title: Alterations of the human gut microbiome in multiple sclerosis

status: Public on May 11 2016

first: Laura

last: Cox

address: 77 Avenue Louis Pasteur

department: Neurology

institute: Brigham and Women's Hospital

summary: The gut microbiome plays an important role in normal immune function and has been implicated in several autoimmune disorders. Here we use high-throughput 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=61) and healthy controls (n=43). Alterations in the gut microbiome in MS include increases in the genera Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signaling and NF-kB signaling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of the genera Prevotella and Sutterella, and decreased Sarcina, compared to untreated patients. MS patients of a second cohort show elevated breath methane compared to controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.

overall_design: T cells and monocytes were collected from healthy controls and patients with multiple sclerosis.  Immune gene expression was measured by the Nanostring nCounter GX Human Immunology Kit v2 (Catalog #115000061).  Comparisons were made between healthy controls, patients with multiple sclerosis, both on and off treatment.

first: Sushrut

last: Jangi

first: Felipe

last: von Glehn

first: Howard

last: Weiner


title: The status of lymph node of resectable distant metastaticcolorectal cancer  (stage Ⅳ) as a prognostic predictor

status: Public on Apr 25 2016

city: Hangzhou

first: jianfie

last: fu

address: 88 Jiefang Road,

department: Cancer Institute

country: China

institute: The Second Affiliated Hospital of Zhejiang University School of Medicine

summary: Both the univariate analysis and multivariate analysis showed that the status of primary lymph node was the strongest predict factor. The subgroup analysis confirmed that the lymph node metastasis was associated to worse prognosis only in stage T3 and T4, rather than in stage T1 and T2. We firstly proposed the hypothesis that the status of lymph node reflected delayed diagnose of the disease, rather than the biological behavior of “seed”. The mRNA profile showed that there was minimal difference between lymph node positive and negative subgroups. The status of lymph node reflected delayed diagnose of the disease, rather than the biological behavior of “seed”.

overall_design: 15 patients registered in our center with resectable mCRC were selected to extract RNA for further analysis, with 7 patients in lymph node negative subgroup and 8 patients in lymph node positive subgroup. The mRNA profiles of all 15 patients were analyzed by Agilent microarray technology to explore the different expression between lymph node negative subgroup and lymph node positive subgroup.

first: Jianfei

last: Fu

first: Lin

last: Feng


title: Vitamin D receptor expression and associated gene signature in tumor stromal fibroblasts predict clinical outcome in colorectal cancer

status: Public on Apr 07 2016

city: Madrid

first: Maria Jesus

last: Larriba

state: Madrid

address: Arturo Duperier 4

department: Cancer Biology

country: Spain

institute: Instituto de Investigaciones Biomedicas "Alberto Sols"

summary: Colorectal cancer (CRC) is a major cause of cancer mortality and a serious health concern worldwide. Vitamin D deficiency is associated with high CRC incidence and mortality, suggesting a protective effect of vitamin D against this neoplasia. Although the antiproliferative and prodifferentiation action of active vitamin D (1alpha,25-dihydroxyvitamin D3, 1,25(OH)2D3) on colon carcinoma cells is well documented, its potential effects on CRC stroma are unknown. Here, we show that high vitamin D receptor (VDR) expression in tumor stromal fibroblasts is associated with better overall and progression-free survival in a large cohort of CRC patients, irrespective of its expression in carcinoma cells. Consistently, 1,25(OH)2D3 inhibits the activation of patient-derived normal and cancer-associated fibroblasts, and their pro-migratory effect on carcinoma cells. Importantly, we show by global transcriptomic analyses that 1,25(OH)2D3 regulates cancer-associated fibroblast gene expression and imposes a gene signature that is associated with longer overall and disease-free survival of CRC patients. Moreover, expression of two genes from the signature, CD82 and S100A4, correlates with stromal VDR expression and clinical outcome in CRC. This study provides the first evidence that vitamin D has protective effects against CRC through the regulation of stromal fibroblasts.

overall_design: Characterization of 1,25(OH)2D3 action on gene expression in primary cultures of colon normal and tumor fibroblasts established from samples from colorectal cancer patients. RNA from seven paired normal and tumor fibroblast primary cultures treated with 1,25(OH)2D3 or vehicle for 48 h were analyzed.

first: Gemma

last: Ferrer-Mayorga

first: Gonzalo

last: Gómez-López

first: Antonio

last: Barbáchano

first: Asunción

last: Fernández-Barral

first: Cristina

last: Peña

first: David

middle: G

last: Pisano

first: Ramón

last: Cantero

first: Federico

last: Rojo

first: Alberto

last: Muñoz

first: María


title: Human neural stem cells transduced with oncogenic elements associated with aggressive medulloblastoma

city: La Jolla

first: Pablo

last: Tamayo

state: CA

address: 3855 Health Sciences Drive MC 0658

department: Moores Cancer Center

country: USA

institute: UCSD

summary: Human neural stem and progenitor cells transformed with c-MYC, dominant-negative p53, constitutively active AKT and hTERT formed tumors in mice that recapitulated Group 3 medulloblastoma in terms of pathology and expression profile

overall_design: Isogenic model systems and mouse xenografts

first: Allison

last: Hanaford

first: Eric

last: Raabe


title: The anti-tumor core molecular targets of TSA in cholangiocarcinoma

status: Public on Mar 15 2016

city: wuhan

first: wei

last: yao

address: NO.1095 of jiefang stree

institute: Tongji hospital

summary: Firstly our study demonstrated that TSA can inhibits cell proliferation, induces cell apoptosis and cell cycle arrest in CCA cell lines in vitro. To identify the target transcripts of TSA to suppress CCA tumorigenesis, mRNA expression profiles were determined by microarray analysis. We chose TFK-1 cells treated by TSA in indicated concentration (IC50) 48 hours for the microarray. Then we found out TACC3 was downregulated, and demonstrated that TACC3 was high expression and may played a role as an target of TSA in inhibiting CCA cells proliferation and migration via in vitro and vivo experiments.

overall_design: We chose TFK-1 cells treated by TSA in indicated concentration (IC50) 48 hours as the experiment sample and without TSA as the control sample to do this microarray  analysis for three times. Then regulated genes would be tested to investigate the potential roles in CCA tumorigenesis,

first: Junchuang

last: He

first: Wei

last: Yao


title: The effects of UV-miRNAs on melanocytes in situ

status: Public on May 24 2016

city: Cleveland

first: Nikki

last: Harter

state: Ohio

address: 10900 Euclid Avenue

department: Biochemistry

institute: Case Western Reserve University

summary: The response of microRNAs (miRNAs) to solar ultraviolet radiation (UVR) in human melanocytes while in their natural environment, and in particular, melanocytes from persons with a history of melanoma versus those from healthy persons, have yet to be described.  Here, we used laser capture microdissection (LCM) to isolate and subsequently profile the expression of miRNAs in a pure population of melanocytes from human volunteers exposed to physiological doses of simulated sunlight (ssUVR).  The majority of the UV-responsive miRNAs in the melanocytes of melanoma patients were down-regulated in expression when compared to those in the melanocytes of healthy individuals.  De-repressed genes associated with these down-regulated UV-miRNAs belonged to regulatory modules involved in controlling the epithelial-to-mesenchymal transition (EMT), apoptosis, and immune-evasion, processes reputedly linked to melanoma.

overall_design: Eight healthy fair-skinned females between the ages of 31 and 38, and nine fair-skinned females with a history of having only one primary melanoma between the ages of 35 to 46, were enrolled in this study to determine the effects of simulated solar ultraviolet radiation (ssUVR) on their melanocytes in situ.

first: M

middle: L


title: Gene expression profiles of retinoblastoma cell lines

status: Public on Mar 31 2016

city: Amsterdam

first: Irsan

last: Kooi

state: Noord-Holland

address: van der Boechorstraat 7

department: Clininical Genetics

country: Netherlands

institute: VU university medical centre

summary: In order to identify the gene targets of frequently altered chromosomal regions in retinoblastoma, a meta-analysis of genome-wide copy number alterations studies on primary retinoblastoma tissue and retinoblastoma cell lines was performed. Published studies were complemented by copy number and gene expression analysis on primary and cell line samples of retinoblastoma. This dataset includes the gene expression data of the retinoblastoma cell lines

overall_design:
This data set contains the gene expression (Affymetrix human genome u133 plus 2.0 PM) results for 7 unique retinoblastoma cell lines. For one of the 7 unique cell lines, 3 RNA isolations were performed and were profiled on seperate arrays, adding up to 9 unique array files. Copy number data for primary retinoblastoma (tumor and blood DNA) and retinoblastoma cell lines are available (controlled-access) at the European Genomics Archive. Gene expression data of primary retinoblastoma is available under GSE59983.

The GSE59983 records represent the primary tissue gene expression data and the CN data will be deposited into a controlled-access database, probably EGA.

middle: E

first: Berber

middle: M

last: Mol

first: Maarten

middle: P

last: Massink

first: Marcus

middle: C

last: de Jong

first: Pim

last: de Graaf

first: Paul

last: van der Valk

first: Hanne

last: Meijers-Heijboer

first: Gertjan

middle: J

last: Kaspers

first: Annette

last: Moll

first: Hein

last: te Riele

first: Jacqueline

last: Cloos

first: Josephine

last: Dorsman


title: Gene expression profiling of blood in hidradenitis suppurativa

status: Public on Mar 11 2016

city: Spring House

first: K

last: Li

state: PA

address: 1400 McKean Road

institute: Janssen R&D

summary:
To acquire a better understanding of the molecular pathogenesis of hidradenitis suppurativa (HS), we performed mRNA microarray studies to compare whole blood gene expression of HS patients to that of healthy normal subjects.
No significant difference was observed in whole blood mRNA expression between HS patients and healthy normal control.

overall_design: Whole blood samples were collected from patients with hidradenitis (n=16) at baseline and healthy normal subjects (n=10) for RNA extraction and microarray analysis.

first: J

last: Blok

first: C

last: Brodmerkel

first: B

last: Horváth

middle: F

last: Jonkman


title: Gene expression profiling of skin and blood in hidradenitis suppurativa

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

overall_design: Refer to individual Series


title: Expression data from human iPSC-derived corneal epithelial cells

status: Public on Mar 09 2016

city: Suita

first: Ryuhei

last: Hayashi

state: Osaka

address: 2-2 Yamadaoka

country: Japan

institute: Osaka University Graduate School of Medicine

summary: We successfully induced corneal epithelial cells from human iPSCs. Then, we perfomed global expression analysis using microarray to compare the character of hiPSC-derived corneal epithelial cells with that of the other kinds of cells.

