title: mRNA profiling of AGS gastric cancer cell line upon CTNNB1 silencing

city: Madurai

first: Kumaresan

last: Ganesan

state: Tamil Nadu

address: School of Biological Sciences,

country: India

institute: Madurai Kamaraj University

summary: Beta-catenin (CTNNB1) is a major component of Wnt signaling pathway and a crucial player in gastric cancer. To delineate the complex transcription program governed by CTNNB1 in gastric cancer cells, CTNNB1 was silenced in AGS, a commonly used Wnt signaling activated gastric cancer cell line and the resultant changes in genome-wide mRNA expression pattern was profiled using Affymetrix Human Gene 1.0 ST Array.

overall_design: Total RNA was isolated from AGS gastric cancer cell line transfected with CTNNB1 siRNA and non-targeting control siRNA and profiled using Affymetrix Human Gene 1.0 ST array.

first: G

last: Kumaresan

first: N

last: Sathiyapandi

first: S

last: Jaishree

first: M

last: Muthulakshmi


title: Establishment of tractable human iPSC-based models for the study and targeting of glioma initiation (Expression)

status: Public on Dec 01 2015

city: La Jolla

first: Robert

middle: E

last: Morey

state: CA

address: 2880 Torrey Pines Scenic Dr

department: Pathology

country: USA

institute: UCSD

summary: Gliomas can originate upon transformation of adult Neural Progenitor Cells (NPCs) to Tumor Initiating Cells (TICs). Studies on human Glioma TICs (GTICs) have focused on the use of primary tumors from which GTICs could be isolated. Therefore investigations on the driver events underlying NPC transformation and human glioma initiation remain limited to the use of human embryonic material. Here we report on the development of strategies for the modeling of human gliomagenesis based on the use of human induced Pluripotent Stem Cells (hiPSCs). Transformation of hiPSC-derived NPCs (iNPCs) by defined genetic alterations led to the establishment of tractable human GTIC models suitable for studying the early steps of gliomagenesis as well as for screening studies. Dysregulation of PI3K, MAPK and p53 signaling in iNPCs led to the acquisition of functional GTIC properties. In vivo transplantation led to the formation of highly aggressive, infiltrative and heterogeneous tumors upon limited dilutions and secondary transplantation, faithfully recapitulating gliomagenesis. Metabolic modulation by chemical approaches compromised GTIC viability. Pilot screening of 101 anti-cancer compounds identified 3 molecules specifically targeting transformed iNPCs and primary GTICs. Together, our results demonstrate the potential of hiPSCs for the functional testing of putative driver mutations underlying human tumorigenesis and pave new avenues for the development of personalized cancer therapeutics.

overall_design: Total RNA from eleven samples, duplicates of a wild-type neural progenitor cells, neural progenitor cells with P53 knockdown, neural progenitor cells with P53 knockdown and inhibition of the PI3K and MAPK signaling pathways, neural progenitor cells with the  inhibition of the PI3K and MAPK signaling pathways, and Glioma Stem Cells as well as a control WA09 human embryonic stem cell line was amplified and then hybridized to a Human Gene 1.0 ST Array (Affymetrix).

first: Louise

last: Laurent

first: Ignacio

last: Sancho-Martinez

first: Juan

middle: I

last: Belmonte


title: mRNA profiling of YCC3 gastric cancer cell line upon CTNNB1 silencing

department: Genetics

summary: Beta-catenin is a major component of Wnt signaling pathway and a crucial player in gastric cancer. To delineate the complex transcription program governed by CTNNB1 in gastric cancer cells, CTNNB1 was silenced in YCC3, a commonly used Wnt signaling activated gastric cancer cell line and the resultant changes in genome-wide mRNA expression pattern was profiled using Affymetrix Human Gene 1.0 ST Array

overall_design: Total RNA was isolated from YCC3 gastric cancer cell line transfected with CTNNB1 siRNA or non-targeting control siRNA and profiled using Affymetrix Human Gene 1.0 ST array.

last: KUMARESAN

last: SATHIYAPANDI

last: JAISHREE

last: MUTHULAKSHMI


title: Novel transcripts associated with lymph node metastasis in triple negative breast cancer [validation cohort]

status: Public on Dec 02 2015

city: New Lambton Heights

first: Kelly

last: Kiejda

state: NSW

address: HMRI

country: Australia

institute: University of Newcastle

summary: Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis. It is characterised by the absence of hormone receptors for estrogen, progesterone, and human epidermal growth factor 2, and as a consequence there are no targeted endocrine treatments available. TNBC patients are more likely to develop metastases and disease relapse than patients with other breast cancer subtypes. The identification of biomarkers that can be used to predict which patient is likely to develop metastatic disease remains a priority since this is the major cause of cancer-related death in these women.

overall_design: To validate results of the gene expression arrays, we used an independent cohort with 16 TNBC primary tumours and 4 normal adjacent tissues, and 48 IDCs from patients with breast cancer other than TNBC.

first: Andrea

last: Mathe

middle: A

last: Avery-Kiejda

first: Michelle

last: Wong-Brown

first: Brianna

last: Morten

first: John

middle: F

last: Forbes

first: Stephen

middle: G

last: Braye

first: Rodney

middle: J

last: Scott


title: Rare CNVs in Lynch Syndrome patients negative for mutations in mismatch repair genes [Affymetrix]

status: Public on Nov 30 2015

city: Brasília

first: Rolando

middle: Andre Rios

last: Villacis

state: DF

address: Asa Norte

department: Genetics and Morphology

country: Brazil

institute: University of Brasília - UnB

type: Genome variation profiling by genome tiling array

summary: Only a small proportion of cases suspected to have Lynch Syndrome (LS) can be explained by mutation in the mismatch repair (MMR) genes. This study aimed to identify rare CNVs that may contribute to an increased risk for hereditary colorectal cancer in patients with MMR proficiency.

overall_design: Genomic DNA was extracted from the blood of 26 unrelated patients who met criteria for LS (Amsterdam or Bethesda). Genomic alterations were evaluated using the CytoScan HD microarray platform.


title: Cytoscan HD arrays data for Nodal marginal zone lymphoma (NMZL)

city: Novara

first: Valeria

last: Spina

state: NO

address: Solaroli, 17

department: Translational Medicine

country: Italy

institute: Amedeo Avogadro University of Eastern Piedmont

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

summary:
Nodal marginal zone lymphoma (NMZL) is one of the few B-cell tumors still remaining orphan of cancer gene lesions. By combining whole exome sequencing (WES), deep sequencing of tumor-related genes, high resolution SNP array and RNAseq, here we aim at characterizing the coding genome of NMZL and at disclosing the pathways that are molecularly deregulated in this lymphoma. The study was based on 35 NMZL (tumor representation >70%) with a diagnosis confirmed by: i) pathological revision of lymph node histology; and ii) lack of clinico-radiological evidence of extranodal or splenic disease either at diagnosis or during follow-up. Consistent with NMZL, the cases investigated: i) lacked CD5, CD10 and cyclin D1 expression, 7q deletion, t(11;14), t(14;18), t(11;18) and t(1;14) translocations; and ii) recurrently harbored +3 (14%), +12 (14%) and preferential usage of the IGHV4-34 gene (17%). WES (HiSeq 2500, Illumina; mean coverage per sample: 38x-114x) and high resolution SNP array (Cytoscan HD, Affymetrix) of tumor/normal DNA pairs from 18 discovery NMZL identified 557 non-synonymous somatic mutations (average: 30.8/case) affecting 504 genes and 51 copy number abnormalities (CNA) (average: 3.2/case). To further characterize mutation recurrence, the 504 discovered genes were investigated in an independent validation panel of 17 NMZL by targeted sequencing of tumor/normal DNA pairs (MiSeq; target region: 1.6 Mb; mean coverage per sample: 171x-386x). The 17 validation NMZL were also assessed for CNA by high resolution SNP arrays. RNAseq of 11 discovery NMZL did not identify any recurrent gene fusion. By compiling the results of WES and high resolution SNP array, 39 genes were recurrently affected in >3/35 (9%) NMZL by mutations (n=30 genes) or focal CNA (n=9 genes). Among these, MLL2 (34%), PTPRD (20%) and NOTCH2 (20%) were most frequently mutated. Overall, recurrently mutated genes pointed to the molecular deregulation of specific programs in NMZL, namely JAK/STAT, NOTCH, NF-κB and toll-like receptor (TLR) signaling, cell cycle, chromatin remodeling/transcriptional regulation and immune escape (Fig. 1A). JAK/STAT signaling was targeted by mutually exclusive lesions in 43% of NMZL, and the protein tyrosine phosphatase receptor delta (PTPRD) tumor suppressor was the most frequently affected gene of this system in 20% of NMZL (Fig. 1B-E). PTPRD inhibits JAK/STAT signaling through the dephosphorylation of active p-STAT3. PTPRD lesions in NMZL were represented by somatic mutations that truncated or modified the tyrosine phosphatase domain, as well as deletions of the entire gene locus, including focal and biallelic losses (Fig. 1B-C). Interrogation of institutional and public genomic datasets revealed that PTPRD mutations are specific for NMZL, being rare or absent in other mature B-cell tumors, including splenic marginal zone lymphoma (Fig. 1D). Other JAK/STAT signaling genes affected in NMZL were JAK2, CXCR4 (6%), PTPN2, JAK3, STAT2, SH2B3 and CUL3 (3%) (Fig. 1E). NF-kB signaling was altered in 54% of NMZL by lesions of TNFAIP3 (14%), BCL10, REL (11%), CARD11 (9%), TRAF3 and BIRC3 (6%). NOTCH signaling was targeted in 40% of NMZL by mutations that alternatively involved NOTCH2 (20%), SPEN (11%), RBPJL (6%), FBXW7, DTX1, ITCH and MAML2 (3%). TLR signaling was targeted in 17% of NMZL, including mutations of MYD88 (9%), IRAK1BP1, PELI2 and SEMP6 (3%). Several cell cycle genes were molecularly deregulated in 43% of NMZL, including CDKN2A, PARK2, PARKG (9%), CDC16, CDCA2 (6%), CCNA1, CCNT2, CDK5, CDK13, CDK20, BTG2, HECA and PLK2 (3%). Most (71%) NMZL harbored genetic lesions affecting epigenetic modifiers (MLL2: 34%; CREBBP: 9%; EP300: 6%; TRRAP: 6%), histones (20%) or transcriptional co-repressors (TBL1XR1: 14%; ARID1A: 14%; RCOR1: 11%; NCOR2: 9%, ARID1B: 9%). Finally, the TNFRSF14 and FAS genes, involved in T cell-mediated tumor surveillance, were disrupted by mutations and/or deletions in 17% and 14% NMZL, respectively. A number of actionable cellular programs are molecularly deregulated in NMZL, including JAK/STAT, NOTCH, NF-κB and TLR signaling, cell cycle and chromatin remodeling. PTPRD lesions are among the most recurrent alterations in NMZL and appear to be specific for this lymphoma type across mature B-cell tumors.
Cytoscan HD arrays (Affymetrix, Santa Clara, CA) experiments were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic samples.

overall_design: Copy number aberration analysis of Cytoscan HD arrays (Affymetrix) was performed for 35 NMZL samples. Paired normal (non-tumoral) DNA samples were available for 23 out of 35 NMZL patients that were analyzed and processed.

