Evidence map›Paper›PMID 27588497›Full record

ArticleOncotarget2016

γ-Secretase inhibitor I inhibits neuroblastoma cells, with NOTCH and the proteasome among its targets.

Carmen Dorneburg, Annika V Goß, Matthias Fischer, Frederik Roels, Thomas F E Barth, Frank Berthold, Roland Kappler, Franz Oswald, Jens T Siveke, Jan J Molenaar and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.1field-weighted citation impact, top 21% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

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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

12 authors at 7 institutions in 2 countries.

Carmen DorneburgDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
Annika V GoßDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
Matthias FischerChildren's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
Frederik RoelsChildren's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
Thomas F E BarthDepartment of Pathology, University Medical Center Ulm, Ulm, Germany.
Frank BertholdChildren's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany.
Roland KapplerDepartment of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
Franz OswaldDepartment of Internal Medicine I, University Medical Center Ulm, Ulm, Germany.
Jens T SivekeDepartment of Internal Medicine, University Hospital Essen, Essen, Germany.
Jan J MolenaarDepartment of Oncogenomics, Academic Medical Center, Amsterdam, The Netherlands.
Klaus-Michael DebatinDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
Christian BeltingerDepartment of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
University Hospital Ulm · DEUniversität Ulm · DEUniversity Hospital Cologne · DEAcademic Medical Center · NLEssen University Hospital · DELudwig-Maximilians-Universität München · DEUniversity of Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As high-risk neuroblastoma (NB) has a poor prognosis, new therapeutic modalities are needed. We therefore investigated the susceptibility of NB cells to γ-secretase inhibitor I (GSI-I). NOTCH signaling activity, the cellular effects of GSI-I and its mechanisms of cytotoxicity were evaluated in NB cells in vitro and in vivo. The results show that NOTCH signaling is relevant for human NB cells. Of the GSIs screened in vitro GSI-I was the most effective inhibitor of NB cells. Both MYCN-amplified and non-amplified NB cells were susceptible to GSI-I. Among the targets of GSI-I in NB cells were NOTCH and the proteasome. GSI-I caused G2/M arrest that was enhanced by acute activation of MYCN and led to mitotic dysfunction. GSI-I also induced proapoptotic NOXA. Survival of mice bearing an MYCN non-amplified orthotopic patient-derived NB xenograft was significantly prolonged by systemic GSI-I, associated with mitotic catastrophe and reduced angiogenesis, and without evidence of intestinal toxicity. In conclusion, the activity of GSI-I on multiple targets in NB cells and the lack of gastrointestinal toxicity in mice are advantageous and merit further investigations of GSI-I in NB.

Indexed as

Amyloid Precursor Protein SecretasesAnimalsApoptosisBrain NeoplasmsCarbamatesCell CycleCell Line, TumorDipeptidesEnzyme InhibitorsFemaleHumansIn Situ Hybridization, FluorescenceMiceMitosisNeoplasm TransplantationNeovascularization, PathologicAmyloid Precursor Protein Secretasesbenzyloxycarbonyl-leucyl-leucyl-norleucinalCarbamatesDipeptidesEnzyme InhibitorsL 685458MYCN protein, humanMYCN protein, mouseN-Myc Proto-Oncogene ProteinNOTCH1 protein, humanOligopeptidesProteasome Endopeptidase ComplexReceptor, Notch1Receptors, Notchin vivoneuroblastomaNOTCHpreclinicalγ-secretase inhibitor

Identifiers

PMID27588497
PMCPMC5325329
OpenAlexW2508136278

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.