title: CEBPA-mediated chromatin structure remodeling controls macrophage-specific differentiation and inflammatory gene expression program.

city: Singapore

first: Michael

last: Poidinger

address: #04-06, 8A Biomedical Grove

department: Bioinformatics

institute: Singapore Immunology Network

summary: Analysis of transcriptional regulation by CEBPA at gene expression level. The hypothesis tested in the present study was that CEBPA regulate genes involved in macrophage differentiation and function. Results provide important information of the transcriptome profiling of HEK293 cells expressing ectopic CEBPA, such as specific CEBPA-responsive genes, up- or down-regulated specific cellular functions.

overall_design: Total RNA obtained from uninfected HEK293 cells and compared to the HEK293 cells infected with the lentiviral vector containing CEBPA.

first: Keh

last: Chin

first: Francesca

last: Zolezzi

first: Josephine

last: Lum


title: Analysis of the transcriptional response to retinoic acid in T47D breast cancer cells with impaired RARA function

status: Public on Jun 01 2017

city: Buffalo

first: Stefano

last: Rossetti

state: NY

address: Elm and Carlton Streets

department: Cancer Genetics

country: USA

institute: Roswell Park Cancer Institute

summary: It has been shown that retinoic acid (RA) can both inhibit and promote cancer cell growth, but the basis of this “paradox” is still not clear. The action of RA is mainly mediated by RA receptors (RARs), which classically function as ligand-activated transcription factors. Upon binding to the RA receptor alpha (RARA), RA modulates the transcription of several RA-target genes involved in multiple cellular processes, including cell proliferation. We have found that functional inhibition of RARA transcriptional function by stable expression of a RARA dominant negative (RARA403) converts T47D breast cancer cells from growth-inhibited to growth-promoted by supraphysiological RA (Ren et al., MCB, 2005, PMID:16287870; Somenzi et al., PloS ONE, 2007, PMID:17786207). We hypothesized that RA-induced cell growth requires both the activation of RA-responsive tumor-promoting signalings and lack of activation of RA-responsive tumor suppressor signalings. To identify these signalings, we analyzed the transcriptional response to RA in our model of the “RA paradox” by using gene expression microarrays.

overall_design: To impair RARA transcriptional function, T47D breast cancer cells were stably transfected with the RARA403 mutant (DNC8 clone). In parallel, T47D were stably transfected with the empty vector to obtain a control clone (LXC5 clone, also called T47D-Ctrl). The two clones were grown with or without RA (1 uM) for 72h, and analyzed on gene expression microarrays to identify genes with differential response to RA in presence or absence of functional RARA transcriptional function. A total of 8 samples were analyzed: LXC5 minus RA, LXC5 plus RA, DNC8 minus RA, DNC8 plus RA, in duplicate.

first: Nicoletta

last: Sacchi


title: Prosurvival long noncoding RNA PINCR regulates a subset of p53 targets in colorectal cancer cells by binding to Matrin 3 [Illumina HumanHT-12 V4.0]

status: Public on May 31 2017

city: Bethesda

first: Yuelin

middle: Jack

last: Zhu

state: MD

address: 9000 Rockville Pike

department: Genetics Branch, Center for Cancer Research

institute: NCI

summary: Thousands of long noncoding RNAs (lncRNAs) have been discovered, yet the function of the vast majority remains unclear. Here, we show that a p53-regulated lncRNA which we named PINCR (p53-induced noncoding RNA), is induced ~100-fold after DNA damage and exerts a critical prosurvival function in colorectal cancer cells (CRC) in vitro and tumor growth in vivo. Targeted deletion of PINCR in CRC cells significantly impaired G1 arrest and induced hypersensitivity to chemotherapeutic drugs. PINCR regulates the induction of a subset of p53 targets involved in G1 arrest and apoptosis, including BTG2, RRM2B and GPX1. Using a novel RNA pulldown approach that utilized endogenous S1-tagged PINCR, we show that PINCR associates with the promoters of these genes by binding to RNA-binding protein Matrin 3 that, in turn, associates with p53. Our findings uncover a critical prosurvival function of a p53/PINCR/Matrin 3 axis in response to DNA damage in CRC cells.

overall_design: HCT116 PINCR WT and PINCR KO cells were kept untreated or treated with 5-FU and RNA samples were collected in triplicates.

first: Ritu

last: Chaudhary

first: Murugan

last: Subramanian

first: Xiao

middle: L

last: Li

middle: J

first: Ashish

last: Lal


title: Prognosis of Stage III Colorectal Carcinomas with FOLFOX Adjuvant Chemotherapy can be Predicted by Molecular Subtype

city: seoul

first: minhee

last: park

address: shinchondong

country: South Korea

institute: student

summary:
Comparison the mRNA expression profiles of 101 CRC tissues to those from matched 35 non-neoplastic colon mucosal tissues from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy in each molecular subtype.
Gene expression–based subtyping is widely accepted as a relevant source of disease stratification. Results provide important information of molecular marker genes for molecular classification.

overall_design: Total RNA obtained from isolated 101 colorectal cancer tissues and theose from matched 35 non-neoplastic colon mucosal tissues.

first: Yujin

last: Kwon

first: Minhee

last: Park

first: Mi

last: Jang

first: Hoguen

last: Kim


title: Gene expression profile of stage I lung adenocarcinoma and matched multi-site non-tumor lung samples

status: Public on May 23 2017

city: Quebec

first: Yohan

last: Bossé

state: Quebec

address: 2725, chemin Sainte-Foy

country: Canada

institute: Laval University

type: Expression profiling by high throughput sequencing

summary: In this study, a unique geographical tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and non-tumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole genome gene expression profiling was performed on all samples (n = 5 specimens x 12 patients = 60). Analyses were carried out to identify genes differentially expressed in tumor compared to adjacent non-tumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in non-tumor tissues with respect to tumor proximity.

overall_design: Gene expression was performed in stage I adenocarcinoma and matched non-tumor lung tissues located at 0, 2, 4, and 6 cm away from the tumor in 12 patients (n = 5 specimens x 12 patients = 60). One tumor sample and two non-tumor specimens located at 0 cm failed QC and were excluded. A total of 57 samples are thus include in this dataset (n = 4-5 specimens x 12 patients).


title: Microarray expression data for tumor and adjacent non-tumor tissues from hepatocellular carcinoma patients

status: Public on May 26 2017

first: Surya Pavan

last: Yenamandra

address: 30, Biopolis street, #07-01 Matrix

country: Singapore

institute: Bioinformatics Institute

summary: Here we aimed to develop a new molecular prognostic stratification system for hepatocellular carcinoma (HCC) patients after liver resection based on common prognostic factors for primary tumors (PTs) and adjacent non-tumor tissues (ANTTs). We studied global mRNA expression profiles from 115 PT tissue samples and 52 ANTT samples derived from 115 HCC patients. Methods for the study included gene expression analysis, Functional Annotation/Gene Ontology analysis and unsupervised survival prognosis approach based on Cox hazards prognosis model. This study provides a practical prognostic system for reliable identification of the high-risk HCC patients subgroup with clearly described deregulated molecular machinery in both PTs and ANTTs.

overall_design: One hundred sixty-seven total RNA samples from hepatocellular carcinoma tumors and adjacent non-tumor liver tissue samples have been obtained with informed consent from patients who underwent radical resection between the years 2000 and 2013 in Singapore General Hospital and collected at the National Cancer Centre of Singapore (NCCS)/SingHealth Tissue Repository. Linked clinical and histo-pathologic data were collected from medical records for all the patients who contributed tumor specimens and were rendered anonymous to protect patient confidentiality. Percentage of HCC patients with HBV infection and cirrhosis were 46% and 54%, respectively. Gene expression data for all the samples were quantified by using whole-genome Illumina HumanHT-12 v4 Expression BeadChip arrays. Raw data for the entire 115 Singapore HCC cohort was obtained via the GenomeStudio; data have been normalized using the RSN method from R-package lumi. Microarray quality control was performed using the arrayQualityMetrics software.

first: Oleg

middle: V

last: Grinchuk

first: Surya

middle: P

first: Vladimir

middle: A

last: Kuznetsov


title: Shear stress induces immunomodulatory signaling in bone marrow mesenchymal stromal cells (MSCs)

city: Houston

first: Pamela

last: Wenzel

state: TX

address: 6431 Fannin St, MSB 4.130

department: Integrative Biology & Pharmacology

institute: University of Texas Health Science Center at Houston

summary: Bone marrow mesenchymal stromal cells (MSCs) regulate homeostasis and trafficking of cells of the blood lineage. In response to traumatic injury or infection, MSCs are believed to mobilize from the bone marrow, but it is largely unknown how egress into circulation impacts MSC function. Here we show that biomechanical forces associated with trafficking of MSCs from the bone marrow into the vasculature contribute uniquely to genetic signaling that reinforces MSC repression of immune cell activation. Laminar wall shear stress (LSS) typical of fluid frictional forces present on the lumen of arterioles stimulates increases in antioxidant and anti-inflammatory mediators, as well as an array of chemokines capable of immune cell recruitment. Importantly, LSS promotes a signaling cascade through COX2 that elevates prostaglandin E2 (PGE2) biosynthesis, permitting MSCs to suppress immune cell activation in the presence of inflammatory cues. Pharmacological inhibition of COX2 depleted PGE2 and impaired the ability of MSCs to block tumor necrosis factor-α (TNF-α) production, supporting a key role for PGE2 in the MSC immunomodulatory response to LSS. Preconditioning of MSCs by LSS ex vivo was an effective means of enhancing therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased numbers of apoptotic and M1-type activated microglia in the hippocampus and by retention of endogenous MSCs in the bone marrow. We conclude that biomechanical forces provide critical cues to MSCs residing at the vascular interface which influence MSC immunomodulatory and paracrine functions, thus providing unique opportunities for functional enhancement of MSCs used in therapeutic applications.

overall_design: We hypothesized that fluid shear stress caused by vascular flow might alter mesenchymal stromal cell (MSC) signaling and function. To mimic arterial force at the vascular wall, we cultured human bone marrow-derived MSCs in microfluidics capable of producing uniform laminar flow at a wall shear stress (LSS) of 15 dyne/cm^2. Bone marrow MSCs were derived from whole bone marrow from independent human donors (AllCells). Cells were passaged into microfluidic IBIDI channels (μ-Slide VI 0.4) at a density of 3x10^6 cells/ml and permitted to attach to the culture surface for 18 hours. Following attachment, a peristaltic pump (REGLO analog MS4/12, Ismatec) was used to produce LSS of 15 dyne/cm2 for 6 hours. Lysis for RNA isolation was conducted immediately after LSS within the microfluidics.


title: A genome-wide loss-of-function screen identifies SLC26A2 as a novel mediator of TRAIL resistance

status: Public on May 29 2017

city: Salt Lake City

first: Aik Choon

last: Tan

state: UT

address: 2000 Circle of Hope

department: Oncological Sciences

institute: Huntsman Cancer Institute

summary: To identify intrinsic mechanismis that mediating Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance , gene expression analysis was performed on MDA-MB-231 cell lines exposed to TRAIL, in parental (Sensitive) or treat to resistance (TTR) conditions.

overall_design: MDA-MB-231 cell lines, parental and treat to resistance (TTR), treated with TRAIL, in triplicate.

