experiment. Lentivirus transduced control vector vs. TOX shRNA vectors on Hut78 and HH cell lines. Biological replicates: 3 control replicates, 3 shRNA tansduced replicates for each cell line.

first: Yuanshen

last: Huang

first: Ming-Wan

last: Su

first: Xiaoyan

last: Jiang


title: Human hepatocarcinoma cells : Huh-7 vs. SNU-739

city: Chuncheon

first: Hyung-Joo

last: Kwon

state: Gangwon-do

address: 1 Hallymdaehak-gil

department: Department of Microbiology

institute: Hallym University College of Medicine

summary: Transcriptional profiling of human hepatocarcinoma comparing Huh-7 and SNU-739.

overall_design: Two-condition experiment, normalized ratio represented by Huh-7/SNU-739. Biological replicates: 2 Huh-7 replicates, 2 SNU-739 replicates.

first: Sanghoon

first: Dongbum

last: Kim

first: Younghee

last: Lee


title: Microarray analysis of H460 parental and H460 holoclone (stem-like cell)-derived tumors

status: Public on Apr 23 2014

city: Boston

first: David

middle: J.

last: Waxman

state: MA

address: 5 Cummington Mall

department: Department of Biology and Bioinformatics Program

institute: Boston University

summary: BACKGROUND: Cancer stem-like cells were isolated from human H460 non-small cell lung cancer cells by limiting dilution assays and by their holoclone morphology, followed by assessment of their self-renewal capacity, tumor growth, vascularity, and tumor blood perfusion.  H460 holoclones were used to implant H460 holoclone-derived tumors, which grew slower than parental H460 tumors, but displayed significant increases in microvessel density and tumor blood perfusion.  Microarray analysis identified  differentially regulated genes in the holoclone-derived tumors, of which many were associated with angiogenesis.  The differentially regulated genes include several small leucine-rich proteoglycans that may modulate angiogenesis and serve as novel therapeutic targets for inhibiting cancer stem cell-driven angiogenesis.(Cancer Letters Vol 346, Issue 1, 28 April 2014, Pages 63–73; PMID: 24334139; PMCID: PMC3947657).

overall_design: Implanted tumors derived from H460 parental cells, or from each of four independent H460 holoclones, were implanted subcutaneously in scid immunodeficient mice. Tumors derived from the 4 holoclones (designated H460/2E1, H460/2H3, H460/3F1, and H460/2E7) were used for global transcriptome/microarray analysis in direct comparison to H460 tumors grown from parental H460 cells. For each H460 holoclone-derived tumor line or H460 parental cell-derived tumor, total RNA was prepared from n=7 to n=10 individual tumors and used to prepare two independent pools of tumor RNA (each pool comprised of RNA isolated n=3-5 tumors) for use in a two color microarray analysis. Tumor RNA pools were prepared by combining equal amounts of RNA from each individual tumor  to minimize the impasct of inter-tumoral variation on gene expression profiles. All RNAs had an RNA integrity number >8.0, determined using an Agilent Bioanalyzer 2100 instrument. cDNAs transcribed from pools of RNA for each holoclone-derived tumor line and for each parental H460 cell-derived tumor pool, were labeled with Alexa 647 or Alexa 555 dyes in a fluorescent reverse pair (dye swap) design for competitive hybridization to Agilent Whole Human Genome Microarrays.

first: Eugene

last: Manley Jr

middle: J


title: Microarray analysis of breast cancer cell lines with different levels of P-cadherin expression treated with the anti-cancer bacterial protein azurin

status: Public on Apr 30 2014

city: Lisboa

first: Nuno

last: Bernardes

state: Lisboa

address: Avenida Rovisco Pais, 1

department: Departamento de Bioengenharia

country: Portugal

institute: Instituto Superior Técnico

summary:
We performed a microarray analysis to compare the expression profile of azurin treated and untreated with different P-cadherin expression levels. We also compared the differentially expressed genes regulated by P-cadherin overexpression. Both cell lines presented an up-regulation of apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. Conversely, invasive MCF-7/AZ.Pcad cells treated with azurin presented a decreased expression of genes associated with cell surface receptors and signal transduction, as well as genes associated with biological adhesion and migration.
Azurin is a bacterial protein from Pseudomonas aeruginosa which exerts an inhibitory activity in cancer cells. In P-cadherin-overexpressing models, a bad prognosis marker in breast cancer increasing invasion and other malignant features, azurin decreases the invasion of cancer cells.   We performed a microarray analysis to compare the expression profile of azurin treated cells with different P-cadherin expression levels. Azurin up-regulated apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. In the contrary, in invasive MCF-7/AZ.Pcad cells, azurin decreased the expression of genes associated with cell surface receptors and signal transduction, as well as biological adhesion. Further, azurin decreased adhesion of cells to proteins from the Extracellular matrix (ECM) and altered protein expression of integrins α6, β4 and β1 and interfered with the ability of these cells to form mammospheres. Altogether, our results further enlighten the anti-cancer effects mediated by azurin in P-cadherin overexpression breast cancer models.

overall_design: Cells were exposed to azurin (100uM) for 48h, after which total RNA was extracted. Control cells were exposed during the same time to PBS buffer solution. Three independent samples for each condition were used treated with different azurin production batches.

first: Asenio

last: Fialho

first: Joana

last: Paredes

first: Raquel

last: Seruca

first: Manuel

last: Santos

first: Laura

last: Carreto

first: Andre

middle: F

last: Vieira

first: Sofia

last: Abreu

first: Ana

middle: S

last: Ribeiro


title: Analysis of the expression of Ataxin-2-target genes

status: Public on Jun 20 2014

city: Suita

first: Yukio

last: Kawahara

state: Osaka

address: 2-2 Yamada-oka

department: Graduate School of Medicine

institute: Osaka University

summary:
We recently identified the RNA targets of Ataxin-2 by using PAR-CLIP. To elucidate the functional role of Ataxin-2 on target-binding, we have knocked down or overexpressed Ataxin-2 in HEK293T cells and extracted RNAs 48 hrs after transfection.
Then, these total RNAs were subjected to whole transcripts microarray analysis to examine how the perturbation of Ataxin-2 expression affects target gene expression.

overall_design:
Ataxin-2 was either knocked down using siRNA or overexpressed using the expression construct of Halo-Ataxin-2.Control siRNA was transfected as a control of knockdown experiment.
The expression construct of Halo-tag alone was used as a control of overexpression experiment.  Forty-eight hrs after transfection, total RNAs were extracted and subjected to microarray analysis.

first: Munetaka

last: Yamamoto

first: Moe

last: Yokoshi


title: DDR1 knockdown in BXPC3 cell line

status: Public on May 01 2014

city: Santa Monica

first: Mike

last: Mattie

address: 1800 Stewart Street

department: Applied Molecular Biology

institute: Agensys Inc

summary: Examination of effect of stable DDR1 knockdown by shRNA on transcriptional profile in BXPC3 cell line to understand role of DDR1 in tumorigenesis.

overall_design: Transcriptional profiles of parental BXPC3 cell line was compared to BXPC3 cells stably transfected with non-target shRNA or DDR1 shRNA, N=3 for each condition.