first: Davide

last: Rossi

first: Gianluca

last: Gaidano


title: Expression profiling of the effect of treatment with GNF-7 on mutant NRAS-positive leukemia cell lines

city: Boston

first: Atsushi

last: Nonami

state: MA

address: 450 Brookline Ave

institute: DFCI

summary:
The complexity of RAS signaling makes targeting RAS challenging. We therefore hypothesized that inhibiting a combination of downstream targets of RAS may potentially lead to an effective therapeutic intervention. We performed a high-throughput chemical screen using a library consisting of multi-targeted inhibitors with the expectation that one or more inhibitors would likely- due to their broad spectrum inhibitory potential- hit critical targets of mutant NRAS. We identified GNF-7, a multi-targeted kinase inhibitor that proved to have high selectivity and sensitivity for leukemia cells with NRAS mutations both in vitro and in vivo.
We used microarrays to determine which transcripts were affected by treatment with GNF-7. We selected a single comparative timepoint, 8 hours post-treatment with GNF-7. GSEA (gene set enrichment analysis) was performed using gene signatures in MSigDB (Molecular Signatures Database) for analysis. This led to the identification of MYC-network genes as being the downstream conduit of the effect of this treatment. We also found that treatment with GNF-7 abolished

overall_design: OCI-AML3 cells and KO52 cells were treated with 1.0μM of GNF-7 for 8 hrs in biologic triplicates.  RNA of cells before and after the treatment was then extracted for global transcriptional profiling using HuGene 1.0 ST chip.

first: James

middle: D

last: Griffin


title: Rare CNVs in Lynch Syndrome patients negative for mutations in mismatch repair genes

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

overall_design: Refer to individual Series


title: Gene expression data of diagnostic childhood T-ALL samples and human thymocytes

status: Public on Nov 20 2015

city: Paris

first: Andre

last: Bortolini Silveira

address: 26 rue d'Ulm

country: France

institute: Institut Curie

summary: Lymphotoxin-mediated activation of the lymphotoxin-β receptor (LTβR) has been implicated in several physiological and pathological processes, including lymphoid organ development, T-cell maturation, and solid and hematopoietic malignancies. Its role in T-cell acute lymphoblastic leukemia (T-ALL) or other T-cell malignancies has remained however to be investigated. Here we show that the genes encoding lymphotoxin (LT)-α and LTβ were expressed in T-ALL patient samples, more abundantly in the TAL/LMO molecular subtype, and in the TEL-JAK2 mouse model of cortical/mature T-ALL. Surface LTα1β2 protein was detected in primary mouse T-ALL cells, but only upon phorbol ester stimulation or absence of microenvironmental LTβR interaction. Indeed, in contrast to leukemic cells collected from transplanted Ltbr–/– mice or from co-cultures with Ltbr–/– mouse embryonic fibroblasts (MEF), those collected from Ltbr+/+ mice or from Ltbr+/+ MEF co-cultures presented no surface LT expression. Supporting the notion that LT signaling plays a role in T-ALL, inactivation of the Ltbr gene in mice resulted in a statistically significant delay in TEL-JAK2-induced leukemia onset. Expression of the Lta and Ltb genes was found to be increased at the early asymtptomatic stages of TEL-JAK2 T-ALL, when only low proportions of malignant thymocytes are present in normal sized thymus. Interestingly, young asymptomatic TEL-JAK2;Ltbr–/– mice presented significantly less leukemic thymocytes than TEL-JAK2;Ltbr+/+ mice. Together, these data indicate that early lymphotoxin expression by T-ALL cells activates LTβR signaling in thymic stromal cells, thus promoting leukemogenesis.

overall_design: Primary T-ALL samples were obtained at diagnosis from bone marrow and/or peripheral blood with high leukemia involvement (>85%), and enriched by density centrifugation over Ficoll-Paque (GE Healthcare). Microarray analysis were performed on samples from patients with newly diagnosed T-ALL accrued from 2000 to 2013 at Centro Infantil Boldrini, Campinas, Brazil. Thymic samples, obtained from children undergoing cardiac surgery, were gently minced in culture medium and subsequently subjected to density centrifugation.

first: André

middle: B

last: Silveira

first: Sílvia

middle: R

last: Brandalise

first: José

last: Yunes

first: Mónica

middle: T

last: Fernandes

first: Marinella

middle: N

last: Ghezzo

first: Vanda

last: Póvoa

first: Ana

last: Ribeiro

first: Ravi

middle: K

last: Kalathur

first: Emmanuel

last: Dejardin

first: Nuno

middle: L

last: Alves

first: Jacques

last: Ghysdael

first: João

last: Barata

last: dos Santos


title: Transcriptomic profiling in Malawian patients with acute hypersensitivity reactions to Nevirapine

city: Liverpool

first: Suparna

last: Mitra

address: Block A: Waterhouse Buildings

department: Department of Molecular and Clinical Pharmacology

country: United Kingdom

institute: University of Liverpool

summary:
Nevirapine is a non-nucleoside reverse transcriptase inhibitor, a class of antiretroviral drug, used for the treatment of HIV-1 infection. Despite its wide use, nevirapine treatment has been associated with a significant incidence of different kind of hypersensitivity reactions (HSRs).
We used microarrays to find significant genes that can relate to Nevirapine-persuaded hypersensitivity reactions in ‘acute’ patients compared to ‘recovered’ and/or ‘tolerant’ patients.

overall_design:
We have selected 18 patients’ samples, 6 from each group (Acute, Recovered, Tolerant) to investigate Nevirapine induced hypersensitivity reactions using transcriptomic profiling based on microarray technology.
Acute:Patient taking nevirapine develops adverse drug reaction (ADR).
Recovered: 6 weeks after acute reaction-not longer taking nevirapine.
Tolerant: Patient on neviraoine and tolerating treatment.

first: Katarzyna

last: Bloch

first: Mas

last: Chaponda

first: Munir

last: Pirmohamed


title: Expression data from HeLa cells with and without human recombinant TIMP-4 treatment

status: Public on Nov 25 2015

city: Mexico City

first: Jorge

last: Melendez-Zajgla

address: Periferico Sur 4809 Col. Arenal Tepepan

country: Mexico

institute: Instituto Nacional de Medicina Genomica

summary: TIMP-4 overexpression increases tumor burden in mice, promotes progenitor cell phenotype and sensitizes cells to apoptosis, by relying on NFkB signaling

overall_design: We used microarrays to detail the molecules and signal transduction pathways modulated by hrTIMP-4


title: Retinoid X Receptor activation reverses the age-related deficiency in myelin debris phagocytosis and enhances remyelination

status: Public on Nov 04 2015

city: Bethesda

first: Kory

last: Johnson

state: MD

address: 10/3B01, 9000 Rockville Pike

department: DIR IT & Bioinformatics

institute: NINDS/NIH

summary: The efficiency of central nervous system (CNS) remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation.  In this study we show that expression of genes involved in the retinoid X receptor (RXR) pathway are decreased with aging in myelin-phagocytosing cells. Loss of RXR function in young macrophages mimics aging by delaying remyelination after experimentally-induced demyelination, while RXR agonists partially restore myelin debris phagocytosis in aged macrophages. The FDA-approved RXR agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in aging human monocytes to a more youthful profile. These results reveal the RXR pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.

overall_design: 24 Human CD14+ monocyte-sorted PBMC samples representing 4 Healthy Volunteers (HV) and 4 Multiple Sclerosis (MS) patients under 3 different treatment conditions.  Condition 1 = (-) Phagocystosis (-) Bexarotene.  Condition 2 = (+) Phagocystosis (-) Bexarotene.  Condition 3 = (+) Phagocystosis (+) Bexarotene.

first: Muktha

middle: S

last: Natrajan

first: Alerie

last: de la Fuente

first: Abbe

middle: H

last: Crawford

first: Eimear

last: Linehan

first: Vanessa

last: Nuñez

first: Tianxia

last: Wu

first: Denise

middle: C

last: Fitzgerald

first: Mercedes

last: Ricote

first: Bibiana

last: Bielekova

first: Robin

last: Franklin


title: Expression profile of human lymphatic endothelial cells under static or oscillatory shear stress conditions in the presence or absence of FOXC2

status: Public on Nov 09 2015

city: Lausanne

first: Nadine

last: Fournier

state: Vaud

address: Agora Cancer Research Center, Bugon 25A

country: Switzerland

institute: Agora Cancer Research Center & Swiss Institute of Bioinformatics

summary:
Lymphatic valves are specialized units regularly distributed along collecting vessels that allow unidirectional forward propulsion of the lymph, and its efficient transport from tissues to the bloodstream. Lymphatic endothelial cells that cover lymphatic valve sinuses are subjected to complex flow patterns, due to recirculation of the lymph during the collecting vessel pumping cycle. They also express high levels of FOXC2 transcription factor.
We used microarrays to study the transcriptional networks controlled by FOXC2 in human lymphatic endothelial cells subjected to oscillatory shear stress or cultured under static conditions.

overall_design: Human lymphatic endothelial cells were transfected with control or FOXC2 siRNAs and subjected to 24-hour oscillatory shear stress (1 dyn/cm2; 1/4 Hz) or kept under static conditions as a control. RNA were amplified and hybridized on Affymetrix Human Gene 1.0 ST Arrays.  The experiment was run twice independently, using each time a different siRNA to knockdown FOXC2, as previously described (Sabine et al, 2012, Dev Cell).

first: Yan

last: Agalarov

last: Zangger

first: Amélie

last: Sabine

first: Muriel

last: Jaquet

first: Mauro

last: Delorenzi

first: Tatiana

middle: V

last: Petrova


title: EIF4E AND EIF4GI HAVE DISTINCT AND DIFFERENTIAL IMPRINTS ON MULTIPLE MYELOMA'S PROTEOME AND SIGNALING

status: Public on Oct 29 2015

city: Tel Aviv

first: Metsada

last: Pasmanik-Chor

address: Ramat Aviv

department: Biology

country: Israel

institute: Tel Aviv University

summary: Accumulating data indicate translation plays a role in cancer biology, particularly its rate limiting stage of initiation. Despite this evolving recognition, the function and importance of specific translation initiation factors is unresolved. The eukaryotic translation initiation complex eIF4F consists of eIF4E and eIF4G at a 1:1 ratio. Although it is expected that they display interdependent functions, several publications suggest independent mechanisms.   This study is the first to directly assess the relative contribution of eIF4F components to the expressed cellular proteome, transcription factors, microRNAs, and phenotype in a malignancy known for extensive protein synthesis- multiple myeloma (MM). Previously, we have shown that eIF4E/eIF4GI attenuation (siRNA/ Avastin) deleteriously affected MM cells' fate and reduced levels of eIF4E/eIF4GI established targets. Here, we demonstrated that eIF4E/eIF4GI indeed have individual influences on cell proteome. We used an objective, high throughput assay of mRNA microarrays to examine the significance of eIF4E/eIF4GI silencing to several cellular facets such as transcription factors, microRNAs and phenotype. We showed different imprints for eIF4E and eIF4GI in all assayed aspects. These results promote our understanding of the relative contribution and importance of eIF4E and eIF4GI to the malignant phenotype and shed light on their function in eIF4F translation initiation complex.