first: Aik

middle: C

first: Christina

last: Garlington

first: Heide

last: Ford


title: BRAF inhibition leads to oxidative phosphorylation and cellular senescence in human melanoma cells

status: Public on May 22 2017

city: Philadelphia

first: Gao

last: Zhang

state: PA

address: 3601 SPRUCE ST

department: Molecular and Cellular Oncogenesis Program

institute: Wistar Institute

summary: Targeting components of the mitogen-activated protein kinase (MAPK) pathway prolongs survival of patients with advanced BRAFV600E melanomas but such an approach is not curative because of the rapid acquisition of numerous resistance mechanisms. Here we analyze melanoma cells that evade MAPK inhibitors by undergoing a senescence-like, slow-growth, phenotype, which leads to acquired resistance. The initial therapeutic response is characterized by an integrated stress response program, including stimulation of autophagic flux, activation of the endoplasmic reticulum machinery, and an enhanced ability of detoxifying reactive oxygen species. Reversibly senescent cells also exhibit an increase in mitochondrial genome copy number and a strong metabolic shift towards oxidative phosphorylation (OxPhos). Inducing mitochondrial dysfunction by co-targeting the MAPK pathway and mitochondrial Hsp90-directed protein folding with specific inhibitors prevented entry of cells into a reversibly senescent state, suppressed mitochondrial energy metabolism and augmented therapy response.

overall_design:
Human melanoma cells were treated with BRAF inhibitor PLX4720 at 10uM.
There are two biological replicates at each time point.

first: Wei

last: Zhi


title: Genome-wide expression profiling after acute radiation doses in recurrent U87-MG cells

city: Menlo Park

first: J. Tyson

last: McDonald

state: CA

address: 333 Ravenswood Avenue

institute: SRI International

summary: To examine short- and long-term gene expression responses following high dose radiation exposure in vitro with the U87-MG cell line.  Samples were examined at 1, 4, 6 or 35 days after irradiation with 8 or 16Gy.

overall_design: Samples were collected at 1, 4, 6 or 35+/-1 days after acute exposure to 8 or 16Gy (48cGy per minute).  Control non-irradiated 0Gy samples were also collected at each time point. Non-normalized data has a total of 48 microarray samples.  The normalized data has a total of 39 samples.  Short-term samples on days 1, 4, and 6 used 3 independent experimental replicates resulting in 27 microarrays (3 experimental conditions × 3 independent replicates × 3 time points).   RNA from replicate1 for days 1, 4 and 6 was run in techincal duplicate (rep1a & rep1b) and the average signal was used for analysis.  Long-term samples on day 35 used four replicates representing 3 independent experimental replicates resulting 12 microarrays.

first: J

middle: T


title: Expression data from healthy donors and AML patients

status: Public on May 12 2017

city: Beijing

first: Ke

last: Li

state: Xicheng

address: Nanwei street A2

department: pharmacology

country: China

institute: IMM

summary:
To identify the top 20 up-regulated genes in CD34+ cells from AML patients in comparison with healthy donors, we examined the microarray gene expression profile of CD34+ blasts from patients with newly diagnosed AML vs CD34+ normal cells from healthy donors.
Despite the fact that combined therapy of all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) or chemotherapy dramatically improves the prognosis of patients with APL, these regimens can cause systemic infections and secondary leukemias. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) associates positively with APL progression and therapeutic resistance. The elevated TRIB3 expression promotes APL by interacting with PML-RARa and suppressing its sumoylation, ubiquitylation and degradation. This represses PML nuclear body assembly, p53-mediated senescence, cell differentiation, and supports cellular self-renewal. Genetically inhibiting Trib3 expression or disturbing the TRIB3/PML-RARa interaction produces potent therapeutic efficacy against APL and has synergic anti-APL effects when used in combination with ATRA or ATO by promoting PML-RARa degradation and PML expression. Our study provides new insight into APL pathogenesis and a new therapeutic option against APL.

overall_design: Total RNA of CD34+ cells from bone marrow from newly diagnosed AML patients and healthy donors  was obtained, and RNA quantity and quality were measured by NanoDrop ND-1000. RNA microarrays were performed.


title: Genome wide expression analysis of mouse xenograft tissues derived from urothelial cancer cell UM-UC3 orthotopic recycling

first: Tiewei

last: Cheng

state: United States

address: 7777 Knight Rd.

institute: UT MD Anderson Cancer Center

summary: Urothelial cancer cells UM-UC3 was orthotopically implanted in mouse bladder wall and then recycled for multiple cycles. Spontaneous tumor tissues including primaries, lymph node metastasis, distant metastasis (lung and bone) and circulating tumor cells (CTCs) were collected and the mRNA expression profiling was examed by microarray

overall_design: Total RNA was obtained from mutilple xenograft tissues and 5 separate tumors for each tissue type (primaries, lynph note metastasis, distant metastasis and CTCs) were derived from UM-UC3 orthotopic recycling

first: Beat

last: Roth

first: Woonyoung

last: Choi


title: Targeting the vulnerability to NAD+ depletion in B-cell acute lymphoblastic leukemia

status: Public on May 01 2017

first: Phillip

middle: H

last: Koeffler

address: 14 Medical Drive

institute: Cancer Science Institute

summary: Although substantial progress has been made in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), the prognosis of patients with refractory or relapsed B-ALL remains dismal. Novel therapeutic strategies are needed to improve the outcome of these patients. KPT-9274 is a novel dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). PAK4 is a serine/threonine kinases and it regulates a variety of protein kinases involved in cell survival, motility and proliferation. NAMPT is a rate-limiting enzyme in the salvage biosynthesis pathway of nicotinamide adenine dinucleotide (NAD), which plays a vital role in energy metabolism. Here, we show that KPT-9274 strongly inhibits B-ALL cell growth regardless of cytogenetic abnormalities. We also demonstrate the potent in vivo efficacy and tolerability of KPT-9274 in orthotopic xenograft murine models using patient-derived BALL cells. Although KPT-9274 affected both PAK4 signaling pathways and NAD+ dependent pathways, B-ALL cell growth inhibition mediated by KPT-9274 was largely abolished by nicotinic acid supplementation, indicating that the inhibitory effect of KPT- 9274 on B-ALL cell growth was mainly exerted by NAD+ depletion through blockade of NAMPT enzyme activity. Moreover, we found that B-ALL cells were especially vulnerable to NAD+ depletion, and the susceptibility to treatment with KPT-9274 was related to the reduced NAD+ reserve in B-ALL cells. NAD+ depletion may be a promising alternative approach to treating patients with B-ALL.

overall_design: cDNA microarray based expression analyses was performed on B-cell ALL cell lines REH, RS4;11 and SEM under control and treated conditions. All experiments were carried out in duplicates.

first: Sumiko

last: Takao

first: Vikas

last: Madan

first: De-Chen

last: Lin

first: Ling-Wen

last: Ding

first: Qiao-Yang

last: Sun

first: Anand

last: Mayakonda

first: Makoto

last: Sudo

first: Xu

last: Liang

first: Chen

last: Ye

first: Yan-Yi

last: Jiang

first: Wenwen

last: Chien

first: Gery

last: Sigal

first: Michael

last: Lill

first: Eugene

last: Park

first: William

last: Senapedis

first: Erkan

last: Baloglu

first: Markus

last: Muschen

first: HP


title: Global gene expression profile of hIAPP-Tg mice, BACE2-KO mice and hIAPP-TgxBACE2-KO mice

status: Public on May 03 2017

city: Barcelona

first: Gema

last: Alcarraz-Vizán

address: Rossello 149

department: Diabetes & Obesity Laboratory

country: Spain

institute: IDIBAPS

summary:
12 weeks old wild type, hIAPP transgenic,  BACE2 deficient and both overexpressing hIAPP and lacking BACE2 mice were taken for the study. Pancreatic islets were isolated at sacrifice. RNA was extracted and hybridized on Affymetrix microarrays.
We used microarrays to determine gene expression changes in pancreatic islets from mice overexepressing hIAPP, mice with a functional deletion in BACE2, mice with both of these modifications and wild type mice.

first: Carlos

last: Castaño

first: Joan-Marc

last: Servitja

first: Anna

last: Novials


title: A genome editing approach to study cancer stem cells in human tumors

status: Public on Apr 28 2017

first: Camille

last: Stephan Otto Attolini

state: Select a State or Province

address: Baldiri Reixac 10

department: Biostatistics and bioinformatics Unit

institute: IRB Barcelona

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

overall_design: Refer to individual Series


title: HCT116 TCF7L1 knockdown Microarray

status: Public on Apr 25 2017

city: Hershey

first: Penn State

last: COM

address: 500 University Drive

department: Genome Sciences Facility

institute: Penn State College of Medicine

summary: Microarray analysis of total RNA extracted from HCT116 cells transduced with control or TCF7L1-targeted shRNA.

overall_design: Total RNA from three biological replicates of each condition was analyzed by microarray to identify differentially expressed transcripts

first: M

last: Eshelman

last: Shah

first: G

middle: S

last: Yochum


title: Identification of the Lgr5+ population in human colorectal samples

summary: Lgr5+ cell population is the stem cell population that fuels intestinal growth in homeostatic conditions. Here, we have labeled with EGFP the Lgr5 expressing population in patient derived organoids, injected them subcutaneously in mice and disaggregated the tumors to sort the EGFP+ population and characterize its gene expression profile. This Lgr5-EGFP population is more proficient in comparison to the negative in propagating tumors both in vitro (assessed by organoid formation) and in vivo (assessed by Tumor initiation experiments)

overall_design: Total RNA was collected from the EGFP+ (Lgr5+) population and EGFP- (Lgr5-) population after FACs sorting

last: Stephan-Otto Attolini

first: Carme

last: Cortina

first: Gemma

last: Turon


title: Genome wide gene expression profile of pancreatic ductal adenocarcinoma (PDAC) cells after knock down of focal adhesion kinase (FAK).

status: Public on Apr 20 2017

city: Baltimore

first: Asma

last: Begum

address: 1650 Orleans street, CRBI Room-230

department: Oncology

institute: Johns Hopkins University

summary: In our experiments, we showed that FAK regulates PDAC clonogenicity and selfrenewal. In order to evaluate the impact of FAK knockdown on the  transcriptomes of PDAC , we knocked down FAK in two PDAC cell lines and compared the gene expression signatures with the cancer stem cell (CSC)associated gene signatures by GSEA analysis. CCS related gene profile was inversely related with FAK-knockdown gene signature.

overall_design: Examination of gene expression pattern in two human PDAC cell lines after knock down of FAK by two distinct shRNAs. Each sample was duplicated. Scrambled hairpin expressing PDAC cells were used as control. Two distinct hairpins against FAK were used to down regulate FAK expression.

