Evidence map›Paper›PMID 40887493›Full record

ArticleScientific reports2025

Circadian rhythms in pediatric high-grade gliomas may contribute to treatment efficacy.

Ella A Nettnin, Cesar A Garcia, Fudhial F Sayed, Ethan Schonfeld, Thien Nguyen, Maria Isabel Barros Guinle, Claudia K Petritsch, Erin M Gibson, Laura M Prolo

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. 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
–field-weighted citation impact
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.

  1. Review
  2. Review
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

9 authors.

Ella A NettninDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Cesar A GarciaDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Fudhial F SayedDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Ethan SchonfeldDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Thien NguyenDivision of Pediatric Hematology/Oncology, Lucile Packard Children's Hospital, Palo Alto, CA, USA.
Maria Isabel Barros GuinleDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Claudia K PetritschDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Erin M GibsonDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Laura M ProloDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA. lmprolo@stanford.edu.

Funding

Berg Scholars Program at Stanford University N/AChambers-Okamura Faculty Scholar in Pediatric Neurosurgery N/ADIPG DMG Research Funding Alliance N/ARally Foundation for Childhood Cancer Research N/AShurl and Kay Curci Foundation Award N/AStanford Maternal and Child Health Research Institute N/A
6 · The paper itself

Abstract

Pediatric high-grade gliomas (pHGG) are highly invasive with poor survival outcomes. Timing of Temozolomide administration has been shown to affect survival of adult patients with glioblastoma. We investigated whether pHGGs express circadian genes rhythmically and whether underlying rhythms affect Temozolomide sensitivity. Circadian gene expression in pediatric gliomas was analyzed using PedcBioPortal. Immunoblotting was used to assess protein levels in patient-derived pHGG lines and in high- and low- grade (pLGG) glioma specimens. Rhythmic gene expression in pHGG lines was measured via qPCR, and Temozolomide efficacy was tested during peak versus trough Bmal1 expression. Patient data revealed significantly different mRNA expression in multiple circadian genes between pHGGs and pLGGs, including higher Bmal1 expression in pHGG specimens and lower Rev-Erbα expression. Significantly higher BMAL1 and CLOCK protein levels and lower REV-ERBα were present in pHGG versus pLGG tissue specimens. Our three pHGG lines displayed rhythmic Bmal1 and Rev-Erbα expression post-synchronization. We found significantly decreased proliferation when Temozolomide was applied during trough versus peak Bmal1 expression. The positive arm of the circadian clock appears upregulated in pHGGs compared to pLGGs. Pediatric HGGs rhythmically express circadian genes and exhibit differential Temozolomide sensitivity based on timing of administration.

Indexed as

Brain NeoplasmsCircadian RhythmGliomaAdolescentAntineoplastic Agents, AlkylatingARNTL Transcription FactorsCell Line, TumorCell ProliferationChildChild, PreschoolCLOCK ProteinsFemaleGene Expression Regulation, NeoplasticHumansMaleNeoplasm GradingAntineoplastic Agents, AlkylatingARNTL Transcription FactorsBMAL1 protein, humanCLOCK protein, humanCLOCK ProteinsNR1D1 protein, humanNuclear Receptor Subfamily 1, Group D, Member 1TemozolomideChronotherapyCircadian medicineCircadian rhythmsPediatric glioblastomaPediatric high-grade gliomaPediatric low-grade glioma

Identifiers

PMID40887493
PMCPMC12399741

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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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.