Evidence map›Paper›PMID 36907773›Full record

ArticleJournal of pediatric surgery2023

Inhibition of PIM Kinases Promotes Neuroblastoma Cell Differentiation to a Neuronal Phenotype.

Janet R Julson, Colin H Quinn, Laura V Bownes, Sara C Hutchins, Jerry E Stewart, Jamie Aye, Karina J Yoon, Elizabeth A Beierle

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of pediatric surgery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
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 2 institutions in 1 country.

Janet R JulsonDivision of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Colin H QuinnDivision of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Laura V BownesDivision of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Sara C HutchinsDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Jerry E StewartDivision of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Jamie AyeDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Karina J YoonDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Elizabeth A BeierleDivision of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. Electronic address: elizabeth.beierle@childrensal.org.
University of Alabama at Birmingham · USChildren's of Alabama · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Omer Jamy · 1985 to 2026
$165.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008361 · NIGMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YACOUBIAN, TALENE ALENE · 1992 to 2024
$16.8M
ROS Modulation of Innate and Adaptive Immunity in RAP30AR048311 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MOUNTZ, JOHN D · 2001 to 2017
$9.5M
Surgical Oncology Research Training ProgramT32CA229102 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI HERBERT CHEN · 2018 to 2026
$3.2M
NCI NIH HHS P30 CA013148NCI NIH HHS T32 CA229102NIAMS NIH HHS P30 AR048311NIGMS NIH HHS T32 GM008361
6 · The paper itself

Abstract

backgroundNeuroblastoma arises from aberrancies in neural stem cell differentiation. PIM kinases contribute to cancer formation, but their precise role in neuroblastoma tumorigenesis is poorly understood. In the current study, we evaluated the effects of PIM kinase inhibition on neuroblastoma differentiation.

methodsVersteeg database query assessed the correlation between PIM gene expression and the expression of neuronal stemness markers and relapse free survival. PIM kinases were inhibited with AZD1208. Viability, proliferation, motility were measured in established neuroblastoma cells lines and high-risk neuroblastoma patient-derived xenografts (PDXs). qPCR and flow cytometry detected changes in neuronal stemness marker expression after AZD1208 treatment.

resultsDatabase query showed increased levels of PIM1, PIM2, or PIM3 gene expression were associated with higher risk of recurrent or progressive neuroblastoma. Increased levels of PIM1 were associated with lower relapse free survival rates. Higher levels of PIM1 correlated with lower levels of neuronal stemness markers OCT4, NANOG, and SOX2. Treatment with AZD1208 resulted in increased expression of neuronal stemness markers.

conclusionsInhibition of PIM kinases differentiated neuroblastoma cancer cells toward a neuronal phenotype. Differentiation is a key component of preventing neuroblastoma relapse or recurrence and PIM kinase inhibition provides a potential new therapeutic strategy for this disease.

Indexed as

Neoplasm Recurrence, LocalNeuroblastomaBiphenyl CompoundsCell DifferentiationCell Line, TumorCell ProliferationHumansPhenotypeProtein Kinase InhibitorsProto-Oncogene Proteins c-pim-1ThiazolidinesAZD1208Biphenyl CompoundsProtein Kinase InhibitorsProto-Oncogene Proteins c-pim-1proto-oncogene proteins pimThiazolidinesAZD1208NeuroblastomaPIM kinaseStem cell

Identifiers

PMID36907773
PMCPMC10198809
OpenAlexW4321206881

What Socratic 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 Socratic graph.