last: Matsui

first: Zeshaan

last: Rasheed


title: The effect of cortex/medulla proportions on molecular diagnoses in kidney transplant biopsies: rejection and injury can be assessed in medulla

status: Public on Apr 27 2017

city: Edmonton

first: Jessica

last: Chang

address: 250 Heritage Medical Research Centre

department: Medicine

institute: University of Alberta

summary: Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses.  Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes e.g. NPHS2, NPHS1, CLIC5, PTPRO, PLA2R1, PLCE1, PODXL and REN.  Using NPHS2 (podocin) to estimate proportion cortex, we examined whether proportion cortex influenced molecular assessment in the Molecular Microscope Diagnostic System. In 1190 unselected kidney transplant indication biopsies (Clinicaltrials.govNCT01299168), only 11% had <50% cortex. Molecular scores for ABMR, TCMR,  and injury were independent of proportion cortex. Rejection was diagnosed in many biopsies that were mostly or all medulla.  Agreement in molecular diagnoses in paired cortex/medulla samples (23/26) was similar to biological replicates (32/37). We conclude that NPHS2 expression can estimate proportion cortex; that proportion cortex has little influence on molecular diagnosis of rejection, and that, although histology cannot assess medulla, rejection does occur in medulla as well as cortex.

overall_design: We studied 26 pairs of cortex/medulla biopsies from 26 patients (4 unpaired), characterizing the clinical and histological features, and defined the mRNA phenotype with Affymetrix expression microarrays. We also studied 37 pairs of biopsies from biological replicates and 12 pairs from technical replicates.

first: Katelynn

last: Madill-Thomsen


title: Gene expression in normal human epidermal keratinocytes treated with poly(I:C)

status: Public on Apr 17 2017

first: Luis

middle: Andres

last: Garza

address: 1550 Orleans St. Suite 204 CRBII Koch

department: Dermatology

institute: Johns Hopkins School of Medicine

summary:
In a rare example akin to organogenesis in adult mammals, large wounds in mice lead to de novo morphogenesis of hair follicles. It is still not fully clear what controls this process, known as Wound Induced Hair Neogenesis (WIHN). In other tissues, prostaglandin E2 (PGE2) is an important effector of regeneration and has been shown to stimulate the Wnt/beta-catenin pathway, which in turn is known to control WIHN. Previously, our group has demonstrated that noncoding dsRNA released during wounding is both necessary and sufficient to stimulate WIHN through TLR3. Here, we hypothesize that dsRNA similarly induces the beta-catenin pathway through PGE2. We find that WIHN levels correlate closely to Wnt7b production in vivo, and that dsRNA potently induces Wnt7b in a manner that requires prostaglandin-endoperoxide synthase 2 (Ptgs2). The Ptgs2 inhibitor celecoxib reduces dsRNA-induced WIHN and Wnt7b, and exogenous PGE2 can rescue WIHN and Wnt7b. These results highlight noncoding dsRNA as a novel upstream coordinator of prostaglandin and Wnt levels in regeneration.
We used microarrays to identify the human keratinocyte genes most upregulated or downregulated by poly(I:C)

overall_design: Normal human epidermal keratinocytes were cultured in the presence or absence of poly(I:C) as described below. Total RNA was extracted and sent for microarray analysis.

first: Amadeus

last: Zhu


title: Characterization by gene expression arrays of the human CRC populations according to the Ki67 and Lgr5 expression levels

summary: In normal intestine, Lgr5 are a pool of rapidly dividing stem cells that gives rise to the whole intestinal crypts. Here we have labelled both Lgr5 and Ki67 genes with fluorescent markers by means of CRISPR/Cas9 in human patient derived organoids (PDO).

overall_design: Total RNA was collected from Lgr+Ki67+, Lgr5+Ki67-, Lgr5-Ki67+ and Lgr5-Ki67- populations sorted by FACS


title: Posttranslationally modified progesterone receptors direct ligand-specific expression of breast cancer stem cell-associated gene programs

status: Public on Apr 10 2017

city: Minneapolis

first: Todd

last: Knutson

state: MN

address: 117 Pleasant St SE

department: Minnesota Supercomputing Institute

institute: University of Minnesota

summary:
Background
Estrogen and progesterone are potent breast mitogens. In addition to steroid hormones, multiple signaling pathways input to estrogen receptor (ER) and progesterone receptor (PR) actions via posttranslational events. Protein kinases commonly activated in breast cancers phosphorylate steroid hormone receptors (SRs) and profoundly impact their activities.
Methods
To better understand the role of modified PRs in breast cancer, we measured total and phospho-Ser294 PRs in 209 human breast tumors represented on 2754 individual tissue spots within a tissue microarray and assayed the regulation of this site in human tumor explants cultured ex vivo. To complement this analysis, we assayed PR target gene regulation in T47D luminal breast cancer models following treatment with progestin (promegestone; R5020) and antiprogestins (mifepristone, onapristone, or aglepristone) in conditions under which the receptor is regulated by Lys388 SUMOylation (K388 intact) or is SUMO-deficient (via K388R mutation to mimic persistent Ser294 phosphorylation). Selected phospho-PR-driven target genes were validated by qRT-PCR and following RUNX2 shRNA knockdown in breast cancer cell lines. Primary and secondary mammosphere assays were performed to implicate phospho-Ser294 PRs, epidermal growth factor signaling, and RUNX2 in breast cancer stem cell biology.
Results
Phospho-Ser294 PR species were abundant in a majority (54%) of luminal breast tumors, and PR promoter selectivity was exquisitely sensitive to posttranslational modifications. Phospho-PR expression and target gene programs were significantly associated with invasive lobular carcinoma (ILC). Consistent with our finding that activated phospho-PRs undergo rapid ligand-dependent turnover, unique phospho-PR gene signatures were most prevalent in breast tumors clinically designated as PR-low to PR-null (luminal B) and included gene sets associated with cancer stem cell biology (HER2, PAX2, AHR, AR, RUNX). Validation studies demonstrated a requirement for RUNX2 in the regulation of selected phospho-PR target genes (SLC37A2). In vitro mammosphere formation assays support a role for phospho-Ser294-PRs via growth factor (EGF) signaling as well as RUNX2 as potent drivers of breast cancer stem cell fate.
Conclusions
We conclude that PR Ser294 phosphorylation is a common event in breast cancer progression that is required to maintain breast cancer stem cell fate, in part via cooperation with growth factor-initiated signaling pathways and key phospho-PR target genes including SLC37A2 and RUNX2. Clinical measurement of phosphorylated PRs should be considered a useful marker of breast tumor stem cell potential. Alternatively, unique phospho-PR target gene sets may provide useful tools with which to identify patients likely to respond to selective PR modulators that block PR Ser294 phosphorylation as part of rational combination (i.e., with antiestrogens) endocrine therapies designed to durably block breast cancer recurrence.

overall_design: The study contains 3 different cell lines (PR-null, PRB-wildtype, PRB-K388R) tested with 8 different treatments in triplicate (8 x 3 x 3 = 72 individual samples). We also included 12 previously published samples (GSE34148) with the same treatments, which increased our total number of samples to 84. From parental T47D-Y (PR-null) human breast cancer cell lines, we created stable clones expressing either (1) an empty vector (pIRESneo3) or (2) the wild type progesterone receptor isoform B (pIRESneo3-PR-B), or (3) pIRESneo3-PR-B-K388R. These three cell lines were co-treated with either (1) vehicle control (ethanol) or (2) progesterone/R5020 10e-8 M, (3) RU486 10e-7 M, (4) onapristone 10e-7 M, (5) aglepristone 10e-7 M, (6) progesterone plus RU486, (7) progesterone plus onapristone, or (8) progesterone plus aglepristone. Treatments were for 6 hours before total RNA harvest. Standard Illumina HT-12v4 chip was used for gene expression analysis.

first: Carol

last: Lange


title: The plant alkaloid chelerythrine binds to chromatin, alters H3K9Ac and modulates global gene expression

city: Bangalore

first: madavan

last: vasudevan

state: Karnataka

address: Kasturi Nagar

country: India

institute: Theomics International Private Limited

summary: Chelerythrine (CHL), a plant alkaloid, possesses antimicrobial, anti-inflammatory and antitumor properties. Although CHL influences several key signal transduction pathways, its ability to interact directly with nucleoprotein complex chromatin, in eukaryotic cells has so far not been looked into. Here we have demonstrated its association with hierarchically assembled chromatin components viz. long chromatin, chromatosome, nucleosome, chromosomal DNA and histone H3 and the consequent effect on chromatin structure. CHL was found to repress acetylation at H3K9. It is more target-specific in terms of gene expression alteration and less cytotoxic compared to its structural analogue sanguinarine.

overall_design: Total RNA was extracted from untreated and CHL treated (10 µM for 6 hours) HeLa cells by Trizol method followed by clean-up and DNase I treatment with QIAGEN RNeasy mini kit (Qiagen). RNA samples in triplicates from different passages before and after treatment using CHL were processed for microarray analysis using Illumina Human HT12 V4 whole genome gene expression profiling platform. Raw data was Quantile normalized and baseline transformation was done to median of all samples using GeneSpring GX 12.5 software (Agilent Technologies Inc, Santa Clara, USA). Differentially expressed probe sets (Genes) upon treatment in comparison to untreated cells were identified by applying Student t-test with a fold-change threshold  of absolute fold-change ≥ 1.1 and a statistically significant t test P value threshold adjusted for false discovery rate < 0.001. Statistically significantly enriched transcripts with a P value adjusted for false discovery rate < 0.05 derived using the hypergeometric distribution test corresponding to differentially expressed genes were determined using student t-test with Benjamini Hocheberg FDR test.

first: Amrita

last: Banerjee

first: Sulagna

last: Sanyal

first: Payal

last: Chakraborty

first: Madavan

last: Vasudevan

first: Chandrima

last: Das

first: Dipak

last: Dasgupta


title: Secretagogin is expressed by developing neocortical GABAergic neurons in humans but not mice and increases neurite arbor size and complexity

city: San Francisco

first: Chandrasekhar

last: Raju

address: 1450 3rd Street

department: Neurosurgery

institute: UCSF

summary: Analysis of gene expression over serial 150um sections of a single gestational week 18 human neocortical specimen. The hypothesis tested with this dataset was that a transcriptional signature of GABAergic neurons could be isolated via unsupervised gene coexpression analysis due to variation in the abundance of this cell type from section to section. This dataset is the second of its kind generated using this method (Gene Coexpression Analysis of Serial Sections, or GCASS).

overall_design: Total RNA obtained from serial sections of a single GW18 human neocortical specimen.


title: ZBTB18 is a repressor of mesenchymal genes in Glioblastoma [JX6]

status: Public on Apr 04 2017

city: Freiburg

first: Maria Stella

last: Carro

address: Breisacherstraße 64

country: Germany

institute: Freiburg University Medical Center

summary: The transcriptional repressor ZBTB18 was overexpressed in the brain tumor xenoline JX6 by lentiviral transduction. Three independent transduction were performed (biological replicates) and analyzed by gene expression aray. Gene set enrichemnt analysis (GSEA) showed changes in the expression of mesenchymal signature. A subset of genes was further valiadted by qPCR. These results indicate a role of ZBTB18 as repressor of mesenchymal genes in Glioblastoma.

overall_design: Total RNA extracted from JX6 transduced with pCHMWS-EGFP-FLAG ZBTB18 lentiviral vector (three biological replicates).

first: V

last: Fedele

first: A

last: Masilamani

first: M


title: ZBTB18 is a repressor of mesenchymal genes in Glioblastoma


title: Genome-wide analysis of rapamycin effect on the glucocorticoid receptor function in human keratinocytes

status: Public on Apr 01 2017

city: Tempe

first: Ben

last: Readhead

state: AZ

address: 797 E. Tyler Street

institute: ASU-Banner Neurodegenerative Disease Research Center

summary: Rapamycin increased negative effect of glucocorticoid fluocinolone acetonide (FA) on gene expression and blunted gene activation by glucocorticoid FA.

