Evidence map›Paper›PMID 24327015›Full record

ArticleBritish journal of cancer2014

An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.

A Linton, Y Y Cheng, K Griggs, Lyn Schedlich, M B Kirschner, S Gattani, S Srikaran, S Chuan-Hao Kao, B C McCaughan, S Klebe and 2 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

27 citing papers in PubMed, 48 citations in OpenAlex.

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  6. Genomics and Functional Genomics of Malignant Pleural Mesothelioma.International journal of molecular sciences · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

A LintonAsbestos Diseases Research Institute (ADRI), University of Sydney, Concord, NSW 2139, Australia.
Y Y ChengAsbestos Diseases Research Institute (ADRI), University of Sydney, Concord, NSW 2139, Australia.
K GriggsDepartment of Anatomical Pathology, Flinders Medical Centre, Bedford, SA, Australia.
Lyn Schedlich
M B KirschnerAsbestos Diseases Research Institute (ADRI), University of Sydney, Concord, NSW 2139, Australia.
S GattaniAsbestos Diseases Research Institute (ADRI), University of Sydney, Concord, NSW 2139, Australia.
S SrikaranAsbestos Diseases Research Institute (ADRI), University of Sydney, Concord, NSW 2139, Australia.
S Chuan-Hao KaoAsbestos Diseases Research Institute (ADRI), University of Sydney, Concord, NSW 2139, Australia.
B C McCaughanCardiothoracic Surgical Unit, Royal Prince Alfred Hospital; The Baird Institute and Sydney Medical School, University of Sydney, Sydney, Australia.
S KlebeDepartment of Anatomical Pathology, Flinders Medical Centre, Bedford, SA, Australia.
N van ZandwijkAsbestos Diseases Research Institute (ADRI), University of Sydney, Concord, NSW 2139, Australia.
G ReidAsbestos Diseases Research Institute (ADRI), University of Sydney, Concord, NSW 2139, Australia.
Asbestos Diseases Research Institute · AUUniversity of Sydney · AUFlinders Medical Centre · AUBaird Institute · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMalignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed.

methodsUtilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients.

resultsGene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in over 10% of cells correlated significantly with a poor prognosis.

conclusionThese results suggest that RNAi-based screening has utility in identifying new targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for treatment of this disease.

Indexed as

RNA InterferenceApoptosisBlood ProteinsCDC2 Protein KinaseCell CycleCell Cycle CheckpointsCell Cycle ProteinsCell Line, TumorCisplatinCytoskeletal ProteinsDNA RepairDNA ReplicationHumansLung NeoplasmsMesotheliomaMesothelioma, MalignantBlood ProteinsCDC2 Protein KinaseCell Cycle ProteinsCisplatinCytoskeletal Proteinsfactor XIIa inhibitorNDC80 protein, humanNuclear ProteinsPolo-Like Kinase 1Protein Serine-Threonine KinasesProto-Oncogene ProteinsPurinesRoscovitine

Identifiers

PMID24327015
PMCPMC3899767
OpenAlexW2035203537

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.