first: Michael

first: Mi

last: Chang


title: Prdm16 Knockout Brown Adipose Tissue

status: Public on Apr 09 2014

city: Cincinnati

first: Hee-Woong

last: Lim

state: Ohio

address: 3333 Burnet Ave. MLC 7024

department: Division of Biomedical Informatics

institute: Cincinnati Children's Hospital Medical Center

summary: Gene expression profile from brown adipose tissues of Prdm16 knockout and wile type mice. Prdm16 is a transcription factor that regulates the thermogenic gene program in brown and beige adipocytes.  However, whether Prdm16 is required for the development or physiological function of brown adipose tissue (BAT) in vivo has been unclear. By analyzing mice that selectively lacked Prdm16 in the brown adipose lineage, we found that Prdm16 was dispensable for embryonic BAT development.

overall_design: Brown adipose tissues were collected from Prdm16 knockout and wiletype mice with 4 biological replicates per condition. Experiment was done in two separate batch for 6-week-old and 11-month-old. Extracted RNA was hybridized to Agilent two-color arrays.

first: Matthew

last: Harms

first: Jeff

last: Ishibashi

first: Wenshan

last: Wang

first: Susumu

last: Goyama

first: Tomohiko

last: Sato

first: Mineo

last: Kurokawa

first: Kyoung-Jae

last: Won

first: Patrick

last: Seale


title: Gene expression profiles of colorectal cancer cells under the three dimensional culture

status: Public on Apr 12 2014

first: Sung Ouk

last: Nam

address: 7-45-1 Nanakuma, Jonan-ku

department: Department of Obstetrics and Gynecology

institute: Faculty of Medicine, Fukuoka University

summary: Colorectal cancer (CRC) shows the high mortality and morbidity. The mortal number of patients and the morbid number of patients with CRC is also increasing. However, the genes which relate to promote tumorigenesis in CRC remain unclear. In order to investigate specific genes and pathways involved in CRC tumorigenesis, we compared genes expressed between three dimensional cultures and control two-dimensional cultures.

overall_design: Total RNA was prepared from the CRC cell lines under the condition of two-dimensional culture and three dimensional culture.

first: Sung-Ouk

first: Fusanori

last: Yotshumoto

first: Kohei

last: Miyata

first: Shingo

last: Miyamoto


title: Acute and long-term responses to radiation in zebrafish

status: Public on Apr 01 2014

city: Augusta

first: Robert

last: Podolsky

state: GA

institute: Georgia Regents University

summary:
A set of changes is identified in the transcription profile associated with the long-term, but not the acute, response to radiation exposure. The study was performed in vivo using zebrafish.
To study the long-term response, 24 hour post-fertilization embryos were exposed to 0.1 Gy (low dose) or 1.0 Gy (moderate dose) of whole-body gamma radiation and allowed to develop for 16 weeks. Liver mRNA profiles were then analyzed using the Affymetrix microarray platform, with validation by quantitative PCR. To be able to compare this to the acute response, 16-week old adults were exposed at the same doses and analyzed after 4 hours.

overall_design: We used 5 treatment groups: A=non-irradiated control, allowed to develop for 16 weeks; B=low-dose (0.1 Gy) irradiated, allowed to develop for 16 weeks; C=high-dose (1.0 Gy) irradiate, allowed to develop for 16 weeks; D=16 week old adults irradiated at low dose (0.1 Gy); E=16 week old adults irradiate at high dose (1.0 Gy)

first: William

last: Dynan


title: Transcriptomic of early embryonic invasion at implantation sites in a murine model.

first: Juan

middle: M

last: Moreno-Moya

summary: Trophoblast Invasion is a complex mechanism that involves several genes and processes that are exquisitely regulated by the mother. Functional genomics has shown that immunomodulatory and proliferation are two essential key processes involved.

overall_design: Adult virgin B6CBA F1/J female mice were mated with CD1 fertile males to induce pregnancy (day 0=vaginal plug). Mice were sacrificed by cervical dislocation. Implantation and inter-implantation sites were divided by sharp dissection 6.5 days post-coitum (dpc) (n=3 mice). Uterine segments included uterine myometrium, stroma, and epithelium. Inter-implantation decidua (ID) were collected and Implantation sites also were divided by sharp dissection to separate extra-embryonic tissue (ET) from surrounding decidua (SD). From the embryo, only the invasive trophoblast formed by the ectoplacental cone was studied too.

first: J

first: A

last: Franchi

first: S

last: Martínez-Escribano

last: Martínez-Conejero

last: Boca

last: Oehninger

last: Horcajadas


title: Perception of fight outcome is needed to activate socially driven changes in brain transcriptome

status: Public on Apr 10 2014

first: José Miguel

last: Simões

address: Rua Jardim do Tabaco 34

department: Eco-Ethology Research Unit

institute: ISPA - Instituto Universitário

summary: Group living animals must be able to express different behavior profiles depending on their social status. This implies that the same genotype may translate into different behavioral phenotypes through socially driven differential gene expression. Here we show for the first time that what triggers the switch between status-specific neurogenomic states is not the objective structure of the social interaction but rather the subjects’ perception of its outcome. For this purpose we had male zebrafish fight either a real opponent or their own image on a mirror. Massive changes in the brain transcriptome were observed in real opponent fighters, which experience either a victory or a defeat. In contrast, mirror fighters, which had no information on fight outcome despite expressing aggressive behavior, failed to activate a neurogenomic response. These results indicate that, even in cognitively simple organisms such as zebrafish, neurogenomic responses underlying changes in social status rely on cognitive appraisal.

overall_design:
Brain samples from zebrafish, Danio rerio were collected after experimental manipulations generated 4 phenotypes regarding social experience: mirror fighters (M), winners of a real opponent fight (W), losers of a real opponent fight  (L); and socially isolated fish (I).
After 30 minutes of experimental manipulation animals were anesthetized with a lethal dose of MS-222 (1000-1500 mg/l) and decapitated. Brains were rapidly collected, homogenized and RNA extracted following standard methods of  RNeasy Lipid Tissue Mini Kit, Qiagen. RNA was then treated with DNase (RNase-free DNase set, Qiagen) to remove possible contaminations with genomic DNA and concentration and purity was estimated by spectrophotometric absorbance in a NanoDrop ND-1000 UV-Vis Spectrophotometer (Nano-Drop Technologies).

first: Magda

middle: C

last: Teles

first: Ana

last: Oliveira

last: Becker

first: Rui


title: The gene expression of aromatase-inhibitor-resistant cell line

city: Sendai

first: Rika

last: Fujii

address: 2-1, Seiryo-machi, Aoba-ku

department: Molecular and functional dynamics

institute: Tohoku University

summary: To identify the genes which have relation to aromatase-inhibitor-resistance, we compared the gene expression of aromatase-inhibitor-resistant cell, A3, with that of parent cell line, T-47D.

overall_design: Because A3 showed remarkable cell proliferation by 1nM Dihydrotestosterone(DHT), cells were cultured with DHTand bicalutamide for 24h, and total RNA was extracted.


