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accession-icon GSE8742
The Induction of Senescence-Like Growth Arrest by Diterpene Esters in Solid Tumor Cells
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

We previously identified the induction of growth arrest with phenotypic characteristics of senescence in melanoma cell lines sensitive to diterpene esters, indicating a therapeutic potential. Here we compared the cytostatic effects of two diterpene esters namely TPA (12-O-tetradecanoylphorbol-13-acetate) and PEP008 (20-O-acetyl-ingenol-3-angelate) in sensitive and resistant cell lines derived from melanoma, breast cancer and colon cancer. We showed the diterpene esters to induce senescence-like growth arrest in the sensitive cells at 100-1000 ng/ml. Use of the pan-PKC inhibitor bisindolylmaleimide-l demonstrated that activation of PKC was required for growth arrest. Full genome expression profiling revealed that pivotal genes involved in DNA synthesis and cell cycle control were down-regulated by treatment in all three sensitive solid tumor models. At the protein level, prolonged down-regulation of E2F-1 and proliferating cell nuclear antigen (PCNA), sustained expression of p21WAF1/CIP1 and dephosphorylation of retinoblastoma (Rb) occurred in the sensitive cells. Although activation of extracellular signal-related kinase (ERK) 1/2 by the diterpene esters occurred in both sensitive and resistant cell lines, the HRASLS3 type II tumor suppressor, which appears to have a role in MAPK pathway suppression, was constitutively elevated in the resistant cell lines compared to their sensitive counterparts. Together, these results demonstrate the ability of the PKC activating drugs TPA and PEP008 to induce growth arrest with characteristics of senescence in solid tumor cell lines derived from a variety of tissue types through a similar mechanism. PKC-activating diterpene esters may therefore have therapeutic potential in a range of solid tumors.

Publication Title

Induction of senescence in diterpene ester-treated melanoma cells via protein kinase C-dependent hyperactivation of the mitogen-activated protein kinase pathway.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP136132
RNASeq of total RNA isolated from self-assembling co-cultures of primary human hepatocytes (SACC-PHHs) mono-infected with HBV, co-infected with HBV/HDV, or uninfected at 8 and 28 days post-infection
  • organism-icon Homo sapiens
  • sample-icon 30 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Here, we examined the host response relative of SACC-PHHs infected with either hepatitis B virus (HBV) alone or both HBV/hepatitis delta virus (HDV) co-infection compared to non-infected controls. Overall design: SACC-PHHs were generated with PHHs from either a single human donor or mixed donors (in total, there were five donors) and co-cultured with 3T3J mouse non-parenchymal cells. These cultures can be persistently infected for up to 1-1.5 months post-challenge and exhibit a transcriptomic profile similar to what's observed in the 3D context of the liver. Note that not all donors and conditions have the same number of replicates.

Publication Title

Analysis of Host Responses to Hepatitis B and Delta Viral Infections in a Micro-scalable Hepatic Co-culture System.

Sample Metadata Fields

Specimen part, Treatment, Subject

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accession-icon GSE67158
Eomes+ natural Th1 (nTh1) T cells share functional features with classical Th1 (cTh1) cells.
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Identification of intrathymic Eomes+ natural Th1 cells creates a novel idea that there is more than one way for the generation of innate CD4 T cells. To more deeply characterize this type of innate T cells, we compared the gene expression profile between nTh1 cells generated in CIITAtg mice and classic Th1 cells differentiated from naive CD4 T cells in Th1-polarizing condition.

Publication Title

Thymic low affinity/avidity interaction selects natural Th1 cells.

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE40295
Genetic and bioinformatics approaches to decipher LGL's function as a tumor suppressor
  • organism-icon Drosophila melanogaster
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome 2.0 Array (drosophila2)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

<i>miR-9a</i> mediates the role of Lethal giant larvae as an epithelial growth inhibitor in <i>Drosophila</i>.

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE19400
S. aureus gene expression following AFN-1252 treatment
  • organism-icon Staphylococcus aureus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix S. aureus Genome Array (saureus)

Description

AFN-1252 is an inhibitor of fatty acid biosynthesis. Gene expression profiles were generated by microarray analysis of S. aureus cells following treatment with AFN-1252, an inhibitor of fatty acid synthesis.

