Evidence map›Paper›PMID 25976165›Full record

ArticlePurinergic signalling2015

Potentiation of temozolomide antitumor effect by purine receptor ligands able to restrain the in vitro growth of human glioblastoma stem cells.

Iolanda D'Alimonte, Eleonora Nargi, Mariachiara Zuccarini, Paola Lanuti, Patrizia Di Iorio, Patricia Giuliani, Lucia Ricci-Vitiani, Roberto Pallini, Francesco Caciagli, Renata Ciccarelli

Open access · bronzeAbstract read
In one paragraph

Article in Purinergic signalling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.0field-weighted citation impact, top 16% 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, 37 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Purinergic system in cancer stem cells.Purinergic signalling · 2025
    Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. The P2X7 Receptor: Central Hub of Brain Diseases.Frontiers in molecular neuroscience · 2020
    Review
  17. Article
  18. Article
  19. Review
  20. 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

10 authors at 3 institutions in 1 country.

Iolanda D'AlimonteDepartment of Medical, Oral and Biotechnology Sciences, University of Chieti-Pescara, via dei Vestini 29, 66100, Chieti, Italy.
Eleonora Nargi
Mariachiara Zuccarini
Paola Lanuti
Patrizia Di Iorio
Patricia Giuliani
Lucia Ricci-Vitiani
Roberto Pallini
Francesco Caciagli
Renata Ciccarelli
University of Chieti-Pescara · ITIstituto Superiore di Sanità · ITUniversità Cattolica del Sacro Cuore · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma multiforme (GBM), the most common and aggressive brain tumor in humans, comprises a population of stem-like cells (GSCs) that are currently investigated as potential target for GBM therapy. Here, we used GSCs isolated from three different GBM surgical specimens to examine the antitumor activity of purines. Cultured GSCs expressed either metabotropic adenosine P1 and ATP P2Y receptors or ionotropic P2X7 receptors. GSC exposure for 48 h to 10-150 μM ATP, P2R ligand, or to ADPβS or MRS2365, P2Y1R agonists, enhanced cell expansion. This effect was counteracted by the PY1R antagonist MRS2500. In contrast, 48-h treatment with higher doses of ATP or UTP, which binds to P2Y2/4R, or 2'(3')-O-(4-benzoylbenzoyl)-ATP (Bz-ATP), P2X7R agonist, decreased GSC proliferation. Such a reduction was due to apoptotic or necrotic cell death but mostly to growth arrest. Accordingly, cell regrowth and secondary neurosphere formation were observed 2 weeks after the end of treatment. Suramin, nonselective P2R antagonist, MRS1220 or AZ11645373, selective A3R or P2X7R antagonists, respectively, counteracted ATP antiproliferative effects. AZ11645373 also abolished the inhibitory effect of Bz-ATP low doses on GSC growth. These findings provide important clues on the anticancer potential of ligands for A3R, P2Y1R, and P2X7R, which are involved in the GSC growth control. Interestingly, ATP and BzATP potentiated the cytotoxicity of temozolomide (TMZ), currently used for GBM therapy, enabling it to cause a greater and long-lasting inhibitory effect on GSC duplication when readded to cells previously treated with purine nucleotides plus TMZ. These are the first findings identifying purine nucleotides as able to enhance TMZ antitumor efficacy and might have an immediate translational impact.

Indexed as

Adenosine A3 Receptor AntagonistsAdenosine TriphosphateAntineoplastic Agents, AlkylatingApoptosisBrain NeoplasmsCaspase InhibitorsCell ProliferationDacarbazineDrug SynergismGlioblastomaHumansLigandsNeoplastic Stem CellsPurinergic P2Y Receptor AntagonistsReceptors, PurinergicReceptors, Purinergic P13'-O-(4-benzoyl)benzoyladenosine 5'-triphosphateAdenosine A3 Receptor AntagonistsAdenosine TriphosphateAntineoplastic Agents, AlkylatingCaspase InhibitorsDacarbazineLigandsPurinergic P2Y Receptor AntagonistsReceptors, PurinergicReceptors, Purinergic P1Receptors, Purinergic P2X7Temozolomide

Identifiers

PMID25976165
PMCPMC4529851
OpenAlexW2202609685

What OpenQuestion holds

Textmetadata
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.