title: Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fueled matrix metalloproteinase production

city: Auckland

first: Cris

last: Print

address: Grafton Campus, Park Rd

country: New Zealand

institute: Auckland University

summary:
In addition to satisfying the metabolic demands of cells, mitochondrial metabolism helps regulate immune cell function. To date, such cell-intrinsic metabolic-immunologic cross-talk has only been described operating in cells of the immune system. Here we show that epidermal cells utilize fatty acid β-oxidation to fuel their contribution to the immune response during cutaneous inflammation. By live imaging metabolic and immunological processes within intact zebrafish embryos during cutaneous inflammation, we uncover a mechanism where elevated β-oxidation-fueled mitochondria-derived reactive oxygen species within epidermal cells helps guide matrix metalloproteinase-driven leukocyte recruitment. This mechanism requires the activity of a zebrafish homolog of the mammalian mitochondrial enzyme, Immunoresponsive gene 1. This study describes the first example of metabolic reprogramming operating within a non-immune cell type to help control its contribution to the immune response. Targeting of this metabolic-immunologic interface within keratinocytes may prove useful in treating inflammatory dermatoses.
In this study, Affymetrix Zebrafish Genome Arrays were used to identify zebrafish Irg1l (a homolog of mammalian IRG1) as a gene up-regulated in response to Salmonella infection.

overall_design: The microarray analysis compared 4 day post fertilisation (dpf) dissected larval zebrafish trunks (approximately 50) that had been injected at 2 dpf with either: (i) PBS (as a negative control) or (ii) live Salmonella enterica serovar Typhimurium bacteria. The study was performed in triplicate.

first: C

middle: G

last: Hall

first: P

last: Crosier


title: Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment

status: Public on Mar 07 2014

city: Xuzhou

first: Hui

last: Wang

address: 209 Tongshan Rd

institute: Xuzhou Medical University

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

overall_design: Refer to individual Series


title: Gene expression profiling of HPV-active,  HPV-inactive and HPV-negative oropharyngeal squamous cell carcinomas

status: Public on Mar 05 2014

city: Columbia

first: Diego

last: Altomare

state: SC

address: 715 Sumter Street, Room 617

department: Department of Drug Discovery and Biomedical Sciences

institute: University of South Carolina

summary: Approximately 25% of all head and neck cancers (HNC), and up to 60% of oropharyngeal cancers (OPC) are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Viral oncoproteins are capable of transforming primary human keratinocytes from either genital or oral epithelia in vitro and most likely play the same role in vivo, by disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and OPC. However, the precise mechanisms by which HPV mediates malignant transformation of keratinocytes in the upper digestive tract epithelia are not entirely clear.  HPV E7-mediated inactivation of pRb results in overexpression of p16INK4A, which is commonly used as a clinical surrogate marker for HPV positivity/activity. However, high p16INK4A alone has insufficient sensitivity and specificity as a biomarker of HPV positivity in different mucosal sub-sites  of HNC. Therefore, increasing emphasis is being placed on the assessment of viral load and E7 oncogene expression, resulting in further classification of HPV positive OPC as HPV-active and HPV-inactive. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct. This study aimed to compare the gene expression profiles of HPV-active, -inactive and -negative OPC and determine their biological differences.

overall_design: ANALYSIS 1: Three-condition, one-color experiment: HPV-active, HPV-inactive and HPV-negative oropharyngeal tumor samples. Biological replicates: 12 HPV Active tumors, 8 HPV Inactive tumors and 16 HPV Negative tumors.

first: Swati

last: Tomar

first: Sangeeta

last: Kowli

first: Susannah

last: Kassler

first: Natalie

last: Sutkowski

first: M

last: Gillespie

first: Kim

middle: E

last: Creek

first: Lucia

last: Pirisi


title: Autophagy is essential for cardiac morphogenesis during vertebrate development

status: Public on Mar 01 2014

city: Dallas

first: James

last: Amatruda

state: TX

address: 5323 Harry Hines Boulevard

department: Pediatrics and Molecular Biology

institute: University of Texas Southwestern Medical Center

summary:
This study examined the effects of genetic knockdown of autophagy genes on vertebrate cardiac development
We performed microarray studies comparing the hearts of control zebrafish embryos to the hearts of embryos with decreased expression of the autophagy genes atg5, becn1 or atg7.  The results provide insight into the role of autophagy in developmental  morphogenesis.

overall_design: Hearts were purified from 3 day-old zebrafish embryos injected with control or autophagy gene-specific morpholino oligonucleotides.  RNA was prepared from all samples and hybridized to zebrafish-specific Affymetricx arrays.

first: Eunmyong

last: Lee

first: Aylwin

last: Ng

first: Ramnik

last: Xavier

first: Beth

last: Levine


title: Expression data from young and old zebrafish brain.

status: Public on Feb 19 2014

city: ANKARA

first: Ayca

last: Arslan Ergul

state: ÇANKAYA

address: Bilkent Üniversitesi UNAM

department: UNAM

country: Turkey

institute: Bilkent University

summary:
Brains are sexually dimorphic in adult zebrafish. We dissected brains from young and old, adult zebrafish, from both males and females.
Brains are not pooled but analyzed as indivual samples.

overall_design: Four groups of wild-type zebrafish (AB strain) were used for this study: young (7.5-8.5 months old) male and female and old (31-36 months old) male and female. There were three animals per group for a total of 12 animals in the study.

last: Arslan-Ergul

first: Michelle

last: Adams


title: Effect of HCV in  B cells and changes in B cell lymphoma (BCL)

status: Public on Feb 09 2014

city: Kagoshima

first: Kyoko

last: Tsukiyama-Kohara

state: Kagoshima

department: Joint Faculty of Veterinary Medicine

institute: Kagoshima University

summary:
Hepatitis C virus (HCV) infection leads to the development of hepatic diseases, as well as extrahepatic disorders such as B-cell non-Hodgkin's lymphoma (B-NHL). To reveal the molecular signalling pathways responsible for HCV-associated B-NHL development, we utilised transgenic (Tg) mice that express the full-length HCV genome specifically in B cells and develop non-Hodgkin type B-cell lymphomas (BCLs). The gene expression profiles in B cells from BCL-developing HCV-Tg mice, from BCL-non-developing HCV-Tg mice, and from BCL-non-developing HCV-negative mice were analysed by genome-wide microarray. In BCLs from HCV-Tg mice, the expression of various genes was modified, and for some genes, expression was influenced by the gender of the animals.
Markedly modified genes such as Fos, C3, LTbetaR, A20, NF-kappaB and miR-26b in BCLs were further characterised using specific assays. We propose that activation of both canonical and alternative NF-kappaB signalling pathways and down-regulation of miR-26b contribute to the development of HCV-associated B-NHL.

overall_design:
Mouse expressing the full-genome HCV in B cells, effect of HCV in B cells and changes in BCL were characterized.
Mouse HCV+ vs HCV- B cell, or HCV+ B cell vs HCV+ BCL of male or female mice.


title: The effect on lincRNA expression by p53 family members.

status: Public on Feb 05 2014

city: Sapporo

first: Masashi

last: Idogawa

institute: Sapporo Medical University

summary: To evaluate the effect on lincRNA expression by p53 family members, we overexpressed p53 family members in H1299 cells and evaluated the lincRNA expression by microarray analysis.

