Evidence map›Paper›PMID 28704425›Full record

ArticlePloS one2017

In vitro nuclear magnetic resonance spectroscopy metabolic biomarkers for the combination of temozolomide with PI3K inhibition in paediatric glioblastoma cells.

Nada M S Al-Saffar, Alice Agliano, Lynley V Marshall, L Elizabeth Jackson, Geetha Balarajah, Jasmin Sidhu, Paul A Clarke, Chris Jones, Paul Workman, Andrew D J Pearson and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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

11 authors at 2 institutions in 1 country.

Nada M S Al-SaffarCancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.ORCID http://orcid.org/0000-0002-1292-0889
Alice AglianoCancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Lynley V MarshallDivisions of Cancer Therapeutics and Molecular Pathology, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
L Elizabeth JacksonCancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Geetha BalarajahCancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Jasmin SidhuCancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Paul A ClarkeCancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
Chris JonesDivisions of Cancer Therapeutics and Molecular Pathology, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Paul WorkmanCancer Research UK Cancer Therapeutics Unit, Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.
Andrew D J PearsonDivisions of Clinical Studies and Cancer Therapeutics, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Martin O LeachCancer Research UK Cancer Imaging Centre, Division of Radiotherapy and Imaging, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Royal Marsden NHS Foundation Trust · GBInstitute of Cancer Research · GB

Funding

Cancer Research UK 16464
6 · The paper itself

Abstract

Recent experimental data showed that the PI3K pathway contributes to resistance to temozolomide (TMZ) in paediatric glioblastoma and that this effect is reversed by combination treatment of TMZ with a PI3K inhibitor. Our aim is to assess whether this combination results in metabolic changes that are detectable by nuclear magnetic resonance (NMR) spectroscopy, potentially providing metabolic biomarkers for PI3K inhibition and TMZ combination treatment. Using two genetically distinct paediatric glioblastoma cell lines, SF188 and KNS42, in vitro 1H-NMR analysis following treatment with the dual pan-Class I PI3K/mTOR inhibitor PI-103 resulted in a decrease in lactate and phosphocholine (PC) levels (P<0.02) relative to control. In contrast, treatment with TMZ caused an increase in glycerolphosphocholine (GPC) levels (P≤0.05). Combination of PI-103 with TMZ showed metabolic effects of both agents including a decrease in the levels of lactate and PC (P<0.02) while an increase in GPC (P<0.05). We also report a decrease in the protein expression levels of HK2, LDHA and CHKA providing likely mechanisms for the depletion of lactate and PC, respectively. Our results show that our in vitro NMR-detected changes in lactate and choline metabolites may have potential as non-invasive biomarkers for monitoring response to combination of PI3K/mTOR inhibitors with TMZ during clinical trials in children with glioblastoma, subject to further in vivo validation.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBrain NeoplasmsCell Line, TumorCell ProliferationChildDacarbazineFuransGlioblastomaHumansLactic AcidPhosphorylcholineProton Magnetic Resonance SpectroscopyPyridinesPyrimidinesTemozolomideBiomarkers, TumorDacarbazineFuransLactic AcidPhosphorylcholinePI103PyridinesPyrimidinesTemozolomide

Identifiers

PMID28704425
PMCPMC5509135
OpenAlexW2734918997

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.