Publication Title

Perturbation of Staphylococcus aureus gene expression by the enoyl-acyl carrier protein reductase inhibitor AFN-1252.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE40294
mRNA microarray of Drosophila melanogaster extratced from cephalic complexes of lgl27S3/lglE2S31 (lgl-null) and FRT82B (wild-type) 3rd instar larvae
  • organism-icon Drosophila melanogaster
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome 2.0 Array (drosophila2)

Description

Affymetrix microarray to detect changes in gene expression between lgl27S3/lglE2S31 and FRT82B larvae

Publication Title

<i>miR-9a</i> mediates the role of Lethal giant larvae as an epithelial growth inhibitor in <i>Drosophila</i>.

Sample Metadata Fields

Age, Specimen part

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accession-icon SRP063624
Expression profiling of centroacinar cells from adult zebrafish pancreas
  • organism-icon Danio rerio
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIlluminaGenomeAnalyzerII

Description

We sequenced mRNA from two preparations of isolated Notch-responsive ductal pancreas cells and compared transcript expression to all other non-Notch-responsive cells from each sample to charactarize zebrafish centroacinar cells. Overall design: Determination of gene expression levels in centroacinar cells and non-centroacinar cells from adult pancreas.

Publication Title

Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE86544
Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

Squamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present. Perineural invasion (PNI) is recognized as one of these high-risk features. The molecular changes during clinical PNI in cSCCHN have not been previously investigated. In this study, we assessed the global gene expression differences between cSCCHN with or without incidental or clinical PNI. The results of the analysis showed signatures of gene expression representative of activation of p53 in tumors with PNI compared to tumors without, amongst other alterations. Immunohistochemical staining of p53 showed cSCCHN with clinical PNI to be more likely to exhibit a diffuse over-expression pattern, with no tumors showing normal p53 staining. DNA sequencing of cSCCHN samples with clinical PNI showed no difference in mutation number or position with samples without PNI, however a significant difference was observed in regulators of p53 degradation, stability and activity. Our results therefore suggest that cSCCHN with clinical PNI may be more likely to contain alterations in the p53 pathway, compared to cSCCHN without PNI.

Publication Title

Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process.

Sample Metadata Fields

Disease, Disease stage

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accession-icon GSE46385
Clinical, Molecular and Genetic Validation of a Murine Orthotopic Xenograft Model of Pancreatic Adenocarcinoma using Fresh Human Specimens
  • organism-icon Homo sapiens
  • sample-icon 40 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

This project describes the establishment and validation of a murine orthotopic xenograft model using fresh human tumor samples that recapitulates the critical components of human pancreatic adenocarcinoma. The authors discuss the proven and theoretical advantages of the model as well as future translational implications.

Publication Title

Clinical, molecular and genetic validation of a murine orthotopic xenograft model of pancreatic adenocarcinoma using fresh human specimens.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE32984
Gene expression profiling of Human Umbilical Vein Endothelial Cells (HUVEC) after treatment with Erg or control antisense (GeneBloc)
  • organism-icon Homo sapiens
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

The endothelial transcription factor Erg (Ets Related Gene) plays an important role in homeostasis and angiogenesis by regulating many endothelial functions including survival and junction stability. Here we show that Erg regulates endothelial cell migration. Transcriptome profiling of Erg-deficient endothelial cells (EC) identified 80 genes involved in cell migration as candidate Erg targets, including regulators of the Rho GTPases. Inhibition of Erg expression in human umbilical vein endothelial cells (HUVEC) resulted in decreased migration in vitro, whilst Erg over-expression using adenovirus caused increased migration. Live-cell imaging of Erg-deficient HUVEC showed a reduction in lamellipodia, in line with decreased motility. Both actin and tubulin cytoskeletons were disrupted in Erg-deficient EC, with a dramatic increase in tubulin acetylation. Amongst the most significant microarray hit was the cytosolic histone deacetylase (HDAC)-6, a regulator of cell migration. Rescue experiments confirmed that HDAC6 mediates the Erg-dependent regulation of tubulin acetylation and actin localization.

Publication Title

The transcription factor Erg regulates expression of histone deacetylase 6 and multiple pathways involved in endothelial cell migration and angiogenesis.

Sample Metadata Fields

Specimen part

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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