overall_design: HaCat cells grown in DMEM supplemented with 10 % Fetal Bovine Serum and 1 X Pen/Strep a day prior to the experiemnt were either pre-treated with 1 μM Rapamycin for 6 h followed by 1 μM of FA for additional 24 h (IB4 and IB8) or were treated with 1 μM of FA alone for 24 h (IB2 and IB6). Control cells used for comparison were either treated with DMSO (vehicle control. IB1 and IB5) or 1 μM of Rapamycin (IB3 and IB7). The experiments were performed in duplicates.

first: Irina

last: Budunova

first: Shivani

last: Agarwal


title: ZBTB18 is a repressor of mesenchymal genes in Glioblastoma [BTSC233]

summary: The transcriptional repressor ZBTB18 was overexpressed in the brain tumor stem cell-like BTSC233 by lentiviral transduction. Three independent transduction were performed (biological replicates) and analyzed by gene expression aray. Gene set enrichemnt analysis (GSEA) showed changes in the expression of mesenchymal signature. A subset of genes was further valiadted by qPCR. These results indicate a role of ZBTB18 as repressor of mesenchymal genes in Glioblastoma.

overall_design: Total RNA extracted from BTSC233 transduced with pCHMWS-EGFP-FLAG ZBTB18 lentiviral vector (three biological replicates).


title: Transcriptome analysis of human T-cell Jurkat cell line in resting cells (t0) and at 8h, 24h and 48h post-activation using Raji B-cells conjugated with superantigen (SEE)

status: Public on Apr 12 2017

city: Edinburgh

first: Jose

middle: Ignacio

last: de las Heras

address: Max Born Crescent

department: Wellcome Trust Centre

country: United Kingdom

institute: University of Edinburgh

summary: Activation of T-cells induces dramatic changes in genome organisation and gene transcription. Here we identify changes in transcriptional profiles at 8h, 24h and 48 post activation

overall_design: Total RNA was isolated from resting and activated Jurkat cells at three separate time points

first: Michael

middle: I

last: Robson

first: Eric

last: Schirmer


title: Gene-expression analysis of iEEC16 endometriosis cells with ARID1A KD

status: Public on Mar 31 2017

city: Los Angeles

first: Ranjani

last: Lakshminarasimhan

state: California

address: 1441 Eastlake ave NOR7336

department: Urology

institute: University of Southern California

summary: Down-regulation of ARID1A in endometriosis cells leads to gene expression alterations.

overall_design: Total RNA obtained from iEEC16 cells transfected with shSCR (SCR) or shARID1A (KD1 and KD2).

first: Claudia

last: Andreu-Vieyra

first: Kate

last: Lawrenson

first: Chris

middle: E

last: Duymich

first: Simon

last: Gayther

first: Gangning

last: Liang

first: Peter

last: Jones


title: Expression data of GFP-high or low cells of LGR5-GFP or KRT20-GFP knock-in human colorectal tumor organoids.

status: Public on Mar 30 2017

city: Tokyo

first: Mariko

last: Shimokawa

address: 35, Shinanomachi, Shinjuku-Ku

country: Japan

institute: Keio University

summary:
We analyzed gene expression of 3 lines LGR5-GFP, 2 lines KRT20-GFP knock-in colorectal tumor organdies.
The cancer stem cell (CSC) theory highlights a self-renewing subpopulation of cancer cells that fuels tumour growth. The existence of human CSCs is mainly supported by xenotransplantation of prospectively isolated cells, but their clonal dynamics and plasticity remain unclear. Here, we show that human LGR5+ colorectal cancer cells serve as CSCs in growing cancer tissues. Lineage-tracing experiments with a tamoxifen inducible Cre knock-in allele of LGR5 reveal the self-renewal and differentiation capacity of LGR5+ tumour cells. Selective ablation of LGR5+ CSCs in LGR5-iCaspase9 knock-in organoids leads to tumour regression, followed by tumour regrowth driven by re-emerging LGR5+ CSCs. KRT20 knock-in reporter marks differentiated cancer cells that constantly diminish in tumour tissues, while reverting to LGR5+ CSCs and contributing to tumour regrowth after LGR5+ CSC ablation. We also show that combined chemotherapy potentiates LGR5+ CSCs targeting. These data provide insights into the plasticity of CSCs and their potential as a therapeutic target in human colorectal cancer.

overall_design: mRNA from EGFP-sorted cells of 5 cultured knock-in organoids were extracted and hybridized to GeneChip PrimeView Human Gene Expression Array, and scanned using GeneChip Scanner 3000 7G.

first: Yuki

last: Ohta


title: IMM_Cleveland LiXX_EAE-Th1 or Th17_Act1 ko mouse_CNS_exp1

status: Public on Mar 28 2017

city: Atlanta

first: Hanjoong

last: Jo

state: GA

address: 1760 Haygood Drive, Health Sciences Research Bldg E170

department: Coulter Department of Biomedical Engineering

institute: Georgia Tech and Emory Univ

overall_design: The goal of these studies is to define the molecular signatures of TH1-induced EAE and TH17-induced EAE through adoptive transfer. We will also define the role of IL-17 signaling in the pathology by comparing cells derived from wild type mice to those derived from mice lacking Act1, a key adaptor required for IL-17 dependent signaling. Brains and spinal cords from animals at peak of disease will be profiled. There are 24 mouse spinal cord samples with key attributes: Th1, Th17, or Unchallenged; wild type or Act1 ko.

first: Carman

last: Julie


title: Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma [Huh7]

status: Public on Mar 19 2017

city: Seoul

first: Jae-Kyung

last: Won

address: 101 Daehak-ro

institute: Seoul National University Hospital

summary: Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients’ survival gain is limited and varies over a wide range depending on patho-genetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucuial to achieve efficient control of HCCs. In this study, we employed a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene ontology and gene set analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum (ER) stress network model combined with in vitro experiments showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low PDI expression group. These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness.

overall_design: Total RNA was extracted from cultured cells and subjected to RT-PCR analysis. HCC cell lines (SNU761, Huh7, Hep3B and HepG2) were treated with sorafenib 3 mM for 24 hours, while the control group was treated with only DMSO.

first: Su

last: Yu

first: Chae

middle: Y

last: Hwang

first: Jung-Hwan

last: Yoon

first: Kwang-Hyun

last: Cho


title: Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma [Hep3B]


title: Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma

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

overall_design: Refer to individual Series


title: Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma [HepG2]


title: Gene expression by basic transcription factor 3 (BTF3）knocked out in HCT116

status: Public on Mar 18 2017

city: Changsha

first: Qi

last: Liu

address: Western Jiefang Road 61#

institute: First Affiliated Hospital of Hunan Normal University

summary: The aim of this research was to confirm the regulatory effect of basic transcription factor 3 (BTF3) on gene expression in the development of rectal cancer.

overall_design: In this research, there were six samples examed including 3 samples of negtive control cells (NC) and 3 samples of BTF3 knocked out cells (KD).

first: Tai-Liang

last: Lu

first: Zhong-Cheng

last: Huang

first: Zhi-Xue

last: Fang

first: Li

last: Yang

first: Hong-Yu

last: Dong

first: Wei-Lin

last: Zhang

first: Xing

first: Meng-Qian

last: Li

first: Xu-Yang

last: Hou

first: Yi-Jia

last: Yi


title: Tamoxifen response and resistance in invasive lobular breast cancer

status: Public on Mar 16 2017

city: Washington

first: Rebecca

middle: B.

last: Riggins

state: DC

address: E412 Research Building, 3970 Reservoir Rd. NW

department: Oncology, and Lombardi Comprehensive Cancer Center

institute: Georgetown University


title: Host transcription profile in nasal epithelium and blood of hospitalized children under two years old with Respiratory Syncitial Virus infection

status: Public on Apr 14 2017

city: Ho Chi Minh City

first: Lien Anh Ha

last: Do

address: 764 Vo Van Kiet, Ward 1, District 5

country: Viet Nam

institute: Oxford University Clinical Research Unit, Vietnam


title: Absence of integrin α3 modulates the integrin landscape of human keratinocytes

city: Lübeck

first: Hauke

last: Busch

state: Schleswig-Holstein

address: Ratzeburger Allee 160

department: Lübeck Institute of Experimental Dermatology

institute: University of Lübeck

summary: Integrins are among the most abundant cell surface receptors constituting the principal adhesion receptors for the extracellular matrix (ECM), providing a physical anchor for the cell and triggering multiple intracellular signalling events. Loss-of function mutations of the integrin α3 gene (ITGA3) have been recently disclosed in patients with interstitial lung disease, congenital nephrotic syndrome and junctional epidermolysis bullosa, a multiorgan disorder with fatal outcome. In these patients, the respiratory function is strongly impaired and the kidneys are variably affected, whereas skin fragility is rather mild, has a delayed onset after birth or remains unrecognized, suggesting that integrin α3 differently influences the development and homeostasis of these organs. Here we employed authentic human keratinocytes bearing a naturally occurring integrin α3 loss-of-function mutation as a prototype to characterize the molecular mechanisms launched by the constitutional absence of this integrin subunit. To validate our findings, we generated new cellular models, including an additional ILNEB patient cell line, ITGA3 rescued and knockdown cells. We show that keratinocytes lacking a functional α3 subunit have an activated cellular phenotype with a switch in the pattern of integrin α subunits on the cell surface. These assure spreading and adhesion of epidermal keratinocytes but also drive the migratory phenotype of these cells.

overall_design: Cell lines were derived in triplicate from primary keratinocytes of a patient with an ITGA3 loss-of-function homozygous mutation and an age and sex matched healthy donor (designated as control, A3- and Co, respectively) by immortalization with the E6E7 genes of the HPV. Normal human keratinocytes (NHK) were obtained from a healthy donor.

first: Melanie

last: Boerries

first: Cristina

last: Has

first: Chiara

last: Pazzagli

first: Yinghong

last: He

first: Leena

last: Bruckner-Tuderman


title: Microarray analysis of CD9high and CD9low progenitors isolated from omental adipose tissue of morbid obese individuals

city: paris

first: veronique

last: PELLOUX

address: 50-52 bld Vincent Auriol

department: UMR 1166 eq 6

country: France

institute: INSERM

summary: Obesity-induced white adipose tissue (WAT) fibrosis is believed to accelerate WAT dysfunction. Two progenitor populations could be distinguished in omental white adipose tissue (oWAT) of morbidly obese individuals based on CD9 expression. In addition, the frequency of CD9high progenitors in oWAT correlates with oWAT fibrosis level, insulin-resistance severity and type 2 diabetes. To further gain insight into the functional differences between the CD9high and CD9low progenitor subsets, we performed transcriptomic profiling of FACS-sorted progenitor populations isolated from oWAT of obese individuals. As CD9low progenitors were markedly decreased in glucose-intolerant or diabetic individuals, we investigated seven women with morbid obesity but without diabetes or glucose intolerance, according to the ADA definition.