overall_design: This study concentrated on a particular cancer model and studied the role of eIF4E and eIF4GI in the design of the cells' proteome. We used an unbiased, high throughput system to evaluate the individual importance of eIF4E and eIF4GI levels in MM. We used models of eIF4E or eIF4GI knocked down (KD) MM cell line RPMI 8226 and profiled their respective translated transcription factors (TF), often tumor suppressors or oncogenes. Furthermore, we assessed the KDs' microRNAs repertoires and cells' phenotype. Significant differences were observed between eIF4E and eIF4GI knockdown imprints.

first: Attar-Schneider

last: Oshrat

first: Michael

last: Lishner

first: Shelly

last: Tartakover-Matalon

first: Liat

last: Drucker


title: High prognostic potential of a transcriptomic signature related to cycling hypoxia: direct application to breast cancer profiling

status: Public on Nov 16 2015

city: Brussels

first: Olivier

last: Feron

address: 53 Avenue E. Mounier, bte B1.53.09

department: Pole of Pharmacology and Therapeutics (FATH)  Institute of Experimental and Clinical Research (IREC)

country: Belgium

institute: Université catholique de Louvain

summary: Purpose.  Temporal and local fluctuations in oxygen levels observed within tumors represent stressful conditions requiring adaptive mechanisms that provide tumor cells with phenotypic alterations to survive and proliferate in this hostile environment. The analysis of the transcriptome associated with such cycling hypoxia could thus represent a prognostic biomarker of cancer progression.  Patients and Methods. We exposed 20 cell lines derived from various tissues to repeated periods of hypoxia/reoxygenation in order to determine a transcriptomic signature of cycling hypoxia (CycHyp). We then used clinical data sets from 2,150 patients with primary breast cancer to estimate a prognostic Cox proportional hazard model and to assess the prognostic performance of the CycHyp signature on independent samples.   Results. The prognostic potential of the CycHyp signature was validated in patients independently of the receptor status of the tumors (HR=1.97; p = 1.8e-12).  The discriminating capacity of the CycHyp signature was further increased in the ER+ HER2- patient populations (HR = 2.34, p = 9e-12) including those with a node negative status receiving or not a treatment (HR = 3.32 and 5.51; p= 5.61e-10 and 8.15e-11, respectively). We also documented the capacity of the CycHyp signature to outperform existing prognostic gene signatures with significantly higher BCR and concordance index. We also showed that the CycHyp signature could identify ER-positive node-negative breast cancer patients at high risk based on conventional clinico-pathologic criteria but who could have been spared from chemotherapy and inversely those patients classified at low risk based on the same criteria but who presented a negative outcome.  Conclusion. This study demonstrates that a gene signature derived from the transcriptomic adaptation of tumor cells to cycling hypoxia is prognostic of breast cancer and offers a unique decision making tool to complement the discrimination of breast cancer patients based on anatomo-pathological evaluation. The prognostic value of CycHyp further confirms the link between cycling hypoxia and cancer progression, and thereby paves the way for a broad applicability to evaluate cancer patient outcomes.

overall_design: Twenty cancer cell lines were exposed to 3 different culture conditions: normoxia (21% O2), continuous hypoxia (1% O2), and cycling hypoxia (24 cycles of 30min normoxia+30 min hypoxia). Gene signatures were generated based on  gene expression differences between Normoxia and continuous hypoxia or cycling hypoxia.

first: Romain

last: Boidot

first: Samuel

last: Branders

first: Thibaut

last: Hellepute

first: Lailla

middle: I

last: Rubio

first: Pierre

last: Dupont


title: Transcriptional profiling of ovarian cancer spheroids reveals genes and related biological pathways associated with cisplatin resistance

city: Stillwater

first: Winyoo

last: Chowanadisai

state: OK

address: 301 Human Sciences

institute: Oklahoma State University

summary:
Characterization of differential gene expression due to cisplatin resistance in human ovarian cancer spheroids by microarray analysis.
In this dataset, we include the expression data obtained from cisplatin-sensitive and cisplatin-resistant human ovarian cancer spheroids.  These data are used to obtain 1316 genes that are differentially expressed in response to cisplatin resistance.

overall_design: 8 total samples were analyzed.  For the pairwise comparison of cisplatin-sensitive to cisplatin-resistant spheroids, genes with a p-value <0.01, a FDR <0.05, and a fold-change ≥2 were selected.

first: Daniel

last: Miller

first: Jamie

middle: E

last: Medina

first: Joshua

middle: W

last: Hamilton

first: Alexander

last: Brodsky

first: Mark

middle: A

last: Messerli

first: Shanta

middle: M


title: Targeting the SIN3A-PF1 Interaction inhibits Epithelial to Mesenchymal Transition and Maintenance of a Stem Cell Phenotype in Triple Negative Breast Cancer (Expression)

status: Public on Nov 02 2015

city: Stirling

first: Kevin

last: Petrie

state: Stirling

address: Stirling

department: Biological and Environmental Sciences

institute: University of Stirling

summary: Triple negative breast cancer (TNBC) is characterized by a poorly differentiated phenotype and limited treatment options. Aberrant epigenetics in this subtype represent a potential therapeutic opportunity, but a better understanding of the mechanisms contributing to the TNBC pathogenesis is required. The SIN3 molecular scaffold performs a critical role in multiple cellular processes, including epigenetic regulation, and has been identified as a potential therapeutic target. Using a competitive peptide corresponding to the SIN3 interaction domain of MAD (Tat-SID), we investigated the functional consequences of selectively blocking the paired amphipathic helix (PAH2) domain of SIN3. Here, we report the identification of the SID-containing adaptor PF1 as a factor required for maintenance of the TNBC stem cell phenotype and epithelial to mesenchymal transition (EMT). Tat-SID peptide blocked the interaction between SIN3A and PF1, leading to epigenetic modulation and transcriptional downregulation of TNBC stem cell and EMT markers. Importantly, Tat-SID treatment led to a reduction in primary tumor growth and disseminated metastatic disease in vivo. In support of these findings, knockdown of PF1 expression phenocopied treatment with Tat-SID both in vitro and in vivo. These results demonstrate a critical role for a complex containing SIN3A and PF1 in TNBC and provide a rational for its therapeutic targeting.

overall_design: Sub-confluent cultures of MDA-MB-231 cells were treated with 1µM Tat-SID peptide or 1µM Tat-Scr scrambled control peptide for 24hr.

first: Yordan

last: Sbirkov


title: Human Endometrial Fibroblasts Derived from Mesenchymal Progenitors Inherit Progesterone Resistance and Acquire an Inflammatory Phenotype in the Endometrial Niche in Endometriosis

status: Public on Oct 01 2015

city: San Francisco

first: Linda

middle: C.

last: Giudice

address: 499 Illinois St., Sixth Floor

department: Center for Reproductive Health at Mission Bay

institute: UC San Francisco

summary:
Herein, we investigated eMSC and eSF freshly isolated from endometrium from women with and without endometriosis and compared them to their respective short- and long-term cultures and subsequent decidualization response to progesterone.
ABSTRACT  Human endometrium undergoes cyclic tissue shedding with ensuing regeneration involving stem/progenitor cells, but the role of multipotent resident endometrial mesenchymal stem cells (eMSC) as progenitors of the endometrial stromal fibroblast (eSF) has not been definitively demonstrated. Progesterone (P4)-driven differentiation (decidualization) of eSF is abnormal in endometriosis, displaying P4-resistance in vivo and in vitro. This study investigated whether eMSC are precursors of eSF and, if so, whether the endometriosis P4-resistant phenotype is inherited from eMSC progenitors or acquired by eSF lineage cells within the endometrial niche. To this end we analyzed the transcriptomes of eMSC and eSF isolated by fluorescence activated cell sorting (FACS) from eutopic endometrium of women with (eMSCFACS.endo, eSFFACS.endo) and without (eMSCFACS.control, eSFFACS.control) endometriosis, and of primary cultures derived from these sorted populations. FACS-isolated eMSC and eSF displayed distinct sets of differentially expressed lineage-associated genes (LG) with >95% of the 200 most highly expressed LG conserved in endometriosis. eSFcontrol in culture maintained in vitro expression of 45% eSF LG; whereas eSFendo displayed less in vitro LG stability, expressing 33% eSF LG. Under the same culture conditions, eMSCcontrol underwent in vitro eSF lineage differentiation (eMSC→eSFcontrol), progressively losing stemness (down-regulated 81% eMSC LG) and acquiring an in vitro eSFcontrol phenotype (up-regulated 55% eSF LG) with minimal transcriptome differences vs. eSFcontrol cultures (19 genes all <2 fold change). Likewise eMSCendo cultures underwent in vitro eSF lineage differentiation (eMSC→eSFendo), down-regulating 77% eMSC LG and up-regulating 50% eSF LG, and there were 78 differentially expressed genes (-2.73 to +2.81 fold change) in eMSC→eSFendo vs. eSFendo. The in vitro disease phenotypes of eSFendo and eMSC→eSFendo shared 49 common genes differentially expressed vs. their control counterparts. However, 78 and 89 genes, respectively, were unique to eSFendo and eMSC→eSFendo, and pathway analysis revealed a proinflammatory phenotype in eSFendo but not eMSC→eSFendo cultures, suggesting divergent niche effects for in vivo vs. in vitro lineage differentiation. Cultures of eSFcontrol and eMSC→eSFcontrol responded to P4 with IGFBP1 secretion, while eSFendo and eMSC→eSFendo cultures did not, demonstrating P4-resistance inherited from eMSCendo. These findings substantiate eMSC as progenitors of eSF and reveal novel aspects of the eSF disease phenotype in endometriosis with P4-resistance inherited from the eMSC and a proinflammatory component acquired by the eSF lineage within the endometrial niche.

overall_design: A totol of 50 samples were used. Samples were analyzed by cell type, disease, and time in culture. Non-Endometriosis samples were used as controls. Comparisons are as follows: eMSCFACS.control vs. eSF FACS.control; eMSC FACS.endo vs. eSF FACS.endo; eMSC FACS.endo vs. eMSC FACS.control; eSF FACS.endo vs. eSF FACS.control; eMSCEarly.control vs. eMSCFACS.control; eMSCLate.control vs. eMSCEarly.control; eSFEarly.control vs. eSFFACS.control; eSFLate.control vs. eSFEarly.control; eMSCEarly.control vs. eSFEarly.control; eMSCLate.control vs. eSFLate.control; eMSCEarly.control vs. eSFFACS.control; eMSCLate.control vs. eSFFACS.control; eSFEarly.control vs. eMSCFACS.control; eSFLate.control vs. eMSCFACS.control; eMSCEarly.endo vs. eMSCFACS.endo; eMSCLate.endo vs. eMSCEarly.endo; eSFEarly.endo vs. eSFFACS.endo; eSFLate.endo vs. eSFEarly.endo; eMSCEarly.endo vs. eSFEarly.endo; eMSCLate.endo vs. eSFLate.endo; eMSCEarly. endo vs. eSFFACS. endo; eMSCLate. endo vs. eSFFACS. endo; eSFEarly. endo vs. eMSCFACS. endo; eSFLate. endo vs. eMSCFACS. endo; eMSCEarly.endo vs. eMSCEarly.control; eMSCLate.endo vs. eMSCLate.control; eSFEarly.endo vs. eSFEarly.control; eSFLate.endo vs. eSFLate.control

first: Fatima

last: Barragan

first: Juan

last: Irwin

first: Shaina

last: Balayan

first: David

last: Erikson

first: Joseph

last: Chen

first: Sahar

last: Houshdaran

first: Terhi

last: Piltonen

first: Trimble

last: B Spitzer

first: Ashley

last: George

last: Rabban

first: Camran

last: Nezhat


title: Comparasion between SKOV3-shRNARELB and SKOV3-shRNALuc

status: Public on Oct 31 2015

city: México

first: Vilma

middle: Araceli

last: Maldonado

state: Distrito Federal

address: Periferico  4809

department: Investigacion

institute: INMEGEN

summary: Analysis of genes differentially expressed in ovarian cancer cells with sirna of Rel B in transient transfections was performed.