overall_design: Total RNA was obtained from human iPSCs (hiPSCs), human iPSC-derived corneal epithelial cells (hiCECs), human corneal limbal epithelial cells (HCECs), human oral keratinocytes (HOKs), human dermal fibroblasts (HDFs) and six weeks-differentiated hiPSCs (hiPSC-derived ocular surface ectoderm, OSE) using the QIAZol reagent. A microarray analysis using Sure Print G3 human 8x60K slides (Agilent technologies) was performed at Takara Bio (Shiga, Japan).

first: Yuki

last: Ishikawa

first: Motokazu

last: Tsujikawa

first: Kohji

last: Nishida


title: Whole blood gene expression from subjects with moderate to severe rheumatoid arthritis

status: Public on Mar 16 2016

first: Alice

last: Walsh

address: Welsh & McKean Roads

department: Immunology

summary: Whole blood (paxgene) gene expression was measured using Affymetrix microarray from 377 individuals with rheumatoid arthritis.

overall_design: RA patient samples were collected from a phase III clinical trial of golimumab in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy (GO-FURTHER) according to trial protocol approved by local Institutional Review Board. A subset of subjects from the entire trial population at baseline (i.e., 377 subjects before golimumab treatment) was utilized. All patients consented to genetic and transcriptomics analyses.

first: Yauheniya

last: Cherkas

last: Huang

first: Sarah

last: Lamberth

first: Carrie

first: Mark

last: Curran

first: Radu

last: Dobrin


title: Gene expression in human prostate cancer (PCa) cell lines upon HIC1 silencing

status: Public on Mar 03 2016

city: Shanghai

first: Mingang

last: Hao

address: NO. 280 South Chongqing Road

department: Department of Biochemistry and Molecular & Cell Biology

institute: Shanghai Jiao Tong University School of Medicine

summary: To explore the role of HIC1 silencing in regulating PCa EMT development, Human Gene Expression Microarrays were searched for altered genes upon silencing HIC1 expression in C4-2B and DU145 cells. According to fold-change screening betweenHIC1-silenced and its respective control cells, both up-regulated and down-regulated genes were shown.

overall_design: Human PCa cell lines C4-2B and DU145 were transfected with lenti-virus (shRNA targeting HIC1 and respective control). HIC1-silenced cells were respectively noted as C4-2B-shHIC1 and DU145-shHIC1. Their respective control cells were respectively noted as C4-2B-shctrl and DU145-shctrl.

first: Jianhua

last: Wang


title: Inhibition of p300 Lysine Acetyltransferase activity by Luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model [mRNA]

status: Public on Jan 03 2016

city: Bangalore

first: madavan

last: vasudevan

state: Karnataka

address: Kasturi Nagar

country: India

institute: Theomics International Private Limited

summary: Chromatin acetylation is attributed with distinct functional relevance with respect to gene expression in normal and diseased conditions thereby leading to a topical interest in the concept of epigenetic modulators and therapy. We report here the identification and characterization of the acetylation inhibitory potential of an important dietary flavonoid, luteolin. Luteolin was found to inhibit p300 acetyltransferase with competitive binding to the acetyl CoA binding site. Luteolin treatment in a xenografted tumor model of head and neck squamous cell carcinoma (HNSCC), led to a dramatic reduction in tumor growth within 4 weeks corresponding to a decrease in histone acetylation. Cells treated with luteolin exhibit cell cycle arrest and decreased cell migration. Luteolin treatment led to an alteration in gene expression and miRNA profile including up-regulation of p53 induced miR-195/215, let7C; potentially translating into a tumor suppressor function. It also led to down-regulation of oncomiRNAs such as miR-135a, thereby reflecting global changes in the microRNA network. Furthermore, a direct correlation between the inhibition of histone acetylation and gene expression was established using chromatin immunoprecipitation on promoters of differentially expressed genes. A network of dysregulated genes and miRNAs was mapped along with the gene ontology categories, and the effects of luteolin were observed to be potentially at multiple levels: at the level of gene expression, miRNA expression and miRNA processing.

overall_design: Cells treated with luteolin exhibit cell cycle arrest and decreased cell migration. Luteolin treatment led to an alteration in gene expression and mRNA profile

first: R

middle: B

last: Selvi

first: A

last: Swaminathan

first: S

last: Chatterjee

first: M

middle: K

last: Shanmugam

first: F

last: Li

first: G

last: Ramakrishnan

middle: S

last: Siveen

last: Chinnathambi

first: Z

last: Emam

middle: A

last: Alharbi

last: Basha

last: Bhat

last: Vasudevan

last: Dharmarajan

last: Sethi

first: T

last: Kundu


title: Effect of human DAI expressed by an oncolytic vaccinia virus on the gene expression of tumor cells (HS294T) and monocytes (THP-1).

status: Public on Mar 01 2016

city: Tampere

first: Dario

last: Greco

address: Arvo ylpön Katu 34

department: Faculty of Medicine and Health Technology

country: Finland

institute: Tampere University

summary:
Human melanoma tumor cells (HS294T) and monocytes (THP-1) were infected with a double deleted (-VGF, -TK) oncolytic vaccinia virus expressing human DAI (DNA-dependent activator of interferon-regulatory factors). Total RNA was collected and gene expresson profiles were determined with Agilent microarray. An oncolytic vaccinia virus that does not express DAI was used to control the effect of DAI and uninfected cells (PBS treated) were used to control the effect of virus infection.
In oncolytic virotherapy the ability of the virus to activate the immune system against tumors is nowadays generally understood to be a key mechanism in full eradication of cancer and for long-term anti-tumor effects. We armed an oncolytic vaccinia virus with DAI to increase the immunogenicity and the vaccine potency of the virus. The aim of this study was to study if the expression of DAI by a replicating vaccinia virus would alter the gene expression profile of infected cells and to study what are the differentially expressed genes.

overall_design: Three-condition experiment: vvdd-tdTomato-hDAI vs. vvdd-tdTomato vs. PBS treated cells. 2 cell lines: HS294T tumor cells and THP-1 monocytes. 3 biological replicates of virus infected cells per cell line and 2 uninfected replicates per cell line. HS294T and THP-1 cells were treated with vvdd-tdTomato-hDAI or vvdd-tdTomato control virus, or with PBS only to have an uninfected control. 16 hours after infection total RNA was extracted and whole genome gene pfofiles were analyzed and differentially expressed genes determined.

first: Mari

last: Hirvinen

first: Vittorio

last: Fortino

first: Vincenzo

last: Cerullo


title: Gene expression profiling of endothelial cells derived from Foxo1(+/+) and Foxo1(-/-) ES cells in response to VEGF

status: Public on Feb 16 2016

city: Kamakura

first: Satoshi

last: Kondo

state: Kanagawa

address: Tebiro 6-10-1

department: New Projects Development Division

institute: Toray Industries,Inc.

summary:
VEGF induces elongation of endothelial cells (ECs) that are derived from wild-type (Foxo1(+/+)) ES cells. VEGF-induced EC elongation is an important process of angiogenesis.
ECs derived from Foxo1(-/-) ES cells fail to elongate in response to VEGF. Gene expression profiling of wild-type and Foxo1(-/-) ECs in the presence or absence of VEGF stimulation identifies responsible genes that regulate EC elongation.

overall_design:
One wild-type (Foxo1(+/+)) ES cell clone and one Foxo1(-/-) ES cell clone were used. ES cells were cultured on OP9 stromal cell layer in the presence or absence of VEGF (10 ng/ml).
After 6.5 days, VE-cadherin+ CD31+ ECs were isolated by FACS and used for total RNA extraction. Three independent experiments were performed for each condition.

first: Kiyomi

last: Tsuji-Tamura

first: Minetaro

last: Ogawa


title: JAK inhibitor has the amelioration effect in lupus-prone mice: the involvement of IFN signature gene downregulation.

city: Urayasu-shi

first: Keigo

last: Ikeda

state: Chiba

address: 2-1-1 Tomioka

department: Institutes for Environmental and Gender Specific Medicine

institute: Juntendo University

summary: We previously reported that JAK/STAT pathway-mediated regulation of IRF-related genes may have an important role in the disease activity of SLE through analyzing the difference of gene expression in peripheral blood CD3+ T cells obtained from SLE patients.  Recently pan-JAK inhibitor (JAKi) tofacitinib (TOFA) were developed and successfully applied to patients with rheumatoid arthritis.  Therefore, the application possibility of TOFA was investigated for the new therapeutic strategy of SLE. Anti-dsDNA antibody and proteinuria were decreased and glomerulo/interstitial nephritis were ameliorated in any TOFA administered SLE mice.  In splenic CD4+ T cell analysis, naïve cells significantly increased and effector/memory cells decreased.  TOFA with dexamethasone (DEXA) therapy showed tendency to indicate stronger inhibitory effect comparing with TOFA or DEXA monotherapy.  The gene expression of Ifit3/IFIT3 that related with anti-viral IFN signaling pathway was significantly suppressed in both CD4+ from SLE mice and CD3+ T cells from SLE patients after treatment. Both TOFA monotherapy and dual therapy with DEXA could suppress nephritis and modify immunological function in SLE mice with different genetic background.  IFN signaling pathway was supposed to be important for the functional mechanism of TOFA to improve the disease condition.  TOFA may contribute to the development of a new therapeutic strategy for SLE.

overall_design: The gene expression analysis was compared among tofacitinib, tofacitinib+dexamethsone, dexamethsone and non-treated control groups and extracted TOFA specific decreased genes in NZBWF1 mice.