overall_design: Omental adipose tissue from 7 obese women with mean BMI of 42.9±1.7kg/m2 and mean age of 40.7±3.3 year-old was digested with collagenase. CD9high and CD9low progenitors from the stromal vascular fraction were FACS-sorted with CD45- CD31- CD34+ CD44+ PDGFRa+ CD9high and CD45- CD31- CD34+ CD44+ PDGFRa+ CD9low. Total RNA was amplified and labeled using Ovation Pico WTA System V2 (NuGEN) and Encore BiotinIL Module (NuGEN) kits according to the manufacturer's protocol.

first: Genevieve

last: Marcelin

first: Veronique

last: Pelloux

first: Karine

last: Clement


title: Microarray expression profiling of mRNAs using RNA extracted from miR-151a-overexpressing and miR-NC overexpressing U87 glioma cells.

status: Public on Mar 15 2017

city: Nanjing

first: zeng

middle: ai

last: liang

address: No.300, Guangzhou Road

department: Department of Neurosurgery

institute: The First Affiliated Hospital of Nanjing Medical University

summary: Using microarray technology, we aimed to produce a list of genes that are downregulated in miR-151a-overexpressing U87 glioma cells in comparison with these overexpressing miR-NC.

overall_design: Microarray expression profiling of mRNAs  were conducted using RNA extracted from miR-151a-overexpressing and miR-NC overexpressing U87 glioma cells.

first: Ailiang

last: Zeng

first: Wei

last: Yan

first: Qi

last: Hu

first: Er

last: Nie

first: Xu

last: Zhou

first: Rui

first: Xin

last: Jin

first: Feng

last: Shen

first: Weining

last: Wu

first: Xiefeng

last: Wang

first: Yongping

last: You


title: Genome-wide analysis of differential gene expression in MDA-MB-231 cells after overnight treatment with riluzole

city: Detroit

first: David

last: Gorski

state: MI

address: 840.2 HWCRC

department: Surgery

institute: Wayne State University School of Medicine

summary: MDA-MB-231 cells were used to determine genes differentially regulated by riluzole, a drug currently used to treat ALS patients

overall_design: The triple-negative breast cancer cell line, MDA-MB-231, was treated overnight with riluzole (25 uM)  or vehicle (DMSO) and genes differentially expressed were determined

first: Cecilia

last: Speyer


title: Global expression data  from HCT-8 human colorectal cancer (CRC) wild type cells (HCT8/WT) and its 5-FU-induced resistant cell line (HCT8/5-FU)

city: FuZhou

first: Guo

last: Zheng

state: FuJian

address: No.1 Xue Yuan Road

department: Department of Bioinformatics

institute: Fujian Medical University

summary:
Complete growth medium RPMI-1640 which contains 10% FCS, 1% Penicillin-Streptomycin Solution was used for cell culture.
Both cell lines were maintained at 37 °C in a humidified atmosphere containing 5% CO2. MTT assay was performed to determine the 5 ‑ FU resistance in both of HCT-8/WT and HCT-8/5-FU cell line.

overall_design: CRC wild type cell (HCT8/WT) and its 5-FU-induced resistant cell line (HCT8/5-FU) , both of which were treated with 5-fluorouracil (5-FU) for 0, 24 and 48 hours, respectively. Three biological replicates of each condition were used for the microarray experiment.

first: Zheng

last: Guo


title: miRNA Signatures indicate Acute Liver Failure in hepatitis E infected pregnant females

city: Bangalore

first: madavan

last: vasudevan

address: Kasturi Nagar

institute: Theomics International Private Limited

summary: Whole genome gene expression profiling and miRNA profiling of Hepatitis E infected pregnant females

overall_design: Illumina based genome wide expression profiling and miRNA profiling was done to identify key genes and miRNAs that could be used as biomarkers for prognosis

first: N

last: Trehanpati

first: V

last: Madavan


title: Microarray analysis of the lncRNAs expression profile in human apheresis platelets during storage

city: Guangzhou

last: Li

state: Guangdong

address: Panfu Road No1

department: Blood transfusion Department

institute: Guangzhou First People's Hospital

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

summary: To investigate the long noncoding RNA (lncRNA) expression profiles in human apheresis platelet during the storage, and predict the potential biological function of lncRNAs in the process of platelet storage lesion. LncRNAs profiles of platelets were tested by Agilent Human lncRNA Array at 2nd, 5th, and 8th day during storage. Seven lncRNAs and four mRNAs were chosen to validate by real-time PCR, the result was consistent with the microarray. Bioinformatics method was applied to predict the function of lncRNAs.

overall_design: Platelet samples were collected from 13 male healthy donors with O blood group.Apheresis platelets were stored at 22±2 ℃ in storage tank and 10 ml sample were collected at 2 day, 5 day, 8 day. Three groups in these samples were used for microarray analysis and the other ten groups were used for qPCR.

first: Yaming

last: Wei


title: Inter-individual variation in genes governing human hippocampal progenitor differentiation is associated with hippocampal volume in adulthood

status: Public on Mar 08 2017

city: London

first: Timothy

last: Powell

address: 16 De Crespigny Park

department: Social, Genetic & Developmental Psychiatry

institute: King's College London

summary: The aim of this study was to investigate the effects of the antidepressants, escitalopram (0 nM, 145 nM, 290 nM, 1160 nM) and nortriptyline (0 nM, 267 nM, 534 nM, 1068 nM), in human hippocampal progenitor cells (HPC0A07/03C), either when proliferating or differentiating. We also considered expression changes occuring when proliferating cells switch to a differentiating state to form young neurons and astrocytes.

overall_design: We assessed the genome-wide expression effects of neural stem cell differentiation. We compared 48 proliferating cell populations of the human hippocampal cell line with 48 cell populations after a 7-day differentiation protocol (1 sample dropped). We performed this analyses using data originally collected to compare the effects of antidepressants on proliferating/differentiating hippocampal progenitor cells; we regressed out the effects of antidepressant drug and dose, biological replicate and array batch in our analyses.

middle: R

first: Tytus

last: Murphy

first: Sang

last: Lee

first: Rodrigo

last: Duarte

first: Hyun

first: Demelza

last: Smeeth

first: Jack

last: Price

first: Gerome

last: Breen

first: Sandrine

last: Thuret


title: Genome-wide analysis of HN-5 cells exposed to the alkylphosphocholine erufosine

city: Heidelberg

first: Shariq

last: Ansari

address: Im Neuenheimer Feld 581

institute: DKFZ

summary: Analysis of gene modulation occurring in OSCC cell line, HN-5, post erufosine exposure was investigated. A dose- and time-dependent change in gene profile was analyzed post 16h, 24h and 48h of erufosine exposure at IC25, IC50 and IC75 concentrations when compared to untreated controls. Results provide important information of the cellular functions modulated by erufosine in OSCC cell lines and gives insight to its mechanism of action at the gene level.

overall_design: Total RNA from HN-5 cell line was obtained after 16h, 24h and 48h post treatment of erufosine at a concentration corresponding to IC25, IC50 and IC75. Change in modulation was compared respective the untreated controls.

first: Martin

last: Berger


title: Gene expression profiles of MV-4-11 AML cells treated HDAC1/2 -selective inhibitor and Azacitidine

city: Boston

first: Jeff

last: Shearstone

state: MA

address: 70 Fargo Street

department: Biology

institute: Acetylon Pharmaceuticals

summary:
Determine the differences in gene expression profiles of MV-4-11 AML cells treated with HDAC1/2-selective inhibition, azacitidine, or the combination of the two agents.
Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in myeloid differentiation and increased proliferation of neoplastic hematopoietic precursor cells. Outcomes for patients with AML remain poor, highlighting the need for novel treatment options. Aberrant epigenetic regulation plays an important role in the pathogenesis of AML, and inhibitors of DNA methyltransferase or histone deacetylase (HDAC) enzymes have exhibited activity in preclinical AML models. Combination studies with HDAC inhibitors plus DNA methyltransferase inhibitors have suggested beneficial clinical activity in AML, however the toxicity profiles of non-selective HDAC inhibitors in the combination setting limit their clinical utility. In this work, we describe the preclinical development of selective inhibitors of HDAC1 and HDAC2, which are hypothesized to have improved safety profiles, for combination therapy in AML. We demonstrate that selective inhibition of HDAC1 and HDAC2 is sufficient to achieve efficacy both as a single agent and in combination with azacitidine in preclinical models of AML, including established AML cell lines, leukemia cells from AML patient bone marrow samples and in vivo xenograft models of human AML. Gene expression profiling of AML cells treated with either an HDAC1/2 inhibitor, azacitidine, or the combination of both have identified a list of genes involved in transcription and cell cycle regulation as potential mediators of the combinatorial effects of HDAC1/2 inhibition with azacitidine. Together, these findings support the clinical evaluation of selective HDAC1/2 inhibitors in combination with azacitidine in AML patients.

overall_design: MV-4-11 AML cells were treated with either azacitidine, the selecitve HDAC1/2 inhibitor ACY-1035, or simulitaneously with both inhibitors for 48 hours. One sample from each treatment group was analyzed.

first: Chengyin

last: Min

first: Nathan

last: Moore

first: Jeffrey


title: Transcriptional profiling of diabetic peripheral neuropathy patients, diabetic patients, and healthy participants

status: Public on Mar 09 2017

city: Ningbo

first: Jin

last: Xu

address: 818 Fenghua Road

institute: Ningbo University

summary: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients, because its pathogenesis remains controversial. In this study, using microarray-based genome-wide expression analyses, we sought to identify both common and distinct mechanisms underlying the pathogenesis of DM and DPN. The results demonstrated that down-regulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.

overall_design: 6 DPN, 6 DM, and 6 CN

first: L

last: Luo

first: J


title: Effect of CCAR2 depletion on the gene expression profile of BJ-hTERT and U2OS cells

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

country: Italy

institute: IRCSS Istituto Nazionale Tumori


title: Effect of CCAR2 depletion on the gene expression profile of U2OS cells

summary: CCAR2 is a nuclear protein recently emerged as a pivotal player of the DNA damage response since it has been found involved in both apoptosis induction and DNA repair. Differently, its role in tumorigenesis and cancer progression is still elusive. In our studies we found that CCAR2 depletion impairs the proliferation of human cancer cell lines, but leaves unaffected the growth of normal immortalized cells. To better investigate this point we performed a genome wide gene expression analyses in U2OS and BJ-hTERT depleted of CCAR2 and we found that loss of this protein causes the deregulation of genes implicated in the AKT pathway specifically in U2OS cells, but not in BJ-hTERT. In accordance with these results we found a reduction in AKT activation in all the tested cancer cell lines depleted of CCAR2, but not in the normal ones. The defective activation of AKT is caused by the upregulation of TRB3 gene in cancer cells depleted of CCAR2 and finally results in the reduction of GSK3β phosphorylation, prevention of G1/S transition and inhibition of cancer cell growth.

overall_design: The human osteosarcoma cell line U2OS was cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% of fetal calf serum. Cells were transfected with control or a pool of 4 specific RIBOXX siRNAs against CCAR2 using RNAiMAX (Thermo Fisher) according to manufacturer proteocols. 6 days after transfection cells were harvested in QIAzol (Qiagen) and the extracted RNA was used for gene expression analyses. Samples were prepared in indipendent triplicates.