overall_design: Two groups were analyzed in triplicate each. The First group was SKOV· cells transfected with iRNARelB and the other group was transfected with siRNALuciferase.

first: C

last: González-Torres

first: J

last: Meléndez-Zajgla

last: Gaytán-Cervantes

first: E

last: Mandujano-Tinoco

first: K

last: Vázquez-Santillán

first: L

last: Jimenez-Hernández

first: G

last: Ceballos-Cancino

first: R

last: Mojíca Espinosa

first: V

last: Maldonado-Lagunas


title: Age gene expression in Healthy leukocytes

city: San Sebastián

last: Otaegui

state: Guipuzcoa

address: Paseo Dr begiristain s/n

department: Neurosciences

country: Spain

institute: Biodonostia Research institute

summary: Both cellular senescence and organismic aging are known to be dynamic processes that start early in life and progress constantly during the whole life of the individual. In this work, with the objective of identifying signatures of age-related progressive change at the transcriptomic level, we have performed a whole-genome gene expression analysis of peripheral blood leukocytes in a group of healthy individuals with ages ranging from 14 to 93 years. A set of genes with progressively changing gene expression (either increase or decrease with age) has been identified and contextualized in a coexpression network. A modularity analysis has been performed on this network and biological-term and pathway enrichment analyses have been used for biological interpretation of each module.     In summary, the results of the present work reveal the existence of a transcriptomic component that shows progressive expression changes associated to age in peripheral blood leukocytes, highlighting both the dynamic nature of the process and the need to complement young vs. elder studies with longitudinal studies that includes middle aged individuals. From the transcriptional point of view, immunosenescence seems to be occurring from a relatively early age, at least from the late 20s/early 30s, and the 49 – 56 y/o age-range appears to be critical. In general, the genes that, according to our results, show progressive expression changes with aging are involved in pathogenic/cellular processes that have classically been linked to aging in humans: cancer, immune processes and cellular growth vs. maintenance.

overall_design: 43 blood samples from healthy individuals

first: D

first: H

last: Irizar


title: Activated neutrophils are associated with pediatric cerebral malaria vasculopathy in Malawian children

status: Public on Oct 30 2015

city: Bronx

first: Johanna

middle: Patricia

last: Daily

state: NY

address: 1301 Morris Park Avenue, Price Center

department: Medicine (Infectious Disease)

institute: Albert Einstein College of Medicine

summary:
We used microarrays to characterize the whole blood global  gene expression profiles in 98 children with P. falciparum cerebral malaria
We associated retinopathy status with host genes and pathways to explore mechanisms of infected red sequestration to the microvasculature in CM

overall_design: Cross sectional study of chidlren with CM, expression profiling derived from study enrollment whole blood sample RNA isolated from sample stored in Tri-Reagent BD; hybridization with Affymetrix Gene Chip Human Gene 1.0 ST Array.

last: Feintuch

middle: P


title: Expression data from Treg subsets sorted from healthy human peripheral blood

city: Cambridge

first: Scott

last: Davis

address: 200 Technology Square, Suite 602

department: Tempero DPU

institute: GSK

summary:
All the sorted Treg cells are gated on CD4+CD25+CD127(low), followed by gating on various subsets using markers indicated in the sample names.
All the sorted Teff cells are gated on CD4+CD25-CD127(hi), and further sorted for CD45RO- and CD45RO+ phenotype.

overall_design: Each Treg and Teff cell subsets were sorted from three different donors. We sought to identify gene expression signature characteristic to specific Treg subsets

first: Jing

last: Hua

first: Tetsuya

last: Yamagata


title: Expression data from human effector CD4 T cells co-cultured with various Treg subsets sorted from  human peripheral blood.

summary:
Teff cells (CD4+CD25-CD127+CD45RO+) were co-cultured with and without sorted Treg subsets plus dendritic cells for 18h.
All the sorted Teff cells are gated on CD4+CD25-CD127(hi), and further sorted for CD45RO- and CD45RO+ phenotype.

overall_design: The impact of different Treg subsets on Teff cell gene expression was analyzed.


title: Expression data from human HSPC with O/E TAL1 or KD/TAL1

status: Public on Oct 23 2015

city: 91400 Orsay

first: Florent

last: Dumont

state: Ile de France

address: 17 avenue des sciences

institute: Université Paris-Saclay

summary:
Analyses of the consequences of up- and down-regulating SCL/TAL1 in human enriched hematopoietic stem progenitor cells (HSPCs).
We used microarrays to detail the global gene expression program of human cord blood HSPCs (CD34+CD38-lowCD34RA-CD90+) in which SCL/TAL1 expression is either up- or down-regulated.

overall_design: We have used lentiviral vector transduction of human cord blood HSPCs to overexpress (O/E) or knock down (KD) SCL/TAL1. Cells were lysed 24 hours after the end of transduction.

first: Aissa

middle: B

last: Youcef

first: Francoise

last: Pflumio


title: MicroRNA profiling of the developing mammary gland identifies miR-184 as a candidate breast tumour suppressor gene (Affymetrix)

city: Sydney

first: Daniel

last: Roden

address: 384 Victoria Street

institute: Garvan Institute

summary: The study of mammalian development has offered many insights into the molecular aetiology of cancer. We previously used analysis of mammary morphogenesis to discover a critical role for GATA-3 in mammary developmental and carcinogenesis. In recent years an important role for MicroRNAs (miRNAs) in a myriad of cellular processes in development and in oncogenesis has emerged. In this study, microRNA profiling of stromal and epithelial cellular subsets microdissected from the developing mouse mammary gland revealed many microRNAs with expression restricted to various cellular subsets. MicroRNA-184 (miR-184) was exclusively expressed in epithelial cells and markedly upregulated during differentiation of the proliferative, invasive cells of the pubertal terminal end bud (TEB) into ductal epithelial cells in vivo and in FACS-sorted mammary stem cells (MaSCs) versus luminal epithelial cells. miR-184 expression was silenced in mouse tumour models compared to non-transformed epithelium and in a majority of breast cancer cell line models. Ectopic reactivation of miR-184 inhibited the proliferation and self-renewal of metastatic triple negative breast cancer (TNBC) cell lines in vitro and delayed tumour formation and reduced metastasis in vivo. Gene expression studies uncovered multi-factorial direct regulation of genes in the AKT/mTORC1 pathway by miR-184. In clinical breast cancer tissues, expression of miR-184 is lost in primary TNBCs while the miR-184 promoter is methylated in a subset of lymph node metastases from TNBC patients. These studies elucidated a new layer of regulation in the PI3K/AKT/mTOR pathway with relevance to mammary development and tumour proliferation and metastasis.

overall_design: Gene expression analysis of MDA-MB-231 cells 48 hours after transfection with mir-184 mimics with negative control comparisons

first: Yuwei

last: Phua

first: Akira

last: Nguyen

first: Ben

last: Elsworth

first: Iva

last: Nikolic

first: Jessica

last: Yang

first: Andrea

last: Mcfarland

first: Roslin

last: Russell

first: Mark

last: Cowley

first: Warren

last: Kaplan

first: Radhika

last: Nair

first: Elena

last: Zotenko

first: Shixiong

last: Tan

first: Carlos

last: Caldas

first: Susan

last: Clark

first: Hossein

last: Kouros-Mehr

first: Alexander

last: Swarbrick


title: Natural killer cell genomic profile is associated with treatment outcome in patients with chronic HCV infection

city: Doha

first: Francesco

middle: Maria

last: Marincola

address: Al Nasr Tower, AL Corniche Street, PO Box 26999

country: Qatar

institute: Sidra Medical and Research Center

summary: Phenotypic and immunogenetic characteristics of NK cells have been recently associated with treatment outcome of HCV infected patients. However, thus far, no global NK patterns predictive of response to antiviral therapy in HCV infection have been identified. We here analyzed phenotypic and transcriptional characteristics of NK cells derived from prospectively followed patients with chronic HCV infection prior to treatment with PEG-IFN/RBV. The results report that the pre-treatment transcriptional patterns of purified NK cells from patients subsequently undergoing a sustained virologic response (SVR) clearly segregated from those of non-responder (NR) patients and surprisingly overlapped with the genomic profile of NK cells from healthy donors and from patients who spontaneously cleared the virus (SR). The treatment outcome was associated with differential surface expression of NKp30 and NKG2D and with the transcriptional expression of molecules involved in post-transcriptional modifications of RNA/protein trafficking and HLA class II signaling. With the development of a highly stringent prediction model (LOOCV p value < 0.00001) we identified a 33 gene signature whose expression predicted with 100% accuracy the outcome of IFN based treatment. None of the genes found to differentiate patients with SVR from NR were related to the IL28B polymorphism. Neither an IL28B CC homozygosis was significantly and clearly associated with SVR in our series of patients. Thus, NK cells are associated to different HCV disease courses and response to treatment and the NK cell evaluation in HCV patients might provide a comprehensive explanation of useful determinants of clinical response in HCV-infected patients subjected to treatment regimens that have IFN as their backbone.

overall_design:
Samples from purified NK cells derived from healthy donor (HD) (n=7), sustained virologic responder (SVR) (n=9), non-responder (NR) (n=10), spontaneously recovered (SR) (n=6) and chronically viremic HCV-infected (CH-HCV) (n=8) individuals (biological repeats) were hybridized to the GeneChip Human Gene 1.0 ST Arrays.
*Non-response (NR) was defined as a breakthrough of HCV RNA during therapy or the reappearance of HCV-RNA after the end-of-treatment.
*Sustained virologic response (SVR) was defined as persistent absence of viremia 6 months after treatment termination.


title: MicroRNA profiling of the developing mammary gland identifies miR-184 as a candidate breast tumour suppressor gene

first: Daniel

last: Roden

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

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Expression data from 36 KRAS-mutant lung adenocarcinomas from the BATTLE-2 clinical trial.

city: Houston

first: Lixia

last: Diao

state: TX

address: 1400 Pressler Steet

department: Bioinfomatics and Computational Biology

institute: University of Texa MD Anderson

summary: In this dataset, we include expression data from 36 KRAS-mutant lung adenocarcinomas from Stage 1 of the BATTLE-2 trial, reflecting patients whose disease has relapsed or progresses following at least one front-line metastatic chemotherapy regimen. Tumor biopsy was performed following informed consent and prior to randomisation to one of the four possible treatment arms.

overall_design: 36 samples overall were analyzed

first: Vassiliki

last: Papadimitrakopoulou

first: John

last: Heymach

first: Ferdinandos

last: Skoulidis


title: A lincRNA connected to cell mortality and epigenetically-silenced in most common human cancers

status: Public on Oct 05 2015

city: Tucson

first: Lukas

last: Vrba

state: AZ

address: 1515 N Campbell Ave

department: Arizona Cancer Center

institute: University of Arizona

summary:
- Gene expression changes linked to two step immortalization of human mammary epithelial cells (HMEC).
- A lincRNA, MORT, associated with the mortal state, was identified
- MORT is silenced by DNA methylation in immortal mammary epithelial cells

