Evidence map›Paper›PMID 20856931›Full record

ArticlePloS one2010

Regulation of heparin-binding EGF-like growth factor by miR-212 and acquired cetuximab-resistance in head and neck squamous cell carcinoma.

Hiromitsu Hatakeyama, Haixia Cheng, Pamela Wirth, Ashley Counsell, Samuel R Marcrom, Carey Burton Wood, Paula R Pohlmann, Jill Gilbert, Barbara Murphy, Wendell G Yarbrough and 6 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
6.8field-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

69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 165 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
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  7. Article
  8. Article
  9. Theranostic Potential ofIndian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2023
    Article
  10. Review
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  12. Article
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  14. Review
  15. P2YOral oncology · 2020
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

9 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 4 institutions in 1 country.

Hiromitsu HatakeyamaDivision of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
Haixia Cheng
Pamela Wirth
Ashley Counsell
Samuel R Marcrom
Carey Burton Wood
Paula R Pohlmann
Jill Gilbert
Barbara Murphy
Wendell G Yarbrough
Deric L Wheeler
Paul M Harari
Yan Guo
Yu Shyr
Robbert J Slebos
Christine H Chung
Vanderbilt University · USUniversity of Wisconsin–Madison · USJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

Molecular signatures of HNSCC in response to targeted therapiesR01DE017982 · NIDCR · VANDERBILT UNIVERSITY · PI CHUNG, CHRISTINE H · 2007 to 2011
$1.9M
EGFR/Radiation Responses and Resistance InteractionsR01CA113448 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI HARARI, PAUL M · 2006 to 2010
$1.3M
NCI NIH HHS R01 CA113448NCI NIH HHS R01-CA-113448NIDCR NIH HHS R01 DE017982NIDCR NIH HHS R01-DE-017982
6 · The paper itself

Abstract

backgroundWe hypothesized that chronic inhibition of epidermal growth factor receptor (EGFR) by cetuximab, a monoclonal anti-EGFR antibody, induces up-regulation of its ligands resulting in resistance and that microRNAs (miRs) play an important role in the ligand regulation in head and neck squamous cell carcinoma (HNSCC). METHODOLOGY/PRINCIPAL

findingsGenome-wide changes in gene and miR expression were determined in cetuximab-sensitive cell line, SCC1, and its resistant derivative 1Cc8 using DNA microarrays and RT-PCR. The effects of differentially expressed EGFR ligands and miRs were examined by MTS, colony formation, ELISA, and western blot assays. Heparin-binding EGF-like growth factor (HB-EGF) and its regulator, miR-212, were differentially expressed with statistical significance when SCC1 and 1Cc8 were compared for gene and miR expression. Stimulation with HB-EGF induced cetuximab resistance in sensitive cell lines. Inhibition of HB-EGF and the addition of miR-212 mimic induced cetuximab sensitivity in resistant cell lines. MicroRNA-212 and HB-EGF expression were inversely correlated in an additional 33 HNSCC and keratinocyte cell lines. Six tumors and 46 plasma samples from HNSCC patients were examined for HB-EGF levels. HB-EGF plasma levels were lower in newly diagnosed HNSCC patients when compared to patients with recurrent disease. CONCLUSIONS/SIGNIFICANCE: Increased expression of HB-EGF due to down-regulation of miR-212 is a possible mechanism of cetuximab resistance. The combination of EGFR ligand inhibitors or miR modulators with cetuximab may improve the clinical outcome of cetuximab therapy in HNSCC.

Indexed as

Drug Resistance, NeoplasmGene Expression Regulation, NeoplasticAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCarcinoma, Squamous CellCell Line, TumorCetuximabDown-RegulationHead and Neck NeoplasmsHeparin-binding EGF-like Growth FactorHumansIntercellular Signaling Peptides and ProteinsMicroRNAsUp-RegulationAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCetuximabHBEGF protein, humanHeparin-binding EGF-like Growth FactorIntercellular Signaling Peptides and ProteinsMicroRNAsMIRN212 microRNA, human

Identifiers

PMID20856931
PMCPMC2938338
OpenAlexW1997976641

What OpenQuestion holds

Textmetadata
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.