title: Bisphenol A Induced the Expression of DNA Repair Genes in Human Breast Epithelial Cells

status: Public on Feb 28 2011

city: Charlottesville

first: Yong

last: Huang

state: VA

address: 1340 Jefferson Park Ave

department: Medicine

institute: University of Viginia

summary: Xenoestrogens are part of a group of agents termed endocrine disruptors because of their capacity to perturb normal hormonal actions. It has been suggested that xenoestrogens may contribute to the development of hormone-dependent cancers, such as breast and endometrial cancers. Bisphenol A (BPA) is polymerized to manufacture polycarbonate plastic and epoxy resins. Human exposure occurs when BPA leaches from plastic-lined food and beverage cans. In the present work we are aiming to determine if BPA has carcinogenic properties by using an in vitro system. For this purpose, the human breast epithelial cells MCF-10F were treated with 10-3M to 10-9M BPA continuously for two weeks. The MCF-10F cells treated with 10-3M and 10-4M BPA died, indicating that these concentrations were toxic for the human breast epithelial cells. The cells treated with 10-5M to 10-9M BPA were evaluated for formation of solid masses in collagen and invasion capacity, both phenotypes that are indicators of cell transformation. MCF-10F treated with 10-5M, 10-6M, 10-7M, 10-8M and 10-9M BPA formed a high percentage of solid masses (34.6%, 20%, 42.4%, 31.8% and 32.2%, respectively). Ten passages after BPA treatments, the invasive capacities of the cells were evaluated using Boyden chambers. The invasion capacity was lower in the cells treated at high concentrations of BPA (10-5M and 10-6M), and there was an increased invasion for the cells treated at low BPA concentration (10-9M), although in all the cases the differences were not significant to the controls. Expression and DNA methylation analysis were performed with the cells treated with 10-5M and 10-6M BPA. We found that these cells showed an increased expression of BRCA1, BARD1, CtIP, RAD51 and BRCC3, all genes involved in DNA repair, and downregulation of PDCD5 and BCL2L11 (also known as BIM), both involved in apoptosis. The upregulation of CtIP was related to hypomethylation of the promoter/exon1 of this gene. Furthermore, BPA induced silencing of BCL2L11 by hypermethylation. This is the first demonstration that BPA induces neoplastic transformation of breast epithelial cells and that aberrant DNA methylation of genes involved in DNA repair and apoptosis could be involved in the initiation of the neoplastic process.

overall_design: MCF-10F, a normal-like Homo sapiens breast epithelial cell (HBEC) line that is ERa-negative PR-negative, was maintained in high calcium medium at 37°C and 5% CO2 until confluent. These cells were treated with different concentrations of BPA continuously for two weeks, adding fresh media every day. As controls, MCF-10F cells were not treated and maintained in the regular media or treated with 0.284% DMSO (vehicle). The cells treated with 10-5M or 10-6M BPA after the invasion assay were collected and expanded during 6 passages. RNA was isolated from the cells using an RNA extraction kit (Qiagen).

first: Sandra

middle: V

last: Fernandez

first: Kara

last: Snider

first: Yan

last: Zhou

first: Jose

last: Russo


title: BRAF Mutation Is Rare in Advanced-Stage Low-Grade Ovarian Serous Carcinomas

status: Public on Mar 04 2011

city: Houston

first: Kwong-Kwok

last: Wong

state: TX

address: T4-3900, 1515 Holcombe Boulevard

department: Gynecologic Oncology and Reproductive Medicine

country: USA

institute: UT M. D. Anderson Cancer Center

summary: Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed.    Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed.

overall_design: Gene expression analysis was performed on five serous borderline tumors with BRAF mutation and five serous borderline tumors without BRAF mutation randomly. RNA was extracted from microdissected tumor cells. Expression profiling was carried out with Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays


title: Identification of an SRF- and androgen-dependent gene signature in prostate cancer

city: Rochester

first: Keith

last: Anderson

state: MN

address: 200 First Street SW

institute: Mayo Clinic

summary: The androgen receptor (AR) is the principal target for treatment of non-organ confined prostate cancer (PCa).  Systems and bioinformatics approaches suggest that considerable variation exists in the mechanisms by which AR regulates expression of effector genes and point towards a role for secondary transcription factors (TFs) therein. We identified a novel indirect mechanism of androgen action in which effects of androgens on PCa cells are mediated by Serum Response Factor (SRF).    To identify and characterize genes and cellular processes that are androgen-regulated in an SRF-dependent manner in PCa, Affymetrix HG-U133 Plus 2.0 GeneChip Array analysis was performed starting from RNA obtained from LNCaP cells in which androgen stimulation was combined with siRNA-mediated SRF silencing.  To this end, LNCaP cells were seeded in 60 mm dishes at a density of 550,000 cells per dish in antibiotic-free medium.  The next day, cells were transfected with siGenome SmartPool siRNA targeting SRF (Dharmacon, Lafayette, CO) or a custom-made control SmartPool targeting luciferase (LUC condition) using Lipofectamine 2000 (Invitrogen, Carlsbad, CA) following the manufacturer’s instructions.  Forty-two hours after transfection, cells were treated with 5nM R1881 or ethanol vehicle.  3 biological triplicates were included per treatment group.  Forty-eight hours later, cells were harvested in Trizol reagent (Invitrogen). RNA was isolated, purified on RNeasy columns (Qiagen, Germantown, MD) and checked for integrity by Agilent testing (Affymetrix, Santa Clara, CA).  cDNA was generated and hybridized to Human Genome U133 Plus 2.0 arrays (Affymetrix) according to the manufacturer’s instructions at the Mayo Clinic Advanced Genomics Technology Microarray Shared Resource core facility.

overall_design: Two-factor factorial design with three biological replicates (12 total samples) using LNCaP or SRF Silenced cells treated with either R1881 or ethanol vehicle.

first: Hannelore

last: Heemers

first: Lucy

middle: J

last: Schmidt

first: Kevin

middle: M

last: Regan

first: Zhifu

last: Sun

first: S

middle: K

first: Karla

last: Ballman

first: Donald

last: Tindall


title: Definition and characterization of the systemic T cell dysregulation in untreated indolent B cell lymphoma and very early CLL

status: Public on Mar 01 2011

city: Freiburg

first: Petros

last: Christopoulos

address: Hugstetter Str. 55

department: Medizin I.

country: Germany

institute: Uniklinik Freiburg

summary: Epidemiological data show that the immune system may control or promote emergence and growth of a neoplastic lymphomatous clone. Conversely, systemic lymphomas, especially myeloma and CLL, are associated with clinical immunodeficiency. This prospective controlled study demonstrates substantially reduced circulating T helper cells, predominantly naive CD4+ cells, in patients with non-leukemic follicular and extranodal marginal zone lymphomas, but not in monoclonal gammopathy and early CLL. These numerical changes were correlated with a preactivated phenotype, hyperreactivity in vitro, presenescence, and a Th2 shift of peripheral T helper cells. No prominent alterations were found in the regulatory T cell compartment. Gene expression profiling of in vitro-stimulated CD4+ cells revealed an independent second alteration of T helper cell physiology which was most pronounced in early CLL but also detectable in FL/eMZL. This pattern consisted of downregulation of proximal and intermediate T-cell receptor signaling cascades and globally reduced cytokine secretion. Both types of T cell dysfunction may contribute to significant immunodeficiency in non-leukemic indolent B-cell lymphomas as demonstrated by refractoriness to hepatitis B vaccination. The precise definition of systemic T cell dysfunction serves as the basis to study its prognostic impact, its relationship to the established influence of the lymphoma microenvironment, and its therapeutic manipulation

overall_design: 8 samples from FL/eMZL patients, 7 samples from CLL patients, 5 samples of MGUS patients, 5 MALT, 16 healthy controls

first: Dietmar

last: Pfeifer

first: Kilian

last: Bartholome

first: Marie

last: Follo

first: Jens

last: Timmer

first: Paul

last: Fisch

first: Hendrik

last: Veelken


title: Cross-species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites

status: Public on Feb 23 2011

city: Odense M

first: Susanne

last: Mandrup

address: Campusvej 55

department: Biochemistry and Molecular Biology

country: Denmark

institute: University of Southern Denmark

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We used chromatin immunoprecipitation combined with deep sequencing to map all binding sites of C/EBPα and PPARγ in human SGBS adipocytes and compared these with the genome-wide profiles from mouse 3T3-L1 adipocytes to systematically investigate what biological features correlate with retention of sites in orthologous regions between mouse and human. Despite a limited interspecies retention of binding sites, several biological features make sites more likely to be retained. First, co-binding of PPARγ and C/EBPα in mouse is the most powerful predictor of retention of the corresponding binding sites in human. Second, vicinity to genes highly upregulated during adipogenesis significantly increases retention. Third, the presence of C/EBPα consensus sites correlate with retention of both factors, indicating that C/EBPα facilitates recruitment of PPARγ. Fourth, retention correlates with overall sequence conservation within the binding regions independent of C/EBPα and PPARγ sequence patterns, indicating that other transcription factors work cooperatively with these two key transcription factors.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: C/EBPα and PPARγ ChIP-seq in mouse 3T3-L1 and human SGBS adipocytes.

first: Søren

middle: F

first: Mette

last: Jørgensen

first: Yun

last: Chen

first: Ronni

last: Nielsen

first: Albin

last: Sandelin


title: Genes regulated by Sox2 in colorectal cancer cell line

city: Seattle

first: Biaoyang

last: Lin

state: WA

address: 550 17th Ave, James Tower suite 550

department: Swedish Neuroscience Institute

institute: Swedish Medical Center

summary:
Knockdown of Sox2 in SW620 colorectal cancer cells decrease their growth rates in vitro and in vivo in xenograft models.
We used microarrays to detail the global programme of gene expression in Sox2 Knockdown sw620 cells compared with mock knockdown sw620 cells

overall_design: Sox2 knockdown sw620 cells and and mock knockdown sw620 cells were cultured in RPMI 1640 cell culture media for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the genes regulated by Sox2 in colorectal cell lines and end (T4) of gastrulation.

first: Xuefeng

last: Fang


title: Clinical Significance of Osteoprotegerin Expression in Human Colorectal Cancer

city: Bunkyo-ku

first: Kaoru

last: Mogushi

state: Tokyo

address: 2-1-1 Hongo

department: Intractable Disease Research Center

country: Japan

institute: Juntendo University

summary:
Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC).
Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients.
Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC.
Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC.

overall_design: Total of 148 microarray datasets obtained from LCM and homogenized tissues of colorectal cancer patients were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software with affy package from BioConductor. Normalization was separately performed for LCM dataset and homogenized tissue dataset. The normalized gene expression levels were presented as log2-transformed values by RMA.