first: Laura

last: Zannini


title: Gene expression profiles of mouse embryonic mesenchymal cells expressing ASPSCR1-TFE3

status: Public on Mar 07 2017

city: Tokyo

first: Takuro

last: Nakamura

address: 3-8-31 Ariake, Koto-ku

department: The Cancer Institute

institute: Japanese Foundation for Cancer Research

summary:
Alveolar soft part sarcoma (ASPS) is a slowly growing but highly metastatic sarcoma that affects adolescents and young adults. Its characteristic alveolar structure is constituted by tumor cell nests and abundant vascular network that is responsible for metastatic activities at the initial stage. Here we have generated a new ex vivo mouse model for ASPS that well recapitulates angiogenic and metastatic phenotypes. In mouse ASPS the tumor cells frequently show tumor intravasation, and the intravascular tumor cells were present as organoid structures covered with hemangiopericytes, which is also the case in human ASPS. High expression of GPNMB, a transcriptional target of ASPSCR1-TFE3, was observed at the intravasation. ASPS tumor cells showed the enhanced activity of transendothelial migration and the activity was inhibited by silencing of Gpnmb, indicating that GPNMB plays an important role in tumor intravasation, one of key steps in cancer metastasis. The present model also enabled to evaluate the function of TFE/MITF family transcription factors, and ASPSCR1-TFEB also possessed definitive but less oncogenic activity than that of ASPSCR1-TFE3. Collectively, our new mouse model is a useful tool to understand oncogenic, angiogenic and metastatic mechanisms of ASPS, to identify important motif within the ASPSCR1-TFE3 fusion protein and to provide a novel therapeutic strategy.
We used microarrays to detail the global programme of gene expression by introduction of ASPSCR1-TFE3 into mouse embryonic mesenchymal cells.

overall_design: Murine embryonic mesenchymal cells were transduced with the ASPSCR1-TFE3 retrovirus or empty retrovirus and gene expression profiles were compared 48 hours after transduction.

first: Miwa

last: Tanaka


title: Effect of CCAR2 depletion on the gene expression profile of BJ-hTERT cells

overall_design: The human normal fibroblast cell line BJ-hTERT was cultured in Dulbecco's Modified Eagle Medium (DMEM)/Medium 199 (4:1) supplemented with 10% of fetal calf serum and 10µg/ml hygromycin B as selection for hTERT transgene. To obtain a population of CCAR2-knock-out (KO) cells we used the CRISPR/Cas9 system as described in Magni et al, Oncotarget 2015. Cells were transfected with the Amaxa Nucleofector Device using the Basic Fibroblast Kit (VPI-1002) and U23 program. A population of 40% cells negative for CCAR2 was initially obtained. Then, after a second round of transfection, a mass culture with the 80% of cells KO for CCAR2  was produced. These cells were then collected in triplicates for RNA extraction and gene expression analyses.


title: Expression data from CD4-CD8-(DN) thymic cells isolated from WT, Ezh2Δ/Δ, p53Δ/Δ, and Ezh2Δ/Δp53Δ/Δ mice

status: Public on Mar 04 2017

city: Kumamoto

first: Goro

last: Sashida

state: Kumamoto

address: 2-2-1 Honjo, Chuo-ku

department: IRCMS

institute: Kumamoto University

summary: Loss-of-function mutations in EZH2 are associated with poor outcomes in patients with early T cell precursor ALL (ETP-ALL).  To understand how EZH2 insufficiency is involved in the pathogenesis of ETP-ALL, we generated mice compound for both Ezh2 and Trp53 conditional deletions.

overall_design: The total bone marrow cells isolated from Cre-ERT2, Ezh2flox/flox;Cre-ERT2, p53flox/flox;Cre-ERT2 and Ezh2flox/flox;p53flox/flox;Cre-ERT2 mice were transplanted into lethally irradiated CD45.1+ wild-type recipient mice. As we deleted Ezh2 and/or p53 at four weeks post transplantation, we performed gene-expression analysis of CD4-CD8-CD44+CD25-(DN1), CD4-CD8-CD44+CD25+(DN2), and CD4-CD8-CD44-CD25+(DN3) cells isolated from the thymus of recipient mice at 3 months post transplantation and CD4-CD8-CD44+CD25+(DN2) leukemic cells isolated from two Ezh2Δ/Δp53Δ/Δ ETP-ALL mice (mouse id; 13 and 19).

first: Atsushi

last: Iwama


title: Gene expression profiles of the mouse model for alveolar soft part sarcoma

overall_design: Refer to individual Series


title: Acriflavine inhibits the epithelial-to-mesenchymal transition in vitro in liver and pancreatic cancer cells (part of study with TGF-b1 stimulation)

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary: Background: Epithelial-to-mesenchymal transition (EMT) is considered an important driving mechanism behind aggressive cancer phenotype. This was recently challenged by the finding that cells can metastasize without undergoing EMT. However, the same studies confirmed the important role of the EMT program in drug resistance. The EMT program is largely dependent on the cell’s microenvironment. Acriflavine (ACF) is a heteroaromatic dye with antibacterial and antiviral effects. Recently, ACF was suggested as anticancer agent for its topoisomerase inhibitor activity. ACF further blocks the hypoxia-inducible factor (HIF) pathway, an important driver of cancer aggressiveness. How ACF works in cancer is however unknown. Aim: Identification of the working mechanism, molecular pathways and signaling of ACF in EMT cancer cells. To this end,  three in vitro models were developed of EMT induction (human pancreatic cancer cells stimulated with TGF-b1, human pancreatic cancer cells stimulated with CoCl2, drug resistance against sorafenib in human liver cancer cells). Only the first model - PANC1 stimulated with TGF-b1 - is discussed in this GEO submission.

overall_design: Five conditions were investigated: (1) untreated PANC1 cells (= controls), (2) PANC1 cells treated with TGFb1, (3) PANC1 cells treated with TGFb1 and ACF, (3) PANC1 cells treated with TGFb1 and Valproate, (5) PANC1 cells treated with ACF only. For each condition three biological replicates were profiled. For the control and the TGFb1 condition, a fourth biological replicate was profiled as well.

first: Jeroen

last: Dekervel

first: Ashenafi

last: Bulle

first: Petra

last: Windmolders

first: Diether

last: Lambrechts

first: Eric

last: Van Cutsem

first: Chris

last: Verslype

first: Jos

last: van Pelt


title: Gene expression in 501mel melanoma cells treated with Salubrinal.

status: Public on Mar 01 2017

city: Oxford

first: Colin

last: Goding

address: ORCRB

institute: LICR, University of Oxford

summary: The primary cause of cancer deaths is metastasis. While studies have identified multiple signals that drive invasiveness, the first step in metastatic colonisation, the reason for cells to move away from the primary tumor is less well understood. Salubrinal inhibits an eIF2-alpha phosphatase and consequently leads to increase eIF2-alpha phosphorylation and inhibition of the eIF2B translation initiation factor, leading to reprogramming of translation. The dataset presented examines the effect of Salubrinal on gene expression over time in the 501mel melanoma cell line compared to control DMSO treated cells. The results were used to generate a gene expression signature that correlates with invasiveness, and the ‘Innate Anti-PD-1 therapy resistance signature'.

overall_design: Total RNA was extracted in triplicate from untreated 501mel cells or collected 12, 24, 48 or 72 hours after treatment with Salubrinal (20 mM).

first: Paola

last: Faletta

first: Luis

last: Sánchez-Del-Campo

first: Jagat

last: Chauhan

first: Robert

last: Siddaway


title: Gene expression in IGR37 melanoma cells grown in DMEM or after transfer to MEM

summary: The primary cause of cancer deaths is metastasis. While studies have identified multiple signals that drive invasiveness, the first step in metastatic colonization, the reason for cells to move away from the primary tumor is less well understood. The dataset presented here examines the effect of different culture conditions on gene expression by comparing expression of a melanoma cell line in nutrient rich DMEM to MEM. The results were used to generate a gene expression signature that correlates in human melanomas to dedifferentiation, invasiveness and drug resistance.

overall_design: Total RNA was extracted in triplicate from IGR37 cells (4 samples) grown in DMEM or transferred to MEM for different times.


title: Gene expression profiles  of mouse alveolar soft part sarcoma

first: Takuro

last: Nakamura

summary:
Alveolar soft part sarcoma (ASPS) is a slowly growing but highly metastatic sarcoma that affects adolescents and young adults. Its characteristic alveolar structure is constituted by tumor cell nests and abundant vascular network that is responsible for metastatic activities at the initial stage. Here we have generated a new ex vivo mouse model for ASPS that well recapitulates angiogenic and metastatic phenotypes. In mouse ASPS the tumor cells frequently show tumor intravasation, and the intravascular tumor cells were present as organoid structures covered with hemangiopericytes, which is also the case in human ASPS. High expression of GPNMB, a transcriptional target of ASPSCR1-TFE3, was observed at the intravasation. ASPS tumor cells showed the enhanced activity of transendothelial migration and the activity was inhibited by silencing of Gpnmb, indicating that GPNMB plays an important role in tumor intravasation, one of key steps in cancer metastasis. The present model also enabled to evaluate the function of TFE/MITF family transcription factors, and ASPSCR1-TFEB also possessed definitive but less oncogenic activity than that of ASPSCR1-TFE3. Collectively, our new mouse model is a useful tool to understand oncogenic, angiogenic and metastatic mechanisms of ASPS, to identify important motif within the ASPSCR1-TFE3 fusion protein and to provide a novel therapeutic strategy.
We used microarrays to detail the global programme of gene expression in mouse ASPS.

overall_design: Murine embryonic mesenchymal cells were transduced with the ASPSCR1-TFE3 retrovirus and transplanted into nude mice. Tumor developed as a subcutaneous mass and histological examination was performed to confirm the ASPS phenotypes. Individual tumor tissues were subjected to microarray analyses. Mixture of mouse normal tissues (bone marrow, brain, colon, heart, kidney, liver, lung, ovary, skin, skeletal muscle) was used as a control.


title: Expression data from ribosomal protein (RP) L23 (RPL23)-KD and NC SKM-1 cells.

status: Public on Feb 25 2017

city: Shanghai

first: Yuekun

last: Qi

state: Shanghai

address: No.600 Yishan Road

department: Department of Hematology

institute: Shanghai Jiao Tong University Affiliated Sixth People’s Hospital

summary:
Ribosomal protein (RP) L23 is a negative regulator of cell apoptosis. RPL23 overexpression is associated with abnormal apoptotic resistance in CD34+ cells derived from patients with higher-risk myelodysplastic syndrome (MDS). However, the mechanism underlying RPL23-induced apoptotic resistance in higher-risk MDS patients is poorly understood.
Gene microarray analysis between RPL23-knockdown (RPL23-KD) and matched control cells (RPL23-NC) was performed to detail global gene expression profiles and to identify differentially expressed genes and potentially involved pathways associated with RPL23 knockdown.

overall_design: Lentiviral vectors carrying LV-RPL23-RNAi-EGFP (KD group) and LV-RPL23-NC-EGFP (NC group) were constructed to transfect SKM-1 cells, and after efficient knockdown of RPL23 expression (validated by qRT-PCR and western blotting), total RNA was isolated from RPL23-KD and NC SKM-1 cells (triplicate per treatment category) and cDNA and biotinylated cRNA were synthesized and hybridized to a GeneChip® PrimeView™ Human Gene Expression Array. (Affymetrix, Santa Clara, USA) according to manufacturer’ instructions.