Abstract:
Immortality is an essential characteristic of human carcinoma cells. We recently developed an efficient, reproducible method that immortalizes human mammary epithelial cells (HMEC) in the absence of gross genomic changes by targeting two critical senescence barriers.  Consistent transcriptomic changes associated with immortality were identified using microarray analysis of isogenic normal finite pre-stasis, abnormal finite post-stasis, and immortal HMECs from four individuals.  277 genes consistently changed in cells that transitioned from post-stasis to immortal. Gene ontology analysis of affected genes revealed biological processes significantly altered in the immortalization process. These immortalization-associated changes showed striking similarity to the gene expression changes seen in The Cancer Genome Atlas (TCGA) clinical breast cancer data.  The most dramatic change in gene expression seen during the immortalization step was the down-regulation of an unnamed, incompletely annotated transcript that we called MORT, for mortality, since its expression was closely associated with the mortal, finite lifespan phenotype.  We show here that MORT (ZNF667-AS1) is expressed in all normal finite lifespan human cells examined to date and is lost in immortalized HMEC.  MORT gene silencing at the mortal/immortal boundary was due to DNA hypermethylation of its CpG island promoter.  This epigenetic silencing is also seen in human breast cancer cell lines and in a majority of human breast tumor tissues.  The functional importance of DNA hypermethylation in MORT gene silencing is supported by the ability of 5-aza-2’-deoxycytidine to reactivate MORT expression.  Analysis of TCGA data revealed deregulation of MORT expression due to DNA hypermethylation in 15 out of the 17 most common human cancers.  The epigenetic silencing of MORT in a large majority of the common human cancers suggests a potential fundamental role in cellular immortalization during human carcinogenesis.

overall_design:
The aim of the study was to determine what genes change in expression during the individual steps of the targeted model immortalization of HMEC.

Design: Post-Stasis vs Pre-Stasis, and Immortal vs Post-Stasis. Biological replicates: 4 HMEC genotypes

first: James

last: Garbe

first: Martha

middle: R

last: Stampfer

first: Bernard

last: Futscher


title: Transcriptome data of multiple sclerosis patients receiving fingolimod therapy [HTA-2_0, CD8+ cells, exon level]

status: Public on Sep 19 2015

city: Rostock

first: Michael

last: Hecker

address: Gehlsheimer Str. 20

department: Department of Neurology

country: Germany

institute: University of Rostock

summary:
We analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used to obtain gene expression profiles of immune cell populations from 10 RRMS patients within the first 3 months of fingolimod treatment.
This GEO entry provides the Affymetrix HTA 2.0 microarray data of peripheral blood CD8+ cells, preprocessed according to the exon level workflow.

overall_design:
EDTA blood samples were taken from all patients immediately before first and second fingolimod administration as well as after 3 months of therapy.
Total RNA of CD8+ cells positively selected from each blood sample was extracted, labeled and hybridized to high-density Affymetrix HTA 2.0 microarrays to quantify the transcript levels.

first: Dirk

last: Koczan

first: Uwe

middle: K

last: Zettl


title: Transferring genomics to the clinic: distinguishing Burkitt and Diffuse large B-cell lymphoma (v4)

status: Public on Sep 30 2015

city: Leeds

first: Chulin

last: Sha

address: Woodhouse Lane

department: School of Mole&Cell Biology

institute: University of Leeds

summary: Gene expression profiling was carried out for RNA extracted from Formalin-fixed, paraffin embedded (FFPE) biopsies of 156 new patients using the Illumina DASL version 4 platform, plus 71 replicate samples from version 3 platform and 12 replicates from GSE32918. Then the patients were classified into BL and DLBCL by moleclar classifier proposed in the article.

overall_design: The molecular classification result of the replicate samples are used to evaluated the reproducibility of the classifier, and the clinic diagnosis were used to compare the agreement with the classifier

first: Sharon

middle: L

last: Barrans


title: Multi-level omics analysis of dystrophin loss and therapeutic restoration in a murine model [microRNA]

status: Public on Sep 24 2015

city: Oxford

first: Thomas

last: Roberts

address: South Parks Road

department: Department of Physiology, Anatomy and Genetics

institute: University of Oxford

summary:
Duchenne muscular dystrophy (DMD) is a classical monogenic disorder, a model disease for genomic studies and a priority
candidate for regenerative medicine and gene therapy. Although the genetic cause of DMD is well known, the molecular pathogenesis of disease and the response to therapy are incompletely understood. Here, we describe analyses of protein, mRNA and microRNA expression in the tibialis anterior of the mdx mouse model of DMD. Notably, 3272 proteins were quantifiable and 525 identified as differentially expressed in mdx muscle (P < 0.01). Therapeutic restoration of dystrophin by exon skipping induced widespread shifts in protein and mRNA expression towards wild-type expression levels, whereas the miRNome was largely unaffected. Comparison analyses between datasets showed that protein and mRNA ratios were only weakly correlated (r = 0.405), and identified a multitude of differentially affected cellular pathways, upstream regulators and predicted miRNA–target interactions. This study provides fundamental new insights into gene expression and regulation in dystrophic muscle.

overall_design: 3 Wt, 4 mdx and 4 Pip6e-PMO treated mdx mice

first: Henrik

middle: J

last: Johansson

first: Graham

last: McClorey

first: Caroline

last: Godfrey

first: K

last: Blomberg

first: Thibault

last: Coursindel

last: Gait

first: C

last: Smith

first: Janne

last: Lehtiö

first: Samir

last: EL-Andaloussi

first: Matthew

last: Wood


title: Cell fate determination by ubiquitin-dependent regulation of ribosome function

city: Berkeley

last: Rape

address: 330F Li Ka Shing Center

department: Molecular and Cell Biology

institute: UC Berkeley

summary: Metazoan development depends on accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates. Differentiation is brought about by global changes to chromatin architecture and transcriptional networks, yet whether other regulatory events support cell fate determination is less well understood. Using a human embryonic stem cell model, we identified the vertebrate-specific ubiquitin ligase Cul3KBTBD8 as an essential regulator of neural crest cell formation. Cul3KBTBD8 monoubiquitylates NOLC1 and its paralog TCOF1, whose mutation underlies the developmental disease Treacher Collins Syndrome that is characterized by a loss of cranial neural crest cells. Ubiquitylation of NOLC1 and TCOF1 drives formation of a platform that connects RNA polymerase I with ribosome modification enzymes, thereby altering the translational program of differentiating cells to support the generation of neural crest cells. We conclude that the dynamic regulation of ribosome function is an important feature of cell fate determination.

overall_design: Affymetrix assays were performed according to the manufacturer's directions on total RNA isolated from three independent samples of human embryonic stem cells (hESC) H1 cells or cells that had been differentiated into embryoid bodies for 6 days. Where indicated, hESC cells were transduced with control shRNA or shRNA targeting KBTBD8 prior to mRNA isolation. HUMAN GENE 1.0 ST ARRAY chips were used.

first: Achim

last: Werner

first: Shintaro

last: Iwasaki

first: Nia

last: Teerikorpi

first: Indro

last: Fedrigo

first: Nicholas

middle: T

last: Ingolia


title: Expression data from biopsies of CIT study patients

status: Public on Sep 10 2015

first: Pilib

last: Ó Broin

address: 1301 Morris Park Ave

summary: We aimed to investigate the effect of increased cold ischemia time (CIT) on gene expression profiles of implantation and clinically indicated biopsies early after transplantation and the impact of basiliximab (BAS) versus rabbit antithymocyte globulin (rATG) induction therapies on clinical outcomes and intragraft molecular features

overall_design: A retrospective, single-centered cohort study was designed to compare the safety and efficacy of rATG versus BAS for induction in patients who received a renal transplantation from a deceased donor between January 2007 and December 2012. Recipients with CIT greater than 20 hours were included in this study. Patients were excluded if they had received a prior transplantation or dual organ transplantation. Patients were followed for 12 months post-transplantation or until patient death, graft lost or lost to follow up. Patients in the rATG group received 1.5 mg per kilogram of body weight given intravenously with the initial dose given intraoperatively. Subsequent doses were given daily through post-operative day 3, for a total dose of 4.5-6.0 mg per kilogram.  Dosing was adjusted based on daily white blood cell and platelet counts. BAS (20 mg given intravenously) was administered intraoperatively and the subsequent dose on day 3 post-transplantation. All patients received maintenance immunosuppression with tacrolimus, prednisone and mycophenolate mofetil. In total. 230 patients were transplanted with a CIT > 20 hours; 174 and 56 patients received rATG and BAS induction, respectively. Gene expression profiling ws carried out on a subset (n=28) of these patients' post transplant biopsies. Of those 28 patients, 16 received rATG and 12 received BAS induction treatment.

first: Enver

last: Akalin


title: Gene expression profiles in control and FOXC1-overexpressing MDA-MB-231 cells

status: Public on Sep 25 2015

city: LOS ANGELES

first: Xiaojiang

last: Cui

address: 8700 BEVERLY BLVD

department: SURGERY

institute: CEDARS SINAI MEDICAL CENTER

summary: FOXC1 is a critical marker for basal-like breast cancer. To explore the role of FOXC1 in regulation of basal-like breast cancer cell function, we performed microarray assays and discovered that some known cancer-related genes were regulated by FOXC1.

overall_design: We transfected a FOXC1 expression vector or the control vector into MDA-MB-231 cells, followed by microarray assays.


title: miRNA expression data from callus in standard fracture healing models and from fibrous tissues in nonunion models in rats on post-fracture day 14

status: Public on Sep 03 2015

city: Kobe

first: Takahiro

last: Waki

state: Hyogo

address: 7-5-1, Kusunoki-cho, Chu0-ku

department: Orthopaedic Surgery

country: Japan

institute: Kobe University Graduate School of Medicine

summary: Profiling of miRNA expressions comparing standard fracture healing models with nonunion models in rats

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus
Human alphaherpesvirus 1
Human alphaherpesvirus 2
Human betaherpesvirus 5
Murid betaherpesvirus 1
human gammaherpesvirus 4
JC polyomavirus
Human immunodeficiency virus 1
Murid gammaherpesvirus 4
Human gammaherpesvirus 8
Merkel cell polyomavirus
Mus musculus cytomegalovirus 2
Betapolyomavirus hominis
Betapolyomavirus macacae

overall_design: 12w, male, Sprague–Dawley rats were used in this study. Animals were randomized to receive either a surgical treatment that has been shown to produce a nonunion or to a standard stabilized closed femoral shaft fracture that is known to successfully heal. The details of these procedures have been previously described. Briefly, to produce standard healing models, a 1.2-mm diameter K-wire was inserted retrograde into the right femoral intramedullary canal and a closed transverse femoral shaft fracture was produced using a three-point bending apparatus with a drop weight . To produce the nonunion, the fractured site was additionally exposed, and the periosteum was cauterized circumferentially for a distance of 2 mm on each side of the fracture . Five animals from each group were euthanized on post-fracture day 14 for microarray analysis.