first: Shunsuke

last: Tsukamoto

first: Toshiaki

last: Ishikawa

first: Satoru

last: Iida

first: Megumi

last: Ishiguro

first: Hiroshi

last: Mizushima

first: Hiroyuki

last: Uetake

last: Tanaka

first: Kenichi

last: Sugihara


title: Sequential gene expression profiling in CLL during treatment

city: Vienna

first: Stefanie

last: Tauber

address: Dr. Bohr-Gasse 9

department: CIBIV

country: Austria

institute: MFPL

summary:
Purpose:
Accurate prediction of clinical response is the prerequisite for individualized therapy in chronic lymphocytic leukemia (CLL). We hypothesized that sequential assessment of gene expression changes early during therapy may well reflect behaviour of the leukemic clone in response to specific drugs.
Patients and Methods:  Gene expression profiles (GEP) were determined in CD19+ selected B-cells from 20 patients treated with fludarabine and cyclophosphamide (FC) (N=10) or FC plus rituximab (FCR) (N=10). Samples were collected in the first cycle before and within 48hours after initiation of treatment. GEP analysis was stratified by clinical response 3 months after start of therapy.
 Results: GEP before treatment detected high expression of 34 genes correlated with response and 32 genes correlated with resistance to therapy. These genes were related to regulation of apoptosis, cell cycle, cell adhesion, and signal transduction. Different results were obtained with sequential GEP: Sixteen genes were up-regulated after rituximab infusion in non-responders. Rituximab therapy resulted in down-regulation of AKT1 indicating involvement of the PI3-kinase pathway in CD20-signaling. Up-regulation of 24 genes after FC (including ITPKB (inositol 1,4,5-trisphosphate 3-kinase) and CD44) and of 36 genes after FCR (including CD49d) was associated with resistance. Down-regulation of CTLA4 correlated with poor response to FC. CD44, CD49d and the PI3-kinase signaling pathway were confirmed as potential therapeutic targets to overcome resistance by (protein analysis) or functional experiments.   Conclusion  Sequential GEP provides rapid and relevant information for prediction of response and resistance. This approach could be used to guide and adapt individualized therapy in CLL.

overall_design: 50 Samples from CD19 selected B-cells, three treatments (rituximab, FC and RFC), 10 replicates for each treatment, 20 replicates for control condition

first: Medhat

last: Shehata

first: Martin

last: Bilban

first: Ulrich

last: Jaeger


title: Assessment of mutation on expression levels

status: Public on Feb 21 2011

city: South San Francisco

first: Peter

last: Haverty

state: CA

address: 1 DNA Way

department: Bioinformatics

institute: Genentech, Inc.

summary: One lung tumor and its adjacent normal were profiled for expression levels with the Affymetrix HGU133 plus 2.0 array.

overall_design: One lung tumor sample and its adjacent normal were assayed on the Affymetrix HG-U133 plus 2.0 array to assess the effects of mutation on expression.

first: William

last: Lee

first: Jiang

last: Zhaoshi

first: Jinfeng

last: Liu

first: Yinghui

last: Guan

first: Jeremy

last: Stinson

first: Peng

last: Yue

first: Yan

last: Zhang

first: Krishna

middle: P

last: Pant

first: Deepali

last: Bhatt

first: Connie

last: Ha

first: Stephanie

last: Johnson

first: Michael

middle: I

last: Kennemer

first: Sankar

last: Mohan

first: Igor

last: Nazarenko

first: Colin

last: Watanabe

first: Andrew

middle: B

last: Sparks

first: David

middle: S

last: Shames

first: Robert

last: Gentleman

first: Howard

last: Stern

first: Ajay

last: Pandita

first: Dennis

middle: G

last: Ballinger

first: Radoje

last: Drmanac

first: Zora

last: Modrusan

first: Somasekar

last: Seshagiri

first: Zemin


title: Pompe disease induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification

status: Public on Feb 17 2011

city: Taipei

first: Pin-hsun

last: Chen

address: 128 Academia Road, Section 2, Nankang

department: Genomic Research Center

country: Taiwan

institute: Academia Sinica

summary: Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.

overall_design: Total RNA were isolated from HESC, HF(Pompe disease), PomD-iPSC, HES-CMLC, and PomD-iPS-CMLC. The series included two HESC lines, two HF(Pompe disease) cell lines, four PomD-iPS cell lines, and HES-CMLC were differentiated from one HESC line(HESC2), PomD-iPS-CMLC were differentiated from 3 PomD-iPS cell lines(PomD-iPSC A10, PomD-iPSC A17, PomD-iPSC B03). Each condition was repeated twice and used HESC as control.

first: Hsiang-Po

last: Huang

first: Pin-Hsun

first: Wuh-Liang

last: Hwu

first: Ching-Yu

last: Chuang

first: Yin-Hsiu

last: Chien

first: Stone

last: Lee

first: Chung-Liang

first: Li-Tzu

last: Li

first: Hsin-Fu

first: Hong-Nerng

last: Ho

first: Chung-Hsuan

first: Hung-Chih

last: Kuo


title: Human umbilical cord blood-derived mesenchymal stem cells from 2 donors

status: Public on Feb 19 2011

city: seoul

first: Eun Ju

address: 28 yongon dong

country: South Korea

institute: seoul natonal university

summary:
screening of signature deterimes the individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells
There is paucity of information whether human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) from separate donors might have different effects on improving myocardial repair after myocardial infarction (MI).

overall_design: We screened cell surface genes by the comparing the cells that showed the best and worst efficacy, respectively, in repairing the infarcted myocardium of rats.

first: Eu


title: Comparison of tenascin-C proficient versus tenascin-C deficient Mouse Embryonic Fibroblasts (MEFs)

status: Public on Feb 22 2011

city: Basel

first: florence

last: Brellier

address: Maulbeerstrasse 66

country: Switzerland

institute: FMI

summary: In order to investigate what signalling pathways are turned on by tenascin-C, we generated Mouse Embryonic Fibroblasts (MEFs) deficient for tenascin-C and compared their gene expression profile to MEFs proficient for tenascin-C.

overall_design: TNC-KO MEFs as well as WT MEFs in which tenascin-C was knocked-down (following stable transfection of a short hairpin RNA) were compared to WT MEFs (expressing strong endogenous levels of tenascin-C).

first: Florence

first: Hans-Rudolf

last: Hotz

first: Tim

last: Roloff

first: Ruth

last: Chiquet-Ehrismann


title: Expression data from human mesenchymal stem cells treated with Wnt3a

status: Public on Feb 16 2011

city: New York

first: Sapna

last: Vijayakumar

address: 1425 Madison Ave

department: Oncological Sciences

institute: Mount Sinai School of Medicine

summary: Wnt signaling is upregulated frequently in several cancers, including sarcomas.  Since, there is cell-context dependent variation in the target gene expression, to identify canonical Wnt targets in sarcomas, we used human mesenchymal stem cells.

overall_design: Human mesenchymal stem cells were treated with 100ng/ml recombinant Wnt3a either 6 hrs or 24 hrs.  Total RNA was extracted from untreated and Wnt3a treated samples using Qiagen's RNA extraction kit.

first: Stuart

middle: A

last: Aaronson


title: Examination of inflammatory transcripts during a transfer model of type I diabetes.

city: Saint Louis

first: Emil

last: Unanue

state: MO

address: 660 S Euclid Ave Box 8118

department: Pathology and Immunology

institute: Washington University School of Medicine

summary: In an accompanying paper we found specific localization of diabetogenic T cells only to islets of Langerhans bearing the specific antigen. Instrumental in the specific localization was the presence of intra-islet dendritic cells bearing the β-cell-peptide-MHC complex. Here we report that the entry of diabetogenic CD4 T cells very rapidly triggered inflammatory gene expression changes in islets and vessels by up-regulating chemokines and adhesion molecules. VCAM-1 expression was notable in blood vessels and so was ICAM-1. ICAM-1 was also found on β-cells. These expression changes induced the entry of non-specific T cells that otherwise did not localize to the islets. In contrast to the entry of diabetogenic CD4 T cells, the entrance of non-specific T cells required a chemokine response and VCAM-1 expression by the islets. Interferon-gamma was important for the early gene expression changes in the islets. By microarray analysis we detected up-regulation of a group of interferon-inducible genes as early as 8 hours post T cell transfer. These studies provide a baseline to examine the development of therapeutics that can modulate islet localization of diabetogenic T cells to control this autoimmune disease.

overall_design: 20 total samples

middle: R

first: Javier

last: Carrero

first: Boris

last: Calderon


title: Microarray expression data from human TCRVg9-positive gamma delta T lymphocytes

status: Public on Feb 15 2011

city: Toulouse

first: Jean Jacques

last: FOURNIE

address: 2 av Hubert Curien

department: oncology

country: France

institute: INSERM

summary:
We used microarrays to detail the global programme of gene expression by circulating TCRVgamma9+ gamma delta T cells isolated from healthy individuals,tested either as resting cells or cells activated by phosphoantigen BrHPP and IL-2at an early(+6hrs)  and a late (+7days) timepoint.
We find that with more “NK cell” genes than alphabeta T cells and more “T cell” genes than NK cells, the circulating TCRVgamma9+ gamma delta T cells cells have a hybrid transcriptome. The gene signature of the activated cells recapitulates their physiological functions: Th1 cytokine, chemokine and cytotoxic activities at first and mitotic activity at later time points. The gene expression pattern of activated normal gamma delta T cells is nevertheless clearly distinctive from that of NK/T and peripheral T cell lymphomas of the gamma delta subtype.

overall_design: Human TCRVg9positive gamma delta T cells were isolated  from PBMC by cell sorting (>98% purity) and activated for RNA extraction and hybridization on Affymetrix microarrays. Samples comprise cells before activation (control time 0), early after activation with BrHPP/IL2 (+6 hours) and at a later timepoint of the activated in vitro culture  with BrHPP/IL2 (day 7).

first: Jean

last: Fournié


title: Gain of the oncostatin M receptor in cervical squamous cell carcinoma is associated with adverse clinical outcome

city: Cambridge

first: Ian

last: Roberts

address: Hills Road

department: Cancer Cell Unit

country: United Kingdom

institute: Hutchison MRC Research Centre

type: Genome variation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Gene expression analysis of 12  B-cell Chronic Lymphocytic Leukemia samples and 5 CD19+ control samples

city: Prague 2

first: Vojtěch

last: Kulvait

address: U Nemocnice 5

department: Institute of Pathological Physiology

country: Czech Republic

institute: Charles University in Prague - 1st Faculty of Medicine

summary:
Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lymphocytic leukemia (B-CLL). In this study, we present evidence that MYB (v-myb myeloblastosis viral oncogene homolog) is overexpressed in a subset of B-CLL patients. MYB physically associates with the promoter of MIR155 host gene (MIR155HG, also known as BIC, B-cell integration cluster) and stimulates its transcription. This coincides with the hypermethylated histone H3K4 residue and spread hyperacetylation of H3K9 at MIR155HG promoter. Our data provide evidence of oncogenic activities of MYB in B-CLL that include its stimulatory role in MIR155HG transcription.
We have studied differentially expressed genes in the whole genome and also in the preselected groups of  MYB target genes and miR-155 microRNA predicted targets.