first: Lingyun

last: Wu


title: RUNX1 induces DNA replication independent active DNA demethylation at SPI1 regulatory regions.

status: Public on Feb 24 2017

city: Yokohama

first: Jing-Ru

last: Li

state: Kanagawa

address: 1-7-22 Suehiro-cho,

department: Devision of Genomic Technology

institute: RIKEN Center for Life Science Technologies,

summary: RUNX1 overexpression in HEK293T cells seems to be no effect to cells

overall_design: This microarray experiment was conducted to see whether the expression of RUNX1 affect HEK293T cells

first: Shubham

last: Goyal

first: Takahiro

last: Suzuki

first: Jing-ru

first: Yuri

last: Shimizu

first: Hajime

last: Nishimura

first: Mami

last: Kishima

first: Shiori

last: Maeda

first: Harukazu


title: Established cell lines and patient-derived xenografts as equally relevant models of aggressive lymphomas

city: Prague 2

first: Vojtěch

last: Kulvait

address: U Nemocnice 5

department: Institute of Pathological Physiology

country: Czech Republic

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

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


title: Ph-like acute lymphoblastic leukemia in adults is characterized by IgH-CRFL2 and JAK2 mutations and poor prognosis [HG-U133B]

status: Public on Feb 28 2017

city: Munich

first: Tobias

last: Herold

address: Marchioninistr. 15

department: Department of Internal Medicine III

institute: University Hospital Grosshadern, Ludwig-Maximilians-University (LMU)

summary: Philadelphia-like B-cell precursor acute lymphoblastic leukemia (Ph-like ALL) is characterized by distinct genetic alterations and inferior prognosis in children and younger adults. The purpose of this study was the genetic and clinical characterization of Ph-like ALL in adults. Among 207 adult B-cell precursor ALL patients, 26 (13%) were classified as Ph-like using Affymetrix microarrays. The incidence of this subtype was 25% among 105 B-cell precursor ALL patients negative for BCR-ABL1 and MLL-translocations (B-other). All patients with IgH-CRLF2 translocation (38% vs 0%; p=0.002) or mutations in JAK2 (44% vs. 0%; p<0.001) were exclusively found in the Ph-like subgroup. Clinical and outcome analyses were restricted to patients treated within GMALL trials 06/99 and 07/03 (n=107). The complete remission (CR) rate after induction was 100% for Ph-like (n=19) and B-other patients (n=40). After induction, significantly fewer Ph-like patients reached molecular CR (33% vs 79%; p=0.01). At 5 years, the Ph-like ALL subgroup had a lower probability of continuous CR (24% vs 62%; p<0.001) and overall survival (22% vs 64%; p=0.006) compared to B-other ALL patients. Subsequent analysis led to a clinically applicable algorithm identifying this patient subset with a specificity of 100%. Our study is the first to demonstrate that the profile of genetic events in adult Ph-like ALL resembles pediatric Ph-like ALL and differs from B-other ALL. The Ph-like phenotype associates with inferior outcomes in intensively treated adult ALL patients. Ph-like adult ALL should be recognized as a distinct, high-risk entity and further research on improved diagnostic and therapeutic approaches is needed.

overall_design: Analysis of 207 samples of bone marrow mononuclear cells (98 Affymetrix HG-U133 2.0 Plus Chip; 109 Affymetrix HG-U133 A&B Set) from adult patients with acute lymphoblastic leukemia (ALL).

first: Martin

last: Neumann

first: Stephanie

last: Schneider

first: Klaus

last: Metzeler

first: Vindi

last: Jurinovic

first: Nikola

last: Konstandin

first: Stefan

last: Bohlander

first: Ulrich

last: Mansmann

first: Wolfgang

last: Hiddemann

last: Dreyling

first: Claudia

middle: D

last: Baldus

first: Karsten

last: Spiekermann


title: Mantle cell lymphoma gene expression profiling array UPF1.

summary:
The dataset contains data from 9 samples hybridized on Illumina HumanHT-12 array.
-patient's primary lymphoma cells obtained from leukemized blood (P7-PBMC)
-non-malignant B-cells isolated from peripheral blood of 5 healthy donors (CTRL)
-lymphoma cell line named UPF1G established from the patient's primary lymphoma cells before cytarabine-based therapy after 63 and 163 days of in vitro cultivation (UPF1G-D63, UPF1G-D163)
-lymphoma cell line named UPF1H established from the pateint's primary lymphoma cells after cytarabine-based therapy after 85 and 185 days of in vitro cultivation (UPF1H-D85, UPF1H-D185)
-cells established by xenotransplantation of UPF1G cell line isolated ex vivo from subcutaneously growing lymphoma (UPF1G-SC)
-cells established by xenotransplantation of UPF1G cell line isolated ex vivo from malignant murine ascites (UPF1G-A)
-cells established by xenotransplantation of UPF1H cell line isolated ex vivo from subcutaneously growing lymphoma (UPF1H-SC)

Samples were sorted using CD19-microbeads (Miltenyi). For xenotransplantation, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice (referred to as NSG mice) were used.

overall_design: Unsummarized data can be obtained from https://bitbucket.org/kulvait/klenermicroarraydata package using data(UPF1) command.

first: Pavel

last: Klener

first: Magdalena

last: Klanova


title: Diffuse large B-cell lymphoma gene expression profiling array VFN-D2.

summary:
The dataset contains data from 12 samples hybridized on Illumina HumanHT-12 array.

-patient's primary lymphoma cells obtained from malignant ascites (P2-A1, P2-A2)
-patient's non-malignant B-cells (CTRL1, CTRL2)
-lymphoma cell line named UPF4D established from the patient's primary lymphoma cells after 15 and 75 days of in vitro cultivation (UPF4D-D15A, UPF4D-D15B, UPF4D-D75)
-cells established by xenotransplantation of UPF4D cell line isolated ex vivo from infiltrated murine kidney (UPF4D-K)
-cells established by xenotransplantation of UPF4D cell line isolated ex vivo from subcutaneously growing lymphoma (UPF4D-SC)
-patient-derived xenograft (PDX) cells named VFN-D2 established by xenotransplantation of primary lymphoma cells into immunodeficient mice isolated ex vivo from the infiltrated murine kidneys (VFN-D2-K1, VFN-D2-K2)
-patient-derived xenograft (PDX) cells named VFN-D2 established by xenotransplantation of primary lymphoma cells  into immunodeficient mice isolated ex vivo from subcutaneously growing lymphoma (VFN-D2-SC).

Samples were sorted using CD19-microbeads (Miltenyi). For xenotransplantation, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice (referred to as NSG mice) were used.

overall_design: Unsummarized data can be obtained using R package klenermicroarraydata available from https://bitbucket.org/kulvait/klenermicroarraydata.


title: Niclosamide ethanolamine reverses gene expression and inhibits growth of hepatocellular carcinoma in vitro and in vivo

city: Grand Rapids

first: Bin

last: Chen

address: 15 Michigan St. NE

institute: Michigan State University

summary: Hepatocellular carcinoma (HCC) is a fatal malignancy with a dismal prognosis. The recent advances in genomics and transcriptomics have led to large volumes of molecular data for HCC, providing an unprecedented opportunity to translate these data into more effective therapeutics. By creating HCC gene expression signatures and comparing with drug response signatures from multiple datasets, we identified four antihelminthics (from over 1000 FDA-approved drugs) that can reverse the HCC disease gene expression. Among these four, niclosamide was the top hit, which we further evaluated in clinically relevant HCC cell lines and patient-derived xenografts (PDX). Given the poor water-solubility and limited systemic bioavailability of niclosamide, we also evaluated its ethanolamine salt (NEN), which has improved solubility and bioavailability. Both niclosamide and NEN significantly inhibited HCC cell proliferation in vitro, which was associated with down-regulation of key proteins involved in the AKT-mTOR, Wnt, Stat3, and EGFR/Ras/Raf signaling pathways. NEN additionally decreased the growth of three PDX models after oral administration (1,5000 ppm in food) for 4-6 weeks. Expression profiling demonstrated that niclosamide and NEN induced highly similar gene expression changes in HepG2 cells and in PDX models, and that both compounds significantly reversed HCC gene expression in vitro and in vivo . Our results suggest that NEN may be a preferred drug candidate for the treatment of HCC.

overall_design: Total RNA obtained from HepG2 cells after treatment with vehicle, NEN, and niclosamide for 6 hours, and from  tumors after treatment with NEN and control for 6 weeks

first: Wei

last: Wei

first: Ma

last: Li

first: Mei-Sze

last: Chua

first: Atul

middle: J

last: Butte

first: Samuel

last: So


first: Vojtěch

last: Kulvait

summary:
Mantle cell lymphoma gene expression profiling array VFN-M3.
The dataset contains data from 10 samples hybridized on Illumina HumanHT-12 array.

-patient's primary lymphoma cells obtained from leukemized blood (P6-PBMC1, P6-PBMC2)
-non-malignant B-cells isolated from peripheral blood of 5 healthy donors (VFN-M3-CTRL1,  	VFN-M3-CTRL2)
-lymphoma cell line named UPF7U established from the patient's primary lymphoma cells after 166 and 226 days of in vitro cultivation (UPF7U-D166, UPF7U-D226)
-cells established by xenotransplantation of UPF7U cell line isolated ex vivo from subcutaneously growing lymphoma (UPF7U-SC)
-patient-derived xenograft (PDX) cells named VFN-M3 established by xenotransplantation of primary lymphoma cells into immunodeficient mice isolated ex vivo from the lymph node like tumor (VFN-M3-LN3)
-patient-derived xenograft (PDX) cells named VFN-M3 established by xenotransplantation of primary lymphoma cells into immunodeficient mice isolated ex vivo from subcutaneously growing lymphoma (VFN-M3-SC1, VFN-M3-SC3).

