Evidence map›Paper›PMID 31638150›Full record

ArticleNeuro-oncology2020

Generation of diffuse intrinsic pontine glioma mouse models by brainstem-targeted in utero electroporation.

Smruti K Patel, Rachel M Hartley, Xin Wei, Robin Furnish, Fernanda Escobar-Riquelme, Heather Bear, Kwangmin Choi, Christine Fuller, Timothy N Phoenix

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

43 citing papers in PubMed, 77 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Smruti K PatelDepartment of Neurosurgery, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Rachel M HartleyDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio.
Xin WeiDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio.
Robin FurnishDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio.
Fernanda Escobar-RiquelmeDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio.
Heather BearResearch in Patient Services, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio.
Kwangmin ChoiDivision of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio.
Christine FullerDepartment of Pathology, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, Ohio.
Timothy N PhoenixDivision of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, Ohio.
University of Cincinnati Medical Center · USAmerican Association of Colleges of Pharmacy · USCincinnati Children's Hospital Medical Center · USLaboratoire d’immunologie intégrative du cancer · FRUniversity of Cincinnati · US

Funding

REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY RESEARCHP30ES006096 · NIEHS · UNIVERSITY OF CINCINNATI · PI YADAV, JAGJIT S · 1992 to 2022
$35.4M
NIEHS NIH HHS P30 ES006096
6 · The paper itself

Abstract

backgroundDiffuse intrinsic pontine gliomas (DIPGs) are highly lethal childhood brain tumors. Their unique genetic makeup, pathological heterogeneity, and brainstem location all present challenges to treatment. Developing mouse models that accurately reflect each of these distinct features will be critical to advance our understanding of DIPG development, progression, and therapeutic resistance. The aims of this study were to generate new mouse models of DIPG and characterize the role of specific oncogenic combinations in DIPG pathogenesis.

methodsWe used in utero electroporation (IUE) to transfect neural stem cells in the developing brainstem with PiggyBac DNA transposon plasmids. Combinations of platelet-derived growth factor B (PDGFB), PdgfraD842V, or PdgfraWT, combined with dominant negative Trp53 (DNp53) and H3.3K27M expression, induced fully penetrant brainstem gliomas.

resultsIUE enabled the targeted transfection of brainstem neural stem cells. PDGFB + DNp53 + H3.3K27M induced the rapid development of grade IV gliomas. PdgfraD842V + DNp53 + H3.3K27M produced slower forming grade III gliomas. PdgfraWT + DNp53 + H3.3K27M produced high- and low-grade gliomas with extended latencies. PDGFB, PdgfraD842V, and PdgfraWT DIPG models display unique histopathological and molecular features found in human DIPGs. H3.3K27M induced both overlapping and unique gene expression changes in PDGFB and PdgfraD842V tumors. Paracrine effects of PDGFB promote disruption of pericyte-endothelial interactions and angiogenesis in PDGFB DIPG mouse models.

conclusionBrainstem-targeted IUE provides a rapid and flexible system to generate diverse DIPG mouse models. Using IUE to investigate mutation and pathohistological heterogeneity of DIPG will provide a valuable tool for future genetic and preclinical studies.

Indexed as

Brain Stem NeoplasmsDiffuse Intrinsic Pontine GliomaDisease Models, AnimalAnimalsElectroporationGene ExpressionMice, Inbred ICRNeovascularization, PathologicNeural Stem Cells3K27MDIPGH3in utero electroporationmouse modelsPDGFBPdgfra

Identifiers

PMID31638150
PMCPMC7442382
OpenAlexW2981885391

What OpenQuestion holds

Textmetadata
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.