overall_design: This study was intended to investigate differentially expressed genes mRNA in 12 B-CLL patient peripheral blood samples in comparison with 5 CD19+ healthy donor peripheral blood samples.

first: Tomáš

last: Stopka

first: Marek

last: Trněný

first: Karin

last: Vargová

first: Jiří

last: Zavadil


title: Involvement of the TGF-β and β-catenin pathways in pelvic lymph node metastasis in early stage cervical cancer

city: Groningen

first: Maartje

last: Noordhuis

department: Gynecologic Oncology

country: Netherlands

institute: University Medical Center Groningen

summary:
Purpose: Presence of pelvic lymph node metastases is the main prognostic factor in early stage cervical cancer patients, primarily treated with surgery. Aim of this study was to identify cellular tumor pathways associated with pelvic lymph node metastasis in early stage cervical cancer.
Experimental Design: Gene expression profiles (Affymetrix U133 plus 2.0) of 20 patients with negative (N0) and 19 with positive lymph nodes (N+), were compared with gene sets that represent all 285 presently available pathway signatures. Validation immunostaining of tumors of 274 consecutive early stage cervical cancer patients was performed for representatives of the identified pathways.
Results: Analysis of 285 pathways resulted in identification of five pathways (TGF-β, NFAT, ALK, BAD, and PAR1) that were dysregulated in the N0, and two pathways (β-catenin and Glycosphingolipid Biosynthesis Neo Lactoseries) in the N+ group. Class comparison analysis revealed that five of 149 genes that were most significantly differentially expressed between N0 and N+ tumors (P<0.001) were involved in β-catenin signaling (TCF4, CTNNAL1, CTNND1/p120, DKK3 and WNT5a). Immunohistochemical validation of two well-known cellular tumor pathways (TGF-β and β-catenin) confirmed that the TGF-β pathway (positivity of Smad4) was related to N0 (OR:0.20, 95%CI:0.06-0.66) and the β-catenin pathway (p120 positivity) to N+ (OR:1.79, 95%CI:1.05-3.05).
Conclusions: Our study provides new, validated insights in the molecular mechanism of lymph node metastasis in cervical cancer. Pathway analysis of the microarray expression profile suggested that the TGF-β and p120-associated non-canonical β-catenin pathways are important in pelvic lymph node metastasis in early stage cervical cancer.

overall_design: For the microarray experiment, we selected fresh frozen primary cervical cancer tissue, containing at least 80% tumor cells, of patients with histologically confirmed N0 (n=20) and of patients with N+ (n=19). The N0 and N+ groups were matched for age, FIGO stage and histology (all squamous cell carcinoma).

first: Rudolf

last: Fehrmann

first: G

last: Wisman

first: Esther

last: Nijhuis

first: Jelmer

last: van Zanden

first: Perry

middle: D

last: Moerland

first: Emiel

last: Ver Loren van Themaat

first: Haukeline

middle: H

last: Volders

first: Mirjam

last: Kok

first: Klaske

last: ten Hoor

first: Harry

last: Hollema

first: Elisabeth

last: de Vries

first: Geertruida

last: de Bock

first: Ate

last: van der Zee

first: Ed

last: Schuuring


title: Expression levels in strained vs. non-strained Calu-3 lung epithelial cells

status: Public on Feb 12 2011

city: Aurora

first: Holger

middle: K.

last: Eltzschig

state: Colorado

address: 19th Avenue

department: Anesthesiology

institute: University of Colorado Denver

summary:
Ventilator induced lung injury can lead to serious conditions like ARDS which are associated with a high mortality (around 30%, Stapleton et al., Chest, 2005). We hypothesized that changes of expression levels of different genes would lead us to the identification of critical target genes, which might influence the inflammation and outcome associated with this condition.
We used human whole genome U133 Plus 2.0 microarrays to detail the changes of gene expression and identified distinct classes of up-regulated genes during this process.

overall_design: Confluent non strained and strained human Calu-3 cells were selected for RNA extraction and hybridization on Affymetrix microarrays. The experiment was performed with 3 replicates.

first: Kelley

last: Brodsky


title: Expression profile of acute monocytic leukemia patients

city: Shanghai

first: Zhaohui

last: Gu

state: Shanghai

address: 197 Rui Jin Road II

department: School of Medicine

country: China

institute: Shanghai Jiao Tong University

summary: To understand the pathogenesis of DNMT3A in acute monocytic leukemia (AML-M5), we identified genes that are expressed differently in leukemia cells from AML-M5 patients collected at diagnosis with DNMT3A mutations (6 cases) compared to those without the mutations (4 cases). Differences of expression level were observed in 889 out of 20,723 (4.3%) annotated genes by using Affymetrix microarray with 469 genes upregulated and 420 genes downregulated.

overall_design: Leukemia cells in bone marrow of acute monocytic leukemia patients were collected at diagnosis for RNA extraction and hybridization on Affymetrix microarrays. 6 cases of AML-M5 samples with DNMT3A mutations and 4 cases of AML-M5 samples wihtout DNMT3A mutations were used.

first: Zhu

last: Chen

first: Sai-Juan


title: Expression profile and whole genome SNP data from acute monocytic leukemia patients

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


title: Biological Similarities Exist between Oligoarticular and Polyarticular Subtypes of JIA Based on Age at Onset

status: Public on Feb 14 2011

city: Cincinnati

first: Michael

last: Barnes

state: OH

address: 3333 Burnet Ave

department: Rheumatology

institute: Cincinnati Childrens Hospital Medical Center

summary:
Objective.  To identify gene expression differences in peripheral blood from patients with early and late onset juvenile idiopathic arthritis (JIA).

Methods.  Peripheral blood mononuclear cells (PBMC) were isolated from 56 healthy controls and 104 patients with recent onset JIA (39 persistent oligoarticular, 45 RF-polyarticular, and 20 systemic). Poly(A) RNA was amplified and labeled using NuGEN Ovation, and gene expression assessed with Affymetrix HG-U133 Plus 2.0 GeneChips®.

Results.  A total of 832 probe sets revealed gene expression differences (false-discovery rate 5%) in PBMC from children with oligoarticular JIA whose disease began before 6 years of age (age at onset [AaO] <6; early onset), compared to subjects whose disease began at 6 years of age or later (AaO ≥6; late onset). In early onset patients there was greater expression of genes related to B-cells, and lesser expression of genes related to cells of the myeloid lineage. Support Vector Machine algorithms identified samples from early or late onset oligoarticular (97% accuracy) or polyarticular (89% accuracy) JIA patients, but not systemic JIA patients or healthy controls. Principal component analysis showed that the major classifier of samples was AaO regardless of whether they had oligoarticular or polyarticular JIA.

Conclusion.  PBMC gene expression analysis reveals biologic differences between early and late onset JIA patients independent of classification based on the number of joints involved. These data suggest AaO may be an important parameter to consider in JIA classification. Furthermore, different pathologic mechanisms may influence AaO, and understanding these processes may lead to improved treatment of JIA.

first: Alexei

last: Grom

first: Susan

last: Thompson

first: Thomas

last: Griffin

first: Lorie

last: Luyrink

first: Robert

last: Colbert

first: David

middle: N

last: Glass


title: Prospective Identification, Isolation, and Profiling of a Telomerase-Expressing Subpopulation of Human Neural Stem Cells, using sox2 Enhancer-Directed Fluorescence-Activated Cell Sorting

status: Public on Feb 25 2011

city: Rochester

first: Steven

last: Goldman

state: NY

address: 601 Elmwood Ave

department: Center for Translational Neuromedicine

institute: University of Rochester

summary: Sox2 is expressed by neural stem and progenitor cells, and a sox2 enhancer identifies these cells in the forebrains of both fetal and adult transgenic mouse reporters. We found that an adenovirus encoding EGFP placed under the regulatory control of a 0.4 kb sox2 core enhancer selectively identified multipotential and self-renewing neural progenitor cells in dissociates of human fetal forebrain. Gene expression analysis of E/sox2:EGFP-sorted neural progenitor cells, normalized to the unsorted forebrain dissociates from which they derived, revealed marked overexpression of genes within the notch and wnt pathways, and identified multiple elements of each pathway that appear selective to human neural progenitors.

overall_design: We used adenoviral E/sox2:EGFP to transduce dissociates of the second trimester human ventricular zone (VZ)/ subventricular zone (SVZ), followed by EGFP-directed fluorescence-activated cell sorting (FACS). The sox2 isolates and unsorted controls from different gestational ages (16-19 wks, n=4) were then subject to RNA extraction and hybridization on Affymetrix microarrays.

first: Su

last: Wang

first: Devin

last: Chandler-Militello

first: Gang

last: Lu

first: Neeta

last: Roy

first: Alex

last: Zielke

first: Romane

last: Auvergne

first: Nancy

last: Stanwood

first: Daniel

last: Geschwind

first: Giovanni

last: Coppola

first: Silvia

last: Nicolis

first: Fraser

last: Sim


title: Expression data from self-deprived regulatory CD4 T cells

status: Public on Feb 09 2011

city: 91400 Orsay

first: Florent

last: Dumont

state: Ile de France

address: 17 avenue des sciences

institute: Université Paris-Saclay


title: Early Relapse in ALL is identified by Time To Leukemia in NOD/SCID mice and is characterized by a gene signature involving survival pathways

status: Public on Feb 10 2011

city: Padova

first: Andrea

last: Zangrando

address: Via Giustiniani, 3

department: Woman and Child's Health

country: Italy

institute: University of Padova

summary:
Gene expression analysis identified a specific signature of differentially expressed genes discriminating TTLshort and TTLlong phenotypes.
Gene expression signatures of xenografted leukemia samples with different TTL phenotypes were analyzed on  cohorts of pediatric BCP-ALL patients.

overall_design: Class comparison between TTLshort and TTLlong patient groups was analyzed by shrinkage t statistic.