first: Maki

last: Fujishiro

first: Kunihiro

last: Hayakawa

first: Mikiko

last: Kawasaki


title: The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer

status: Public on Feb 01 2016

city: RENNES

first: Nathalie

last: THERET

address: 2 avenue Pr Leon Bernard

department: INSERM U1085

country: France

institute: University of Rennes 1

summary: TRAIL (TNF-Related Apoptosis Inducing Ligand) is a well-known apoptosis inducer, which activates the extrinsic death pathway. It is pro-apoptotic on colon cancer cells, while not cytotoxic towards normal healthy cells. However, its clinical use is limited by resistance which occurs in approximately 50% of cancer cells. SCFA (Short Chain Fatty Acids) are also known to specifically induce apoptosis of cancer cells. In accordance, we have shown that food grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via the production and release of SCFA (propionate/acetate) acting on mitochondria. Here, we investigated possible synergistic effect between Propionibacterium freudenreichii and TRAIL. We hypothesized that acting on both extrinsic and intrinsic death pathways may exert a synergistic pro-apoptotic effect. Whole transcriptomic analysis demonstrated that propionibacterial supernatant or propionibacterial metabolites (propionate and acetate), in combination with TRAIL, boosted pro-apoptotic gene expression in HT29 human colon cancer cells. The revealed synergistic pro-apoptotic effect, depending on death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and on caspase-8, caspase-9 and caspase-3 activation, was more lethal on cancer cells than on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Finally, milk fermented only by P. freudenreichii induced apoptosis of HT29 cells and enhanced cytotoxic activity of TRAIL, as did P. freudenreichii culture supernatants or its metabolites SCFA. These results open new perspectives for the use of food grade P. freudenreichii-containing products in order to potentiate TRAIL-based cancer therapy in colorectal cancer.

overall_design: Cells were either untreated (reference sample) or treated with  C3/C2 (propionate and acetate), SN (propionibacterial supernatant), TRAIL, TRAIL+C3/C2 and TRAIL+SN. Together, 6 different conditions in quadriplicate (24 experiments )

first: Fabien

last: Cousin

first: Sandrine

last: Jouan-Lanhouet

last: Théret

first: Catherine

last: Brenner

first: Elodie

last: Jouan

first: Gwenaelle

last: LeMoigne-Muller

first: Marie-Thérèse

last: Dimanche-Boitrel

first: Gwenael

last: Jean


title: mRNA/microRNA expression profiles of HCC or CCC patients' liver, together with those of non-tumor part tissues

status: Public on Dec 21 2015

city: Tokyo

first: Y-H.

last: Taguchi

state: Non-US/Canada

address: 1-13-27 Kasuga,Bukyo-ku

department: Physics

institute: Chuo University

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

summary:
11 CCC and 5 HCC patients' tumor and non-tumor parts tissues are extracted. Then total RNA are purified from tissues and mRNA and miRNA profiles
are measured using agilent one color microarrays designed for mRNA or microRNA expression profiles.

overall_design: Tumor and non-tumor parts are extracted from obtained tissues.

first: Y-h

first: Yoshiki

last: Murakami


title: Gene expression profiling of skin in hidradenitis suppurativa

status: Public on Jan 11 2016

first: K

last: Li

summary:
To acquire a better understanding of the molecular pathogenesis of HS, we performed mRNA microarray studies to compare gene expression in lesional skin to healthy skin of HS patients.
A significant difference was observed in mRNA expression between lesional and clinically healthy skin of HS patients.

overall_design: Skin biopsy samples (n=30, LS: lesion, NL: non-lesion) were collected at baseline from patients with hidradenitis for RNA extraction and microarray analysis.

first: J

last: Blok

first: C

last: Brodmerkel

first: B

last: Horváth

first: M

last: Jonkman


title: Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms that Correlate with Worse Long-term Outcomes

status: Public on Jan 15 2016

first: Sunil

last: Kurian

address: 10550 N Torrey Pines Road

department: Molecular and Experimental Medicine

institute: The Scripps Research Institute

summary: Rationale: Interstitial fibrosis and tubular atrophy (IFTA) is found in ~25% of 1-year biopsies post-transplant(1, 2). It correlates with decreased graft survival when histological evidence of inflammation is present¬.(3-5) Identifying the etiology of IFTA is important because longterm graft survival has not changed as expected given improved therapies and a dramatically reduced incidence of acute rejection.(6-8)    Methods: Gene expression profiles of 234 samples were obtained with matching clinical and outcome data (7 transplant centers). 81 IFTA samples were divided into subphenotypes by the degree of inflammation on histology: IFTA with acute rejection (AR), IFTA with inflammation and IFTA without inflammation. Samples with AR (n=54) and normally functioning transplants (TX; n=99) were used in comparisons.   Conclusions:  Gene expression profiling of all IFTA phenotypes were strongly enriched for cAR gene dysregulation pathways, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. We also found that the relative expression of AR-affiliated genes correlated with future graft loss in IFTA samples without inflammation. We conclude that undetected and/or undertreated immune rejection is leading to IFTA and graft failure.

overall_design: RNA was extracted from biopsy samples using the RNEasy kit (Qiagen), biotinylated cRNA prepared using Ambion MessageAmp Biotin II and hybridized to Affymetrix HG U133 Plus PM peg arrays (http://affymetrix.com/index.affx). Probe intensity data were log2–transformed and normalized using a custom-designed frozen Robust Multichip Average (fRMA). Low-variance and low signal probes were filtered according to industry standards, resulting in a filtered gene list with 17,564 transcripts.

first: Brian

middle: D

last: Modena


title: Gene regulation during differentiation of ovarian cancer stem cells

status: Public on Dec 31 2015

city: Chuo-ku

first: koji

last: okamoto

state: Tokyo

address: 5-1-1 Tsukiji

department: Division of Cancer Differentiation

institute: National Cancer Center Research Institute

summary: To identify genes that are regulated during differentiation of ovarian cancer stem cells, we performed whole genome micrroarray expression profiling. Human ovarinan cancer stem cell were cultivated in vitro under sphere-forming conditions, and induced to differentiate in the presence of serum upon attached plates. Total RNA extracted from cells were used for single-color microarray analyses with Agilent Whole Human Genome Oligo Microarrays.

overall_design: Gene expression in human ovarian cancer stem cells was measured before and after their differentiation in vitro

first: Koji

last: Okamoto


title: A genomic screen for long noncoding RNA genes epigenetically silenced by aberrant DNA methylation in colorectal cancer

status: Public on Nov 13 2015

city: Sapporo

first: Hiromu

last: Suzuki

state: Hokkaido

address: S1, W17, Chuo-ku

department: Department of Molecular Biology

institute: Sapporo Medical University

summary: Long noncoding RNAs (lncRNAs) have emerged as key components in multiple cellular processes, although their physiological and pathological functions are not fully understood. To identify cancer-related lncRNAs, we screened for those that are epigenetically silenced in colorectal cancer (CRC). Through a genome-wide analysis of histone modifications in CRC cells, we found that the transcription start sites (TSSs) of 1,027 lncRNA genes acquired trimethylation of histone H3 lysine 4 (H3K4me3) after DNA demethylation. Integrative analysis of chromatin signatures and the DNA methylome revealed that the promoter CpG islands (CGIs) of 66 lncRNA genes contained cancer-specific methylation. By validating the expression and methylation of lncRNA genes in CRC cells, we ultimately identified 20 lncRNAs, including ZNF582-AS1, as targets of epigenetic silencing in CRC. ZNF582-AS1 is frequently methylated in CRC cell lines (87.5%), primary CRCs (77.2%), colorectal adenomas (44.7%) and advanced adenomas (87.8%), suggesting that this methylation is an early event during colorectal tumorigenesis. Methylation of ZNF582-AS1 is associated with poor survival of CRC patients, and ectopic expression of ZNF582-AS1 suppressed colony formation by CRC cells. Our findings offer insight into the association between epigenetic alterations and lncRNA dysregulation in cancer and suggest that ZNF582-AS1 may be a novel tumor-suppressive lncRNA.

overall_design: HCT116 cells were transfected with a ZNF582-AS1 expression vector or an empty vector. Seventy-two hours after transfection, total RNA was extracted and gene expression profiles were analyzed.

first: Kohei

last: Kumegawa

first: Reo

last: Maruyama


title: The mRNA expression of FaDu-Ctrl, FaDu-ARID3B cells

status: Public on Dec 01 2015

city: Taipei

first: Tsai-Tsen

last: Liao

state: State...

address: No.201, Sec.2, Shih-Pai Rd. Peitou, Taipei, Taiwan, 11221, R.O.C

country: Taiwan

institute: Institute of Clinical Medicine

summary:
Microarray analyses for the identification of differences in gene expression patterns have increased our understanding of the molecular mechanism of ARID3B in HNSCC.We used gene expression analysis data from FaDu-ARID3B and FaDu-pCDH to identify differentially expressed probes.
The expression of the embryonic stem cell (ESC) signature in cancer cells indicates the coordinated regulation of the stemness genes in cancer stem cells, which are responsible for cancer initiation and dissemination. let-7 family microRNAs are crucial regulators for stem cell differentiation. In cancer cells, let-7 suppresses cancer stemness through targeting different oncogenes such as c-Myc, RAS, and HMGA2. However, most let-7 target genes are oncogenes rather than stemness factors, and the mechanism of let-7-repressed stemness is unclear. Here we demonstrate that let-7 supresses the formation of AT-rich interacting domain 3B (ARID3B) complex through targeting the expression of ARID3B, the interacting partner ARID3A, and importin 9. ARID3B complex recruits histone demethylase 4C (KDM4C) to the regulatory region of stemness genes for reducing histone 3 lysine 9 trimethylation, resulting in an open configuration of the chromatin of stemness genes. In cancer tissues, ARID3B expression correlates with the nuclear ARID3A expression and a worse prognosis. This result highlights the role of let-7 in regulating stemness through histone modifications.

overall_design: The plasmids pCMVΔR8.9, pDVsVg (from the National RNAi Core Facility, Taiwan) and expression lentivectors (pCDH-GFP, pCDH-ARID3B) were co-transfected into 293T cells for virus packaging. The virus-containing supernatant was collected at 48 and 72 hours after transfection. While virus transduction, FaDu cells were infected with 10-fold virus concentrates supplemented with 8 μg/ml polybrene. pCDH-GFP as vector control.

first: Yang

last: Muh-Hwa

first: Liao

last: Tsai-Tsen


title: Gene expression influenced by SF3B1 inhibitor, FR901464 or SF3B1 gene mutations in colorectal cancer cells

status: Public on Sep 30 2015

city: Nishinomiya

first: Tomoki

last: Yamano

state: Hyogo

address: 1-1 Mukogawa-cho

department: Department of Surgery

institute: Hyogo College of Medicine

summary: DLD1, HCT116, DLD1 - derived FR resistant clone DLD FR1, and HCT116 - derived FR resistant clone CT FR1, were assessed for change of gene expression induced by FR901464

overall_design: Cells were incubated with or without 10 ng/ml of FR901464 for 24h.