first: Sang

middle: Y

last: Lee

last: Niikura

first: Yoshihiro

last: Dogaki


title: Expression data from multiple myeloma cells

status: Public on Sep 08 2015

city: Catanzaro

first: Maria

middle: Teresa

last: Di Martino

state: Catanzaro

address: V.le Europa

department: Experimental and Clinical Medicine

institute: Magna Graecia University

summary: Melphalan-induced modulation of miR-221/222 levels in MM cells. Melphalan-resistant U266/LR7 cells showed the highest induction of miR-221/222 after drug exposure. To study the transcriptome perturbation induced in MM cells following the combination of miR-221/222 inhibitors plus melphalan we used the whole gene expression data

overall_design: total RNA was obtained after single or combination treatment of the Melphalan-resistant U266/LR7 cells and the parental cell line U266/s

first: Annamaria

last: Gullà


title: Identification and characterization of human Natural Killer (NK) lineage restricted progenitors

status: Public on Sep 01 2015

city: Lund

first: Shamit

last: Soneji

address: Solvegatan 19

country: Sweden

institute: BMC

summary:
Natural killer (NK) cells represent one of three lymphoid lineages and play a vital role in controlling viral infections and cancer. In contrast to B and T lymphopoiesis where cellular and regulatory pathways have been extensively characterized, the cellular stages of early human NK-cell commitment remain poorly understood
Here we described a novel NK-lineage restricted progenitor (NKP) in fetal development, umbilical cord blood and adult bone marrow. We used microarrays to detail the global programme of gene expression genes of this new progenitor.

overall_design: Global gene expression analysis was performed on the NKP, multipotent progenitors LMPP, common lymphoid progenitor candidate and mature NK cells purified from Cord blood CD34+ cells (3-4 replicates, 2 experiments)

first: Virginie

last: Renoux


title: Differential gene regulation in miR-223 overexpressing pulmonary epithelial cell line compared to control cell line

city: Aurora

first: Viola

last: Dengler

state: CO

address: 12700 E 19th Avenue, Mailstop B112, Research Complex 2, Room 7124

department: Anesthesiology

institute: UC Denver

summary: Acute lung injury (ALI) is characterized by acute respiratory failure in the setting of non-cardiogenic pulmonary edema, causing acute respiratory distress syndrome (ARDS) in patients and contributes significantly to mortality of critically illness. The main goal of our study is to elucidate the role of miRNAs in neutrophil-epithelial communication during pulmonary inflammation and thereby identifying novel targets for therapy of acute lung injury (ALI). In our studies we identified a miR-223-dependent neutrophil-epithelial crosstalk during ALI. Activated neutrophils (PMN) and pulmonary epithelial cells come into a close spatial relationship during ALI. And, since previous studies had indicated the possibility that inflammatory cell-dependent release of miRNA-containing microvesicles could function as a means of exchanging genetic information from a donor to a target cell, we assessed PMN-elicited alterations of pulmonary epithelial miRNA expression in an experimental co-culture setup. This approach provided a selective and extremely robust readout: While other miRNAs were not or only moderately altered in their expression, pulmonary-epithelial-expressed miR-223 was significantly induced after 4 or 6h of co-incubation. Additional in vitro and in vivo studies clearly demonstrate that this increase of epithelial miR-223 is not due to miR-223 transcriptional induction, but instead PMN-dependent and caused by shuttling miR-223 from PMN into pulmonary epithelial cells. To address the functional role of miR-223-dependent neutrophil-epithelial crosstalk during ALI, we exposed mice to ventilator-induced ALI and observed robust induction of pulmonary miR-223 during ALI, while increases of miR-223 were completely abolished after antibody-depletion of PMN. Moreover, studies of alveolar epithelial cells isolated from mice with ALI showed robust increases of miR-223, indicating that miR-223 is shuttled from PMN towards alveolar epithelia during ALI in vivo. Functional studies revealed that gene-targeted mice for miR-223 experience a more severe phenotype during ALI as compared to controls, while their phenotype could be resuscitated by nanoparticle-mediated overexpression of miR-223 in the lungs. In summary, these studies reveal a novel role of miR-223-dependent neutrophil-epithelial crosstalk representing an anti-inflammatory pathway that can be targeted for ALI treatment.

overall_design: Due to our observation that pulmonary epithelial cells at baseline express essentially no miR-223, and miR-223 expression is dramatically increased following co-culture with PMN, we decided to emulate the transcriptional changes of miR-223. To define a potential miR-223 target gene in pulmonary epithelial cells that could have functional relevance during ALI we pursued studies on differential gene expression in miR-223 by generating pulmonary epithelial cells with lentiviral-mediated overexpression of miR-223 and to subsequently expose those cells to a microarray analysis. We performed an expression profiling of 4 samples (n=2 for each cell line) using an industry-standard whole human gene array (Affymetrix Human Gene 1.0 ST Array). Quality analysis using Partek Genomics Suite 6.6 revealed high confidence in the quality of the microarray data and all samples met 'Quality Assurance/Quality Control' (QA/QC) criteria.

last: Neudecker

first: Holger

last: Eltzschig

first: Bifeng

last: Gao

first: An

last: Doan

first: Ted

last: Shade


title: Effects of miRNA-mediated TET2 in prostate cancer

city: Itabashi-ku

first: Ken-ichi

last: Takayama

address: Sakaecho

institute: Tokyo Metropolitan Institute of Gerontology

summary:
Prostate cancer is the most common cancer in men. We identified that miR-29 family is the most androgen-responsive  miRNA in hormone-refractory prostate cancer cells. For the screening of miR-29b target, we performed microarray analysis in two prostate cancer cells. Because TET2 is the primary target of miR-29 family by our analysis, we also performed TET2 signaling by microarray.
In order to investigate the downsteam signals mediated by TET2 and miR-29b, we performed comprehensive analysis of gene expression in positive prostate cancer cell lines after siTET2 or miR-29b treatment.

overall_design: Observation of gene expression changes after treatmet with siRNA targeting TET2 or miR-29b in prostate cancer cell lines with microarray.

first: Satoshi

last: Inoue


title: Peripheral blood mononuclear cell gene expression pre-/post- oral glucose challenge

city: Rovereto

first: Melissa

last: Morine

address: Via Manifattura 1

institute: The Microsoft Research - University of Trento Centre for Computational and Systems Biology

summary: Acute metabolic challenges provide insight on how the body responds to metabolic stress. In this study, we assessed transcriptomic response in peripheral blood mononuclear cells (PBMC) to an acute glucose challenge.

overall_design: Participants consumed 75 g glucose (anhydrous) in 150 mL of water. PBMCs were collected at baseline and 60 minutes post-challenge for RNA extractin and microarray hybridization


title: Peripheral blood mononuclear cell gene expression pre-/post- oral lipid challenge

summary: Acute metabolic challenges provide insight on how the body responds to metabolic stress. In this study, we assessed transcriptomic response in peripheral blood mononuclear cells (PBMC) to an acute lipid challenge.

overall_design: Participants consumed 100 mL Calogen (Nutricia, Ireland) combined with 50 mL Liquid Duocal (SHS Nutrition, Netherlands) for a total of 150 mL with a fat content of 54 g. PBMCs were collected at baseline and 240 minutes post-challenge


title: Multi-level omics analysis of dystrophin loss and therapeutic restoration in a murine model

first: Thomas

middle: C

last: Roberts

platform_organism:
Mus musculus
synthetic construct


title: Peripheral blood mononuclear cell gene expression pre-/post- acute metabolic challenge


title: Expression data from neural crest cells and neural crest cell-derived MSCs from human pluripotent stem cells of FOP patients and controls

status: Public on Sep 17 2015

city: Kyoto

first: Makoto

last: Ikeya

address: 53 kawahara-cho, shogoin

department: Center for iPS Cell Research and Application(CiRA)

institute: Kyoto University

summary: NCCs and NCC-derived MSCs were induced from FOP-iPSCs and control iPSCs, and their expresion profiles were compared.

overall_design: Comparison of gene expressions among hiPSCs, hESCs, hNCCs and hNC-MSCs from FOP-iPSCs and control-iPSCs.

first: J

last: Toguchida

first: M


title: Kidney gene expression profile following the transplant-induced reactivation of MCMV

status: Public on Aug 27 2015

city: Des Moines

first: Chunfa

last: Jie

state: IA

address: 3200 Grand Ave

institute: Des Moines University

summary:
Reactivation of latent HCMV is a significant infectious complication of organ transplantation, and current therapies target viral replication once reactivation of transcriptionally silent, latent virus has already occurred.  The specific molecular pathways that activate viral gene expression are not well understood.  Our studies aim to identify these factors, with the goal of developing novel therapies that prevent transcriptional reactivation in transplant recipients.  MCMV is a valuable model for studying latency and reactivation of CMV induced by organ transplantation.  We previously demonstrated that transplantation of MCMV-latently infected kidneys into allogeneic recipients induces transcriptional reactivation of immediate early (IE) gene expression within 48 hr.
We used microarrays to profile global mouse kidney gene expression associated with transcriptional reactivation of MCMV immediate early gene expression at 48 hr after transplant of MCMV latently infected kidneys into allogeneic recipients.  We identified differentially expressed genes and pathways associated with both early acute rejection and reactivation of MCMV.

overall_design: control vs. allograft

first: Mary

last: Hummel


title: Expression data from human 3D skin models in response to IL-31 treatment

status: Public on Feb 29 2016

city: Aachen

first: Bernhard

last: Luscher

address: Pauwelsstrasse 30

department: Biochemistry

institute: RWTH Aachen University

summary:
Atopic dermatitis, a chronic inflammatory skin disease with increasing prevalance, is closely associated with skin barrier defects. A cytokine related to disease severity and inhibition of keratinocyte differentiation is IL-31. To identify its molecular targets, IL-31-dependent gene expression was determined in 3-dimensional organotypic skin models.
In this data set we include expression data from human 3D skin models treated with or without IL-31 for 2, 8, 24 and 48 hours.  As a source of keratinocytes HaCaT cells were used. These are immortalized primary keratinocytes. Human dermal fibroblasts were derived from a skin biopsy.

overall_design: A total of 8 samples were analyzed. We compared the control vs the IL-31 treated sample for each time point.

first: Christian

last: Cornelissen

first: Yvonne

last: Marquardt


title: Transcriptome data of multiple sclerosis patients receiving fingolimod therapy [HTA-2_0, CD4+ cells, exon level]

first: Michael

last: Hecker

summary:
We analyzed the gene expression patterns of different blood cell types before and during fingolimod treatment in a group of patients with relapsing-remitting multiple sclerosis (RRMS).
Affymetrix Human Transcriptome Arrays (HTA) 2.0 were used to obtain gene expression profiles of immune cell populations from 10 RRMS patients within the first 3 months of fingolimod treatment.
This GEO entry provides the Affymetrix HTA 2.0 microarray data of peripheral blood CD4+ cells, preprocessed according to the exon level workflow.

overall_design:
EDTA blood samples were taken from all patients immediately before first and second fingolimod administration as well as after 3 months of therapy.
Total RNA of CD4+ cells positively selected from each blood sample was extracted, labeled and hybridized to high-density Affymetrix HTA 2.0 microarrays to quantify the transcript levels.