first: Lueder

last: Meyer

first: Geertruy

last: te Kronnie


title: Expression data of glioblastoma stem-like (GS) cell lines, conventional glioma cell lines and primary tumors

city: Hamburg

first: Hauke

middle: Simon

last: Guenther

address: Martinistraße 52

department: Neurochirurgie

institute: UKE

summary:
We compared a large panel of human glioblastoma stem-like (GS) cell lines,  corresponding primary tumors and conventional glioma cell lines to identify cell lines that preserve the transcriptome of human glioblastomas most closely, thereby allowing identification of shared therapeutic targets.
We used Affymetrix HG-U133 Plus 2.0 microarrays to compare human glioblastoma stem-like (GS) cell lines,  corresponding primary tumors and conventional glioma cell lines.

overall_design: We extracted total RNA from 32 conventional glioma cell lines, 12 GS cell lines (8 in two different passages), 7 clonal sublines derived from two GS lines, 12 original tumors, and 4 monolayer cultures established from the same tumors as GS-lines using standard serum conditions.

first: Alexander

last: Schulte

last: Günther

first: Katrin

last: Lamszus


title: Expression data from Tregs purified from WT-CD3KO or IIKO-CD3KO chimeras

summary:
Disruption of TCR /MHC class II interactions leads rapidly to alterations of the common CD4 Treg transcriptional signature
Self-deprived, non-functional Tregs were compare to fully functional Tregs by microarrays.

overall_design: CD3ε-/- mice were lethally irradiated and their immune system reconstituted with WT mouse (WT-CD3KO chimeras) or IIKO mouse (IIKO-CD3KO) Bone Marrow cells. Twenty eight days later, peripheral Tregs from these chimeras were purified for RNA extraction and hybridization on Affymetrix microarrays.

first: Bruno

last: Lucas


title: Fibroblast triggered gene expression in tumor

status: Public on Feb 08 2011

city: Stanford

first: Junhee

last: Seok

address: 318 Campus Drive W310 - Davis Lab

institute: Stanford University

summary: Personalized biological insights into heterogeneous tumors, such as breast cancer could improve clinical management. While genomic analysis has contributed significantly towards dissecting breast cancer heterogeneity, limitations in clinical application are partly rooted in the inter-tumor variability arising from a largely uncharacterized interactive exchange between diverse cell types in the tumor microenvironment. Here we first identified a common response signature to stromal coculture across breast cancer of varying clinicopathologic phenotypes. Proximity to fibroblasts resulted in gene transcript alterations of >2-fold for 107 probe sets, collectively designated as Fibroblast Triggered Gene Expression in Tumor (FTExT). Prominent features of tumor cell response included transcript repression related to biofunctions encompassing inflammatory signaling, cell movement, cell death, and cell growth and proliferation. In an evaluation of intertumor heterogeneity, the FTExT classifier stratified moderate and high histopathologic grade breast cancer according to clinical outcome (dataset 1, n=401, p=0.031; dataset 2, n=200, p=0.013), delineating a novel phenotype of stromal crosstalk underlying the prognostic potential of tumor grade. Extending correlative data through functional analysis of stromal-epithelial cocultures of both malignant and nonmalignant derivation, significant differences in cell cycle regulation, rate of proliferation, resistance to therapy-induced apoptosis, and growth arrest were observed in FTExT-based subgroups. Instead of a stromal impact that is uniformly cancer promoting, our data demonstrate striking variability in tumor cell response that directly contributes to contrasting functional aggressiveness of malignant breast tissue. Our findings uniquely reveal dynamically interacting paracrine components underlying the molecular and functional heterogeneity of breast cancer, thus presenting novel opportunities for tumor targeting.

overall_design:
10 tumor samples cocultured with fibroblast were profiled in their gene expression with microarrays, and compared with 7 tumor samples cultured without fibroblast. Immortalized tumor cell lines of varying histologic grade were developed and maintained in a growth median as described in Dairkee, et al., Oncogene, 2007. In the coculture set up,
epithelial cells were seeded in 6-well plates, and fibroblasts in 0.4 μm inserts with hanging geometry (BD Biosciences, Franklin Lakes, NJ) at a 3:1 ratio in a common pool of growth medium for 3-day harvests. Controls were comprised of each epithelial sample maintained in the
absence of fibroblast-seeded inserts under the same culture conditions.

first: Gloria

last: Luciani

first: Aejaz

last: Sayeed

first: Stacey

last: Champion

first: William

last: Goodson

first: Wenzhong

last: Xiao

first: Micheal

last: Mindrinos

first: Ronald

middle: W

last: Davis

first: Shanaz

last: Dairkee


title: Gene expression analysis during morphogenesis of Human umbilical vein endothelial cells

first: Hongryeol

last: Park

address: seodaemun-gu yonsei-ro

department: biochemstry

institute: yonsei univ.

summary: Gene expression profiles during the differentiation of HUVEC on matrigel were analyzed.

overall_design: RNA was isolated from Human umbilical vein endothelial cell during morphogenesis. HG-U133 plus 2.0 microarray (54675 human genes; Affymetrix Santa Clara, CA, USA) was performed.

first: Young-Guen

last: Kwon

first: Jeong-Ki

last: Min


title: Gene expression in IGROV1 SP and non-SP cells

city: London

first: Wei

last: Dai

address: Du Cane Road

department: Sugery and Cancer

institute: Imperial College London

summary: Side populations have recently been identified in ovarian cancers and may play an important role in post treatment relapse and resistance to chemotherapeutic drugs. In this study, we aimed to identify the differential expression between IGROV1 SP and NSP on Affymetrix HG-U133plus2 microarrays. We found ovarian tumour SP cells frequently over-express the multi-drug resistance associated P-glycoprotein (ABCB1) by Rank Product (FDR<0.05), and by geneset enrichment analysis, embryonic stem cell-associated ‘NOS’ signature (Notch/Oct4/Sox2 regulated genes) and Polycomb Repressive Complex 2 (PRC2) genes were over-expressed, while PRC2-repressed target genes were significantly under-expressed in the SP from ovarian cell lines compared to non-SP (FDR<10-4).

overall_design: Cells were isolated using Hoechst 33342 cell sorting without other treatment. The experiment was carried out in triplicates: 3 SP samples and 3  non-SP samples

first: Robert

last: Brown

first: Sian

last: Rizzo


title: Characterization of the transcriptional roles of NME2

city: Delhi

first: Vinod

middle: Kumar

last: Yadav

state: Delhi

address: Mall Road

country: India

institute: IGIB

type: Genome binding/occupancy profiling by genome tiling array


title: Expression profile of lung adenocarcinoma, A549 cells following targeted depletion of non metastatic 2 (NME2/NM23 H2)

summary: Non-metastatic 2 (NME2) is an established metastases suppressor in multiple human cancer types. However, the molecular mechanisms of NME2 action remain insufficiently resolved. We recently validated the transcription regulatory activity of NME2 with respect to control of proto-oncogene c-MYC expression. We hypothesized that large scale transcriptional potential of NME2 may be at the core of metastases suppression by NME2. Using a combination of high throughput genomic assays such as chromatin immunoprecipitation coupled to promoter array hybridization (ChIP-chip) and gene expression profiling, we characterized the transcriptional roles of NME2. Specifically, we found a set of NME2 target genes which changed expression upon selective depletion of NME2 in a lung cancer cell line, A549. The analysis of gene expression suggested control of various biological pathways esp. cell adhesion and apoptosis by NME2 target genes which could be important in regulation of metastases.

overall_design: For transcriptome analysis, total RNA was purified from A549 cells transiently silenced for NME2 (siRNA duplex against NME2/ NM23 H2(Santa Cruz)) or transfected with control siRNA duplexes. Isolated RNA was converted to cDNA, transcribed in vitro to synthesize biotinylated cRNA, and hybridized to Affymetrix HG-U133 plus 2.0 GeneChip oligonucleotide microarrays, according to manufacturer’s instructions. Three biological replicates were averaged and significance analysis performed using GCOS (P <0.005 of fold change).

first: Ram

last: Thakur

first: Akinchan

last: Kumar

first: Richa

last: Basundra

first: Shantanu

last: Chowdhury


title: Expression data from pericardial and subcutaneous adipose tissue and adipocytes

status: Public on Feb 01 2011

city: Boston

first: Frank

last: Lau

state: MA

address: 185 Cambridge St - CPZN 4500

institute: Center for Regenerative Medicine

summary: To better characterize the role of whole pericardial adipose tissue (PCAT) in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between pericardial and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals.

overall_design:
Patients who underwent elective coronary artery bypass grafting and/or cardiac valve replacement surgeries participated in the study. Pericardial adipose tissue and subcutaneous adipose tissue were harvested from patients.

3 of the 53 samples were of inadequate quality and were not included in the analysis.

first: Chad

last: Cowan


title: Expression data from aged spermatogonial stem cells

status: Public on Feb 04 2011

city: houston

first: Zhiyv

last: Niu

state: tx

address: One baylor plaza, 506E

department: Animal Biology

institute: University of Pennsylvania

summary:
In vitro and in vivo aging of mouse spermatogonial stem cells alters stem cell function based on quantitative spermatogonial stem cell transplantation analyses.
We used microarrays to identify differential gene expression in vitro and in vivo aged spermatogonial stem cells to identify potential causes of observed phenotypic differences in aged spermatogonial stem cell function.

overall_design: Spermatogonial stem cells were isolated from young and serial-transplanted aged mouse donors and cultured for short and long periods.  Spermatogonial stem cells were isolated from cultures and subjected to microarray analysis to identify differential gene expression.

first: Jonathan

last: Schmidt

first: Ralph

middle: L

last: Brinster


title: Genes upregulated by HLX

city: Wien

first: Julia

last: Testori

address: Lazarettgasse 19

department: Vascular Biology and Thrombosis Research

institute: Medical University Vienna

summary: HLX was found as a VEGF-A induced gene in HUVEC (B.Schweighofer, submitted). In order to detect genes regulated by HLX HUVEC were infected by recombinant adenovirus expressing HLX for 4, 8, 16 and 32h. RNA was isolated and subjected to microarray analysis using Affymetrix microarray.

overall_design: HUVEC were infected with a MOI of 40 with either HLX expressing or empty adenovirus for 4, 8, 16 or 32 hours. HUVEC without an adenovirus infection were used as control.Total RNA was isolated with Trizol according to the instructions of the manufacturer. Gene expression was analysed with Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays according to the Affymetrix protocol.

first: Martin

last: Bilban

first: Erhard

last: Hofer


title: Threshold of Biologic Response of the Small Airway Epithelium to Low Levels of Tobacco Smoke

status: Public on Feb 02 2011

city: New York

first: Yael

last: Strulovici-Barel

address: 1300 York Avenue

department: Department of Genetic Medicine

institute: Weill Cornell Medical College

summary: Background: Healthy individuals exposed to low levels of cigarette smoke have a decrement in lung function and higher risk for lung disease compared to unexposed individuals. We hypothesized that healthy individuals exposed to low levels of tobacco smoke must have biologic changes in the small airway epithelium compared to healthy unexposed individuals.   Methods: Small airway epithelium was obtained by bronchoscopy from 121 individuals; microarrays assessed genome wide gene expression, and urine nicotine and cotinine were used to categorized subjects as “nonsmokers,” “active smokers,” and “low exposure.”  The gene expression data was used to determine the threshold and ID50 of urine nicotine and cotinine at which the small airway epithelium showed abnormal responses.   Results: There was no threshold of urine nicotine without an abnormal small airway epithelial response, and only a slightly above detectable threshold abnormal response for cotinine. The nicotine ID50 for nicotine was 25 ng/ml and cotinine 104 ng/ml.  Conclusions: The small airway epithelium detects and responds to low levels of tobacco smoke with transcriptome modifications. This provides biologic correlates of epidemiologic studies linking low level tobacco smoke exposure to lung health risk, health, identifies genes in the lung cells most sensitive to tobacco smoke and defines thresholds at the lung epithelium responds to inhaled tobacco smoke.

overall_design:
Affymetrix arrays were used to assess the gene expression data of smoking-responsive genes in the in small airway epithelium obtained by fiberoptic bronchoscopy of 48 healthy non-smokers (non-smoker or Nsaets), 65 healthy smokers (smoker), 7 symptomatic smokers (SYMs) and a healthy occasional smoker (OcSs).