title: miR-200 overexpression in colorectal cancer lines

status: Public on Sep 01 2015

first: Louis

last: Vermeulen

address: Meibergdreef 9

department: Center for Experimental Molecular Medicine

institute: Academic Medical Center

summary: Unsupervised classification of gene expression profiles has resulted in the identification of biologically and clinically distinct colon cancer subtypes (CCSs). The subtype that associates with poor clinical outcome displays a mesenchymal gene expression profile. No driver mutation has been identified for this category and patients are heterogeneous with regard to commonly used clinical markers. Here we report a regulatory network consisting of the miR-200 family members that tunes the majority of genes differentially expressed in the poor prognosis CCS, including genes involved in the epithelial-mesenchymal transition (EMT) process. Our data indicate that the epigenetic silencing of the miR-200 family by promoter methylation is identifying the mesenchymal CCS and is predictive of disease-free survival in this malignancy. We demonstrate that the molecular features of poor prognosis colon cancer - expression of EMT-associated genes and miR-200 promoter methylation - can already be installed at the premalignant stage, suggesting a highly malignant potential of specific colon cancer precursor lesions.

overall_design: Three colorectal cancer cell lines that display methylated miR-200 loci have been used to overexpress miR-200 family members from both loci separatedly or simultaneously.

first: Evelyn

last: Fessler

first: Jan

last: Medema

first: Xin

last: Wang


title: Sixty-two lung squamous precancerous and cancer samples obtained from brochoscopy

status: Public on Sep 25 2015

city: Beijing

first: Ning

last: An

address: NO.17 Pan Jiayuan Nan Li, Chao Yang District

institute: Chinese academy of medical sciences

summary: To further development of our gene expression signature for survival prediction, we conducted expression profiles of lung squamous carcinoma precancerous and cancer samples.

overall_design: Precancerous progression and cancer samples of LSQC were collected from 62 cases through bronchoscopy in Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences. The biopsy samples included 23 precancerous progression cases [5 cases with mild or moderate dysplasia (P1) and 18 cases with carcinoma in situ (P2)], and 39 lung squamous carcinoma cases (11 Stage I, 13 Stage II, 8 Stage III and 7 Stage IV cases).

first: An

last: Ning

first: Tong

last: run


title: CD24 suppresses malignant phenotype by downregulation of SHH transcription through STAT1 inhibition in breast cancer cells [HCC1937]

status: Public on Nov 30 2015

city: Fukuoka

first: Hideya

last: Onishi

address: 3-1-1 Maidashi, Higashi-ku

department: Department of Cancer Therapy and Research

institute: Graduate School of Medical Sciences, Kyushu University

summary: We describe a relationship between CD24 and the Hedgehog (Hh) ligand Sonic Hedgehog (SHH), and reveal a role for this relationship in the induction of a malignant phenotype in breast cancer. Anchorage-dependent proliferation, anchorage-independent proliferation, invasiveness, and tumorigenicity in breast cancer cells (BCCs) transfected with siRNA and plasmid targeting Hh signaling, CD24, and STAT1 were investigated. CD24 siRNA-transfected BCCs demonstrated higher expression of SHH and GLI1, increased anchorage-independent proliferation, enhanced invasiveness and superior tumorigenicity compared with control. Conversely, CD24 forced-expressing BCCs possessed decreased SHH and GLI1 expression, anchorage-independent proliferation, and invasiveness. Suppression of SHH decreased invasiveness through inhibition of matrix metalloproteinase (MMP)-2 expression, GLI1 expression, anchorage-independent proliferation, tumorigenicity, and tumor volume in vivo in CD24 siRNA-transfected BCCs. DNA microarray analysis identified STAT1 as a connection between CD24 and SHH. CD24 siRNA-transfected BCCs with concurrent STAT1 inhibition exhibited decreased SHH expression, invasiveness, anchorage-independent proliferation, tumorigenicity, and tumor volume in vivo. Consistently, STAT1 over-expression induced elevated SHH expression, invasiveness, and anchorage-independent proliferation in BCCs. These results suggest that CD24 suppresses development of a malignant phenotype by down-regulating SHH transcription through STAT1 inhibition.

overall_design: We focus on the BCSC marker CD24, and the Hh ligand SHH, and reveal a role for these molecules in the induction of a malignant phenotype in breast cancer.

first: Kumi

last: Suyama

first: Akira

last: Imaizumi

first: Kentaro

last: Shinkai

first: Masayo

last: Umebayashi

first: Makoto

last: Kubo

first: Yusuke

last: Mizuuchi

first: Yoshinao

last: Oda

first: Masao

last: Tanaka

first: Masafumi

last: Nakamura

first: Mitsuo

last: Katano


title: CD24 suppresses malignant phenotype by downregulation of SHH transcription through STAT1 inhibition in breast cancer cells [MCF-7]


title: CD24 suppresses malignant phenotype by downregulation of SHH transcription through STAT1 inhibition in breast cancer cells

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

overall_design: Refer to individual Series


title: Identification of microRNA-27b target genes in breast cancer cell lines

status: Public on Jun 18 2015

first: Ryou-u

last: Takahashi

address: 1-1, Tsukiji 5-chome, Chuo-ku

department: Division of Molecular and Cellular Medicine

summary: To identify the microRNA-27b (miR-27b) target genes in luminal-type breast cancer cells, we performed the microarray analysis using miR-27b knockdown MCF7-luc cell line (MCF7-luc anti-miR-27b), miR-27b overexpressing MCF7-luc cell line (MCF7-luc miR-27b o.e.) and their contro cell line (MCF7-luc anti-NC).

overall_design: After establishing MCF7-luc anti-miR-27b, MCF7-luc miR-27b o.e. and MCF7-luc anti-NC using lentivirus vector, we performed the microarray analysis.

first: Takahiro

last: Ochiya

first: Fumitaka

last: Takeshita

last: Yamamoto

first: Kayo

last: Minoura


title: MMP-14 deficient vs wild-type E14 Dlk+ cells and MMP-14 deficient vs wild-type P1 liver

status: Public on Dec 25 2015

first: Satoshi

last: Kondo

summary:
Transcriptional profiling of E14 Dlk+ cells derived from Matrix metalloproteinase (MMP)-14 deficient (KO) mice comparing those from littermate wild-type (WT) mice. RNA samples were extrated from FACS-sorted Dlk+CD45-CD71-Ter119- cells derived from E14.5 livers.
Transcriptional profiling of postnatal day (P)1 livers derived from MMP-14 deficient (KO) mice comparing those from littermate wild-type (WT) mice. RNA samples were extrated from whole livers derived from P1 mice.

overall_design: Two-condition experiment, MMP-14 KO vs WT E14 Dlk+ cells and MMP-14KO vs. WT whole livers. Total RNA samples in MMP-14 KO vs WT E14 Dlk+ cells were extracted from FACS-sorted Dlk+CD45-CD71-Ter119- cells derived from E14.5 livers.  MMP-14 KO and WT E14 Dlk+ cells samples were RNA solutions extracted from 100000 cells derived from three MMP-14 KO livers and three WT livers, respectively. Total RNA samples in MMP-14KO vs. WT whole livers were extracted from E18.5 whole livers.  MMP-14KO and WT whole livers samples were mixture of RNA solutions derived from two MMP-14 KO livers and two WT livers, respectively.

first: Sei

last: Kakinuma


title: Gene Expression Profiles of Transplanted Kidneys from Deceased Donors with Severe Acute Kidney Injury

status: Public on May 22 2015

city: La Jolla

first: Sunil

last: Kurian

summary: One and four month formalin-fixed paraffin embedded biopsies from 48 kidney transplant recipients (24 AKI donors, 24 non-AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). At one month, there were 898 differentially expressed genes in the AKI group (p-value <0.005; FDR <10%), but by 4-months there were no longer any differences.

overall_design: One and four month formalin-fixed paraffin embedded (FFPE) biopsies from 48 kidney transplant recipients (24 AKI donors, 24 controls; 96 total samples) were profiled using Affymetrix U133PM Plus PM plate arrays on a GeneTitan MC instrument. All samples were selected from the SCD cohort only. AKI donor and controls samples were matched by date of transplantation. Total RNA was extracted from four 20-micron sections using Ambion RecoverAll Total Nucleic Acid Kit and processed for chip hybridization using the new Affymetrix SensationPlus™ FFPE Amplification and 3’ IVT Labeling kit according to the manufacturer’s protocol.  Quantile data normalization by RMA and analysis was performed using Partek Genomics Suite for PDR-corrected differential gene expression by ANOVA. Pathway mapping was performed using Ingenuity Pathway Analysis (IPA).


title: GLI1-regulated genes in human mammary epithelial cells and human breast cancer cells

status: Public on Apr 28 2015

city: Nagakute

first: Kenji

last: Kasai

state: Aichi

address: 1-1 Yazakokarimata

department: Department of Pathology

institute: Aichi Medical University School of Medicine

summary: To clarify transcriptional target genes of GLI1 in human mammary epithelial cells and breast cancer cells, primary culture cells of human mammary epithelium HMEC and breast cancer cell line MCF-7 were lentivirally transduced by either GLI1 or its control LacZ. Their RNA samples were served for expression analysis using AGILENT human 8x60K cDNA microarray.

overall_design: Array analysis of HMEC and MCF-7 expressing either GLI1 or LacZ. 1 color method was employed.

first: S

last: Inaguma

first: K

first: M

last: Riku

first: H

last: Ito

last: Ikeda


title: Murine ES Cells: Control vs. ETV4/5 double KO

status: Public on Sep 13 2015

summary: ETS-related transcription factors ETV4 and ETV5 play crucial roles for organogenesis and morphogenesis.  We compared the transcriptional profiles between wild-type and ETV4 and ETV5 double knockout (ETV4/5 dKO) ES cells by an oligo DNA microarray analysis.  Self-renewal capacity and pluripotency are known to be controlled by an ES cell-specific transcription factor network; therefore, we focused on transcription-associated genes. Of 1258 transcription-related genes, 47 genes were significantly downregulated and 98 genes were significantly upregulated in ETV4/5 dKO ES cells.  Several genes whose expression is specific to undifferentiated ES were repressed in ETV4/5 dKO ES cells.  In contrast, expression of differentiation markers was enhanced in ETV4/5 dKO ES cells.

overall_design: Transcriptional profiles between wild-type and ETV4/5 dKO ES cells were examined by an oligo DNA microarray analysis. ES cells were cultured on gelatin-coated dishes with LIF-supplemented ES cell medium.  Total RNAs were isolated from wild-type and ETV4/5 dKO ES cells and subjected to microarray analysis.