overall_design: lincRNA expression was measured in H1299 cells infected with adenovirus expressing LacZ, p53, p63a, p63g, p73a and p73b.


title: NAC, Tiron and Trolox impair GBM tumorigenic cell survival by mechanisms independent from antioxidant activity

status: Public on Mar 04 2014

city: Genova (GE)

first: Massimiliano

last: Monticone

address: Largo R. Benzi, 10

country: Italy

institute: IRCCS AOU San Martino – IST, Genova

summary: The aim of this study is to determine if, using antioxidant drugs, it is possible to interfere with the proliferative capabilities of the human glioblastoma (GBM) tumor-initiating cells (TICs).

overall_design: To establish which cellular processes are activated in GBM TICs by the antioxidants NAC, Tiron and Trolox, we generated and analyzed the gene expression profiles after treatment with these compounds and with H2O and EtOH (vehicles).

first: Razieh

last: Taherian

first: Sara

last: Stigliani

first: Luca

last: Longo

first: Antonio

last: Daga

first: Simona

last: Zupo

first: Stefano

last: Monteghirfo

first: Walter

last: Giaretti

first: Mariella

last: Dono

first: Patrizio

last: Castagnola


title: Effect of mmu-miR-193b-3p and miR-365a-3p ectopic expression on the transcriptome of mouse cutaneous Squamous Cell Carcinoma cells

status: Public on Feb 03 2014

city: Valbonne - Sophia-Antipolis

first: Kevin

last: Lebrigand

address: 660 route des lucioles

country: France

institute: IPMC/CNRS

summary: The mouse mSCC-20 cell line was transfected with 5nM of mmu-pre-miR-193b-3p, pre-miR-365a-3p or pre-miR-NC1. Total RNAs were extracted 30 h after transfection and hybridized on microarrays.

overall_design: One color experiment with 3 experimental conditions : miR-NC1- (n=4), miR-193b-3p- (n=2) and miR-365-3p- (n=2) transfected cells, corresponding to a total of 8 samples.

first: R

last: Rezzonico

first: C

last: Gastaldi

first: B

last: Mari

first: P

last: Barbry

first: A

last: Popa

first: K


title: A549, human alveolar adenocarcinoma cell, treated with aldehyde

status: Public on Mar 18 2014

city: Seoul

first: Yoon

last: Cho

address: hwarang-ro 14

institute: KIST

summary: To gain deeper insight into the mechanism of toxicity, it is important to identify and characterize mRNAs profiles involved in responses to specific classes of toxicants in conjunction with their impact on gene expression levels. However, few reports have described the effects of toxicants on mRNA expression profiles. Taking into account the prominent role of mRNAs in cancer development, progression, cell cycle control, and proliferation-related processes, it is likely that mRNAs are involved in the toxic response induced by carcinogens. Aldehydes are a well-characterized class of human carcinogens. In the present study, we documented the different expression profiles of mRNAs in environmental carcinogen-exposed A549 cells by mRNA microarray analysis.

overall_design: To evaluate the change in mRNA expression levels, human alveolar cells(A549) were exposed to seven lower-molecular-weight saturated aliphatic aldehyde (LSAAs) for 48h. mRNA expression analysis was conducted using a  4x44k human whole genome oligo microarray (Agilent Technologies, USA).

first: Jae-Chun

last: Ryu


title: Changes of the gene expression profiling induced by fenofibrate

status: Public on Mar 13 2014

city: Shanghai

first: Ting

last: Li

address: No.270 Dong’an Road

department: Department of Medical Oncology

institute: Fudan University Shanghai Cancer Center

summary: To make investigation of the apoptosis-inducing effect of fenofibrate, the Gene expression profile chip was used to compare the changes between the control group (0μM for 24h) and fenofibrate treatment group (50μM for 24h) in MDA-MB-231 cell lines.

overall_design: Fenofibrate induced gene expression in MDA-MB-231 cell lines was measured at 24 hours after exposure to doses of 0 and 50μM fenofibrate.

first: Xichun

last: Hu


title: Butyrate Induced Changes in Wnt Signaling-Specific Gene Expression in Colorectal Cancer Cells

status: Public on Jan 16 2014

city: Scranton

first: Michael

last: Bordonaro

address: 525 Pine Street

department: Basic Sciences

institute: The Commonwealth Medical College

summary: To identify Wnt target genes whose expression is differentially modulated by butyrate

overall_design: Doxycycline inducible DN-Tcf4 expression was used to repress Wnt signaling, cells were treated with butyrate or mock treated.  Genes differentially regulated by butyrate in the absence of doxycycline but not in its presence (> 2 -fold, P < 0.01) were evaluated.

first: Darina

last: Lazarova

first: Christopher

last: Chiaro


title: Expression profiling of the retinal pigment epithelium in zebrafish smarca4 mutant

status: Public on Jan 03 2014

city: West Lafayette

first: Yuk Fai

last: Leung

state: IN

address: 915 W. State Street

department: Biological Sciences

institute: Purdue University

summary: Purpose: The purpose of this study was to develop a framework for analyzing RPE expression profiles from zebrafish eye mutants.   Methods: The fish model we used was smarca4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4), a retinal dystrophic mutant that the retinal phenotype and expression profiles were previously characterized. Histological and Affymetrix GeneChip analyses were conducted to define the RPE defects and underlying differential expression respectively.   Results: Histological analysis indicates that smarca4 RPE was formed but its differentiation was abnormal. In particular, ultra-structural analysis of smarca4 RPE by transmission electron microscopy showed a number of defects in melanogenesis, suggesting that the cytoskeletal dynamics was impaired. To compare the expression profile of normal wild-type (WT) and smarca4 RPE, their retinas and RPE-attached retinas were microdissected and the gene expression values of these tissues measured by Affymetrix GeneChip analysis. The RPE expression values were then estimated from these samples using an approach previously established by us. A factorial analysis was conducted using the expression values of RPE, retinal as well as the whole-embryo samples. Specific rules (contrasts) were built using the coefficients of the resulting fitted model to select for three groups of genes: 1) Smarca4-regulated RPE genes, 2) Smarca4-regulated retinal genes, and 3) Smarca4-regulated RPE genes that are not differentially expressed in the retina. The latter group consists of 39 genes that are highly related to cytoskeletal dynamics, melanogenesis, paracrine and intracellular signal transduction.   Conclusions: Our analytical framework can potentially identify genes in zebrafish mutants that both retina and RPE are affected by the underlying mutation.