YSB and LO contributed equally to the study.

first: Larsson

last: Omberg

first: Michael

last: O'Mahony

first: Cynthia

last: Gordon

first: Charleen

last: Hollmann

first: Ann

middle: E

last: Tilley

first: Jacqueline

last: Salit

first: Jason

last: Mezey

first: Ben-Gary

last: Harvey

first: Ronald

last: Crystal


title: Gene expression profiling of skeletal muscles treated with a soluble activin type IIB receptor

first: Fedik

last: Rahimov

address: 3 Blackfan Circle, CLS 15030.4

department: Genetics

institute: Boston Children's Hospital

summary: Inhibition of the myostatin signaling pathway is emerging as a promising therapeutic means to treat muscle wasting disorders. Activin type IIB receptor is the putative myostatin receptor, and a soluble activin receptor (ActRIIB-Fc) has been demonstrated to potently inhibit a subset of TGF-β family members including myostatin. In order to determine reliable and valid biomarkers for myostatin pathway inhibition, we assessed gene expression profiles for quadriceps muscles from mice treated with ActRIIB-Fc compared to mice genetically lacking myostatin and control mice.

overall_design: RNA extracted from quadriceps muscles of four classes of two-month-old female mice were analyzed with Affymetrix microarrays: control mice, myostatin-null mice, mice treated with one dose of ActRIIB-Fc and mice treated with four doses of ActRIIB-Fc. An initial study used 3 mice from each class, and an independent follow-up study used 8 myostatin-null mice and 5 mice from each of the other 3 classes.


title: Prediction of lymph node involvement in breast cancer from primary tumor tissue using gene expression profiling and miRNAs.

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary: Lymph node involvement is the most important prognostic factor in breast cancer, but little is known about the underlying molecular changes. First, to identify a molecular signature associated with nodal metastasis, gene expression analysis was performed on a homogeneous group of 96 primary breast tumors, balanced for lymph node involvement. Each tumor was diagnosed as a poorly differentiated, estrogen positive, her2-neu negative invasive ductal cancer. (Affymetrix Human U133 Plus 2.0 microarray chips). A model, including 241 genes was built and validated on an internal and external dataset performed with Affymetrix technology. All samples used for validation had the same characteristics as the initial tumors. The area under the ROC curve (AUC) for the internal dataset was 0.646 and 0.651 for the external datasets. Thus, the molecular profile of a breast tumor reveals information about lymph node involvement, even in a homogeneous group of tumors. However, an AUC of 0.65 indicates only a weak correlation. Our model includes multiple kinases, apoptosis related and zinc ion binding genes. Pathway analysis using the Molecular Signatures Database revealed relevant gene sets (BAF57, Van 't Veer). Next, miRNA profiling was performed on 82/96 tumors using Human MiRNA microarray chips (Illumina). Eight miRNAs were significantly differentially expressed according to lymph node status at a significance level of 0.05, without correcting for multiple testing. The analysis of the inverse correlation between a miRNA and its computationally predicted targets point to general deregulation of the miRNA machinery potentially responsible for lymph node invasion. In conclusion, our results provide evidence that lymph node involvement in breast cancer is not a random process.

overall_design:
Gene expression profiling: A training set of 96 patients and an independent internal dataset of 20 patients balanced for lymph node involvement was selected from the multidisciplinary breast centre database

miRNA profiling not provided in this Series.

first: A.

last: Smeets

last: Daemen

first: I.

last: Van den Bempt

first: O.

last: Gevaert

first: B.

last: Claes

first: H.

last: Wildiers

first: R.

last: Drijkoningen

first: P.

last: Van Hummelen

first: D.

last: Lambrechts

last: De Moor

last: Neven

first: C.

last: Sotiriou

first: T.

last: Van Dorpe

last: Paridaens


title: Gene expression data of non-leukemic individuals before and during in-vivo glucocorticoid treatment

city: Bolzano

first: Johannes

last: Rainer

address: Via A. Volta 21

department: Institute for Biomedicine

institute: Eurac Researc

summary:
Article title: Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells.

Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and constitute a central component in the therapy of lymphoid malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling glucose metabolism, was identified by us previously as a GC response gene in expression profiling analyses performed in children with ALL during initial systemic GC mono-therapy. Since deregulation of glucose metabolism has been implicated in apoptosis induction, this gene and its relatives PFKFB1, 3, and 4 were further analyzed. Expression analyses in additional ALL children, non-leukemic individuals and leukemic cell lines confirmed frequent PFKFB2 induction by GC in most systems sensitive to GC-induced apoptosis, particularly in T-ALL cells. The 3 other family members, in contrast, were not or weakly expressed (PFKFB1 and 4) or not induced by GC (PFKFB3). Conditional PFKFB2 over-expression in the CCRF-CEM T-ALL in vitro model revealed that its 2 splice variants (15A and 15B) did not have any detectable effect on survival or cell cycle progression. Moreover, neither PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC-induced apoptosis. Our data suggest that, at least in the model system investigated, PFKFB2 is not an essential upstream regulator of the anti-leukemic effects of GC.

overall_design: Gene expression profiles of 4 non-leukemic individuals (1 healthy and 3 with epilepsy) were generated from mononuclear cells isolated from peripheral blood samples before, and after 2, 6, and 24 hours of in-vivo glucocorticoid treatment.

first: Michela

last: Carlet

first: Kristina

last: Janjetovic

first: Stefan

last: Schmidt

first: Renate

last: Panzer

first: Georg

last: Mann

first: Martina

last: Prelog

first: Bernhard

last: Meisted

first: Christian

last: Ploner

first: Reinhard

last: Kofler


summary:
Gene expression data of glucocorticoid resistant and sensitive acute lymphoblastic leukemia cell lines for the article: Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases  (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells

Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and constitute a central component in the therapy of lymphoid malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling glucose metabolism, was identified by us previously as GC response gene in expression profiling analyses performed in children with ALL during initial systemic GC mono-therapy. Since deregulation of glucose metabolism has been implicated in apoptosis induction, this gene and its relatives PFKFB1, 3, and 4 were further analyzed. Expression analyses in additional ALL children, non-leukemic individuals and leukemic cell lines confirmed frequent PFKFB2 induction by GC in most systems sensitive to GC-induced apoptosis, particularly in T-ALL cells. The 3 other family members, in contrast, were not or weakly expressed (PFKFB1 and 4) or not induced by GC (PFKFB3). Conditional PFKFB2 over-expression in the CCRF-CEM T-ALL in vitro model revealed that its 2 splice variants (15A and 15B) did not have any detectable effect on survival or cell cycle progression. Moreover, neither PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC-induced apoptosis. Our data suggest that, at least in the model system investigated, PFKFB2 is not an essential upstream regulator of the anti-leukemic effects of GC.
Generation of the GC sensitive and resistant clones is described in Parson et al. FASEB J 2005 (Pubmed id 15637111). In brief GC sensitive clones were generated by limiting dilution subcloning from the GC sensitive T-ALL cell line CCRF-CEM-C7H2. To generate GC resistant clones the CCRF-CEM-C7H2 cell line was clutured in the presence of 10E-7 M dexametasone.

overall_design: Gene expression profiles of glucocorticoid (GC) resistant and sensitive T-ALL cells during GC treatment and corresponding control samples (cells treated with carrier control). GC induced regulation of PFKFB2 was determined in the various cell lines based on the expression intensities of the corresponding probe sets in GC treated and control samples.


city: Durham

first: Daphne

last: Friedman

state: NC

address: 101 Science Drive, Room 2121, CIEMAS Bldg

institute: Duke University Medical Center

summary:
[original title] LMP-420: a novel purine nucleoside analogue with potent cytotoxic effects for chronic lymphocytic leukemia cells and minimal toxicity for normal hematopoietic cells.

LMP-420 induces cytotoxicity and apoptosis to CLL cells in vitro without any negative effects to normal immune cells.
This gene expression experiment compares CLL cells treated with LMP-420 versus media alone to investigate the mechanism of action of LMP-420.

overall_design: CLL cells from 13 patients were treated with LMP-420 or media for 24 hours, then RNA was extracted and assayed on U133Plus2 GeneChips.

first: Yvonne

middle: M

last: Mowery

first: J

last: Weinberg

first: Margaret

last: Kennedy

first: Karen

last: Bond

first: Joseph

middle: O

last: Moore

first: Mark

middle: C

last: Lanasa

first: Jon

last: Gockerman

first: Louis

middle: F

last: Diehl

first: Salvatore

middle: V

last: Pizzo

first: George

last: Cianciolo


title: Identification of Growth arrest and DNA-damage-inducible gene beta (GADD45beta) as a Novel Tumor Suppressor in Pituitary Gonadotrope Tumors

status: Public on Jan 31 2011

city: Aurora

first: Michael

last: Edwards

state: CO

address: 12700 East 19th Avenue, Box C272

department: Pulmonary

institute: UC Denver

summary: Gonadotrope or null cell pituitary tumors present clinically with signs of hypogonadism and hypopituitarism, together with visual disturbances due to mass effects. Since there are no medical therapies, surgery and/or radiation are the only therapeutic options.   To identify dysregulated genes and/or pathways that may play a role in tumorigenesis and/ or progression, molecular profiling was performed on 14 gonadotrope tumors and 9 normal human pituitaries from autopsy samples.  Principle component analysis (PCA) revealed clear discrimination between tumor and normal pituitary gene expression profiles. Bioinformatic analysis identified specific genes and pathways that were highly differentially regulated, including a cohort of putative downstream effectors of p53 were repressed in gonadotrope pituitary tumors, including GADD45β, GADD45γ and Reprimo with concomitant downregulation of the upstream regulator, PLAGL1.  PLAGL1 reexpression in gonadotrope cells did not directly modulate the downstream targets. Further functional analysis of GADD45β was performed. Overexpression of GADD45β  in mouse gonadotrope cells blocked proliferation, increased rates of apoptosis in response to growth factor withdrawal and increased colony formation in soft agar. In contrast to prior studies with GADD45γ, methylation interference assays showed no evidence of epigenetic modification of the GADD45β promoter in pituitary tumors. Thus, our data suggest that many components downstream of p53 are suppressed in gonadotrope pituitary tumors. A novel candidate, GADD45β is low in tumors and reexpression blocks proliferation, survival and tumorigenesis in gonadotrope cells. Unlike GADD45γ, GADD45β is not methylated to block its expression. Together these studies identify new targets and mechanisms to explore concerning pituitary tumor initiation and progression.

