Evidence map›Paper›PMID 28099441›Full record

ArticlePloS one2017

PUMA and NF-kB Are Cell Signaling Predictors of Reovirus Oncolysis of Breast Cancer.

Chandini Thirukkumaran, Zhong-Qiao Shi, Ponnampalam Thirukkumaran, Joanne Luider, Karen Kopciuk, Jason Spurrell, Kate Elzinga, Don Morris

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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.0field-weighted citation impact, top 7% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

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  7. The synergistic anticancer effects of ReoT3D, CPT-11, and BBI608 on murine colorectal cancer cells.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2020
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  8. Recent advances of oncolytic virus in cancer therapy.Human vaccines & immunotherapeutics · 2020
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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

8 authors at 2 institutions in 1 country.

Chandini ThirukkumaranTranslation Research Laboratories, Tom Baker Cancer Centre, Calgary, Alberta, Canada.ORCID http://orcid.org/0000-0002-2740-1176
Zhong-Qiao ShiTranslation Research Laboratories, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Ponnampalam ThirukkumaranAlberta Provincial Laboratories, Hospital Dr N.W., Calgary, Alberta, Canada.
Joanne LuiderCalgary Laboratory Services, Foothills Medical Centre, Calgary, Alberta, Canada.
Karen KopciukDept of Cancer Epidemiology and Prevention Research, Cancer Control Alberta, AHS, Holy Cross Centre, SW, Calgary, Alberta, Canada.
Jason SpurrellTranslation Research Laboratories, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Kate ElzingaTranslation Research Laboratories, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Don MorrisTranslation Research Laboratories, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Foothills Medical Centre · CAUniversity of Calgary · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeReovirus is a ubiquitous RNA virus that exploits aberrant signaling pathways for its replication. The oncolytic potential of reovirus against numerous cancers under pre-clinical/clinical conditions has been documented by us and others. Despite its proven clinical activity, the underlying mechanisms of reovirus oncolysis is still not well elucidated. If reovirus therapy is to be optimized for cancer, including breast cancer patients, it is imperative to understand the mechanisms of reovirus oncolysis, especially in treatment of resistant tumour. EXPERIMENTAL APPROACH AND

resultsIn the present study global gene expression profiling was utilized as a preliminary roadmap to tease-out pivotal molecules involved in reovirus induced apoptosis in breast cancer. Reovirus treated HTB133 and MCF7 breast cancer cells revealed transcriptional alteration of a defined subset of apoptotic genes and members of the nuclear factor-kappa B (NF-kB) family and p53 upregulated modulator of apoptosis (PUMA) were prominent. Since NF-kB can paradoxically suppress or promote apoptosis in cancer, the significance of NF-kB in reovirus oncolysis of breast cancer was investigated. Real time PCR analysis indicated a 2.9-4.3 fold increase in NF-kB p65 message levels following reovirus infection of MCF7 and HTB133, respectively. Nuclear translocation of NF-kB p65 protein was also dramatically augmented post reovirus treatment and correlated with enhanced DNA binding. Pharmacologic inhibition of NF-kB lead to oncolytic protection and significant down regulation of PUMA message levels. PUMA down regulation using siRNA suppressed reovirus oncolysis via significantly repressed apoptosis in p53 mutant HTB133 cells.

conclusionsThis study demonstrates for the first time that a prominent pathway of reovirus oncolysis of breast cancer is mediated through NF-kB and that PUMA upregulation is dependent on NF-kB activation. These findings represent potential therapeutic indicators of reovirus treatment in future clinical trials.

Indexed as

ApoptosisApoptosis Regulatory ProteinsBreast NeoplasmsCell Line, TumorElectrophoretic Mobility Shift AssayHumansMCF-7 CellsOncolytic VirotherapyProto-Oncogene ProteinsReoviridaeRNA InterferenceRNA, Small InterferingSignal TransductionTranscription Factor RelAApoptosis Regulatory ProteinsBBC3 protein, humanProto-Oncogene ProteinsRELA protein, humanRNA, Small InterferingTranscription Factor RelA

Identifiers

PMID28099441
PMCPMC5243128
OpenAlexW2572206440

What OpenQuestion holds

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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.