overall_design: The gene expression levels of three independent replicates of WT whole embryos (WA52), WT retinas (WR52), WT RPE-attached retinas (WRR52), smarca4/yng retinas (YR52), smarca4 RPE-attached retinas (YRR52) and smarca4 whole embryos (YA52) were measured by Affymetrix Zebrafish Whole Genome Arrays. All samples were collected at 52 hpf. The probe-level data of these sample groups were background adjusted, normalized and summarized by a robust multiarray average (RMA) algorithm. RPE expression values were estimated from the comparison between the retinal and RPE-attached retinal samples of the same genotype based on a method we previously developed (Leung et al., Invest Ophthalmol Vis Sci. 2007; 48:881). Then, a 3x2 factorial design was used to analyze the expression values of three kinds of tissue (T): whole embryo, retina and RPE in two kinds of mutation (M) background: WT and smarca4. Using the coefficients from the fitted models, contrasts were built to identify candidate genes that fulfilled specific criteria. The false discovery rate (FDR) q-value cutoff for a contrast was 0.001. Several contrasts were ultimately combined to allow for selection of genes that were regulated by Smarca4 in the retina and RPE. These include 1) Smarca4-regulated RPE genes, 2) Smarca4-regulated retinal genes, and 3) Smarca4-regulated RPE genes that are not differentially expressed in the retina.

first: Liyun

last: Zhang

first: Ping

last: Ma

first: Wenxuan

last: Zhong

first: Yuk


title: Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts

status: Public on Dec 31 2013

city: Kyoto

first: Junichi

last: Taniguchi

address: Kitashirakawa-Oiwakecho, Sakyo-Ku

department: Department of Chemistry, Graduate School of Science

institute: Kyoto University


title: Metabolic programs orchestrated by the activated Ha-ras and Îroteins in mouse liver tumors [miRNA]

status: Public on Feb 10 2014

city: Basel

first: Jonathan

last: Moggs

address: Fabrikstrasse 2

country: Switzerland

institute: Novartis

summary: The process of hepatocarcinogenesis in the diethylnitrosamine (DEN) initiation/phenobarbital (PB) promotion mouse model involves the selective clonal outgrowth of cells harboring oncogene mutations in Ha-ras, B-raf, or Ctnnb1. Here, we have characterized mouse liver tumors harboring either Ctnnb1 or Ha-ras mutations via integrated molecular profiling at the transcriptional and translational and post-translational levels. In addition, metabolites of the intermediary metabolism were quantified by high resultion 1H magic angle nuclear magnetic resonance (HR-MAS NMR). We have identified tumor characteristic genotype-specific differences in mRNA and miRNA expression, protein levels, and post-translational modifications and in metabolite levels that facilitate the molecular and biochemical stratification of tumor phenotypes. Bioinformatic integration of these data at the pathway level led to novel insights into tumor genotype-specific aberrant cell signaling and in particular to a better understanding of alterations in pathways of the cell intermediary metabolism, which are driven by the constitutive activation of the β-Catenin and Ha-ras oncoproteins in tumors of the two genotypes.

overall_design: Male C3H/HeJ mice received a single i.p. injection of DEN (10 or 90µg/g body weight) at 2, or 6 weeks of age. After a treatment-free interval of 2 weeks, the C3H/HeJ mice were either kept on a diet containing 0.05% PB or on a PB-free control diet for 28 to 36 weeks before they were sacrificed. Ha-ras- or Ctnnb1-mutated tumors and control tissues were isolated and either flash frozen in liquid nitrogen and stored at -80°C, or prepared for immunohistochemistry.

first: Elif

last: Unterberger

last: Schwarz

first: Johannes

last: Eichner

last: Römer


title: Ginger compound [6]-shogaol activates Nrf2 in human colon epithelial cells

status: Public on Apr 23 2014

city: Camden

first: Xiaoxin

middle: Luke

last: Chen

state: NJ

address: 403 Haddon Avenue

institute: Coriell Institute for Medical Research

summary: To identify the direct molecular targets of 6S, gene microarrays were used to profile gene expression in HCT-116 cells treated with 6S (20 uM for 24 h) comparing with HCT-116 cells treated with DMSO (control).

overall_design: Two-class comparisons. HCT-116 cells treated with 6S (20 uM for 24 h) vs. HCT-116 cells treated with DMSO control;Biological replicates: 4 replicates for each group.

first: Hao

first: Shengmin

last: Sang

middle: L


title: ALDH1A3-mediated gene expression in MDA-MB-231 cells and MDA-MB-468 cells

status: Public on Feb 04 2014

city: Halifax

first: Paola

last: Marcato

state: Nova Scotia

address: 11F11, 5850 College Street

department: Pathology

institute: Dalhousie University

summary: To determine the effect ALDH1A3 expression on global gene expression in MDA-MB-231 cells and MDA-MB-468 cells

overall_design: In MDA-MB-231 cells, ALDH1A3 was overexperssed (have low endogenous levels of ALDH1A3) and compared to MSCV empty vector control. In MDA-MB-468 cells that have high endogenous levels of ALDH1A3, ALDH1A3 expresion was reduced with ALDH1A3 shRNA1 and compared to scramble shRNA control.

first: Patrick

last: Lee


title: Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment (dataset 2)

first: Hui

last: Wang

state: Jiangsu

summary: Medical research focuses on disease-specific genes. By contrast, here we systematically examined the roles of shared genes for disease susceptibility and as therapeutic and diagnostic targets. Meta-analysis of all published disease-related genome-wide association studies (GWAS) showed that T helper (Th) cell differentiation was the most shared pathway. Expression profiling data from highly diverse CD4+ T cell-associated diseases revealed shared disease-associated genes, which were enriched for Th cell differentiation, but also metabolic and proliferative pathways. This pleiotropy suggested that altered functions of shared genes could generally increase disease susceptibility. Indeed, compared to specific genes, the shared genes were enriched for disease-associated SNPs identified by all published disease-related GWAS. To examine if the shared genes induced disease-relevant pathways, we focused on transcription factors (TFs) that induced Th differentiation. Those TFs were enriched among the shared genes, as well as for disease-associated SNPs identified by GWAS, and disease-phenotypes in mice knock-out studies. Original GWAS and profiling data from patients with multiple sclerosis and allergy confirmed enrichment of disease-associated SNPs in the TFs, and that the TFs were differentially expressed at early disease stages, and their targets increased in parallel with disease development. From a clinical perspective, the shared genes were significantly enriched for known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed that shared or specific genes could be used to stratify patients for individualized medicine. Our findings show that shared disease genes generally increase disease susceptibility and are important therapeutic and diagnostic targets.

overall_design: Patients with multiple sclerosis (MS) display variations in response to natalizumab treatment. PBMCs were collected from 8 high responders (HR) and 8 low responders (LR) to natalizumab treatment. CD4+ T cells were cultured for 48h. Cells were activated with anti-CD3 and anti-CD28 mAbs (0.5 µg/mL), either with natalizumab (25 µg/mL BiogenIdec) or without additional stimulus. Gene expression analysis was performed using SurePrint G3 Human Gene Expression 8X60K microarrays.

first: Mika

last: Gustafsson

first: Måns

last: Edström

first: Fredrik

last: Barrenäs

first: Sören

last: Bruhn

first: Ingrid

last: Kockum

first: Tomas

last: Olsson

first: Colm

last: Nestor

first: Jan

last: Ernerudh

first: Mikael

last: Benson


title: Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts (Agilent 1-color)

first: Junichi

last: Taniguchi

summary: Artificial epigenetic switches are of increasing demand owing to the critical role of the dynamic epigenome in orchestrating genome-wide transcriptional activation. Recently, we divulged that certain epigenetically active small molecules called SAHA-PIPs containing the cell permeable pyrrole-imidazole polyamides (PIPs) as DNA recognition module and a histone deacetylases inhibitor SAHA as functional module, is capable of triggering targeted transcriptional activation of pluripotency and germ cell genes in mouse and human fibroblasts, respectively. Through microarray studies and functional analysis, here we demonstrate the first ever example about the remarkable ability of 32 different SAHA-PIPs to trigger transcriptional activation of their own unique set of genes and noncoding RNAs. QRT-PCR studies validated that certain SAHA-PIPs could induce several therapeutically important genes including KSR2 and SEMA6A to suggest its potential use as reagents capable of targeted transcriptional activation and as probe(s) to identify the functional relevance of the uncharacterized genes.