overall_design: To elucidate mechanisms involved in pituitary tumorigenesis and progression, we performed individual gene expression microarray analysis using Affy U133 Plus 2.0 GeneChips comparing 14 gonadotrope tumors with 9 normal pituitary samples obtained at autopsy.

first: Katherine

last: Michaelis

middle: G

last: Wierman

first: Aaron

middle: J

last: Knox

first: Mei

last: Xu


title: DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes

city: Lille

first: Joel

last: Haas

address: 1 Rue du Professeur Calmette

institute: Institut Pasteur de Lille

summary: Murine embryonic fibroblasts were isolated from WT and DGAT1,DGAT2-KO (D1D2KO) animals. mRNA was isolated from cells untreated (UNDIFF) or treated (DIFF) according to standard differentiation protocol for adipocytes (Harris, C, et al. JLR 2011).

overall_design: 12 Samples total: 3 biological replicates of 3 undifferentiated wild type and D1D2KO mice and 3 biological replicates of 3 differentiated wild type and D1D2KO mice.

first: Charles

last: Harris

first: Robert

last: Farese


title: Expression profiling in Williams-Beuren Syndrome patient fibroblast cell lines

city: Lausanne

first: Charlotte

middle: N.

last: Henrichsen

address: Quartier Sorge

department: Center for Integrative Genomics

institute: University of Lausanne

summary:
Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by aa 1.5 Mb microdeletion on human chromosome 7. Although the molecular cause of the disorder is well-established, little is known about the global impact of the deletion on gene expression. Here we profiled the transcriptomes of fibroblast cell lines from 8 young girls with WBS, and 9 sex- and age-matched control individuals

Keywords: disease state analysis, gene expression profiling

overall_design: Skin fibroblast of 8 WBS and 9 control individuals were obtained from the cell culture collections of the “Centre de Biotechnologie Cellulaire, Hospices Civils de Lyon, Hôpital Debrousse”, Lyon, France. Appropriate informed consent was obtained for each sample by the physicians in charge. Human skin fibroblasts were grown in HAM F-10, supplemented with 10% fetal bovine serum and 1% antibiotics (Invitrogen). Total RNA was prepared using TriZOL Reagent (Invitrogen) and RNeasy Mini Columns (Qiagen) according to the manufacturers’ instructions.

first: Gabor

last: Csardi

first: Marie-Therese

last: Zabot

first: Sven

last: Bergmann

first: Giuseppe

last: Merla

first: Alexandre

last: Reymond


title: APC colon stage II

status: Public on Jan 28 2011

city: Marseille

first: Sylviane

last: Olschwang

address: 232 boulevard Sainte-Marguerite

department: Centre de Recherches en Cancérologie de Marseille

institute: Institut Paoli-Calmettes

summary: Analysis of expression profiles in stage II colon cancer according to the APC gene status

overall_design: retrospective study


title: Hormone-Independence of Prostate Cancer Cells is Supported by the Androgen Receptor without Binding to Classical Response Elements

city: Toledo

last: Trumbly

address: 3000 Arlington Avenue

department: Biochemistry and Cancer Biology

institute: University of Toledo

summary: Treatment of late passage (LP50) LNCaP cells with R1881 (androgen) and AR shRNA identified a gene program controlled by androgen receptor in the absence of androgen.

overall_design: Gene expression in late passage (LP50) LNCaP cells that had enhanced androgen-independent growth was determined in androgen-depleted medium in response to R1881 or AR knock down via AR shRNA

first: Mesfin

last: Gonit

first: Juan

last: Zhang

first: Marcela

last: d’Alincourt Salazara

first: Hongjuan

last: Cui

first: Aymen

last: Shatnawi

first: Manohar

last: Ratnam


title: Antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells

status: Public on Jan 29 2011

city: Bloomington

first: Meng

last: Li

state: IN

address: 1001 E 3rd Street

department: Medical Sciences

institute: Indiana University

summary:
Full title: Expression data from antisense miRNA-221/222 (si221/222) and control inhibitor (GFP) treated fulvestrant-resistant breast cancer cells
The expression of miR-221/222 were found to be upregulated in fulvestrant resistant breast cancer cells MCF7-FR compared to its drug-sensitive counterpart MCF7.
To investigate the role of miR-221/222 in acquired resistance to fulvestrant, we lowered the level of miR-221/222 in MCF7-FR cells using miRNA inhibitors (antagomirs), and compared gene expression profiles before and after treatment.

overall_design: Fulvestrant-resistant breast cancer cells MCF7-FR (originated from drug-sentitive breast cancer model cell line MCF7) were transient-transfected by antigomirs targeting miR221 or  miR222 (i.e. si221, si222).  All three cell lines, MCF7-FR, siR221, siRNA222 were subjected to gene expression profiling.


title: Gene responses to TGF-beta receptor inhibition in glioblastoma

status: Public on Jan 27 2011

city: Barcelona

first: Joan

last: Seoane

address: Vall d'Hebron 119-129

country: Spain

institute: VHIO

summary:
TGF-beta has an oncogenic response in glioblastoma and it is considered to be a therapeutic target. We evaluated the effect of TGF-beta inhibition in glioblastoma.
Differential gene expression analysis of patient-derived primary cultured glioblastoma cells treated with the TGF-beta receptor inhibitor, LY2109761

overall_design: 11 patient-derived cell cultures from 11 patients were treated with 2microM of the TGF-beta receptor inhibitor, LY2109761, for 3 hours or left untreated and RNA was isolated and microarray analysis was performed


title: Efficient Generation of Transgene-Free Induced Pluripotent Stem Cells from Normal and Neoplastic Bone Marrow and Cord Blood Mononuclear Cells

city: Madison

first: Igor

last: Slukvin

state: WI

address: 1220 Capitol Court

department: Department of Pathology and Laboratory Medicine

country: USA

institute: University of Wisconsin

summary:
global gene expression were compared among human blood iPSC, human fibroblas iPSC, human embryonic stem cells, human bone marrow MNC and human forskin fibroblast
Reprogramming blood cells to induced pluripotent stem cells (iPSCs) provides a novel tool for modeling blood diseases in vitro. we demonstrated that iPSCs free of transgene and vector sequences could be efficiently generated from human bone marrow and cord blood mononuclear cells using non-integrating episomal vectors. The reprogramming described here is up to 100 times more efficient, occurs 1 to 3 weeks faster as compared to the reprogramming of fibroblasts, and does not require isolation of progenitors or multiple rounds of transfection. This approach provides an opportunity to explore banked normal and diseased cord blood and bone marrow samples without the limitations associated with virus-based methods.

overall_design: Compare the global gene expression of iPSs from different sources, ESCs and Somatic cells

first: Kejin

last: Hu

first: Junying

last: Yu

first: Kran

last: Suknuntha

first: Shulan

last: Tian

first: Karen

last: Montgomery

first: Kyung-Dal

last: Choi

first: Ron

last: Stewart

first: James

middle: A

last: Thomson

middle: I


title: HMGA2 overexpression

status: Public on Feb 06 2011

city: Fukushima

first: Kazuhiko

last: Ikeda

state: Fukushima

address: 1 Hikariga-oka

department: Blood Transfusion and Transplantation Immunology

institute: Fukushima Medical University

summary: Overexpression of high mobility group AT-hook 2 (HMGA2) associated with truncations of its 3’ untranslated region (UTR) with let-7 micro RNA-complementary sequences have been identified in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we generated transgenic mice (∆Hmga2 mice) with a 3’UTR-trncated Hmga2 cDNA that overexpress Hmga2 mRNA and protein in hematopoietic organs. ∆Hmga2 mice showed proliferative hematopoiesis that mimicked a myeloproliferative neoplasm (MPN)-like phenotype with increased numbers of all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis, and erythropoietin-independent erythroid colony formation compared to wild-type mice. ∆Hmga2 BM-derived cells took over most of hematopoiesis in competitive repopulations during serial BM transplants. When we bred mice with circulating PNH cells (Piga- mice) with ∆Hmga2 mice, the lack of GPI-linked proteins did not add an additional clonal advantage to the ∆Hmga2+ cells. In summary, our results showed that the overexpression of a 3’UTR-truncated Hmga2 leads to a proliferative hematopoiesis with clonal advantage, which may explain clonal expansion in PNH or MPN at the level of HSC.

overall_design: Eight independent preparations of RNA, which included each 2 samples of KLS cells and MEP cells from ∆Hmga2 mice and 2 each from WT mice. Each preparation was made from 4 or 6 mice.

first: Philip

last: Mason

first: Monica

last: Bessler


title: Expression data from human (h-) growth hormone-treated and untreated chimeric mouse liver repopulated with human hepatocytes

status: Public on Jan 25 2011

city: Tokyo

first: Fuyuki

last: Miya

address: 35 Shinanomachi, Shinjuku-ku

department: School of Medicine

institute: Keio University

summary: We generated h-hepatocyte chimeric mice with livers that were predominantly repopulated with h-hepatocytes in a h-growth hormone (GH)-deficient state. Using microarray profiles, comparison between h-hepatocytes from h-GH-treated and untreated mice identified 14 GH-up-regulated and four GH-down-regulated genes, including IGF-1, SOCS2, NNMT, IGFLS, P4AH1, SLC16A1, and SRD5A1, and FADS1 and AKR1B10, respectively.

overall_design: The chimeric mice were treated or untreated with h-GH at 2.5 mg/kg b.w. /day for 2 weeks before sacrifice. Hepatocytes or liver tissue were isolated from the mouse livers and their cDNAs were used  for microarray analysis.