first: Tadayuki

last: Akagi

first: Takashi

last: Yokota


title: Response to TGFB in colon fibroblasts

status: Public on Jan 28 2015

city: Sabadell

first: Antoni

last: Berenguer-LLergo

state: Barcelona

address: Parc del Taulí, 1

department: A8G2 Group - Rheumatology Service

institute: Parc Taulí Research and Innovation Institute (I3PT)

summary: We obtained gene expression signatures from TGF-beta treated fribroblasts. Upregulated genes predict poor prognosis in Colorectal Cancer.

overall_design: Fibroblasts extracted from human normal colon mucosa were treated with TGF-β1 for 8 hours. Gene expression profiles for treated or untreated fibroblasts were measured in duplicate using HG-133+PM Affimetrix arrays.

first: Alexandre

last: Calon


title: Modeling the early phenotype at the neuromuscular junction of spinal muscular atrophy using patient-derived iPSCs

status: Public on Jan 31 2015

city: Kyoto

first: Megumu

last: Saito

address: 53, Shogoin-Kawahara

institute: Kyoto University

summary: Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations of the survival of motor neuron 1 (SMN1) gene. In the pathogenesis of SMA, pathological changes of the neuromuscular junction (NMJ) precede the motor neuronal loss. Therefore, it is critical to evaluate the NMJ formed by SMA patients’ motor neurons (MNs), and to identify drugs that can restore the normal condition. We generated NMJ-like structures using motor neurons (MNs) derived from SMA patient-specific induced pluripotent stem cells (iPSCs), and found that the clustering of the acetylcholine receptor (AChR) is significantly impaired. Valproic acid and  antisense oligonucleotide treatment ameliorated the AChR clustering defects, leading to an increase in the level of full-length SMN transcripts. Thus, the current in vitro model of AChR clustering using SMA patient-derived iPSCs is useful to dissect the pathophysiological mechanisms underlying the development of SMA, and to evaluate the efficacy of new therapeutic approaches.

overall_design: To compare the gene expression pattern between control and patient derived iPSCs

first: Michiko

last: Yoshida

first: Akira

last: Watanabe


title: Separation of mouse ES cell-derived mesodermal cells based on the expression of Flk1, PDGFRa and CAR.

summary: We found that mouse ES cell-derived Flk1+ cells could be subdivided into three population by the expression of PDGFRa and CAR (Flk1+PDGFRa-CAR-, Flk1+PDGFRa-CAR+, and Flk1+PDGFRa+CAR+).   Therefore, global gene expression analysis was perfomed by microarray to characterize these mesodermal subsets.

overall_design: RNA isolated from five separate experiments was pooled and used for comparison

last: Tashiro

first: N

last: Hirata

first: A

last: Okada

first: T

last: Yamaguchi

last: Takayama

last: Mizuguchi

last: Kawabata


title: Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease

status: Public on Mar 12 2015

city: Boston

first: Manoj

last: Bhasin

state: MA

address: 330 Brookline Avenue  RN 380E

institute: Beth Israel Deaconess Medical Center

summary: Patients with chronic illnesses such as Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD) often have reduced quality of life. IBS is characterized by abdominal pain/discomfort associated with altered bowel function, such as diarrhea or constipation, without gross structural changes or inflammation [1]; IBD is characterized by gross inflammation in the gastrointestinal (GI) tract which can result in symptoms such as abdominal pain, cramping, diarrhea and bloody stools.  IBS and IBD can profoundly affect quality of life and are influenced by stress and resiliency.The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. In this study IBS and  IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. We performed Peripheral blood transcriptome analysis to identify genomic correlates of the RR-MBI.

overall_design: This pilot, single center, single-arm, open-label study utilized an RR-MBI for the treatment of IBS and IBD using elicitation of the RR through meditation techniques and cognitive skill building, as established by the Benson-Henry Institute for Mind Body Medicine at the Massachusetts General Hospital (BHI).Blood was collected at baseline and after 9 weeks for transcriptional expression profiling in PAXgene (Qiagen) tubes. Total RNA was isolated from whole blood samples and gene expression profile was assessed on IBS and IBD patients with paired pre- and post-intervention samples using HT U133 Plus PM Array plates (Affymetrix, Santa Clara, CA).

first: Braden

last: Kuo

first: Gregory

last: Fricchione

first: Herbert

last: Benson

first: Towia

last: Libermann

first: Joshua

last: Korzenik

first: John

middle: W

last: Denninger


title: Gene expression profiling of primary human retinoblastoma

status: Public on Jul 01 2015

city: Amsterdam

first: Irsan

last: Kooi

address: van der Boechorstraat 7

department: Clininical Genetics

institute: VU university medical centre

summary:
Background
Retinoblastoma is a pediatric eye cancer associated with RB1 loss or MYCN amplification (RB1+/+MYCNA). There are controversies concerning the existence of molecular subtypes within RB1-/- retinoblastoma. To test whether these molecular subtypes exist, we performed molecular profiling.

Methods
Genome-wide mRNA expression profiling was performed on 76 primary human retinoblastomas. Expression profiling was complemented by genome-wide DNA profiling and clinical, histopathological, and ex vivo drug sensitivity data.

Findings
RNA and DNA profiling identified major variability between retinoblastomas. While gene expression differences between RB1+/+MYCNA and RB1-/- tumors seemed more dichotomous, differences within the RB1-/- tumors were gradual. Tumors with high expression of a photoreceptor gene signature were highly differentiated, smaller in volume and diagnosed at younger age compared to tumors with low photoreceptor signature expression. Tumors with lower photoreceptor expression showed increased expression of genes involved in M-phase and mRNA and ribosome synthesis and increased frequencies of somatic copy number alterations.

Interpretation
Molecular, clinical and histopathological differences between RB1-/- tumors are best explained by tumor progression, reflected by a gradual loss of differentiation and photoreceptor expression signature. Since copy number alterations were more frequent in tumors with less photoreceptorness, genomic alterations might be drivers of tumor progression.

overall_design: Fresh frozen material from 76 primary human retinoblastoma samples were profiled with Affymetrix human genome u133 plus 2.0 PM microarray

first: Berber

last: Mol

first: Annette

last: Moll

first: Paul

last: van der Valk

first: Marcus

last: de Jong

first: Pim

last: de Graaf

first: Antoinette

middle: Y

last: Schouten-van Meeteren

first: Hanne

last: Meijers-Heijboer

first: Gertjan

last: Kaspers

first: Hein

last: te Riele

first: Jacqueline

last: Cloos

first: Josephine

last: Dorsman


title: Gene expression profiles in PHH-iPSCs, PHH-HLCs, PHHs, and HepG2

status: Public on Nov 12 2014

first: Kazuo

last: Takayama

state: Kyoto

address: Shogoin Kawaharacho 53, Sakyo-ku

department: Center for iPS Cell Research and Application

summary: Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPSHLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drugmetabolizing capacity and drug responsiveness.

overall_design: PHH-iPSCs, PHH-HLCs, PHHs, and HepG2 were pooled from three independent experiments, and then microarray analysis was performed.

first: Hiroyuki

last: Mizuguchi


title: Expression Data for HT-1080 cells exposed to ETP, QUE and MMS

status: Public on Dec 01 2014

city: Research Triangle Park

first: Rebecca

last: Clewell

state: NC

address: 6 Davis Drive

department: Institute for Chemical Safety Sciences

institute: The Hamner Institutes for Health Sciences

summary: As part of a larger effort to provide proof-of-concept in vitro only risk assessments, we have developed a suite of high throughput assays for key readouts in the p53 DNA damage response toxicity pathway: DSB DNA damage (p-H2AX), permanent chromosomal damage (micronuclei; MN), p53 activation, p53 transcriptional activity, and cell fate (cell cycle arrest, apoptosis,MN).  Dose-response studies were performed with these protein and cell fate assays, together with whole genome transcriptomics, for three prototype chemicals: etoposide (ETP), quercetin (QUE) and methyl methanesulfonate (MMS).  Data were collected in a human cell line expressing wild-type p53 (HT1080) and results were confirmed in a second p53 competent cell line (HCT 116).   At chemical concentrations causing similar increases in p53 protein expression, p53-mediated protein expression and cellular processes showed substantial chemical-specific differences. These chemical-specific differences in the p53 transcriptional response appear to be determined by augmentation of the p53 response by co-regulators.  More importantly, dose-response data for each of the chemicals indicates that the p53 transcriptional response does not prevent MN induction at low concentrations.  In fact, the no observed effect levels (NOELs) and benchmark doses (BMDs) for MN induction were less than or equal to those for p53-mediated gene transcription regardless of the test chemical, indicating that p53’s post-translational responses may be more important than transcriptional activation in the response to low dose DNA damage.  This effort demonstrates the process of defining key assays required for a pathway-based, in vitro-only risk assessment, using the p53-mediated DNA damage response pathway as a prototype.

overall_design:
HT1080 cells were grown in 24-well plates.  Cells were treated with vehicle, ETP, QUE, or MMS for 24 hr. Total RNA extracted from the exposed cells was then used with Affymetrix Microarrays to identify transcriptional gene changes

Please note that the unit for all the chemical concentrations is micromolar (uM).


title: Transcriptional Program of Kpna2 (Importin-α2) Regulates Cellular Differentiation-Coupled Circadian Clock Development in Mammalian Cells

status: Public on Nov 13 2014

city: Kamakura

first: Satoshi

last: Kondo

address: Tebiro 6-10-1

institute: Toray Industries,Inc.

summary: The circadian clock in mammalian cells is cell-autonomously generated during the cellular differentiation process, but the underlying mechanisms are not understood. Here we show that perturbation of transcriptional program by constitutive expression of c-Myc and Dnmt1 ablation disrupts the differentiation-coupled emergence of the clock from mouse embryonic stem cells (ESCs). Using these model ESCs, 484 genes are identified by global gene expression analysis as factors correlated with differentiation-coupled circadian clock development. Among them, we find the misregulation of Kpna2 (Importin-α2) during the differentiation of the c-Myc over-expressed and Dnmt1-/- ESCs, in which sustained cytoplasmic accumulation of PER proteins is observed. Moreover, constitutive expression of Kpna2 during the differentiation culture of ESCs significantly impairs clock development and KPNA2 facilitates cytoplasmic localization of PER1/2. These results suggest that the programmed gene expression network regulates the differentiation-coupled circadian clock development in mammalian cells, at least in part via post-transcriptional regulation of clock proteins.

