Evidence map›Paper›PMID 38907776›Full record

ArticleCellular and molecular neurobiology2024

Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology.

Paula M Wagner, Santiago J Fornasier, Mario E Guido

Abstract read
In one paragraph

Article in Cellular and molecular neurobiology, 2024. 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
–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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. 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

3 authors.

Paula M WagnerCentro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC)-CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina. pwagner@unc.edu.ar.ORCID http://orcid.org/0000-0003-0458-873X
Santiago J FornasierCentro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC)-CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina.
Mario E GuidoCentro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC)-CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina. mario.guido@unc.edu.ar.ORCID http://orcid.org/0000-0002-5485-4904

Funding

Agencia Nacional de Promoción Científica y Técnica FONCyT, PICT 2017-631, PICT 2020-0613Consejo Nacional de Investigaciones Científicas y Tecnológicas de la República Argentina (CONICET) PIP 2014Secretaría de Ciencia y Tecnología de la Universidad Nacional de Córdoba SeCyT- UNC, Consolidar 2018-2022
6 · The paper itself

Abstract

The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12-15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase 1 ε/δ (CK1ε/δ) with specific inhibitors (CHIR99021 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption after Per2 knockdown expression in GBM-derived cells. CHIR99021-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition compared to control cells. The combined treatment of CHIR99021 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone. Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects GBM cell biology.

Indexed as

Brain NeoplasmsGlioblastomaCell Line, TumorCell MovementCell SurvivalCircadian ClocksCLOCK ProteinsCytosolGlycogen Synthase Kinase 3HumansPeriod Circadian ProteinsPyridinesPyrimidinesReactive Oxygen SpeciesChir 99021CLOCK ProteinsGlycogen Synthase Kinase 3Period Circadian ProteinsPyridinesPyrimidinesReactive Oxygen SpeciesChronotherapyCircadian rhythmGlioblastomaMetabolic oscillator

Identifiers

PMID38907776
PMCPMC11193694

What OpenQuestion holds

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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.