Evidence map›Paper›PMID 25378634›Full record

ArticleNeuro-oncology2015

Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors.

Seung Ah Choi, Jung Won Choi, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Kyung Duk Park, Dayoung Eum, Sung-Hye Park, Il Han Kim, Seung-Ki Kim

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
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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

10 authors at 3 institutions in 1 country.

Seung Ah ChoiDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Jung Won ChoiDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Kyu-Chang WangDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Ji Hoon PhiDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Ji Yeoun LeeDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Kyung Duk ParkDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Dayoung EumDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Sung-Hye ParkDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Il Han KimDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Seung-Ki KimDivision of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., K.-C.W., J.H.P., J.Y.L., D.E., S.-K.K.); Adolescent Cancer Center, Seoul National University Cancer Hospital, Seoul, Republic of Korea (S.A.C., J.W.C., J.H.P., J.Y.L., K.D.P., D.E., S.-K.K.); Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Republic of Korea (K.D.P.); Department of Pathology, Seoul National University Children's Hospital, Seoul, Republic of Korea (S-H.P.); Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea (I.H.K.).
Seoul National University Hospital · KRSeoul National University · KRSeoul National University Children's Hospital · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAtypical teratoid/rhabdoid tumors (AT/RT) are among the most malignant pediatric brain tumors. Cells from brain tumors with high aldehyde dehydrogenase (ALDH) activity have a number of characteristics that are similar to brain tumor initiating cells (BTICs). This study aimed to evaluate the therapeutic potential of ALDH inhibition using disulfiram (DSF) against BTICs from AT/RT.

methodsPrimary cultured BTICs from AT/RT were stained with Aldefluor and isolated by fluorescence activated cell sorting. The therapeutic effect of DSF against BTICs from AT/RT was confirmed in vitro and in vivo.

resultsAT/RT cells displayed a high expression of ALDH. DSF demonstrated a more potent cytotoxic effect on ALDH(+) AT/RT cells compared with standard anticancer agents. Notably, treatment with DSF did not have a considerable effect on normal neural stem cells or fibroblasts. DSF significantly inhibited the ALDH enzyme activity of AT/RT cells. DSF decreased self-renewal ability, cell viability, and proliferation potential and induced apoptosis and cell cycle arrest in ALDH(+) AT/RT cells. Importantly, DSF reduced the metabolism of ALDH(+) AT/RT cells by increasing the nicotinamide adenine dinucleotide ratio of NAD(+)/NADH and regulating Silent mating type Information Regulator 2 homolog 1 (SIRT1), nuclear factor-kappaB, Lin28A/B, and miRNA let-7g. Animals in the DSF-treated group demonstrated a reduction of tumor volume (P < .05) and a significant survival benefit (P = .02).

conclusionOur study demonstrated the therapeutic potential of DSF against BTICs from AT/RT and suggested the possibility of ALDH inhibition for clinical application.

Indexed as

Acetaldehyde Dehydrogenase InhibitorsAldehyde DehydrogenaseAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsCell Cycle CheckpointsCell SurvivalDisulfiramFemaleHumansInfantInfant, NewbornMaleMiceMice, NudeAcetaldehyde Dehydrogenase InhibitorsAldehyde DehydrogenaseAntineoplastic AgentsDisulfiramaldehyde dehydrogenaseatypical teratoid/rhabdoid tumorsbrain tumor initiating cellsdisulfiramsirtuin

Identifiers

PMID25378634
PMCPMC4483115
OpenAlexW2334194959

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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.