overall_design: One sample is used to acquire the expression profile per cell type and treatment

first: Yasuhiro

last: Umemura

first: Nobuya

last: Koike

first: Tsuguhiro

last: Matsumoto

first: Seung-Hee

last: Yoo

first: Zheng

last: Chen

first: Noriko

last: Yasuhara

first: Joseph

last: Takahashi

first: Kazuhiro

last: Yagita


title: Field of Cancerization in Peripheral Airway Epithelium: miRNA

status: Public on Jan 06 2015

city: new york

first: Jun-Chieh

middle: James

last: Tsay

state: NY

address: 562 First Ave. NBV 7N27

department: Medicine

institute: NYU Langone Medical Center

summary:
Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer.
This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients.

overall_design: We collected peripheral airway brushings from the contral-lateral lung of the tumor from cancer patients (n=17) and smoker controls (n=13); Total RNA were obtained from the peripheral airway epithelium.

first: William

middle: N

last: Rom


title: Expression data from peritoneal biopsies of patients with encapsulating peritoneal sclerosis, patients undergoing first implantation of a peritoneal dialysis catheter, and patients undergoing abdominal surgery for non-peritoneal conditions

status: Public on Nov 04 2014

first: Manoj

last: Bhasin

summary:
Expression data from peritoneal biopsies of patients with encapsulating peritoneal sclerosis (EPS), patients undergoing first implantation of a peritoneal dialysis catheter (PD), and patients undergoing abdominal surgery for non-peritoneal conditions (controls)
We used microarrays to determine the transcriptional profiles of peritoneal membrane in patients with encapsulating peritoneal sclerosis (EPS), patients undergoing first insertion of a peritoneal dialysis cathetier (PD), and uremic patients without history of PD or EPS, undergoing abdominal surgery for non-peritoneal problems (CON)
Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD), characterized by marked inflammation and severe fibrosis of the peritoneum, and associated with high morbidity and mortality.  EPS can occur years after termination of PD and, in severe cases, leads to intestinal obstruction and ileus requiring surgical intervention. Despite ongoing research, the pathogenesis of EPS remains unclear. We performed a global transcriptome analysis of peritoneal tissue specimens from EPS patients, PD patients without EPS, and uremic patients without history of PD or EPS (Uremic). Unsupervised and supervised bioinformatics analysis revealed distinct transcriptional patterns that discriminated these three clinical groups. The analysis identified a signature of 219 genes expressed differentially in EPS as compared to PD and Uremic groups.  Canonical pathway analysis of differentially expressed genes showed enrichment in several pathways, including antigen presentation, dendritic cell maturation, B cell development, chemokine signaling and humoral and cellular immunity (P value <0.05). Further interactive network analysis depicted effects of EPS-associated genes on networks linked to inflammation, immunological response, and cell proliferation. Gene expression changes were confirmed by qRT-PCR for a subset of the differentially expressed genes. EPS patient tissues exhibited elevated expression of genes encoding sulfatase1, thrombospondin 1, fibronectin 1 and alpha smooth muscle actin, among many others, while in EPS and PD tissues mRNAs encoding leptin and retinol-binding protein 4 were markedly down-regulated, compared to Uremic group patients. Immunolocalization of Collagen 1 alpha 1 revealed that Col1a1 protein was predominantly expressed in the submesothelial compact zone of EPS patient peritoneal samples, whereas PD patient peritoneal samples exhibited homogenous Col1a1 staining throughout the tissue samples.  The results are compatible with the hypothesis that encapsulating peritoneal sclerosis is a distinct pathological process from the simple peritoneal fibrosis that accompanies all PD treatment.

overall_design: Total RNA was isolated from frozen peritoneal biopsy specimens obtained at time of surgery.  RNA was hybridized to Affymetrix arrays, and analyzed.  Select transcripts were subjected to validation by rt-pcr and by immunodetection.

first: Seth

last: Alper

first: Fabian

middle: R

last: Reimold

first: M

last: Alscher

first: Niko

last: Braun


title: MYC is an early response regulator of human adipogenesis in adipose stem cells

first: Michael

middle: B.

last: Black

state: North Carolina

address: 100 Capitola Dr., Suite 106

institute: Scitovation, LLC.

summary:
MYC is induced early in human adipose stem cells in response to a standard MDIR adipogenic cocktail. The objective of this experiment was to identify key gene networks impacted by MYC loss-of-function in a mixed donor pool of human derived adipose stem cells.
Microarray analysis was used to identify up- and -down regulated genes in control vs MYC knockdown adipose stem cells in response to adipogenic stimulus

overall_design: Two sets of MYC siRNA oligos (pooled and s9129) were used to knockdown MYC 72 hours prior to induction of adipogenesis. Non-targeting siRNA was used as a control. Samples were induced to differentiate for 72 hours to assess early gene expression changes. Control samples not exposed to adipogenic cocktail were included as a reference. 3 independent replicates were run for each sample.

first: Chad

last: Deisenroth

first: Linda

last: Pluta

first: Russell

last: Thomas


title: Enhancement by Aneustat (OMN54) of docetaxel anticancer activity in a patient-derived prostate cancer tissue xenograft model

status: Public on Oct 23 2014

city: Vancouver

first: Shawn

last: Anderson

state: BC

address: 2660 Oak Street

country: Canada

institute: Vancouver Prostate Centre

summary:
Purpose: To determine whether docetaxel therapy of advanced prostate cancer can be improved by using docetaxel in combination with Aneustat (OMN54), a multivalent botanical drug candidate undergoing a Phase-I Clinical Trial, and to identify the molecular action of this drug combination.

Experimental Design: Human metastatic, androgen-independent C4-2 prostate cancer cells and NOD-SCID mice bearing PTEN-deficient, metastatic and PSA-secreting, patient-derived subrenal capsule LTL-313H prostate cancer tissue xenografts were treated with docetaxel and Aneustat, either alone or in combination. Culture growth (at 48 hours) and xenograft size (at 3 weeks) were determined and animal health monitored. Xenografts were gene expression profiled using gene expression microarrays. Androgen receptor (AR) expression and AKT phosphorylation were examined.

Results: Aneustat markedly inhibited C4-2 cell replication in a dose-dependent manner in vitro, reducing AR expression and AKT phosphorylation. Aneustat was not as effective as docetaxel in inhibiting LTL-313H xenograft growth. When combined, Aneustat and docetaxel markedly and synergistically enhanced anti-tumor activity without inducing major host toxicity, even leading to complete growth inhibition and tumor shrinkage not obtained with the single drugs. AR expression and AKT signalling in the xenografts were inhibited by docetaxel+Aneustat, but not by the single agents. Expression microarray analysis indicated that docetaxel+Aneustat led to expanded anticancer activity, in particular to targeting of cancer hallmarks that were not affected by the drugs on their own.

Conclusion: Our findings, obtained with a clinically relevant prostate cancer model, suggest, for the first time, that docetaxel-based therapy of advanced human prostate cancer may be improved by combining docetaxel with Aneustat.

overall_design: NOD-SCID mice bearing PTEN-deficient, metastatic and PSA-secreting, patient-derived subrenal capsule LTL-313H prostate cancer tissue xenografts were treated with docetaxel and Aneustat, either alone or in combination. Eight xenograft samples, comprising two untreated controls, two treated with OMN54 alone, two treated with Docetaxel alone, and two treated with OMN54 + Docetaxel in combination, were gene expression profiled using microarrays.

first: Sifeng

last: Qu

first: Kendric

last: Wang

first: Hui

last: Xue

first: Yuwei

first: Rebecca

last: Wu

first: Chengfei

last: Liu

first: Colin

last: Collins

first: Yuzhuo


title: The difference of gene expression signatures between CD146+ and CD146- cells in malignant rhabdoid tumor

status: Public on Nov 01 2014

first: Seishiro

last: Nodomi

address: 54 Kawahara-cho, Shogoin, Sakyo-ku

department: Pediatrics

institute: Graduate School of Medicine, Kyoto University

summary: To uncover the molecular mechanisms by which CD146+ malignant rhabdoid tumor cells exhibited higher tumorigenic potential, microarray analysis was carried out to compare gene expression profiles between CD146+ and CD146− cells isolated from three cell lines

overall_design: RNA was isolated from the purified CD146+ and CD146− cells by FACS


title: Gene expression of CD14+ cells from RA, PsA and PsO patients with Infliximab treatment

status: Public on Oct 29 2014

city: Rochester

first: Christopher

last: Ritchlin

address: 601 Elmwood Ave, BOX695

department: School of Medicine and Dentistry

institute: University of Rochester Medical Center

summary:
objection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases
Method: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment

overall_design: Between April 2007 and June 2009, 31 patients with active RA, PsA and Ps who were naïve to anti-TNF agents, were recruited from the Faculty Rheumatology Clinics at the University of Rochester Medical Center after informed, written consent was obtained in a protocol approved by the Research Subjects Review Board at the University of Rochester Medical Center.  Of the 31 subjects, 9 had active RA  and 12 had PsA  despite treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs). Also, 10 patients with extensive Ps (>5% BSA) documented by a dermatologist, were enrolled and they were examined by a rheumatologist to exclude the presence of inflammatory arthritis.  Nineteen healthy controls were also recruited.

first: Shealy

last: Dave


title: Synovial biopsies from RA and PsA patients and skin biopsies from Psoriasis patients under Infliximab treatment

summary: Object: to understand Infliximab treatment effect on the molecular expression of tissue at disease site

overall_design: 4mm punch biopsies were performed on involved and uninvolved skin at baseline in 5 Ps patients. A repeat biopsy was performed at week 2 after IFX therapy at a site adjacent to the baseline biopsy of involved skin. Synovial biopsies were performed on the knee of 3 RA and 3 PsA paired-subjects with a Parker Pearson biopsy needle (Dyna Medical, London, Canada) under ultrasound guidance at baseline and repeated on the same knee at week 10

first: Dave

last: Shealy


title: Long noncoding RNA as putative biomarkers for protstate cancer detection

status: Public on Oct 17 2014

city: Durham

first: Jian-Liang

last: Li

address: 111 TW Alexander Dr

institute: NIEHS

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

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

overall_design: Refer to individual Series


title: Gene expression of CD14- cells from RA, PsA and PsO patients with Infliximab treatment

summary:
objection: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases
Method: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment.


