Evidence map›Paper›PMID 34545699›Full record

ArticleCancer medicine2021

Does timing matter in radiotherapy of hepatocellular carcinoma? An experimental study in mice.

Soha A Hassan, Amira A H Ali, Dennis Sohn, Ulrich Flögel, Reiner U Jänicke, Horst-Werner Korf, Charlotte von Gall

Open access · goldAbstract read
In one paragraph

Article in Cancer medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Hepatocellular Carcinoma Around the Clock.Current oncology (Toronto, Ont.) · 2026
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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

7 authors at 3 institutions in 2 countries.

Soha A HassanInstitute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.ORCID 0000-0001-8566-4727
Amira A H AliInstitute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Dennis SohnLaboratory of Molecular Radiooncology, Clinic and Policlinic for Radiation Therapy and Radiooncology, Medical Faculty of Heinrich-Heine-University, Düsseldorf, Germany.
Ulrich FlögelDepartment of Molecular Cardiology, Heinrich-Heine-University, Düsseldorf, Germany.
Reiner U JänickeLaboratory of Molecular Radiooncology, Clinic and Policlinic for Radiation Therapy and Radiooncology, Medical Faculty of Heinrich-Heine-University, Düsseldorf, Germany.
Horst-Werner KorfInstitute of Anatomy I, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.ORCID 0000-0002-5051-0303
Charlotte von GallInstitute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Heinrich Heine University Düsseldorf · DEMansoura University · EGSuez University · EG

Funding

DAADHeinrich-Heine-University Düsseldorf
6 · The paper itself

Abstract

This study investigates whether a chronotherapeutic treatment of hepatocellular carcinoma (HCC) may improve treatment efficacy and mitigate side effects on non-tumoral liver (NTL). HCC was induced in Per2::luc mice which were irradiated at four time points of the day. Proliferation and DNA-double strand breaks were analyzed in irradiated and nonirradiated animals by detection of Ki67 and γ-H2AX. Prior to whole animal experiments, organotypic slice cultures were investigated to determine the dosage to be used in whole animal experiments. Irradiation was most effective at the proliferation peaks in HCC at ZT02 (early inactivity phase) and ZT20 (late activity phase). Irradiation effects on NTL were minimal at ZT20. As compared with NTL, nonirradiated HCC revealed disruption in daily variation and downregulation of all investigated clock genes except Per1. Irradiation affected rhythmic clock gene expression in NTL and HCC at all ZTs except at ZT20 (late activity phase). Irradiation at ZT20 had no effect on total leukocyte numbers. Our results indicate ZT20 as the optimal time point for irradiation of HCC in mice at which the ratio between efficacy of tumor treatment and toxic side effects was maximal. Translational studies are now needed to evaluate whether the late activity phase is the optimal time point for irradiation of HCC in man.

Indexed as

ChronotherapyAnimalsBlood Cell CountCarcinoma, HepatocellularCell ProliferationCLOCK ProteinsDNA DamageDown-RegulationGene ExpressionHistonesKi-67 AntigenLiver NeoplasmsMaleMiceMice, Inbred C57BLMice, TransgenicClock protein, mouseCLOCK Proteinsgamma-H2AX protein, mouseHistonesKi-67 Antigenclock geneshepatocellular carcinomaKi67radiotherapyγ-H2AX

Identifiers

PMID34545699
PMCPMC8559477
OpenAlexW3201316137

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.