first: Chise

last: Tateno

first: Miho

last: Kataoka

first: Rie

last: Utoh

first: Asato

last: Tachibana

first: Toshiyuki

last: Itamoto

first: Toshimasa

last: Asahara

first: Tatsuhiko

last: Tsunoda

first: Katsutoshi

last: Yoshizato


title: Identifying Molecular Effects of Diet through Systems Biology: Influence of Herring Diet on Sterol Metabolism and Protein Turnover in Mice

status: Public on Jan 24 2011

city: Little Rock

first: Intawat

last: Nookaew

address: 4301 W Markham St

department: Department of Biomedical Informatics

institute: University of Arkansas for Medical Sciences

summary: Identifying molecular effects between herring and beef diet in Ldlr-/- mice

overall_design: The transcriptome of the three tissues, which are liver, muscle and adipose tissue, were used for indentify the influence of diet on metabolism. Ldlr-/- mice were fed with either a beef diet or a herring diet.

first: Brit

last: Gabrielsson

first: Agneta

last: Holmäng

first: Ann-sofie

last: Sandberg

first: Jens

last: Nielsen


title: Global gene expression analysis of six cadmium-transformed UROtsa cell isolates

city: Grand Forks

first: Donald

last: Sens

state: ND

address: 1301 North Columbia Road

department: Pathology

institute: University of North Dakota

summary: The immortalized human urothelial cell line, UROtsa, was transformed in six parallel cultures with continual passaging in1 µM Cd+2 until the cells were able to attain the ability to form colonies in soft agar and subcutaneous tumors in nude mice.  The gene expression profiles between cadmium-transformed and control samples were compared and the differentially expressed genes were identified.

overall_design: Six independent Cadmium-transformed UROtsa cell cultures, three control UROtsa cell cultures

first: Scott

last: Garrett

first: Seema

last: Somji

first: Kurt

last: Zhang


title: Gene expression profiles of human effector CD8+ T cell subsets

city: Port St. Lucie

first: Hiroshi

last: Takata

state: FL

address: 9801 SW Discovery Way

institute: Vaccine & Gene Therapy Institute of Florida

summary: Effector CD8+ T cells are believed to be terminally differentiated cells having cytotoxic activity and the ability to produce effector cytokines such as INF-γ and TNF-α. We investigated the difference between CXCR1+ and CXCR1- subsets of human effector CD27-CD28-CD8+ T cells.  Both subsets similarly expressed cytolytic molecules and exerted substantial cytolytic activity, whereas only the CXCR1- subset had IL-2 productivity and self-proliferative activity and was more resistant to cell death than the CXCR1+ subset.  These differences were explained by the specific up-regulation of CAMK4, SPRY2, and IL-7R in the CXCR1- subset and that of pro-apoptotic DAPK1 in the CXCR1+ subset.  The IL-2 producers were more frequently found in the IL-7R+ subset of the CXCR1- effector CD8+ T cells than in the IL-7R- subset.  IL-7/IL-7R signaling promoted cell survival only in the CXCR1- subset.  The present study has highlighted a novel subset of effector CD8+ T cells producing IL-2 and suggests the importance of this subset in the homeostasis of effector CD8+ T cells.

overall_design: To find the genes that potentially cause the difference in IL-2 productivity and cell survival between the CXCR1+ and CXCR1- human effector CD8+ T cell subsets, we performed microarray gene expression analysis.  We highly purified each CD3+CD8+ subset for this analysis (> 95.3%) from 5 healthy individuals, and then compared the gene expression profiles of each subset.

first: Takuya

last: Naruto

first: Masafumi

last: Takiguchi


title: Expression data from Burkitt lymphoma cases

status: Public on Jan 20 2011

city: Bologna

first: pier paolo

last: piccaluga

address: via massraenti 9

department: Hematology and Oncological Sciences "L. and A. Seràgnoli"

institute: University of Bologna

summary:
Burkitt lymphoma is the commonest cancer in children in Africa. We compared the gene expression profiles of African Burkitt lymphoma patients with those of cases presented in  Western countries in both immunocompetent (sporadic Burkitt lymphoma) and HIV-infected patients (immunodeficiency associated Burkitt lymphoma).
We used microarrays to detail the global programme of gene expression in different subtypes of Burkitt lymphoma.

overall_design: Lymph-node biopsies were collected at diagnosis. Gene expression profiles were generated with the Affymetrix HG U133 2.0 plus microarray

first: Pier

middle: P

last: Piccaluga


title: Expression data from Tregs adoptively transferred in MHC II competent or deficient recipients

city: 91400 Orsay

first: Florent

last: Dumont

address: 17 avenue des sciences

institute: Université Paris-Saclay

summary:
Disruption of TCR /MHC class II interactions leads rapidly to alterations of the common CD4 Treg transcriptional signature
Self-deprived, non-functional Tregs were compare to fully functional Tregs by microarrays.

overall_design: Total T cells from the periphery of WT mice were adoptively transferred  into CD3ε-/- recipient mice lacking or not MHC class II molecule expression (MHC II- or MHC II+ recipient mice, respectively). Five days later, peripheral Tregs transferred in MHC II - competent (CD4CD25B6) or - deficient (CD4CD25IIko) recipient were purified for RNA extraction and hybridization on Affymetrix microarrays.

first: Bruno

last: Lucas


title: Comparison of endometrial expression in patients which underwent previous recurrent abortions, implantation failure after IVF/ICSI compared to control fertile

status: Public on Jan 22 2011

city: Clamart

first: Nathalie

last: Lédée

address: 157 rue de la porte de trivaux

department: Hopital Antoine Béclère, Pavillon Jean Dalsace

institute: INSERM UMRS-783, université Paris XI

summary: In order to identify pre-conceptional endometrial dysregulations, we compared the endometrial expression between fertile and IF and RM patients

overall_design: Total RNA were extracted and used for hybridizing Affymetrix chips (GeneChip Human Genome U133 Plus2.0 Array). Data were normalised by gcRMA method and raw p-values adjusted by Bonferroni procedure (1%). Endometrial biopsy was performed in non conceptional cycle in the middle luteal phase-(5 women were selected in each group).

first: N

first: C

last: Munaut


title: Mechanisms of Biofilm Formation in Two Escherichia coli O157:H7 Lineages

status: Public on Jan 19 2011

city: Gyeongsan-Si

first: Jintae

last: Lee

state: Gyeongsangbuk-Do

address: 214-1 Daedong

department: Chemical engineering

institute: Yeungnam University

summary: Two lineages of enterohemorrhagic (EHEC) Escherichia coli O157:H7 (EDL933, Stx1+ and Stx2+) and 86-24 (Stx2+) were investigated in regards to biofilm formation on an abiotic surface.  Strikingly, EDL933 strain formed a robust biofilm while 86-24 strain formed no biofilm on either a polystyrene plate or a polyethylene tube.  To identify the genetic mechanisms of different biofilm formation in two EHEC strains, DNA microarrays were first performed and phenotypic assays were followed.  In the comparison of the EDL933 strain versus 86-24 strain, genes (csgBAC and csgDEFG) involved in curli biosynthesis were significantly induced while genes (trpLEDCB and mtr) involved in indole signaling were repressed.  Additionally, a dozen of phage genes were differentially present between two strains.  Curli assays using a Congo red plate and scanning electron microscopy corroborate the microarray data as the EDL 933 strain produces a large amount of curli, while 86-24 forms much less curli.  Also, the indole production in the EDL933 was 2-times lower than that of 86-24.  It was known that curli formation positively regulates and indole negatively regulates biofilm formation of EHEC.  Hence, it appears that less curli formation and high indole production in the 86-24 strain are majorly responsible for no biofilm formation.

overall_design: For the microarray experiments, E. coli O157:H7 EDL933 and 86-24 were inoculated in 25 ml of LB in 250 ml shake flasks with overnight cultures that were diluted 1:100. Cells were shaken at 250 rpm and 37°C for an absorbance of 4.0 at 600 nm.  Cells were immediately chilled with dry ice and 95% ethanol (to prevent RNA degradation) for 30 sec before centrifugation in 50 ml centrifuge tubes at 13,000 g for 2 min; cell pellets were frozen immediately with dry ice and stored -80°C.  RNA was isolated using Qiagen RNeasy mini Kit (Valencia, CA, USA).  RNA quality was assessed by Agilent 2100 bioanalyser using the RNA 6000 Nano Chip (Agilent Technologies, Amstelveen, The Netherlands), and quantity was determined by ND-1000 Spectrophotometer (NanoDrop Technologies, Inc., DE, USA).

first: Jin-Hyung

first: MooHwan

last: Cho

first: Thomas

middle: K

last: Wood


title: Knockdown of KSHV viral interferon-regulatory factor 3 (vIRF-3) in primary effusion lymphoma (PEL) cells by RNA-Interference

city: Erlangen

first: Frank

last: Neipel

address: Schlossgarten 4

department: Virologisches Institut

country: Germany

institute: Universitaetsklinikum Erlangen

summary:
Kaposi’s sarcoma-associated hepesvirus (KSHV) encodes four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3) is expressed in latently infected PEL cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon response.
In order to identify cellular genes regulated by vIRF-3, cells from the PEL cell line BC-3 (KSHV positive) were transfected with either siRNAs targeted at vIRF-3 (si463 or si716s) or a negative control siRNA without homology to a known gene (siN, siNs).

overall_design: A total of 4 samples were analyzed. This includes two samples with silencing of vIRF-3 expression via RNA-interference (si463 or si716s) and two samples transfected with a negative-control siRNA (siN, siNs). Expression of vIRF-3 was reduced by approximately 75% as estimated by Western blot analysis.

first: K

last: Schmidt

first: E

last: Wies

first: F


title: MMRC expression reference collection

city: Cambridge

first: Michael

middle: Anthony

last: Chapman

address: 7 Cambridge Center

institute: Broad Institute

summary: The MMRC reference collection is a dataset of gene expression profiling, array comparative genomic hybridization, and re-sequencing created as a resource for the Multiple Myeloma research community.

overall_design:
CD138 purified bone marrow cells from patients with newly diagnosed and relapsed Multiple Myeloma.