title: The effect of Tumor Necrosis Factor Receptor 1 (TNFR1) loss on gene expression in beta-catenin-deprive colon cancer cells

status: Public on Oct 02 2014

city: Halifax

first: Kirill

last: Rosen

state: NS

address: ARC, CRC, 5849 University Ave

institute: Dalhousie University

summary: Human colon carcinoma cells SKCO1 were deprived of either beta-catenin alone or beta-catenin together with TNFR1 and changes in mRNA levels were examined before and after TNFR1 ablation

overall_design: SKCO1 cells were transfected with either beta-catenin-specific siRNA alone or beta-catenin-specific siRNA together with a TNFR1-specific siRNA and changes in mRNA levels were examined before and after TNFR1 ablation


title: Gene expression of biopsies, CD14+ and CD14- cells from RA, PsA and PsO patients with Infliximab treatment


title: Gene and microRNA expression in normal and tumoral esophageal squamous cell lines

status: Public on Sep 20 2014

city: Sakai

first: OSAMU

last: ISHIBASHI

address: 1-1 Gakuen-cho, Naka-ku

department: Grad Sch Life & Environmental Sciences

institute: Osaka Prefecture University

platform_organism:
Homo sapiens
Human alphaherpesvirus 1
Human alphaherpesvirus 2
Cytomegalovirus
Lymphocryptovirus
Rhadinovirus
JC polyomavirus
Human immunodeficiency virus 1
Merkel cell polyomavirus
Betapolyomavirus hominis
Betapolyomavirus macacae


title: The change of mRNA expression in murine immortalized podocyte after miR-26a silencing

status: Public on Oct 01 2014

first: Satoshi

last: Kondo

department: New Projects Development Division

summary: The change of mRNA expression in murine immortalized podocyte were analyzed after miR-26a silencing. These results provide a basical information of molecular pathology in podocyte biology.

overall_design: Mouse podocytes immortalized by temperature sensitive SV40 were used. Podocyte cultures grown at 33 °C were trypsinized and then cultured with RPMI-1640 without antibiotics in 24-well plates at 60–70% confluence for 2 days. On day 3, an anti-miR negative control (40 pmol) or the miR-26a miRNA inhibitor (40 pmol) was transfected to podocytes. The cells were analyzed after culturing for 24 hour.

first: Osamu

last: Ichii


title: Gene expression in normal and tumoral esophageal squamous cell lines

summary: This study was designed to identify genes aberrantly expressed in esophageal squamous cell carcinoma (ESCC) cells.

overall_design: Three esophageal squamous cell carcinoma-derived cell lines and one normal human esophageal squamous cell line were analyzed.

first: Ichiro

last: Akagi

last: Ishibashi


title: P0-cre marked neural crest cells in murine embryo

status: Public on Aug 01 2014

summary: To elucidate the molecular features of craniofacial versus trunk neural crest cells (NCCs), we utilized P0-Cre/Floxed-EGFP mice that specifically label NCCs (Yamauchi et al., 1999 (PMID 10419695)). Craniofacial and trunk regions were isolated from P0-Cre/Floxed-EGFP mouse embryos at embryonic day E12.5, and dissociated cells were analyzed by flow cytometory in regard to the intensity of EGFP.

overall_design: In this study, we performed at least duplicate experiments for each of the four groups (Craniofacial EGFP+, Trunk EGFP+, Craniofacial EGFP-, Trunk EGFP-). Total of 9 samples.

first: Kunie

last: Hagiwara

first: Noriko

last: Osumi


title: Gene expression profiling in mouse livers after administration of both hydrogen-rich water and hydrogen gas

summary: Molecular hydrogen is a hopeful agent for oxidative stress-related and/or inflammatory disorders. However, the molecular mechanism for these therapeutic effects of hydrogen still remains to be fully elucidated. We examined whether molecular hydrogen alters gene expression levels in normal mouse livers by DNA microarray analysis. We identified 140 mouse genes that were upregulated (31 genes) or downregulated (109 genes) after three weeks of the inhalation of 2% hydrogen-containing air with oral intake of hydrogen-rich water. Ingenuity Pathway Analysis revealed that hydrogen influenced expression of NF-kB- and NFAT-regulated genes. Western blot analysis showed that hydrogen attenuated Erk, p38 MAPK, and NF-kB signaling in mouse livers.

overall_design: We divided 10-week male BALB/c mice into two groups: 1) control group: fed with control water in air (n=4), 2) hydrogen-treated group: fed with hydrogen-rich water in 2% hydrogen/98% air (n=4). Hydrogen-rich water (0.7mM dissolved hydrogen) was generated from distilled water with 0.44 mM Na2SO4 using Aquela Blue, a water-electrolyzing device to produce electrolyzed hydrogen-saturated water near neutral pH (MiZ Co., Ltd, Fujisawa, Japan). The control water was prepared by gently stirring hydrogen-rich water in open air for 24 hours. Hydrogen-rich water or control water was administrated ad libitum to the mice with a 50-ml closed glass vessel equipped with an outlet line having a ball bearing. After 3-week rearing, the mice were sacrificed and their livers were removed for RNA extraction. We mixed equal amount of RNA from four mice in each group (control vs. hydrogen-treated) and compared gene expression profile by microarray.

first: Masatoshi

last: Ichihara

first: Sayaka

last: Sobue


title: Comparative analysis of gene expression of radioresistant prostate cancer cells and prostate cancer progenitors

status: Public on Jul 15 2014

city: Dresden

first: Vasyl

last: Lukiyanchuk

address: Handelallee 26

country: Germany

institute: OncoRay

summary: By employing a global gene expression profiling, we performed analysis of the molecular pathways which are deregulated in DU145 ALDH+ prostate cancer progenitors and DU145-RR radioresistant cells.

overall_design: Non-sorted, ALDH-negative, and ALDH-positive populations were analyzed, both for parental DU145 cell line and for its radioresistant sub-line. Three independent experiments were performed

first: Anna

last: Dubrovska

first: Claudia

last: Peitzsch


title: Gene expression profiles of mouse embryonic fibroblasts (MEFs), induced cardiomyocytes (iCMs) and heart

status: Public on Jul 03 2014

summary:
Global gene expression patterns of the iCMs shift from a MEF state toward a cardiac-like phenotype by Gata4/Mef2c/Tbx5 (GMT) or GMT/miR-133 transduction at 3, 7 and 18 days after transduction (D3, D7 and D18)
MiR-133 silenced fibroblast signatures in parallel with cardiac gene activation, and Snai1 overexpression inhibited the effects of miR-133-mediated cardiac reprogramming.

overall_design: MEFs were used for negative control, mouse heart tissue for positive control. Gene expression profiles were compared among MEFs, iCMs and heart. 23474 probes were analyzed in each experiment.

first: Naoto

last: Muraoka

first: Masaki

last: Ieda


title: Microarray analysis of IdHP cells compared to LKS, Control ProB and E2A-/- progenitors

status: Public on Jun 01 2014

summary: Self-renewal potential and multipotency are hallmarks of the stem cell1-3. It is generally conceived that acquisition of such a stemness requires rejuvenation of somatic cells through reprogramming of genetic and epigenetic status. We show here that a simple blockage of cell differentiation is sufficient to make stem cells. By over-expression of transcriptional repressor Id3 in murine hematopoitic progenitor cells and cultivation of these cells in B cell induction conditions, cells exhibit developmental arrest and enter a self-renewal cycle. These cells can be maintained in vitro almost limitlessly, and the long-term cultured cells exhibited robust multi-lineage reconstitution when transferred into irradiated mice. These cells can be cloned and re-expanded with 50% of plating efficiency, indicating that virtually all cells are self-renewing. Equivalent progenitors were produced from progenitors in human cord blood. Thus produced stem cells will be useful as the source of cells for immune cell therapy.

overall_design: Four samples

first: Tomokatsu

last: Ikawa

first: Hiroshi

last: Kawamoto


title: Gene expression signatures for breast cancer cells metastatic to bone marrow

city: Tokyo

first: Yusuke

last: Yoshioka

address: 5-1-1, Tsukiji, Chuo-ku

institute: National Cancer Center Research Institute

summary: To clarify and compare gene expression profile of each cell line, we have employed microarray expression profiling.  The expression of many genes was similar in MM231-D3H2LN-GFP-BM2 cells parental cells, MM231-D3H2LN-GFP cells; however, the expression of genes related to the cell cycle was decreased in the BM2 cells compared with the parental cells. We also confirmed that the global gene expression patterns of the CD44+ and CD44- MM231-D3H2LN-GFP-BM2 cells were similar, although some genes which encode proteins that breast cancer cell dormancy, such as SRC and ERBB2  were increased and decreased, respectively, in the CD44- population.

overall_design: The gene expression of breast cancer cells metastatic to bone marrow and those with or without expression of cancer stem cell marker were measured.

first: Makiko

last: Ono

first: Nobuyoshi

last: Kosaka


title: EBV Modulates Host Cell microRNA-194 to Promote IL-10 Production and B Lymphoma Cell Survival

status: Public on Sep 10 2014

city: Stanford

first: Purvesh

last: Khatri

state: California

address: 279 Campus Dr. Beckman Center B235A

department: BMIR

institute: Stanford University

summary: The purpose of this study was to investigate the effect of EBV infection on host cell miR and to characterize the miRNome in EBV+ B cell lymphomas from patients with PTLD. A qPCR array was used to measure the expression level of 377 previously identified miRs from RNA isolated from three sources: total B cells isolated from healthy individuals (n=4), lymphoblastoid cell lines (LCL) generated by transformation of normal B cell with the B95-8 lab strain of EBV (n=4) and EBV+ B cell lines isolated from patients with PTLD (n=6).

overall_design: miRNA expression was assayed in total B cells samples (n = 4, in duplicate), in lymphoblastoid cell lines (n = 4, in duplicate) and in spontaneous lymphoblastoid cell lines derived from PTLD patients with EBV+ B cell lymphomas (n = 6 in duplicate). The expression of miRNA in the B cell samples was used as a control.

first: Aleishia

last: Harris-Arnold

first: Christopher

last: Arnold

first: Steven

last: Schaffert

first: Olivia

middle: L

last: Hatton

first: Sheri

last: Krams

first: Carlos

middle: O

last: Esquivel

last: Martinez


title: Gene expression profiles of induced cardiomyocytes(iCMs)

first: Satoshi

last: Kondo

state: Kanagawa

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Comparison of RNA-Seq and Microarray in Transcriptome Profiling During T Cell Activation

status: Public on Mar 11 2014

city: San Diego

first: Anton

last: Bittner

state: CA

address: 3210 Merryfield Row

department: Systems Biology

institute: Janssen R&D

summary: Samples in this study probe the gene expression kinetics in human CCR6+ Th17 memory T cells activated under Th17 condition.  Human CCR6+ Th17 memory T cells were purified from PBMC and gene expression was studied over a time course of 3 days after activation under Th17 condition. RNA from these samples was also profiled using RNA-Seq to compare different transcriptome profiling technologies.

overall_design:
PBMCs were purified from whole blood from a healthy donor. CD4+ cells were isolated by negative selection, followed by CCR6+ purification by positive selection.  Two replicates of 6 time points were taken following stimulation in Th17 polarizing conditions.

