Evidence map›Paper›PMID 28562336›Full record

ArticleOncotarget2017

Synergistic targeting of malignant pleural mesothelioma cells by MDM2 inhibitors and TRAIL agonists.

Loredana Urso, Ilaria Cavallari, Micol Silic-Benussi, Lorena Biasini, Giulia Zago, Fiorella Calabrese, Pier Franco Conte, Vincenzo Ciminale, Giulia Pasello

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. MicroRNA-215-5p Treatment Suppresses Mesothelioma Progression via the MDM2-p53-Signaling Axis.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Article
  9. Review
  10. 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

9 authors at 3 institutions in 1 country.

Loredana UrsoDepartment of Surgery, Oncology and Gastroenterology, University of Padova, 35128, Padova, Italy.
Ilaria CavallariImmunology and Molecular Oncology Unit, Veneto Institute of Oncology, IRCCS, 35128, Padova, Italy.
Micol Silic-BenussiImmunology and Molecular Oncology Unit, Veneto Institute of Oncology, IRCCS, 35128, Padova, Italy.
Lorena BiasiniImmunology and Molecular Oncology Unit, Veneto Institute of Oncology, IRCCS, 35128, Padova, Italy.
Giulia ZagoMedical Oncology Unit 2, Veneto Institute of Oncology, IRCCS, 35128, Padova, Italy.
Fiorella CalabreseDepartment of Cardio-Thoracic and Vascular Sciences, University of Padova, 35128, Padova, Italy.
Pier Franco ConteDepartment of Surgery, Oncology and Gastroenterology, University of Padova, 35128, Padova, Italy.
Vincenzo CiminaleDepartment of Surgery, Oncology and Gastroenterology, University of Padova, 35128, Padova, Italy.
Giulia PaselloMedical Oncology Unit 2, Veneto Institute of Oncology, IRCCS, 35128, Padova, Italy.
Istituti di Ricovero e Cura a Carattere Scientifico · ITUniversity of Padua · ITIstituto Oncologico Veneto · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Malignant Pleural Mesothelioma (MPM) is a chemoresistant tumor characterized by low rate of p53 mutation and upregulation of Murine Double Minute 2 (MDM2), suggesting that it may be effectively targeted using MDM2 inhibitors. In the present study, we investigated the anticancer activity of the MDM2 inhibitors Nutlin 3a (in vitro) and RG7112 (in vivo), as single agents or in combination with rhTRAIL.In vitro studies were performed using MPM cell lines derived from epithelioid (ZL55, M14K), biphasic (MSTO211H) and sarcomatoid (ZL34) MPMs. In vivo studies were conducted on a sarcomatoid MPM mouse model.In all the cell lines tested (with the exception of ZL55, which carries a biallelic loss-of-function mutation of p53), Nutlin 3a enhanced p21, MDM2 and DR5 expression, and decreased survivin expression. These changes were associated to cell cycle arrest but not to a significant induction of apoptosis. A synergistic pro-apoptotic effect was obtained through the association of rhTRAIL in all the cell lines harboring functional p53. This synergistic interaction of MDM2 inhibitor and TRAIL agonist was confirmed using a mouse preclinical model. Our results suggest that the combined targeting of MDM2 and TRAIL might provide a novel therapeutic option for treatment of MPM patients, particularly in the case of sarcomatoid MPM with MDM2 overexpression and functional inactivation of wild-type p53.

Indexed as

AnimalsAntineoplastic AgentsApoptosisBiomarkers, TumorCell Cycle CheckpointsCell Line, TumorDrug SynergismHumansImidazolesLung NeoplasmsMesotheliomaMesothelioma, MalignantMiceMutationPiperazinesPleural NeoplasmsAntineoplastic AgentsBiomarkers, TumorImidazolesnutlin 3PiperazinesProtein Kinase InhibitorsProto-Oncogene Proteins c-mdm2TNF-Related Apoptosis-Inducing LigandMDM2mesotheliomap53RG7112TRAIL

Identifiers

PMID28562336
PMCPMC5546476
OpenAlexW2612178153

What OpenQuestion holds

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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.