Evidence map›Paper›PMID 25985904›Full record

ArticleThe Journal of infectious diseases2015

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes to Adopt a Tumorigenic Phenotype.

Sujittra Chaiyadet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm K Jones, Michael S Johnson, Lynne Turnbull, Cynthia B Whitchurch, Jeremy Potriquet, Marut Laohaviroj and 6 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
8.4field-weighted citation impact, top 2% 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

85 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  5. Article
  6. Review
  7. Transcriptomic profiling of Kupffer cells exposed toFood and waterborne parasitology · 2025
    Article
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  9. Review
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  12. RETRACTED: PTEN Deficiency Induced by Extracellular Vesicle miRNAs fromInternational journal of molecular sciences · 2024
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  16. Article
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25 more citing papers are in PubMed but not listed here.

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

16 authors at 6 institutions in 4 countries.

Sujittra ChaiyadetBiomedical Sciences, Graduate School Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns.
Javier SotilloCentre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns.
Michael SmoutCentre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns.
Cinzia CantacessiCentre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns Department of Veterinary Medicine, University of Cambridge.
Malcolm K JonesQIMR Berghofer Medical Research Institute, Brisbane School of Veterinary Sciences, University of Queensland, Gatton.
Michael S JohnsoniThree Institute, University of Technology Sydney, Australia.
Lynne TurnbulliThree Institute, University of Technology Sydney, Australia.
Cynthia B WhitchurchiThree Institute, University of Technology Sydney, Australia.
Jeremy PotriquetQIMR Berghofer Medical Research Institute, Brisbane.
Marut LaohavirojDepartment of Pathology.
Jason MulvennaQIMR Berghofer Medical Research Institute, Brisbane.
Paul J BrindleyDepartment of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, George Washington University, Washington D.C.
Jeffrey M BethonyDepartment of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, George Washington University, Washington D.C.
Thewarach LahaDepartment of Parasitology, Faculty of Medicine, Khon Kaen University, Thailand.
Banchob SripaDepartment of Pathology.
Alex LoukasCentre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns.
Australian Institute of Tropical Health and Medicine · AUQIMR Berghofer Medical Research Institute · AUUniversity of Technology Sydney · AUGeorge Washington University · USJames Cook University · AUKhon Kaen University · TH

Funding

Targeting parasite-host communication to combat liver fluke-induced bile duct cancerR01CA164719 · NCI · GEORGE WASHINGTON UNIVERSITY · PI Paul J Brindley, THEWARACH LAHA · 2012 to 2026
$5.0M
Pathogenesis of Opisthorchiasis induced persistent periductal fibrosis and CCAP50AI098639 · NIAID · KHON KAEN UNIVERSITY · PI SRIPA, BANCHOB · 2012 to 2016
$1.6M
NCI NIH HHS R01 CA164719NIAID NIH HHS P50 AI098639
6 · The paper itself

Abstract

backgroundThroughout Asia, there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes, including chronic inflammation and secretion of parasite proteins into the biliary epithelium, drive infection toward cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

methodsVarious microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterized the EV proteome and associated changes in cholangiocytes after EV uptake, and we detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and interleukin 6 (IL-6) secretion was measured to assess the impact of EV internalization.

resultsEVs were identified in fluke culture medium and bile specimens from infected hosts. EVs internalized by cholangiocytes drove cell proliferation and IL-6 secretion and induced changes in protein expression associated with endocytosis, wound repair, and cancer. Antibodies to an O. viverrini tetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes.

conclusionsThis is the first time that EVs from a multicellular pathogen have been identified in host tissues. Our findings imply a role for O. viverrini EVs in pathogenesis and highlight an approach to vaccine development for this infectious cancer.

Indexed as

EndocytosisAnimalsBileCell ProliferationCell Transformation, NeoplasticCricetinaeEpithelial CellsExtracellular VesiclesHumansMass SpectrometryMicroscopyOpisthorchiasisOpisthorchisPhenotypeProteomeProteomecancercholangiocarcinomaextracellular vesiclesliver flukeOpisthorchis viverrini

Identifiers

PMID25985904
PMCPMC4621255
OpenAlexW2097761110

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.