This submission represents the transcriptome component of the study.

first: Mike


title: Expression data comparing LNCaP cells infected with miR-616 vs. empty vector control

status: Public on Jan 15 2011

city: Hong Kong

first: Stephanie

last: Ma

address: Rm 47, 1/F, Lab Block, Faculty of Medicine Bldg, 21 Sassoon Rd, Pok Fu Lam

department: School of Biomedical Sciences

country: Hong Kong

institute: The University of Hong Kong

summary:
To identify candidate downstream mRNA target(s) for hsa-miR-616
Affymetrix Human Genome U133 Plus GeneChip 2.0

overall_design: miR-616 or empty vector control was stably overexpressed in LNCaP prostate cells using lentivirus


title: MMRC expression and aCGH reference collection

status: Public on Jan 26 2011

type:
Expression profiling by array
Genome variation profiling by array

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

overall_design: Refer to individual Series


title: Promotion of Lung Tumorigenesis By Beta-catenin

city: Philadelphia

first: Eugenia

middle: Cristina

last: Pacheco-Pinedo

state: PA

address: 421 Curie Boulevard

department: Department of Medicine - Cardiovascular Institute - Institute for Regenerative Medicine

institute: University of Pennsylvania

summary:
Although mutations in Kras are present in 21% of lung tumors, there is a high level of heterogeneity in phenotype and outcomes amongst lung cancer patients suggesting the importance of other pathways. Wnt/β-catenin signaling is a known oncogenic pathway that plays a well defined role in colon and skin cancer but its role in lung cancer remains unclear. We show that activation of Wnt/β-catenin in the bronchiolar epithelium of the adult lung does not promote tumor development by itself. However, activation of Wnt/β- catenin signaling leads to a dramatic increase in tumor formation both in overall tumor number and size compared to KrasG12D alone. We show that activation of Wnt/β- catenin signaling significantly alters the KrasG12D tumor phenotype resulting in a phenotypic switch from bronchiolar epithelium to the highly proliferative distal progenitors found in the embryonic lung. This is associated with a decrease in E- cadherin expression at the cell surface which may increase metastasis in Wnt/β-catenin signaling positive tumors. Together, these data suggest that activation of Wnt/β-catenin signaling in combination with other oncogenic pathways in lung epithelium may lead to a more aggressive phenotype due to the imposition of an embryonic distal progenitor phenotype accompanied by decreased E-cadherin expression.
We performed microarray analysis of control murine lung, CC10-cre:KrasG12D, and CC10-cre:Ctnnb1ex3flox:LSL-KrasG12D double mutant micro-dissected murine lung tumors to determine their transcriptional phenotype.

overall_design: Lungs of five-month-old mice were PBS inflated and all the tumors in each lobe were dissected.  The total number of tumors obtained from three out of the 5 pulmonar lobes of each animal was called a sample the other two lobes were saved in case there were problems and the array needed to be repeated. Trizol was used to isolate RNA for microarray analysis. Samples & Genotypes: control murine lung n=2 animals, CC10-cre:KrasG12D n=2 animals, and CC10-cre:Ctnnb1ex3flox:LSL-KrasG12D n=2 animals.

first: Amy

last: Durham

first: Kathleen

last: Stewart

first: Ashley

last: Goss

first: Min

last: Lu

first: Francesco

last: DeMayo

first: Edward

last: Morrisey


title: The study of sex differences during the innate immune response against coxsackievirus B3 (CVB3)-induced myocarditis (12hr post infection)

status: Public on Jan 14 2011

city: Baltimore

first: DeLisa

last: Fairweather

state: MD

address: 615 N Wolfe St

department: Environmental Health Sciences

institute: Johns Hopkins University

summary: Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 hours (h) after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis.

overall_design: Groups consisted of Infected Males, Infected Females, Uninfected Males and Uninfected females. There are 5 mice per group. A total of 20 samples were analyzed in this experiment.

first: Jennifer

last: Onyimba

last: Coronado

first: Amanda

last: Garton

first: Joseph

middle: B

last: Kim

first: Adriana

last: Bucek

first: Djahida

last: Bedja

last: Gabrielson

middle: R

last: Guilarte


title: Regulation of HB-EGF by miR-212 and acquired cetuximab-resistance in head and neck cancer

city: Nashville

first: Christine

middle: H.

last: Chung

state: TN

address: 777 PRB

department: Internal Medicine

institute: Vanderbilt University

summary: To determine the mechanism of cetuximab-resistance in head and neck cancer, a cetuximab-sensitive cell line (SCC1) and its cetuximab-resistant derivative (1Cc8) were analyzed for differentially expressed genes using DNA microarrays. 900 differentially expressed genes were found using the statistical cut-off point of one-way ANOVA with FDR less than 1%.

overall_design:
The SCC1 and 1Cc8 cell lines were grown in biological triplicates. Total RNA was isolated and array experiments were performed.

The supplementary file 'GSE21483_differentially_expressed_genes.txt' includes the list of differentially expressed genes that were identified.

middle: H

first: Hiromitsu

last: Hatakeyama


title: Gene expression profile in response to doxorubicin-rapamycin combined treatment of HER-2 overexpressing human mammary epithelial cell lines

status: Public on Jan 13 2011

city: São Paulo

middle: Priscila

last: Trapé

state: São Paulo

address: Av. Dr Arnaldo

department: Radiologia e Oncologia

country: Brazil

institute: Faculdade de Medicina Universidade de São Paulo

summary: HER-2 positive breast cancers frequently sustain elevated AKT/mammalian target rapamycin (mTOR) signaling which has been associated with resistance to doxorubicin treatment in the clinic. In our study we investigated if the mTOR inhibitor rapamycin increased the sensitivity to doxorubicin therapy in HB4a, a luminal normal mammary cell line; C5.2, a transformed cell derived from HB4a transfected with HER-2 and SKBR3 that exhibits HER-2 amplification. Flow cytometry analysis showed that the combination treatment for 24 hours with rapamycin 20nM and doxorubicin caused accumulation of HB4a and C5.2 cells in S-G2/M. Otherwise in SKBR3 cells, we observed a relative depletion of cells in S-G2/M and concomitant accumulation in G0/G1 of 10% of the cells. The analysis of IC50 of doxorubicin alone and in combination with rapamycin indicated that the sensitivity was increased 2.37 fold in HB4a, 2.46 in C5.2 and 1.87 in SKBR3, suggesting that rapamycin might have enhanced the effects of doxorubicin. Changes in gene expression resulting from co-treatment demonstrated that functional groups of genes with roles in cell cycle, proliferation, apoptosis regulation were represented in the 3 cells analysed. Other biological functions were exclusively associated with each cell suggesting that the inhibition of mTOR activation induced by HER-2 is complex and depends on the cellular context.

overall_design: Five independent experiments were performed for each treatment conditions: HB4a,  C5.2 and SKBR3 cell lines were treated  with vehicle  (DRC), 20 nM of RAPAMYCIN alone (R) and 30  nM of DOXORUBICIN alone (D). The combined treatment consisted of 20 nM of RAPAMYCIN associated with 30 nM DOXORUBICIN of (DR). Total RNA extraction and hybridization  on Affymetrix microarrays.

first: Maria-Lucia

last: Katayama

first: Rosimeire

last: Roela


title: Increased Cell Surface Fas Expression is Necessary to Sensitize Lung Fibroblasts to Fas Ligation-Induced Apoptosis: Implications for Fibroblast Accumulation in Idiopathic Pulmonary Fibrosis.

city: Aurora

first: Michael

last: Edwards

address: 12700 East 19th Avenue, Box C272

department: Pulmonary

institute: UC Denver

summary: Idiopathic pulmonary fibrosis (IPF) is associated with the accumulation of collagen-secreting fibroblasts and myofibroblasts in the lung parenchyma. Many mechanisms contribute to their accumulation, including resistance to apoptosis. In previous work, we showed that exposure to the pro-inflammatory cytokines, TNF-α and IFN-γ reverses fibroblast resistance to apoptosis. The goal of this study was to investigate the underlying mechanism. Based on an initial interrogation of the transcriptomes of unstimulated and TNF-α and IFN-γ-stimulated primary lung fibroblasts and the lung fibroblast cell line, MRC5, we show here that among Fas-signaling pathway molecules, Fas expression was increased ~6-fold in an NF-κB and p38mapk-dependent fashion.  Prevention of the increase in Fas expression using Fas siRNAs blocked the ability of TNF-α and IFN-γ to sensitize fibroblasts to Fas ligation induced-apoptosis; while enforced adenovirus-mediated Fas overexpression was sufficient to overcome basal resistance to Fas-induced apoptosis. Examination of lung tissues from IPF patients revealed low to absent staining of Fas in fibroblastic cells of fibroblast foci. Collectively, these findings suggest that increased expression of Fas is necessary and sufficient to overcome the resistance of lung fibroblasts to Fas-induced apoptosis. They also suggest that approaches aimed at increasing Fas expression by lung fibroblasts and myofibroblasts may be therapeutically relevant.

overall_design: To investigate the mechanism by which TNF-α and IFN-γ reprogram fibroblasts from resistance to sensitivity to Fas-ligation-induce apoptosis, we exposed human primary lung fibroblasts from an IPF patient (FS087) and non-disease control subject (N78) and the human fetal lung fibroblast cell lung (MRC-5) to TNF-α (10 ng/ml) and IFN-γ (50 U/ml) for 36 hr and analyzed changes in their transcriptomes using Affymetrix microarrays.

first: David

middle: W

last: Riches

first: Murry

last: Wynes

first: Chris

middle: D

last: Coldren


title: NSCLC cells treated with Gefitinib

first: Kathryn

last: Ware

department: Craniofacial Biology

institute: University of Colorado Denver

summary:
About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
We used microarray to look at global gene expression changes in untreated cells vs gefitinib treated cells to identify key characters for the acquisition of resistance.

overall_design: NSCLC cells, H322c, were cultured 4 days in media containing 1μM gefitinib or 0.1% DMSO as a control.  On day 4, RNA was extracted and submitted for microarray hybridization.

first: Lydia

last: Heasley

first: Marianne

last: Marshall

first: Trista

last: Hinz

first: Paula

last: Hercule

first: Lindsay

last: Marek

first: Barbara

last: Helfrich


title: Ectopic activation of ARHGAP8 in melanoma promotes cell motility

city: East Melbourne

first: Cameron

middle: N

last: Johnstone

state: Vic

address: 2 St. Andrew's Place

department: Research Division

country: Australia

institute: Peter MacCallum Cancer Centre

summary: ARHGAP8 was expressed at negligible levels in normal melanocytes but was ectopically activated in approximately 10% of melanoma specimens and melanoma cell lines. ARHGAP8 was ectopically expressed in ARHGAP8-negative M14 melanoma cells using the pIRES2 vector (Clontech), producing a bicistronic ARHGAP8-ires-eGFP mRNA. M14 cells stably transfected with vector control or N-terminally FLAG-tagged ARHGAP8 were cultured in 2D or 3D embedded growth conditions and then subjected to gene expression profiling using Affymetrix U133_Plus_2 gene chips.

overall_design: M14 cells stably transfected with pIRES2 alone or pIRES2 containing N-terminally FLAG-tagged ARHGAP8 were cultured in 2D or 3D conditions for 4 d as described. Total RNA was isolated using Trizol reagent (Invitrogen) and processed for application to Affymetrix gene chips.

first: Mark

last: Bowser

first: Anil

last: Rustgi