Evidence map›Paper›PMID 38570263›Full record

ArticleJournal of pediatric surgery2024

PIM Kinase Inhibition Sensitizes Neuroblastoma to Doxorubicin.

Janet R Julson, Colin H Quinn, Nazia Nazam, Laura V Bownes, Jerry E Stewart, Elizabeth A Beierle

Open access · greenAbstract read
In one paragraph

Article in Journal of pediatric surgery, 2024. 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
0.7field-weighted citation impact, top 30% 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, 2 citations in OpenAlex.

  1. Review
  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

6 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.
Nazia NazamDivision 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.
Jerry E StewartDivision of Pediatric Surgery, Department of Surgery, 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

backgroundChemoresistance contributes to relapse in high-risk neuroblastoma. Cancer cells acquire resistance through multiple mechanisms, including drug efflux pumps. In neuroblastoma, multidrug resistance-associated protein-1 (MRP1/ABCC1) efflux pump expression correlates with worse outcomes. These pumps are regulated by PIM kinases, a family of serine-threonine kinases, overexpressed in neuroblastoma. We hypothesized PIM kinase inhibition would sensitize neuroblastoma cells by modulating MRP1.

methodsKocak database query evaluated ABCC1, PIM1, PIM2, and PIM3 expression in neuroblastoma patients. SK-N-AS and SK-N-BE(2) cells were treated with doxorubicin or the pan-PIM kinase inhibitor, AZD1208. Flow cytometry assessed intracellular doxorubicin accumulation. AlamarBlue assay measured viability. The lethal dose 50% (LD

resultsKocak database query demonstrated positive correlation between PIM genes and ABCC1. PIM kinase inhibition increased intracellular doxorubicin accumulation in both cell lines, suggesting PIM kinase regulation of MRP1. Isobolograms showed synergy between AZD1208 and doxorubicin.

conclusionsThe correlation between PIM and ABCC1 gene expression suggests PIM kinases may contribute to neuroblastoma chemotherapeutic resistance. PIM kinase inhibition increased intracellular doxorubicin accumulation. Combination treatment with AZD1208 and doxorubicin decreased neuroblastoma cell viability in a synergistic fashion. These findings support further investigations of PIM kinase inhibition in neuroblastoma. TYPE OF STUDY: Basic Science Research. LEVEL OF EVIDENCE: NA.

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsDoxorubicinDrug Resistance, NeoplasmNeuroblastomaProto-Oncogene Proteins c-pim-1Antibiotics, AntineoplasticBiphenyl CompoundsCell Line, TumorDrug SynergismHumansProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsThiazolidinesAntibiotics, AntineoplasticATP-Binding Cassette, Sub-Family C ProteinsAZD1208Biphenyl CompoundsDoxorubicinmultidrug resistance-associated protein 1PIM1 protein, humanPIM2 protein, humanPIM3 protein, humanProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-pim-1proto-oncogene proteins pimThiazolidinesDrug resistanceMRP1NeuroblastomaPIM kinase

Identifiers

PMID38570263
PMCPMC11164644
OpenAlexW4392869224

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.