first: Dirk

last: Koczan

first: Uwe

last: Zettl


title: Reversion of FMR1 methylation and silencing by editing the triplet repeats in Fragile-X iPSC-derived neurons

status: Public on Aug 18 2015

city: Jerusalem

first: Nissim

last: Benvenisty

state: Israel

address: Edmond Safra Campus Givat Ram

department: Genetics

institute: Hebrew University

summary: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability, resulting from a CGG repeat expansion in the fragile X mental retardation 1 (FMR1) gene. Here we report a strategy for CGG repeat correction using CRISPR/Cas9 for targeted deletion in both embryonic stem cells and induced pluripotent stem cells derived from FXS patients. Following gene correction in FXS induced pluripotent stem cells, FMR1 expression was restored and sustained in neural precursor cells and mature neurons. Strikingly, after removal of the CGG repeats, the upstream CpG island of the FMR1 promoter showed extensive demethylation, an open chromatin state, and transcription initiation. These results suggest a silencing maintenance mechanism for the FMR1 promoter that is dependent on the existence of the CGG repeat expansion. Our strategy for deletion of trinucleotide repeats provides further insights into the molecular mechanisms of FXS and future therapies of trinucleotide repeat disorders.

overall_design: Affimetrix HuGene-1_0-st-v1 array of 2 fragile X syndrome derived neurons

first: Tomer

last: Halevy

first: Chul-Yong

last: Park

first: Dong-Wook

last: Kim

first: Ofra

last: Yanuka

first: Jae

middle: S

last: Lee

first: Jin

last: Sung

first: Dongjin


title: Expression data from BRAF-mutant melanoma cell lines

status: Public on Aug 26 2015

city: East Melbourne

first: Petranel

last: Ferrao

address: St. Andrew's Place

department: Cancer Research

institute: Peter MacCallum Cancer Centre

summary: Melanoma cell lines  were assessed for differences in gene expression patterns between the lines sensitive and resistant to BRAF and MEK inhibitor drugs.

overall_design: 22 BRAF-mutant melanoma cell lines were assessed for response to BRAF and MEK inhibitors in a 3 day drug treatment dose response assay. Based on the IC50, 18 lines were found to be responsive to BRAF or MEK inhibition and 4 were resistant. Normalised gene expression data generated from experimental replicate affymetrix arrays was assessed to identify differential patterns of inherent gene expression between the cell lines grouped as drug-responsive or drug-resistant. This were used to idenify specific candidate genes and pathways associated with inherent BRAF/MEK inhibitor drug resistance in melanoma cells.

first: Karen

middle: E

last: Sheppard

first: Rachel

last: Ramsdale

first: Robert

middle: N

last: Jorissen

first: Jason

last: Ellul

first: Grant

middle: A

last: McArthur

first: Richard

last: Pearson


title: Bowel miRNA expression profiles of infants with gastrointestinal conditions

status: Public on Aug 24 2015

city: Hong Kong

first: Kathy

middle: YY

last: Chan

address: Rm84041, 6/F, Clinical Science Building, Prince of Wales Hospital, Shatin, N.T.

department: Paediatrics

country: Hong Kong

institute: The Chinese University of Hong Kong

summary: We have employed miRNA microarray expression profiling to identify miRNA differentially expressed in neonatal bowel tissues with different gastrointestinal conditions.

overall_design: Bowel tissues were collected from infants who underwent surgery treatment for necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP). Infants with other non-inflammatory, congenital intestinal conditions were employed as the Surgical-Control. Differential miRNA microarray analysis was performed.

first: Pak-Cheung

last: Ng

last: Li


title: Global expression profile in a combined study in low grade meningiomas and schwannomas shows upregulation in PDGF, CDH1, SLIT2 and MET.

status: Public on Aug 30 2015

city: Badalona

first: Miguel

last: Torres-Martin

state: Barcelona

address: Carretera de Canyet, s/n

department: Clinical Genomics Unit

institute: Hospital Universitari Germans Trias i Pujol

summary:
Background: Schwannomas and grade I meningiomas are non-metastatic neoplasms that shares the common mutation of gene NF2. They usually appear in Neurofibromatosis type 2 patients. Currently, there is no drug treatment available for both tumors, so the use of wide expression technologies is crucial to find those therapeutic targets.

Methodology: Affymetrix Human Gene 1.0 ST was used to test global gene expression in 22 meningiomas, 31 schwannomas and, as non-tumoral controls, 3 healthy meningeal tissues, 8 non-tumoral nerves and 1 primary Schwann cells culture. A non-stringent P-cutoff and fold change were used to establish deregulated genes.

Results and discussion: We found a subset of genes that were upregulated in meningiomas and schwannomas when compared to their respectively healthy tissue, including PDGFD, CDH1, SLIT2 and MET. Thus, those genes could be more thoroughly studied as targets in a possible combined treatment.

first: Luis

last: Lassaletta

first: Jose

middle: M

last: de Campos

first: Alberto

last: Isla

first: Javier

last: Gavilan

first: Barbara

last: Melendez

last: Castresana

first: Juan

last: Rey


title: Cytomegalovirus promotes maintenance and growth of glioblastoma stem cells [Human gene expression]

status: Public on Aug 13 2015

city: Newark

first: Saleena

last: Ghanny

address: 185 South Orange Ave

institute: Rutgers University

summary:
Primary human GBM stem like cells were infected with HCMV TR strain (MOI=1) and treated with IE siRNA (a combination of oligos targeting IE1 and IE2 HCMV genes)
72 hours following siRNA treatment, RNA was harvested using Qiagen and divided equally for profiling using Affymetrix arrays and HCMV arrays.

overall_design: Primary human glioma stem cells were maintained in neurosphere growth conditions, treated with IE1 and control siRNA for 48-72h prior to RNA harvesting. RNA was hybridized to Affymetrix Genechips.

first: Liliana

last: Soroceanu


title: Expression data from primary culture human myometrial cells

city: london

first: kaiyu

last: lei

state: London

address: ducan road

department: Surgery and Cancer

institute: imperial college london

summary:
Inflammation plays a central role in many human diseases. Human parturition also resembles an inflammatory reaction, where progesterone (P4) and progesterone receptors (PRs) have already been demonstrated to suppress contraction-associated gene expression. In our previous studies, we have found that the progesterone actions, including progesterone-induced gene expression and progesterone’s anti-inflammatory effect, are mediated by PR, GR or both.
In this study, we used microarrays to find P4 and IL-1β responsive genes and which  IL-1β responsive genes were repressed by P4. These data may provide a broader view of gene networks and cellular functions regulated by P4 and  IL-1βin human myometrial cells. In our future study, this will also help us understand the role of PR and GR in human parturition.

overall_design: Primary cultures of human myometrial cells were grown from myometrial biopsies obtained at the time of elective caesarean section. Cells were exposed to different stimuli, IL-1β (5ng/mL) and P4 (10 µM), either alone or in combination for 6 h, and then total RNA were extracted from each culture. Three comparisons were carried out including: 1. V vs. P4; 2. V vs. IL-1β; 3. IL-1β vs. IL-1β+P4.

first: Kaiyu

last: Lei

first: Suren

last: Sooranna

first: Mark

last: Johnson


title: TLR2/6 agonists and IFNlambda induce CXCL10 from melanoma

city: Doha

first: Francesco

last: Marincola

address: Al Nasr Tower, AL Corniche Street, PO Box 26999

institute: Sidra Medical and Research Center

summary: Melanoma is the most lethal form of skin cancer. Clinical efforts to combat melanoma include immune therapies whose benefit depends on antitumor T-cells, to target and to clear melanoma. However, most tumors lack significant immune infiltration prior to therapy, and some immune therapies are hindered by a persistent lack of immune-cell infiltration. Chemokines can promote T-cell migration into tumors; therefore, agents that induce T-cell attracting chemokines in the tumor microenvironment could potentially improve the clinical activity of current immune therapies for melanoma. CXCL10 has been implicated as a critical chemokine supporting T-cell infiltration into the tumor microenvironment. Here we report that combination treatment of human melanoma cell lines with Toll-like receptor (TLR) 2/6 agonists MALP-2 or FSL-1 +IFNlambda synergize to induce production of immune-cell attracting chemokines CCL3 and CXCL10 by melanoma cells. We find that TLR2 and TLR6 are widely expressed on human melanoma cells, and that stimulation of fresh patient melanoma specimens with TLR2/6 agonists+IFNlambda induces CXCL10 production from melanoma cells, endothelial and immune-cells. Furthermore, ex vivo migration assays demonstrate that stimulation of melanoma cells with TLR2/6 agonists+IFNlambda increases CD4+ and CD8+ T-cell migration toward melanoma. Collectively, these data identify a novel synergy of TLR2/6 agonists+IFNlambda for inducing CXCL10 production by melanoma cells and suggest that intralesional administration of TLR2/6 agonists+IFNlambda may improve immune signatures in melanoma metastases and have value in combination with other immune therapies, by supporting better T-cell migration to melanoma.

overall_design: Melanoma cell line samples for VMM1 (n=7) were two samples left untreated and others stimulated overnight at 37C with TLR agonists: LPS (10 ug/mL), CpG ODN (5 ug/mL), Resiquimod (5 ug/mL), Imiquimod (25 ug/mL) (Imgenex), poly-ICLC (20 ug/mL) (Oncovir Inc, Washington, DC). Melanoma cell line samples for DM93 (n=5) were one sample left untreated and others stimulated overnight at 37C with TLR agonists: LPS (10 ug/mL), Resiquimod (5 ug/mL), Imiquimod (25 ug/mL) (Imgenex), poly-ICLC (20 ug/mL) (Oncovir Inc, Washington, DC). Melanoma cell line samples for DM122 (n=6), Ramos (n=6), HEK293 (n=6), TLR7 HEK293 (n=6) and DM13 (n=6) were one sample left untreated and others stimulated overnight at 37C with TLR agonists: LPS (10 ug/mL), CpG ODN (5 ug/mL), Resiquimod (5 ug/mL), Imiquimod (25 ug/mL) (Imgenex), poly-ICLC (20 ug/mL) (Oncovir Inc, Washington, DC). Melanoma cell line samples for VMM39 (n=2) were one sample left untreated and the other stimulated overnight at 37C with TLR agonist: Imiquimod (25 ug/mL) (Imgenex). For HMVECad (n=6), one sample was left untreated and others stimulated overnight at 37C with TLR agonists: LPS (10 ug/mL), CpG ODN (5 ug/mL), Resiquimod (5 ug/mL), Imiquimod (25 ug/mL) (Imgenex), poly-ICLC (20 ug/mL) (Oncovir Inc, Washington, DC). For HUVEC (n=6), one sample was left untreated and others stimulated overnight at 37C with TLR agonists: LPS (10 ug/mL), CpG ODN (5 ug/mL), Resiquimod (5 ug/mL), Imiquimod (25 ug/mL) (Imgenex), poly-ICLC (20 ug/mL) (Oncovir Inc, Washington, DC).


title: Gene expression analysis of directly converted brown adipocytes (dBAs). [human]

status: Public on Aug 12 2015

first: Kenta

last: Yamamoto

address: Kajicho 465

department: Immunology

institute: Kyoto Prefectural University of Medicine

summary:
Comparasion of each cell mRNA expression pattern
Human fibroblasts were directly converted into brown adipocytes (dBAs) by transducing some transcription factors. To characterize the dBAs more in detail, RNA extracted from the human WAs, human dBAs, and human iPS-derived brown adipocytes (iBAs) were subjected to DNA microarray analysis, and global gene expression profiles of the cells were compared.

