Evidence map›Paper›PMID 26445453›Full record

ArticleJournal of experimental & clinical cancer research : CR2015

Crizotinib-induced antitumour activity in human alveolar rhabdomyosarcoma cells is not solely dependent on ALK and MET inhibition.

Francesca Megiorni, Heather P McDowell, Simona Camero, Olga Mannarino, Simona Ceccarelli, Milena Paiano, Paul D Losty, Barry Pizer, Rajeev Shukla, Antonio Pizzuti and 2 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 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 3 institutions in 2 countries.

Francesca MegiorniDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy. francesca.megiorni@uniroma1.it.
Heather P McDowellDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy. hdominici@tin.it.
Simona CameroDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy. simona.camero@uniroma1.it.
Olga MannarinoDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy. o.mannarino@libero.it.
Simona CeccarelliDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. simona.ceccarelli@uniroma1.it.
Milena PaianoDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy. milena.paiano@uniroma1.it.
Paul D LostyDepartment of Paediatric Surgery, Alder Hey Children's NHS Foundation Trust; Academic Paediatric Surgery Unit, University of Liverpool, Eaton Road, L12 2AP, Liverpool, UK. paul.losty@liverpool.ac.uk.
Barry PizerDepartment of Oncology, Alder Hey Children's NHS Foundation Trust, Eaton Road, L12 2AP, Liverpool, UK. barry.pizer@alderhey.nhs.uk.
Rajeev ShuklaDepartment of Perinatal and Paediatric Pathology, Alder Hey Children's NHS Foundation Trust, Eaton Road, L12 2AP, Liverpool, UK. rajeev.shukla@alderhey.nhs.uk.
Antonio PizzutiDepartment of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy. antonio.pizzuti@uniroma1.it.
Anna ClericoDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy. anna.clerico@uniroma1.it.
Carlo DominiciDepartment of Paediatrics and Infantile Neuropsychiatry, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy. carlo.dominici@uniroma1.it.
Sapienza University of Rome · ITAlder Hey Children's NHS Foundation Trust · GBUniversity of Liverpool · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRhabdomyosarcoma (RMS) is the most commonly diagnosed malignant soft tissue tumour in children and adolescents. Aberrant expression of Anaplastic Lymphoma Kinase (ALK) and MET gene has been implicated in the malignant progression of RMS, especially in the alveolar subtype. This observation suggests that crizotinib (PF-02341066), a kinase inhibitor against ALK and MET, may have a therapeutic role in RMS, although its antitumour activity in this malignancy has not yet been studied.

methodsRH4 and RH30 alveolar RMS (ARMS) cell lines were treated with crizotinib and then assessed by using proliferation, viability, migration and colony formation assays. Multiple approaches, including flow cytometry, immunofluorescence, western blotting and siRNA-based knock-down, were used in order to investigate possible molecular mechanisms linked to crizotinib activity.

resultsIn vitro treatment with crizotinib inhibited ALK and MET proteins, as well as Insulin-like Growth Factor 1 Receptor (IGF1R), with a concomitant robust dephosphorylation of AKT and ERK, two downstream kinases involved in RMS cell proliferation and survival. Exposure to crizotinib impaired cell growth, and accumulation at G2/M phase was attributed to an altered expression and activation of checkpoint regulators, such as Cyclin B1 and Cdc2. Crizotinib was able to induce apoptosis and autophagy in a dose-dependent manner, as shown by caspase-3 activation/PARP proteolytic cleavage down-regulation and by LC3 activation/p62 down-regulation, respectively. The accumulation of reactive oxygen species (ROS) seemed to contribute to crizotinib effects in RH4 and RH30 cells. Moreover, crizotinib-treated RH4 and RH30 cells exhibited a decreased migratory/invasive capacity and clonogenic potential.

conclusionsThese results provide a further insight into the molecular mechanisms affected by crizotinib in ARMS cells inferring that it could be a useful therapeutic tool in ARMS cancer treatment.

Indexed as

AdolescentAnaplastic Lymphoma KinaseAntineoplastic AgentsApoptosisAutophagyCaspase 3CDC2 Protein KinaseCell Line, TumorCell MovementCell ProliferationCell SurvivalChildCrizotinibCyclin B1Cyclin-Dependent KinasesEnzyme ActivationALK protein, humanAnaplastic Lymphoma KinaseAntineoplastic AgentsCaspase 3CCNB1 protein, humanCDC2 Protein KinaseCDK1 protein, humanCrizotinibCyclin B1Cyclin-Dependent KinasesExtracellular Signal-Regulated MAP KinasesIGF1R protein, humanMET protein, humanP62 protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-metPyrazolesPyridinesReactive Oxygen SpeciesReceptor, IGF Type 1Receptor Protein-Tyrosine KinasesReceptors, SomatomedinRNA-Binding ProteinsRNA, Small Interfering

Identifiers

PMID26445453
PMCPMC4596370
OpenAlexW1863071403

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LicenceCC BY
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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.