overall_design: Gene induction by each individual SAHA-PIP was measured after treating human dermal fibroblasts at 48 h time-point. Two libraries of SAHA-PIPs (SAHA-PIP 1-16 and 17-32) were investigated in different experiments and each experiment includes a vehicle (DMSO) treatment as a negative control.

first: Ganesh

last: Pandian

first: Hiroshi

last: Sugiyama


title: Human ILC2 cells stimulated with IL-25, IL-33, or TSLP

city: South San Francisco

first: Alex

last: Abbas

state: CA

address: 1 DNA Way

department: Bioinformatics

institute: Genentech, Inc.

summary: ILC2 cells are a newly described cell type whose biology and contribution to disease are poorly understood. ILC2 cells are activated by allergens, viral infection, and/or epithelial damage via IL-33 and IL-25. ILC2 cells require IL-2, IL-7, IL-25 and IL-33 for their survival and expansion. In mice, ILC2s produce multiple mediators primarily associated with type 2 inflammation (IL-13, IL-5, IL-4, IL-6, IL-9, IL-10, GM-CSF, amphiregulin). ILC2 cells may contribute to the pathology of asthma through multiple mediators that include IL-13-independent pathways. Our goal is to compare transcriptional profiles of IL-33- or IL-25-activated ILC2 cells from blood to characterize these cells and to identify marker(s) that can be utilized to detect them in human tissue.

overall_design: ILC2 cells (Lineage negative, CRTH2+, CD161+, CD127+) were purified from human blood of 5 different donors by flow cytometry. The ILC2 yield ranged from 20,000 to 165,000 cells per donor (0.001-0.008% WBC). Purified ILC2s were expanded in vitro in the presence of IL-2, IL-7, IL-33 and IL-25 (each at 50 ng/ml) for 7-10 days. Expanded cells maintained the ILC2 phenotype (Lineage negative, CRTH2+, CD161+, CD127+). The cells were rested for 2 days in the presence of 1 ng/ml IL-2 and IL-7 and then treated in the presence of 1 ng/ml IL-2 and IL-7 with either media control, IL-25 (50 ng/ml), IL-33 (50 ng/ml), and/or TSLP (50 ng/ml) in combination, for 6 or 24 hours. Whole RNA was isolated via the RNeasy kit (Qiagen). Stratagene Universal Human Reference RNA was used as the reference.

first: Alexander

first: Vladimir

last: Carrozzi

first: Jane

last: Grogan

first: Rajita

last: Pappu


title: Gene expression signatures in the skin of focal palmoplantar keratoderma (FPPK) patients, and cell lines transfected with mutant TRPV3

status: Public on Dec 24 2013

city: Seattle

first: Ji-Hoon

last: Cho

state: WA

address: 401 Terry Avenue North

institute: Institute for Systems Biology

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

overall_design: Refer to individual Series


title: Control vs CRB2 cKO retinas at early postnatal time points

city: Amsterdam

first: Celso

middle: Henrique

last: Freitas Alves

address: Meibergdreef 47

department: Neuromedical Genetics

institute: Netherlands Institute for Neuroscience

summary: We used microarray gene profiling to study the transcriptome of retinas lacking CRB2 during late retinal development. Unexpectedly, the retinas of newborn mice lacking CRB2 showed no changes in the transcriptome during retinal development.

overall_design: Comparison between Control and CRB2 null retinas at different time points (P0, P3, P6 and P10)

first: C

middle: H

last: Alves

first: K

last: Bossers

first: A

last: Essing

first: SS

last: wagemakers

first: P

last: van der Spek

first: J

last: Verhaagen

last: Wijnholds


title: Gene expression signatures in the skin of focal palmoplantar keratoderma (FPPK) patients

summary: We identified a number of affected pathways through transcriptome analysis on the skin biopsy samples of the FPPK patients. Our findings suggest that TRPV3 dysfunction may increase apoptotic activity, inhibit keratinocyte differentiation and disturb the intricate balance between proliferation and differentiation state of keratinocytes in the skin.

overall_design: From a 37-year-old Chinese male (II-7) and his 12-year-old son (III-7), biopsies from unaffected and affected skin tissues were obtained and their transcriptome profiles were analyzed in order to identify molecular changes related with the pathology of FPPK.

first: Yuqing

last: He

first: Kai

last: Wang


title: Gene expression signatures of 293T cell lines transfected with mutant TRPV3

overall_design: To understand the effect of TRPV3 mutation, transcriptome of 293T cell lines transfected with mutant TRPV3 were profiled in time-course manner (16, 24 and 40hr).


city: Hannover

first: Oliver

last: Dittrich-Breiholz

address: Carl-Neuberg-Str. 1

department: Research Core Unit Genomics

institute: Medical School Hannover

summary:
THOC5, a member of the mRNA export complex, is essential for hematopoiesis in vivo and is required for CSF-1 induced macrophage differentiation, thereby playing a key role in the mRNA export of immediate early genes induced by CSF-1 stimulation.
Hematopoiesis, growth, differentiation, and commitment to a restricted lineage are guided by a timely expressed set of cytokine receptors and their down-stream transcription factor genes. Transcriptional control mechanisms of gene expression during differentiation were mainly studied by focusing on the cis- and trans-element in promoters, however, the role of mRNA export machinery during differentiation have not been adequately examined. A member of the mRNA export complex, THOC5 which is a substrate for the macrophage-colony stimulating factor (CSF-1) receptor, ATM kinase, or protein kinase C, is an essential element in the maintenance of hematopoiesis in adult mice. Using tamoxifen inducible THOC5 knockout mice, we show here that the depletion of THOC5 impaired myeloid differentiation, but does not influence terminally differentiated organs. Furthermore, an in vitro study showed that the depletion of THOC5 in bone marrow cells results in abnormal CSF-1 induced macrophage differentiation. Transcriptome analysis using cytoplasmic RNA derived from macrophages reveals that only 99 genes were down-regulated 3 days after the depletion of THOC5, however, immediate early genes induced by CSF-1 stimulation, such as Ets family genes, and regulators of myeloid differentiation HoxA1, Id1, Id3 were THOC5 direct target mRNAs, suggesting that THOC5 plays a key role in myeloid  differentiation.

