Evidence mapPaperPMID 30546006Full record

ArticleCell death & disease2018

Efficacy of arginine depletion by ADI-PEG20 in an intracranial model of GBM.

Justyna Magdalena Przystal, Nabil Hajji, Combiz Khozoie, Alexander Renziehausen, Qingyu Zeng, Fernando Abaitua, Amin Hajitou, Keittisak Suwan, Elizabeth Want, John Bomalaski and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

37 citing papers in PubMed, 55 citations in OpenAlex.

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  14. [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024
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  20. Glioblastoma Metabolism: Insights and Therapeutic Strategies.International journal of molecular sciences · 2023
    Review
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

14 authors at 4 institutions in 2 countries.

Justyna Magdalena PrzystalPhage Therapy Group, Division of Brain Sciences, Imperial College London, London, UK.
Nabil HajjiJohn Fulcher Neuro-Oncology Laboratory, Division of Brain Sciences, Imperial College London, London, UK.
Combiz KhozoieJohn Fulcher Neuro-Oncology Laboratory, Division of Brain Sciences, Imperial College London, London, UK.
Alexander RenziehausenJohn Fulcher Neuro-Oncology Laboratory, Division of Brain Sciences, Imperial College London, London, UK.
Qingyu ZengJohn Fulcher Neuro-Oncology Laboratory, Division of Brain Sciences, Imperial College London, London, UK.
Fernando AbaituaJohn Fulcher Neuro-Oncology Laboratory, Division of Brain Sciences, Imperial College London, London, UK.
Amin HajitouPhage Therapy Group, Division of Brain Sciences, Imperial College London, London, UK.
Keittisak SuwanPhage Therapy Group, Division of Brain Sciences, Imperial College London, London, UK.
Elizabeth WantDepartment of Cancer and Surgery, Imperial College, London, UK.
John BomalaskiPolaris Pharmaceuticals Inc., San Diego, California, USA.
Peter SzlosarekCenter for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, UK.
Kevin O'NeillJohn Fulcher Neuro-Oncology Laboratory, Division of Brain Sciences, Imperial College London, London, UK.
Tim CrookSt Luke's Cancer Centre, Egerton Road, Guildford, UK.
Nelofer SyedJohn Fulcher Neuro-Oncology Laboratory, Division of Brain Sciences, Imperial College London, London, UK. n.syed@imperial.ac.uk.
Imperial College London · GBMount Vernon Cancer Centre · GBPolaris (United States) · USQueen Mary University of London · GB

Funding

Cancer Research UK 25887Medical Research Council G0701159
6 · The paper itself

Abstract

Glioblastoma multiforme (GBM) remains a cancer with a poor prognosis and few effective therapeutic options. Successful medical management of GBM is limited by the restricted access of drugs to the central nervous system (CNS) caused by the blood brain barrier (BBB). We previously showed that a subset of GBM are arginine auxotrophic because of transcriptional silencing of ASS1 and/or ASL and are sensitive to pegylated arginine deiminase (ADI-PEG20). However, it is unknown whether depletion of arginine in peripheral blood in vivo has therapeutic activity against intracranial disease. In the present work, we describe the efficacy of ADI-PEG20 in an intracranial model of human GBM in which tumour growth and regression are assessed in real time by measurement of luciferase activity. Animals bearing intracranial human GBM tumours of varying ASS status were treated with ADI-PEG20 alone or in combination with temozolomide and monitored for tumour growth and regression. Monotherapy ADI-PEG20 significantly reduces the intracranial growth of ASS1 negative GBM and extends survival of mice carrying ASS1 negative GBM without obvious toxicity. The combination of ADI-PEG20 with temozolomide (TMZ) demonstrates enhanced effects in both ASS1 negative and ASS1 positive backgrounds.Our data provide proof of principle for a therapeutic strategy for GBM using peripheral blood arginine depletion that does not require BBB passage of drug and is well tolerated. The ability of ADI-PEG20 to cytoreduce GBM and enhance the effects of temozolomide argues strongly for its early clinical evaluation in the treatment of GBM.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsArginineArgininosuccinate SynthaseBrain NeoplasmsCell Line, TumorCell ProliferationGlioblastomaHumansHydrolasesMicePolyethylene GlycolsTemozolomideXenograft Model Antitumor AssaysADI PEG20ArginineArgininosuccinate SynthaseHydrolasesPolyethylene GlycolsTemozolomide

Identifiers

PMID30546006
PMCPMC6294248
OpenAlexW2903614074

What Socratic 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 Socratic graph.