overall_design: 6 samples

first: Tsunao

last: Kishida

first: Toshiro

first: Osam

last: Mazda


title: Inhibition of EZH2 in THP-1 cells

status: Public on Aug 04 2015

city: Omaha

first: Jessi

last: Winkler

state: Nebraska

address: DRC I

department: Exp Neuroscience and Pharmacology

institute: UNMC

summary: Macrophages play a key role in both innate and adaptive immunity, but our knowledge on the changes in transcription regulation that occurs during their differentiation from monocytes is still limited. In this study, we used a meta-analysis followed by a systems biology approach for the identification of differentially expressed genes between monocytes and macrophages and possible regulators of these changes in transcription. Based on the pattern of gene expression change, transcription regulator analysis predicted a decrease in Enhancer of Zeste homolog 2 (EZH2), a histone 3 lysine 27 methyl transferase, activity after differentiation of monocytes into macrophages. This inhibition was validated by a significant decrease in trimethylated H3K27 during differentiation of both human primary monocytes into macrophages and the THP-1 cell line into macrophage-like cells. Overexpressing EZH2 during differentiation of monocytes and THP-1 cells obstructs cellular adhesion, thus preventing the first step in differentiation. Another facet of macrophage differentiation is the cessation of proliferation, and inhibition of EZH2 by the small molecule inhibitor GSK126 in THP-1 cells indeed impedes proliferation. This study shows an important part for epigenetic changes during monocyte differentiation. It highlights the role of EZH2 activity behind the changes needed in adhesion and proliferation mechanisms for macrophage formation.

overall_design: THP-1s were treated with the EZH2 inhibitor GSK126 for phenotypic and genotypic analysis.

first: Jessica

first: Howard

last: Fox


title: Unexpected Inflammatory Effects of Intravaginal Gels (Universal Placebo Gel and Nonoxynol-9) on the Upper Female Reproductive Tract: an Experimental Crossover Study

status: Public on Aug 10 2015

city: San Francisco

first: Linda

last: Giudice

state: CA

address: 513 Parnassus Ave. HSE 1619

department: OBGYN and RS

institute: University of California, San Francisco

summary: Intravaginal HIV microbicides could provide women with a self-controlled means for HIV prevention, but results from clinical trials have been largely disappointing. We postulated that unrecognized effects of intravaginal gels on the upper female reproductive tract (FRT) might contribute to the lower-than-expected efficacy of HIV microbicides. In this observational crossover study, 28 healthy female volunteers used no product (control cycle) or used a nightly application of intravaginal nonoxynol-9 gel [N9] as a 'failed' microbicide or the universal placebo gel [UPG] as a 'safe' gel, from the end of menses to the mid-luteal phase (intervention cycles). They then underwent sample collection for measurements of T-cell phenotypes, transcriptional profiling, and protein levels from 3 anatomic sites above the vagina: the cervical transformation zone, the endocervix and the endometrium. We used hierarchical statistical models to estimate mean (95% CI) intervention:control fold-changes in relevant phenotype levels. Exposure to N9 and UPG generated a common 'harm signature' that included transcriptional up-regulation of inflammatory genes CCL20 and IL8 in the cervix, decreased protein concentrations of secretory leukocyte protease inhibitor and increased percentages of terminally differentiated CD4+ effector T-cells in the endocervix, and transcriptional up-regulation of inflammatory mediators KIR3DS1, glycodelin-A, and osteopontin in the endometrium. These results underscore the need to consider the effects of microbicide agents and gel excipients on the upper FRT in studies of vaginal microbicides. Given the  pro-inflammatory effects of UPG on the upper FRT, it may not be a suitable placebo for microbicide trials.

overall_design:
Upper tract effects of intravaginal gels in women.
This is a cross sectional study involving control samples versus treatment for two tissue types.

first: Karen

last: Smith-McCune

first: Joseph

last: Chen

first: Ruth

last: Greenblatt

last: Shacklett

first: Uma

last: Shanmugasundaram

first: Joan

middle: F

last: Hilton

first: Brittni

first: Fatima

last: Barragan

last: Irwin

first: Margaret

last: Takeda

first: Jane

last: Pannell

first: Jean

last: Perry


title: PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells

status: Public on Aug 07 2015

first: Martin

last: Zenke

state: NRW

address: Universitatsklinikum Aachen, RWTH

department: Cell Biology

institute: Institute for Biomedical Engineering

summary: Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different H3K4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs.

overall_design: 6 samples were hybridized GeneChip Human Gene 1.0 ST Arrays (Affymetrix)

last: Varagnolo

first: Qiong

last: Lin

first: Nadine

last: Obier

first: Christoph

last: Plass

first: Johannes

last: Dietl

first: Rainer

last: Claus

first: Albrecht

last: Müller


title: CNA data from The human glioblastoma cell culture resource: validated cell models representing all molecular subtypes

status: Public on Aug 20 2015

city: Uppsala

first: Sven

last: Nelander

address: Rudbecklab

institute: Uppsala Universitet

summary: To meet the present shortage of relevant GBM cell (GC) lines we developed a library of annotated and validated cell lines derived from surgical samples of GBM patients, maintained under conditions to preserve GSC characteristics. This collection, which we call the Human Glioblastoma Cell Culture (HGCC) resource, consists of a biobank of GC lines and an associated database containing high-resolution molecular data.

overall_design: DNA isolated from GC lines using the DNeasy blood and tissue kit (Qiagen) was profiled on Affymetrix Cytoscan arrays at the Uppsala Academic Hospital Array and Analysis facility, in accordance with the manufacturer’s instructions.

first: Lene

last: Uhrbom


title: Effects of bisphenol A on gene expression in adipocytes from lean children: association to metabolic disorders

status: Public on Jul 09 2015

city: Torino

first: Raffaele

last: Calogero

state: To

address: Via Nizza 52

department: Molecular Biotechnology Center

institute: University of Torino

summary: Bisphenol A (BPA) is a xenobiotic endocrine disrupting chemical. In vitro and in vivo studies indicated that BPA alters endocrine-metabolic pathways in adipose tissue increasing the risk of developing metabolic disorders. BPA effects on human adipocytes, specifically in children, are poorly investigated. To investigate in childhood the effect of exposure to BPA on metabolic disorders we analyzed in vitro the effects of environmentally relevant doses of BPA on gene expression of mature human adipocytes from pre-pubertal lean patients and on related physiological outcomes. Adipocytes from children were treated in vitro with BPA and gene expression was evaluated by qRT-PCR. Genome wide analyses were performed using GeneChip® Human Gene 1.0 ST array. Lipid content in adipocytes was estimated by ORO staining and Triglyceride Quantification Kit. Secreted IL-1β, in adipocytes culture medium, and insulin, in PANC-1 culture medium, were performed using ELISA assays. BPA was found to promote up-regulation of ERα and ERRγ, and down-regulation of GPR30 expression modulating estrogen signaling and following a non-linear dose-response. Microarray data analysis demonstrated that BPA increases the gene expression of pro-inflammatory cytokines and lipid metabolism-related FABP4 and CD36 in adipocytes. PCSK1 resulted the most interesting gene being down-regulated by BPA thus impairing insulin production in pancreas. BPA promotes inflammation and lipid metabolism dysregulation in adipocytes from lean children. Moreover, PCSK1 can be a key gene in BPA action modulating insulin production. Exposure to BPA in childhood may be an important risk factor in developing obesity and metabolic disorders.

overall_design: Three prototypic situations were analyzed (5 replication each): untreated cells (C), 10 nM BPA treated cells (BPA), 1 nM 17-β Estradiol treated cells (ES).

first: Ciro

last: Menale

first: Maria

last: Piccolo

first: Grazia

last: Cirillo

first: Alfonso

last: Papparella

first: Luigi

last: Mita

first: Emanuele

last: Miraglia Del Giudice

first: Nadia

last: Diano

first: Damiano

middle: G

first: Stefania

last: Crispi


title: Gene expression of CD8+ T cells isolated from human subjects during acute and convalescent phase of EBV infection

status: Public on Jul 22 2015

city: Worcester

first: Thomas

last: Greenough

state: MA

address: 373 Plantation Street

department: Program in Molecular Medicine

institute: University of Massachusetts Medical School

summary: Affymetrix HuGene ST 1.0 microarrays were used to study and compare gene expression in peripheral blood CD8+ T cells of human patients with Acute Infectious Mononucleosis (AIM; acute EBV infection) and during convalescence  (CONV; 6-12 months after AIM visit). Blood samples were drawn from ten human patients with AIM and again during their covalescence (CONV). Peripheral blood mononuclear cells were isolated and cryopreserved. Paired AIM and CONV samples were thawed and CD8+ T cells purified with magnetic beads. RNA was isolated and processed for hybridization according to the Affymetrix protocol

overall_design: CD8+ T cells acute and convalescent phase of EBV infection (10 subjects)


title: Gene expression profiles in HepG2 cells treated with the methanol leaf extract of Tamarindus indica (T. indica)

status: Public on Aug 01 2015

city: Onna-son, Kunigami-gun

first: Nurhanani

last: Razali

state: Okinawa

address: 1919-1 Tancha

department: Membranology

institute: Okinawa Institute of Science and Technology Graduate University (OIST)

summary: The leaf extract of T. indica had been reported to posses high phenolic content and showed high antioxidant activities. However, scientific data on the molecular mechanisms underlying the beneficial properties of the leaf extract are still lacking. In this study, the effects of the leaf extract on the expression of genes in cultured HepG2 cells were investigated using microarray technology. The leaf extract significantly regulated the expression of genes involved with consequential impact on the coagulation system, cholesterol biosynthesis, xenobiotic metabolism signaling and antimicrobial response.

overall_design: HepG2 cells were seeded and treated with an IC20 concentration of the methanol leaf extract of T. indica for 24 h. Following this, cells were trypsinized and then preciptated by centrifugation. Cells were washed with phosphate buffer saline (PBS) before total cellular RNA (tcRNA) were extracted from the cells. tcRNA from both untreated and T. indica leaf-treated HepG2 cells were selected for RNA extraction and hybridization on Affymetrix microarrays. All experiments were done in triplicate. The microarray analysis was performed on Affymetrix Human Gene 1.0 S.T Array according to the manufacturer's protocol. The gene sets were then subjected to analysis of variance (ANOVA) in the Partek Genomics Suite software to determine significantly expressed genes which was set according to P value less than 0.05 and fold change difference of equal to or greater than 1.5.

first: Razali

last: Nurhanani

first: Mat-Junit

last: Sarni

first: Abdul-Aziz

last: Azlina


title: Leishmania major infection-induced changes in the small RNA transcriptome of host macrophages.

status: Public on Aug 03 2015

city: Würzburg

first: Claus

middle: Juergen

last: Scholz

address: Josef-Schneider-Str. 2

department: Core Unit SysMed

institute: University Hospital Würzburg

summary:
Protozoan parasites of the genus Leishmania are the causative agent of leishmaniasis, one of the 13 most important tropical diseases. Leishmania persists as endo-parasite in host macrophages, where it uses multiple strategies to manipulate the microbicidal host cell functions and to escape from the host immune system. Understanding how Leishmania interacts with host macrophages during uptake, differentiation, intracellular replication, and release might be the key to develop new drugs in target-directed approaches to treat patient with leishmaniasis.
Short non-coding RNAs are known to regulate the expression of protein-coding genes at post-transcriptional level. Characterization of these processes during Leishmania infection provides deeper insight in the interaction between host and parasites.

overall_design: Here, we generated miRNA expression profiles from bone marrow-derived macrophages (BMDM) at 4h and 24h post infection (p.i.) with Leishmania major and respective controls.

first: Benjamin

last: Frank

first: Heike

last: Weber

first: Uta

last: Schurigt