overall_design: In each of two biological experiments (called rep1 and rep2 below) six different cytoplasmic RNA samples were generated from bone marrow derived macrophages. These different samples (conditions) correspond to: 1) Cells from ERT2 Cre control mice at day 0, 2) Cells from ERT2 Cre control mice at day 3 of differentiation, 3) Cells from ERT2 Cre control mice at day 3 of differentiation stimulated with tamoxifen, 4) Cells from ERT2 Cre Thoc5 (flox/flox) mice at day 0, 5) Cells from ERT2 Cre Thoc5 (flox/flox) mice at day 3 of differentiation, 6) Cells from ERT2 Cre Thoc5 (flox/flox) mice at day 3 of differentiation stimulated with tamoxifen. Day 0 samples of a given genotype were utilized as common reference in two microarrays and were accordingly co-hydridized against both 3-days differentiated samples (treated or none with tamoxifen) of the same genotype and biological experiment. Thus, four dual-color microarrays from each of the two biological replicate series were performed (giving rise to 8 dual-color microarrays in total). The complete set of microarrays from the second biological experiment (rep2) was performed with inverted labeling directions (dye-swap approach).

first: Doan

last: Tran

first: Shashank

last: Saran

first: Susanne

last: Niemann-Seyde

first: Sabine

last: Klebba-Färber

first: Alexandra

last: Koch

first: Michael

last: Kracht

first: Robert

last: Klopfleisch

first: Teruko

last: Tamura


title: 2',3,5-Trimethoxychalcone (MC-23)-induced gene expression in MiaPaCa2 cells

status: Public on Jan 21 2014

first: YoungHan

last: Lee

address: 120 Neungdong-ro, Gwangjin-gu

institute: Konkuk University

summary: 2',3,5-Trimethoxychalcone (MC-23) triggers apoptosis independently of p53 in MiaPaCa2 cells. To understand the mechanism of action of MC-23, we analysed the gene expression profiles in MiaPaCa2 cells treated with 10 μM MC-23 for 6, 12, or 24 h using the Agilent human 44K oligonucleotide V2 microarray. Out of the 34,127 genes in the array, MC-23 upregulated ~3% and downregulated. Notably, a large number of genes associated with apoptosis (such as BAX, BAK), chaperones (such as HSPA1/HSP70, HSPA5/GRP78/BiP), and the unfolded protein response (such as IRE1α, CHOP/DDIT3/GADD153, XBP1, ATF4, ATF6) were highly up-regulated by MC-23 treatment, suggesting that ER stress is associated with MC-23-induced apoptosis.

overall_design: Global gene expression profile was measured at 6, 12, and 24 hours after exposure to doses of 10 μM MC-23 in MiaPaCa2 cells. Three independent experiments were performed at each time using different experiments.

first: SoonYoung

last: Shin

first: JongMin

first: Hyuk

last: Yoon

first: Dongsoo

last: Koh

first: Yoongho

last: Lim


title: Gene expression profiling of African American vs European American HPV-negative oropharyngeal squamous cell carcinomas

status: Public on Mar 05 2014

city: Columbia

first: Diego

last: Altomare

address: 715 Sumter Street, Room 617

institute: University of South Carolina

summary: Head and neck cancer (HNC) is the fifth most common malignancy worldwide with an annual mortality rate of 200,000. About 90% of HNC can be classified as head and neck squamous cell carcinomas (HNSCC), of which approximately 75% are attributed to alcohol and tobacco consumption and 25% are associated with human papillomavirus (HPV), predominantly HPV16. HPV-associated OPC have better prognosis and a more favorable response to therapy as compared to HPV-negative tumors. Differences in risk factors, age of presentation, clinical behavior and gene expression profiles indicate that HPV-positive and HPV-negative tumors develop via different molecular mechanisms and are biologically distinct.   African American (AA) males have a higher incidence of HNC than any other racial/gender group, and a mortality rate almost three-fold that observed in European American (EA) males. Overall, AA patients tend to present with more HPV-negative OPC and have worse prognosis as compared to both HPV-positive and HPV-negative HNSCC in EA patients. Despite the unveiling of differential gene expression patterns, genetic and epigenetic profiles and the compilation of a mutational landscape along with preliminary TCGA data of HPV-related and unrelated HNC, the molecular determinants of the racial disparity in HNC are yet to be identified.   This study aimed to compare the gene expression profiles of HPV-negative HNSCC from AA and EA patients, and determine their biological differences.

overall_design: ANALYSIS 2: Two-condition, on-color experiment:  African American (AA) vs European American (EA) HPV-negative oropharyngeal squamous cell carcinomas. Biological replicates: 8 African American and 8 European American.

first: Swati

last: Tomar

first: Sangeeta

last: Kowli

first: Susannah

last: Kassler

first: Natalie

last: Sutkowski

first: M

middle: B

last: Gillespie

first: Kim

last: Creek

first: Lucia

last: Pirisi


title: Efficacy and molecular mechanism of a glycoside compound inhibiting abnormal prion protein formation in prion-infected cells

status: Public on Feb 22 2014

city: Sendai

first: Keiko

last: Nishizawa

address: Seiryo-machi 2-1,Aoba-ku

department: Department of Neurochemistry

institute: Tohoku University Graduate School of Medicine

summary: This report describes our study of the efficacy and the potential mechanism underlying the anti-prion action of a new anti-prion compound having a glycoside structure in prion-infected cells. The study revealed involvements of two factors in the mechanism of the compound action: interferon and a microtubule nucleation activator, phosphodiesterase 4D interacting protein. In particular, phosphodiesterase 4D interacting protein was suggested to be important in regulating the trafficking or fusion of prion protein-containing vesicles or structures in cells. The findings of the study are expected to be useful not only for the elucidation of cellular regulatory mechanisms of prion protein, but also for the implication of new targets for therapeutic development.

overall_design: Prion-infected N167 cells were treated with either anti-prion glycoside compound (Gly-9) or control glycoside compound (Gly-14) at a dose of 5 μg/mL for three days. Then, gene expression profiles were analyzed by DNA microarray analysis. Experiments were performed in quadruplicate.

first: Katsumi

last: Doh-ura


title: Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts (Agilent 2-color)

first: Junichi

last: Taniguchi

overall_design: Gene induction by a SAHA-PIP and SAHA was measured after treating human dermal fibroblasts at 48 h time-point. Experiment includes a vehicle (DMSO) treatment as a negative control.

first: Ganesh

last: Pandian

first: Hiroshi

last: Sugiyama


title: THP-1 cells treated with CXCL14

status: Public on Dec 17 2013

city: Setagaya-ku

first: Kosuke

last: Tanegashima

state: Tokyo

address: 2-1-6 Kamikitazawa

institute: Tokyo Metropolitan Institute of Medical Science

summary: Monocytic leukemia cell line, THP-1 cells are known to respond to CXCL14. To identfy transcriptional regulation of CXCL14 signalling, we analyse gene expression changed with CXCL14 treatment.

overall_design: THP-1 treated with CXCL14 or PBS treated sample were used.

