Evidence map›Paper›PMID 27641670›Full record

ArticleBiochemical and biophysical research communications2016

Identification of early gene expression changes in primary cultured neurons treated with topoisomerase I poisons.

Sharyn L Rossi, Casey J Lumpkin, Ashlee W Harris, Jennifer Holbrook, Cinsley Gentillon, Suzanne M McCahan, Wenlan Wang, Matthew E R Butchbach

Abstract read
In one paragraph

Article in Biochemical and biophysical research communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.2field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 5 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Sharyn L RossiCenter for Applied Clinical Genomics, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
Casey J LumpkinCenter for Applied Clinical Genomics, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Department of Biological Sciences, University of Delaware, Newark, DE, USA.
Ashlee W HarrisCenter for Applied Clinical Genomics, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
Jennifer HolbrookBiomolecular Core Laboratory, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
Cinsley GentillonCenter for Applied Clinical Genomics, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Department of Biological Sciences, University of Delaware, Newark, DE, USA.
Suzanne M McCahanCenter for Pediatric Research, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Bioinformatics Core Facility, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA.
Wenlan WangCenter for Applied Clinical Genomics, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Center for Pediatric Research, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
Matthew E R ButchbachCenter for Applied Clinical Genomics, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Center for Pediatric Research, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA; Department of Biological Sciences, University of Delaware, Newark, DE, USA; Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: butchbach@nemoursresearch.org.
Alfred I. duPont Hospital for Children · US

Funding

Predictive Modeling & Optimal Control Framework for Model-Based Epidemic Response in DelawareP20GM103446 · NIGMS · UNIVERSITY OF DELAWARE · PI MELINDA K DUNCAN · 2012 to 2026
$67.2M
Center for Pediatric ResearchP20GM103464 · NIGMS · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · PI SHAFFER, THOMAS H · 2012 to 2014
$5.6M
Center for Pediatric Research Pilot ProgramP30GM114736 · NIGMS · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · PI SHAFFER, THOMAS H · 2015 to 2019
$5.1M
NIGMS NIH HHS P20 GM103446NIGMS NIH HHS P20 GM103464NIGMS NIH HHS P30 GM114736
6 · The paper itself

Abstract

Topoisomerase 1 (TOP1) poisons like camptothecin (CPT) are currently used in cancer chemotherapy but these compounds can have damaging, off-target effects on neurons leading to cognitive, sensory and motor deficits. To understand the molecular basis for the enhanced sensitivity of neurons to CPT, we examined the effects of compounds that inhibit TOP1-CPT, actinomycin D (ActD) and β-lapachone (β-Lap)-on primary cultured rat motor (MN) and cortical (CN) neurons as well as fibroblasts. Neuronal cells expressed higher levels of Top1 mRNA than fibroblasts but transcript levels are reduced in all cell types after treatment with CPT. Microarray analysis was performed to identify differentially regulated transcripts in MNs in response to a brief exposure to CPT. Pathway analysis of the differentially expressed transcripts revealed activation of ERK and JNK signaling cascades in CPT-treated MNs. Immediate-early genes like Fos, Egr-1 and Gadd45b were upregulated in CPT-treated MNs. Fos mRNA levels were elevated in all cell types treated with CPT; Egr-1, Gadd45b and Dyrk3 transcript levels, however, increased in CPT-treated MNs and CNs but decreased in CPT-treated fibroblasts. These transcripts may represent new targets for the development of therapeutic agents that mitigate the off-target effects of chemotherapy on the nervous system.

Indexed as

Gene Expression RegulationAnimalsAntigens, DifferentiationAntineoplastic AgentsCamptothecinCells, CulturedDNA Topoisomerases, Type IEarly Growth Response Protein 2FibroblastsGADD45 ProteinsMicroscopy, FluorescenceNeuronsOligonucleotide Array Sequence AnalysisProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-fosAntigens, DifferentiationAntineoplastic AgentsCamptothecinDNA Topoisomerases, Type IDYRK3 protein, ratEarly Growth Response Protein 2Egr2 protein, ratGadd45b protein, ratGADD45 ProteinsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene Proteins c-fosRNA, MessengerTopoisomerase I InhibitorsActinomycin DCamptothecinCortical neuronDNA damage responseDyrk3Immediate early geneMicroarrayMotor neuronβ-lapachone

Identifiers

PMID27641670
PMCPMC5048596
OpenAlexW2518718316

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.