Samples were sorted using CD19-microbeads (Miltenyi). For xenotransplantation, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice (referred to as NSG mice) were used.

overall_design: Unsummarized data can be obtained from https://bitbucket.org/kulvait/klenermicroarraydata package using data (VFN-M3) command.


title: Gene expression profile analysis of Regulatory T cell-conditioned dendritic cells to elucidate the mechanisms underpinning dendritic cell suppression in graft versus host disease (GvHD)

city: Newcastle

first: John

last: Casement

address: Framlington Place

department: Bioinformatics Support Unit

institute: Newcastle University

summary: Gene expression profiling of Treg-conditioned dendritic cells (DCs) compared to LPS-matured DCs and immature DCs. The hypothesis tested in the present study was that Treg conditioning alters the gene expression profile of DCs to result in that of a semi-mature phenotype. The results provide important information on how Tregs modulate DC function.

overall_design: Total RNA was obtained from mature DC and Treg-conditioned DC following 24 hr 100 ng/ml LPS treatment. RNA was isolated from immature DC at the same time-point to serve as a control.

first: Lindsay

last: Nicholson

first: Xiao-nong

last: Wang


title: Ph-like acute lymphoblastic leukemia in adults is characterized by IgH-CRFL2 and JAK2 mutations and poor prognosis [HG-U133A]

first: Tobias

last: Herold

first: Martin

last: Neumann

first: Stephanie

last: Schneider

first: Klaus

last: Metzeler

first: Vindi

last: Jurinovic

first: Nikola

last: Konstandin

first: Stefan

last: Bohlander

last: Mansmann


title: Whole genome expression profiling of melanoma-derived induced pluripotent cancer cells in comparison to the parental melanoma cells and to human induced pluripotent stem cells.

first: Jochen

last: Utikal

address: Im Neuenheimer Feld 280

department: Clinical Cooperation Unit Dermato-Oncology

institute: German Cancer Research Center

summary: Reprogramming of HT144 melanoma cells to pluripotency. Aim of the study was to demonstrate the amenability of melanoma cells to reprogramming. Results demonstrate that iPCCs cluster closer to iPSCs than to their parental cells of origin.

overall_design: Total RNA from reprogrammed HT144-induced pluripotent cancer cells compared to parental HT144 melanoma cells and two iPSC lines.

first: Mathias

last: Bernhardt


title: Genome-wide analysis of HeyA8 human ovarian cancer cells co-incubated with platelets under low attachment conditions

city: Houston

first: Monika

last: Haemmerle

address: 1881 East Rd

department: Gynecological Oncology

institute: UT MD Anderson Cancer Center

summary: Analysis of gene expression changes in cancer cells upon interaction with platelets. The hypothesis tested in the present study was to test whether platelets can influence anoikis resistance and metastasis in ovarian cancer by influencing genes which are important for apoptosis, metastasis and proliferation. Results provide important informations of the response of HeyA8 human ovarian cancer cells upon platelet interaction and provide insights on platelet-regulated gene expression changes related to increased cancer cell survival under low attachment/anoikis conditions.

overall_design: Total RNA obtained from HeyA8 human ovarian cancer cells co-incubated with or without mouse platelets for 24 hours under low attachment conditions

first: Anil

middle: K

last: Sood


title: Genome-wide siRNA screen of genes regulating the Lipopolysaccharide-induced TNF-α response in human macrophages

status: Public on Feb 23 2017

city: Bethesda

first: Timothy

middle: G

last: Myers

state: MD

address: 50 South Drive, Room 5509

department: Research Technologies Branch

institute: National Institute of Allergy and Infectious Diseases

summary: The mammalian innate immune system senses many bacterial stimuli through the toll-like receptor (TLR) family. Activation of the TLR4 receptor by bacterial lipopolysaccharide (LPS) is the most widely studied TLR pathway due to its central role in host responses to gram-negative bacterial infection and its contribution to endotoxemia and sepsis. Here we describe a genome-wide siRNA screen to identify genes regulating the human macrophage TNF-α response to LPS. We include a secondary validation screen conducted with six independent siRNAs per gene to facilitate removal of off-target screen hits. We also provide microarray data from the same LPS-treated macrophage cells to facilitate downstream data analysis. These data provide a resource for analyzing gene function in the predominant pathway driving inflammatory cytokine expression in human macrophages.

overall_design: THP-1 cells were stimulated with 0 and 10 ng/ml of LPS separately for 4hrs. Three replicates for each condition.

first: Jing

last: Sun

last: Katz

first: Bhaskar

last: Dutta

first: Ze

first: Iain

last: Fraser


title: Effects of TCPOBOP on gene expression in wild type and Cyp2b9/10/13-null mouse liver

city: Research Triangle Park

first: Christopher

last: Corton

state: NC

address: 109 TW Alexander Dr.

institute: US-EPA

summary: Analysis of publicly available gene expression profiling results indicated a strong coupling of CAR and Nrf2 activation. We hypothesized that the activation of CAR regulated Cyp enzymes contributes to oxidative stress that leads to Nrf2 activation. To test this hypothesis, we examined activation of both CAR and Nrf2 transcriptional biomarkers in wild type and Cyp2b9/10/13-null mice after treatment with the CAR activator TCPOBOP.

overall_design: Eight to ten-week old WT or Cyp2b9/10/13-null male and female mice (n = 4-6) were injected with autoclaved corn oil or TCPOBOP (Sigma) dissolved in autoclaved corn oil at 3 mg/kg.  Forty-eight hours later mice were weighed and euthanized by CO2 asphyxiation, livers excised, weighed, diced, and snap frozen for RNA extraction and stored at -80oC. Gene expression in the livers of the mice was evaluated using Affymetrix mouse 430PM arrays.

first: Chris

first: John

last: Rooney

first: William

last: Baldwin


title: Genome-wide siRNA screen of genes regulating the Lipopolysaccharide-induced responses in mammalian macrophages

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: B-cell receptor driven MALT1 activity regulates MYC signaling in mantle cell lymphoma

city: Münster

first: Michael

last: Grau

state: Nordrhein-Westfalen

address: Albert-Schweitzer-Campus 1

department: Faculty of Medicine

institute: University of Münster

summary: Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of BCR signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 (CBM) complex that transfers BCR signaling to the NF-kB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls a MYC-driven gene expression network predominantly through increased MYC protein stability. Thus our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1 induced MYC regulation is not restricted to MCL, but represents a common mechanism of MYC regulation. MYC itself is pivotal for MCL survival as its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy in targeting the MALT1-MYC axis in MCL patients.

overall_design: Gene expression in Mino and Rec cells induced by treatment with 50 µM z-VRPR-fmk was compared with that induced by treatment with DMSO.

first: Georg

last: Lenz


title: Genome-wide analysis of Mtb-infected THP1 cells in response to resveratrol treatment

first: Bernett

last: Lee

address: 8A Biomedical Grove #03-06 Immunos

institute: Singapore Immunology Network

summary: Analysis of resveratrol-treated cells at gene expression level. The hypothesis tested in the present study was that resveratrol can improve Mycobacterium tuberculosis (Mtb) treatment. Results provide important information of the host response to Mtb infection when given resveratrol, such as resveratrol-mediated modulation of inflammatory pathways induced upon infection.

overall_design: Total RNA obtained from Mtb-infected THP1 cells subjected to resveratrol treatment or not, and compared to uninfected THP1 cells over 24 hours.

first: Catherine

last: Cheng

last: Poidinger

first: Amit

last: Singhal


title: Undifferentiated cells and xenografts of human pluripotent stem cells and embryonal carcinoma cells.

city: Leiden

first: M.

middle: J.

last: Bouma

address: Einthovenweg 20

department: Anatomy & Embryology

country: Netherlands

institute: LUMC

summary:
Here we analyzed undifferentiated cells and perfomed the Teratoma assay for a normal human embryonic stem cell line (H9(+Dox)), a human embryonic stem cell line with a mesendodermal differentiation bias (H9Hyb), a normal human induced pluripotent stem cell line (LU07), a human induced pluripotent stem cell line with reactivated transgenes (LU07+Dox) and a human embryonal carcinoma cell line (EC).
The ability to form teratomas in vivo containing multiple somatic cell types is regarded as functional evidence of pluripotency for human pluripotent stem cells (hPSCs). Since the Teratoma assay is animal-dependent, laborious and only qualitative, the PluriTest and the hPSC ScoreCard assay have been developed as in vitro alternatives. Here we compared normal hPSCs, induced hPSCs (hiPSCs) with reactivated reprogramming transgenes and human embryonal carcinoma (hEC) cells in these assays. While normal hPSCs gave rise to typical teratomas, the xenografts of the hEC cells and the hiPSCs with reactivated reprogramming transgenes were largely undifferentiated and malignant. The hPSC ScoreCard assay confirmed the line-specific differentiation propensities in vitro. However, when undifferentiated cells were analysed with PluriTest only hEC cells were identified as abnormal whereas all other cell lines were indistinguishable and resembled normal hPSCs. Our results indicate that pluripotency assays are best selected on the basis of intended downstream applications.

overall_design: Total RNA from 3-5 passages of undifferentiated cells and 3-4 xenografts were analyzed

first: Marga


title: LS174T treatment with Selamectin

status: Public on Feb 22 2017

city: Geneva

first: Ariel

last: Ruiz i Altaba

address: 1 rue Michel Servet

department: GEDEV

country: Switzerland

institute: University of Geneva Medical School

summary: The goal of this experiment was to determine the expression signature in colon cancer LS174T cell line after selamectin treatment. The current study of selamectin is continuation of our previous work,  PMID: 25143352.

overall_design: LS174T cells were treated with DMSO or 5uM Selamectin for 16h. Cells were then collected, RNA extracted and used for expression analysis.

last: Altaba

first: Monika

last: Kuciak

first: Chandan

last: Seth


title: WNT-TCF response blockade by a small molecules


title: Illumina bead array -/+ UV ASCC3 long isoform shRNA knockdown cells

status: Public on Feb 21 2017

city: London

first: Laura

last: Williamson

address: 1 Midland Road

institute: The Francis Crick Institute

summary: The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown of transcript elongation and restriction of gene activity to the promoter-proximal ~25 kilobases is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter transcript isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The protein-coding ASCC3 isoform counteracts the function of the non-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and noncoding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage

overall_design: MRC5VA non-targeting shRNA control and MRC5VA ASCC3 long isoform (NM_006828.3) targeting shRNA cells were left untreated or UV irradiated 15 J/m2, followed by 20 hours recovery. RNA extracted from 3 biological replicates per sample were analyzed on Illumina Human HT-12 bead expression array.

first: Marco

last: Saponaro

first: Stefan

last: Boeing

first: Philip

last: East

first: Richard

last: Mitter

first: Theodoros

last: Kantidakis

first: Gavin

middle: P

last: Kelly

first: Anna

last: Lobley

first: Jane

last: Walker

first: Bradley

last: Spencer-Dene

last: Howell

first: Nik

last: Matthews

first: Aengus

last: Stewart

first: Jesper

last: Svejstrup


title: Illumina bead array -/+ UV ASCC3 short isoform knockout cells

overall_design: MRC5VA parental cells and MRC5VA ASCC3 short isoform (NM_022091.4) knockout cells were left untreated or UV irradiated 15 J/m2, followed by 20 hours recovery. RNA extracted from 3 biological replicates per sample were analyzed on Illumina Human HT-12 bead expression array.

first: Michael


title: Long-lasting WNT-TCF response blocking and epigenetic modifying activities of withanolide F in human cancer cells

first: Ariel

last: Ruiz i Altaba

summary: The WNT-TCF signaling pathway participates in adult tissue homeostasis and repair, and is hyperactive in a number of human diseases including cancers of the colon. Whereas to date there are no antagonists approved for patient use, a potential problem for their sustained use is the blockade of WNT signaling in healthy tissues, thus provoking potentially serious co-lateral damage.  Here we have screened a library of plant and microorganism small molecules for novel WNT signaling antagonists and describe withanolide F as a potent WNT-TCF response blocker. This steroidal lactone inhibits TCF-dependent colon cancer xenograft growth and mimics the effects of genetic blockade of TCF and of ivermectin, a previously reported WNT-TCF blocker. However, withanolide F is unique in that it imposes a long-lasting repression of tumor growth, WNT-TCF targets and cancer stem cell clonogenicity long after drug treatment

overall_design: LS174T cells were treated with DMSO or 5uM CAP2 or ivermectin for 16h. Cells were then collected, RNA extracted and used for expression analysis.

last: Altaba