first: Takahiko

last: Hara


title: Role of interleukin-4 in the licensing of dendritic cells for the induction of Th2 responses [B]

status: Public on Feb 19 2014

city: Cantoblanco

first: Juan

middle: Carlos

last: Oliveros

state: Madrid

address: Darwin 3

institute: CNB, CSIC

summary: T helper type 2 (Th2) responses are crucial for defense against infections by helminths and are responsible for the development of allergic reactions that can lead to severe clinical disorders, such as asthma or anaphylaxis, and ultimately to death. The induction of Th2 responses requires a specific activation process, triggered by specialized dendritic cells (DCs), by which naive CD4+ Th0 cells acquire the capacity to produce Th2 cytokines. However, the mechanistic basis of the functional specialization enabling DCs for the initiation of Th2 responses has remained elusive. Here we show that interleukin-4 (IL-4), a cytokine produced by basophils, mast cells and Th2-polarized CD4+ T helper cells, exerting a crucial function during anti-helminths and allergic Th2 responses, has a key role in the licensing/conditioning of DCs for the induction of Th2 responses, by bloking their potential to produce Th1-driving cytokines, such as IL-12, IL-18 and IL-23.

overall_design: Microarray analyses (duplicates) were used to compared the transcriptional profile of monocyte-derived dendritic cells (moDCs) cultured with GM-CSF in the absence or presence of interleukin-4: IL4-moDCs versus C-moDCs.

first: Carlos

last: Ardavín

first: María

last: López-Bravo


title: Identification of MAX signature on MAX deficient SCLC cell lines

status: Public on Dec 28 2013

city: L'Hospitalet de Llobregat

first: Manel

last: Esteller

state: Barcelona

address: Hospital Duran i Reynals Av. Gran Via s/n km, 2.7

department: PEBC

institute: IDIBELL

summary: To development our gene expression approach, we have employed whole genome microarray expression profiling as a discovery platform to identify genes  potentialy regulated by the transcription factor MAX.Human SCLC cell lines waere analyzed for mutations at the MAX locus. Those cell lines that were found mutated in MAX and showed no MAX protein expression were used as a models to restore the expression of MAX transcription factor, and Identify MAX signature on Human  SCLC.

overall_design: Human SCLC cell lines were hybridyzed in the following manner according for different conditions (Mock -Ø, MAX, shBRG1, MAX-shBRG1): 3 different biological samples for Mock, 3 different biological samples for MAX, 3 different samples for shBRG1 and 3 replicates of the same sample for MAX-shBRG1.

first: Octavio

middle: A

last: Romero Ferraro

first: Manuel

last: Torres Diz

first: Montse

last: Sánchez-Céspedes


title: Gene expression signatures of HaCaT cell lines transfected with mutant TRPV3

first: Ji-Hoon

last: Cho

overall_design: To understand the effect of TRPV3 mutation, transcriptome of HaCaT cell lines transfected with mutant TRPV3 were profiled in time-course manner (16, 24 and 40hr).

first: Yuqing

last: He

first: Kai

last: Wang


title: Myeloid cells or lung fibroblasts treated with IL-4 or IL-13

first: Alex

last: Abbas

summary: IL-4 and IL-13 are cytokines involved in type 2 immune responses involved in atopic asthma and other diseases. They have a partially overlapping set of cognate receptors whose roles are incompletely understood. Here we explore the effects of these cytokines on various cells related to human lung disease in order to assess the global similarities and contrasts in the genes whose expression their ligation modulates.

overall_design: Monocytes, monocyte-differentiated (6 days, then 24h rest) macrophages, or normal primary lung fibroblasts were cultured on matrigel and treated for 6 or 24 hours with IL-4 (10 ng/ml), IL-13 (10ng/ml), IL-10 (20 ng/ml), TGFb (10 ng/ml), or dexamethasone (0.5 uM) before harvest.

first: Alexander

middle: R

first: Joseph

last: Arron

first: Sanjay

last: Chandriani

first: Daryle

last: DePianto

first: Elsa

last: N'Diaye-Dulac

first: Jackson

last: Egen

first: Rajita

last: Pappu

first: Vladimir

last: Carrozzi


title: Microarray data from zebrafish embryos (ZFE) exposed for 48-hr periods to oil emulsions collected from GoM shoreline sites following the Deepwater Horizon blowout.

status: Public on Dec 03 2013

city: New York

first: Rui

last: Xiao

state: NY

address: 630 West 168th Street

department: Anesthesiology

institute: Columbia University

summary: Zebrafish embryos/larvae are a choice model system for studying early stages of vertebrate development and how these stages can be perturbed by environmental stressors. Petrochemical combustion products elicit developmental toxicity that is associated with transcriptome changes in zebrafish embryos (ZFE). We used microarrays to characterize transcriptome changes in ZFE that had been exposed in the laboratory to oil emulsions collected from the GoM shoreline, ~9 weeks after the Deepwater Horizon blowout.

overall_design: ZFE were exposed to oil emulsions collected (July 1-4, 2010) at the shoreline in Gulfport, MS, Fort Morgan, AL and Perdido Key, FL. ZFE were exposed to emulsions, consisting of varying amounts of alkanes, polynuclear aromatic hydrocarbons (PAHs), sand and seawater that had been “buttered” on the bottom of cups, in which ZFE were suspended in zebrafish medium. ZFE development was monitored by light microscopy.  Control ZFE were suspended in zebrafish medium without emulsions. Gross developmental abnormalities, including axial changes, altered swimming patterns and yolk sac and pericardial sac swelling were noted and photographed.   ZFE were collected at 48-hr intervals, after exposures had begun, and either placed in clean medium for up to 48 hours more, or, were collected immediately for RNA extraction. and hybridization on Affymetrix zebrafish microarrays, each containing 14,900 probe sets. We extracted RNA from all 30 ZFE in each cup for microarray analysis.

first: Arthur

last: Penn

first: Kevin

last: Kleinow

first: Frances

last: Xin

first: Allen

last: Bui

first: Zakia

last: Perveen

first: Paula

last: Polk


title: Global Expression of Molecular Transporters in the Human Vaginal Tract

status: Public on Jan 29 2014

city: Duarte

first: Charles

middle: David

last: Warden

address: 1500 East Duarte Rd

department: Department of Molecular and Cellular Biology

institute: City of Hope

summary: Pre-exposure chemoprophylaxis using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries.

overall_design: The genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women (20-56 years old) undergoing gynecologic surgeries was measured.

first: Marc

last: Baum

first: Manjula

last: Gunawardana

first: Richard

last: Pyles


title: Hypoxic conditioned medium from human amniotic fluid-derived mesenchymal stem cells accelerates skin wound healing through TGF-ß/SMAD and PI3K/Akt pathways

status: Public on Dec 18 2013

city: Seoul

first: Seungkwon

last: You

address: Anam-dong Sungbuk-go

institute: Korea University

summary: Transcriptional profiling of human amniotic fluid-derived mesenchymal stem cells (AF-MSCs) comparing normal condition-cultured AF-MSCs with hypoxia condition-culture AF-MSCs ES cells. The latter improves the proliferation and survival of AF-MSCs, and makes AF-MSCs secret more growth factors. Goal was to determine the effects of hypoxia condition on global AF-MSCs gene expression.

overall_design: Two-condition experiment, Nor AF-MSCs vs. Hypo AF-MSCs. Experimantal replicates: 2 (1-1 vs. 1-2; 2-1 vs. 2-2). Biological replicates: 2 normal replicates, 2 treated replicates.

first: Eun

middle: K

last: Jun

first: Qiankun

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