This submission represents microarray component of study.

first: Shanrong

last: Zhao

first: Wai-Ping

last: Fung-Leung

first: Xuejun

last: Liu

first: Hongtao

last: Fan

first: Karen

last: Ngo

first: Susan

last: Stephens


title: Sox9 duplications cause Sry-negative XX sex-reversal in dogs

status: Public on Aug 05 2014

city: Pavia

first: Elena

last: Rossi

state: Pavia

address: forlanini 14

department: Molecular Medicine

country: Italy

institute: University of Pavia

type: Genome variation profiling by genome tiling array

summary: Sexual development in mammals is based on a complicated and delicate network of genes and hormones that have to collaborate in a precise manner. The dark side of this pathway is represented by pathological conditions, wherein sexual development does not occur properly either in the XX and the XY background. Among them a conundrum is represented by the XX individuals with at least a partial testis differentiation even in absence of SRY. This particular condition is present in various mammals including the dog. Seven dogs characterized by XX karyotype, absence of SRY gene and testicular tissue development were analysed by Array-CGH. In two cases the array-CGH analysis detected an interstitial heterozygous duplication of chromosome 9. The duplication contained the SOX9 coding region.In this work we provide for the first time a causative mutation for the XXSR condition in the dog. Moreover this report supports the idea that the dog represents a good animal model for the study of XXSR condition caused by abnormalities in the SOX9 locus.

overall_design: Seven dogs from different breeds have been considered in this study. All clinical activities and surgical experiments on the dogs were carried out following the Federation of European Laboratory Animal Science Association’s recommendations and European Union legislation (Council Directive 86/609/EEC). During the research no animals were sacrificed.  Array-CGH was performed using a custom Agilent Canine Genome CGH Microarray 180 K (Agilent Technologies, Santa Clara, California, USA) and processed according to the manufacturer’s protocol. The arrays were analyzed with the Agilent scanner and the Feature Extraction software (v10.7.3.1). A graphical overview was obtained using the CGH analytics software (v7.0.4.0). The DNA extracted from a normal female (boxer breed) was used as the control in all cases. Sox9 duplications detected by array CGH were confirmed by Real-Time-qPCR .

first: Orietta

last: Radi

first: Lisa

last: De Lorenzi

first: Annalisa

last: Vetro

first: Debora

last: Groppetti

first: Enrico

last: Brigliardi

first: Cecilia

last: Luvoni

first: Ada

last: Rota

first: Giovanna

last: Camerino

first: Orsetta

last: Zuffardi

first: Pietro

last: Parma


title: Gene expression profile of STIM1 deficiency for cardiac remodeling in response to pressure overload by transverse aortic constriction (TAC)

status: Public on Jul 01 2014

first: Satoshi

last: Kondo

summary: STIM1 is a Ca2+ sensor of intracellular Ca2+ stores and essentially activates the Ca2+ entry channels of the plasma membrane. STIM1 is predicted to activate transient receptor potential canonical (TRPC) channels and Orai channels, and has a critical role in promoting the development of cardiac hypertrophy.

overall_design: Gene array experiments were performed to analyze the effects of STIM1 deficiency using total RNA from the left ventricles of WT sham, WT TAC, STIM1KO sham and STIM1KO TAC 4 weeks after the operation.

first: Takayoshi

last: Ohba


title: Identification of GATA6 target genes in LS174T colorectal cancer cells using gene expression arrays

status: Public on May 20 2014

city: Barcelona

first: Camille

last: Stephan Otto Attolini

state: Select a State or Province

address: Baldiri Reixac 10

department: Biostatistics and bioinformatics Unit

institute: IRB Barcelona

summary: Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 competes with beta-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been previously linked to increased susceptibility to develop CRC. Hence, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation.

overall_design: Total RNA was collected from biological replicates of LS174T colorectal cancer cells transduced with either short hairpin against GATA6 (shGATA6) or non-silencing control (NS) grown in DMEM supplemented with 10% FBS in the presence of doxycycline (dox: 1 µg mL-1; Sigma Aldrich) or vehicle (70% ethanol) for a period of 72h. Short hairpins were designed and cloned into doxycycline inducible pTRIPZ lentiviral vector (Open Biosystems). Additionally a 4-hydoxy tamoxifen inducible system was used to inducibly block beta-catenin/TCF activity for a period of 36h. Briefly, the ERT2 domain from the pCMV-CRE-ERT2 (Feil et al., 1996) was amplified by PCR and cloned into a modified FUGW lentiviral vector backbone (Lois et al., 2002). NTCF was then amplified byPCR from the pCDNA3.1-NTCF-NLS (van de Wetering et al., 2002) and cloned in frame upstream of the ERT2 from the FUW-CMV-ERT2 (ET) to create the FUW-CMV-NTCF-ERT2 (NET). Total RNA was extracted using the TRIzol® Plus RNA Purification Kit (Life Technologies).

last: Stephan-Otto Attolini

first: Gavin

last: Whissell


title: Ring1B Promotes Hepatic Stem/Progenitor Cell Expansion via Simultaneous Suppression of Cdkn1a and Cdkn2a

status: Public on Apr 01 2014

city: Yokohama City

first: Yasuharu

last: Ueno

address: 3-9  Fuku-ura, Kanazawa-ku

department: Graduate School of Medicine

institute: Yokohama City University

summary: The expansion of hepatic stem/progenitor cells requires Ring1B-mediated epigenetic silencing of Cdkn1a and Cdkn2a, demonstrating that Ring1B simultaneously regulates multiple CDKI in tissue stem/progenitor cells.

overall_design: Comparison of gene expression profiles between Ring1B KO and WT murine liver cells at E13.5

first: Hiroyuki

last: Koike


title: Acetylated Histone Reader Brd4 functions as Repair Adaptor in Immunoglobulin Class Switch Recombination

status: Public on Jun 20 2014

summary: Class Switch Recombination (CSR) is a B cell specific genomic alteration induced by activation induced cytidine deaminase (AID)-dependent DNA break, followed by repair and recombination at the immunoglobulin heavy-chain locus. The involvement of several chromatin-associated factors in promoting AID-induced DNA break formation has been reported. However, the involvement of chromatin adaptors at the repair phase of CSR remains unknown. Here, we provide evidence that acetylated histone reader Brd4 is critical to the repair and recombination step of CSR. Brd4 was recruited to the AID-induced DNA break region, and depletion of Brd4 from the S region chromatin by knockdown or a chemical inhibitor JQ1 causes CSR impairment without affecting AID-induced DNA break generation. Such inhibition of Brd4 suppressed the accumulation of 53BP1 and UNG at the cleaved S regions, perturbed switch donor-switch acceptor microhomology length and reduced Igh/c-myc translocation. We conclude that Brd4 serves as a histone-reader platform required for the recruitment of CSR repair components.

overall_design: Brd4 were depleted from the chromatin by either siRNA treatment or JQ1 (40nM) addition in CH12F3-2A cells in the presence of CIT stimulation. RNA from each samples were extracted and relative difference in transcript level were compared with control RNAi- and DMSO-treated, CIT-stimulated samples.

first: Andre

last: Stanlie

first: Ashraf

last: Yousif

first: Hideo

last: Akiyama

first: Jun

last: Qi

first: James

middle: E

last: Bradner

first: Tasuku

last: Honjo

first: Nasim

last: Begum


title: Gene expression profiling of HPV-negative oropharyngeal cancers and Normal benign uvula, tonsil

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: 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. This study aimed to compare the gene expression profiles of HPV-negative oropharyngeal squamous cell carcinoma (OPC) and normal benign uvula/tonsil tissues and determine what biological processes and pathways are affected in HPV-negative OPCs.

overall_design: ANALYSIS 6: Two-condition, one-color experiment:  HPV-negative oropharyngeal tumor samples and  normal benign uvula/tonsil tissues. Biological replicates:  16 HPV negtive samples and 4 Normal samples.

first: Swati

last: Tomar

first: Sangeeta

last: Kowli

first: Susannah

last: Kassler

first: Natalie

last: Sutkowski

first: M

last: Gillespie

first: Kim

last: Creek

first: Lucia

last: Pirisi


title: Gene expression profiling of HPV-active oropharyngeal cancers and Normal benign uvula, tonsil

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. 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 OPCs and normal benign uvula/tonsil tissues and determine what biological processes and pathways are affected in HPV-active tumors.

overall_design: ANALYSIS 5: Two-condition, one-color experiment:  HPV-active oropharyngeal tumor samples and  normal benign uvula/tonsil tissues. Biological replicates:  12 HPV active samples and 4 Normal samples.


title: Gene expression profiles of oral and oropharyngeal cancers from European American and African American patients

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

overall_design: Refer to individual Series


title: Gene expression profiling of HPV-inactive and HPV-negative oropharyngeal cancers

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. 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-negative and HPV-inactive OPCs from both African American and European American patients, and determine their biological and racial differences.

overall_design: ANALYSIS 4: Four-condition, one-color experiment:  African American (AA) HPV-inactive, African American (AA) HPV-negative,  European American (EA) HPV-inactive, European  American (EA) HPV-negative oropharyngeal tumor samples. Biological replicates:  4 AA HPV Inactive samples, 8 AA  HPV Negative samples, 4 EA HPV Inactive samples and 8 EA HPV Negative samples,


title: Gene expression profiling of European American HPV-active,  HPV-inactive and HPV-negative oral and oropharyngeal cancers

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. According to some reports, the rate of HPV-associated tumors is much lower in AA patients as compared to EA patients in United States. This study aimed to compare the gene expression profiles of HPV-active, -inactive and -negative OPCs from european american patients, and determine their biological differences.

overall_design: ANALYSIS 3: Three-condition, one-color experiment: HPV-active, HPV-inactive and HPV-negative oropharyngeal tumor samples from  european american patients. Biological replicates: 8  HPV Negative Tumors. 4  HPV Inactive Tumors. 11 HPV Active Tumors.