Evidence map›Paper›PMID 39392921›Full record

ArticleNeuro-oncology2025

Synergistic combination of perphenazine and temozolomide suppresses patient-derived glioblastoma tumorspheres.

Jun Pyo Hong, Ran Joo Choi, Jin-Kyoung Shim, Kibyeong Kim, Ryong Nam Kim, HyeJoung Cho, Seo Jin Kim, Sohyun Kim, Nam Hwa Kim, Hun Ho Park and 6 more

Abstract read
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  5. Review
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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

16 authors.

Jun Pyo HongBrain Tumor Translational Research Laboratory, Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
Ran Joo ChoiBrain Tumor Translational Research Laboratory, Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jin-Kyoung ShimBrain Tumor Translational Research Laboratory, Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
Kibyeong KimBrain Tumor Translational Research Laboratory, Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
Ryong Nam KimBrain Tumor Translational Research Laboratory, Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
HyeJoung ChoBrain Tumor Translational Research Laboratory, Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
Seo Jin KimBrain Tumor Translational Research Laboratory, Department of Biomedical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
Sohyun KimDepartment of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Nam Hwa KimDepartment of Premedical, Yonsei University College of Medicine, Seoul, Republic of Korea.
Hun Ho ParkDepartment of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.ORCID 0000-0002-2526-9693
Ju Hyung MoonDepartment of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Eui Hyun KimDepartment of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Wan-Yee TeoInstitute of Molecular and Cell Biology, A*STAR, Singapore, Singapore.
Seungsoo ChungDepartment of Physiology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Jong Hee ChangDepartment of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Seok-Gu KangBrain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.ORCID 0000-0001-5676-2037

Funding

Bio&Medical Technology Development ProgramICT & Future Planning NRF2022M3C1A309202211Korea Health Industry Development InstituteKorea Health Technology R&D ProjectKorean Government NRF-2022R1A2B5B03001199Ministry of Health & Welfare, Republic of Korea RS-2024-00438443Ministry of ScienceNational Research Foundation of KoreaPioneer Research Center ProgramYonsei University College of Medicine 6-2023-0179
6 · The paper itself

Abstract

backgroundGlioblastoma (GBM), a primary malignant brain tumor, has a poor prognosis, even with standard treatments such as radiotherapy and chemotherapy. In this study, we explored the anticancer effects of the synergistic combination of perphenazine (PER), a dopamine receptor D2/3 (DRD2/3) antagonist, and temozolomide (TMZ), a standard treatment for GBM, in patient-derived human GBM tumorspheres (TSs).

methodsThe biological effects of the combination of PER and TMZ in GBM TSs were assessed by measuring cell viability, ATP, stemness, invasiveness, and apoptosis. Changes in protein and mRNA expression were analyzed using western blotting and RNA sequencing. Co-administration of PER and TMZ was evaluated in vivo using a mouse orthotopic xenograft model.

resultsThe Severance dataset showed that DRD2 and DRD3 expressions were higher in tumor tissues than in the tumor-free cortex of patients with GBM. DRD2/3 knockout by CRISPR/Cas9 in patient-derived human GBM TSs inhibited cell growth and ATP production. The combined treatment with PER and TMZ resulted in superior effects on cell viability and ATP assays compared to those in single treatment groups. Flow cytometry, western blotting, and RNA sequencing confirmed elevated apoptosis in GBM TSs following combination treatment. Additionally, the combination of PER and TMZ downregulated the expression of protein and mRNA associated with stemness and invasiveness. In vivo evaluation showed that combining PER and TMZ extended the survival period of the mouse orthotopic xenograft model.

conclusionsThe synergistic combination of PER and TMZ has potential as a novel combination treatment strategy for GBM.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsGlioblastomaPerphenazineTemozolomideAnimalsAntineoplastic Agents, AlkylatingApoptosisCell ProliferationDrug SynergismFemaleHumansMaleMiceMice, NudePrognosisAntineoplastic Agents, AlkylatingPerphenazineReceptors, Dopamine D2Receptors, Dopamine D3TemozolomideDRD2/3glioblastomaperphenazinetemozolomidetumorsphere

Identifiers

PMID39392921
PMCPMC11889716

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.