Evidence map›Paper›PMID 27840845›Full record

ArticleCellular and molecular gastroenterology and hepatology2016

Overexpressed Claudin-1 Can Be Visualized Endoscopically in Colonic Adenomas In Vivo.

Emily F Rabinsky, Bishnu P Joshi, Asha Pant, Juan Zhou, Xiyu Duan, Arlene Smith, Rork Kuick, Shuling Fan, Asma Nusrat, Scott R Owens and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Targeting claudins in cancer: diagnosis, prognosis and therapy.American journal of cancer research · 2021
    Review
  10. Article
  11. Article
  12. Multiplexed Imaging Strategy to Distinguish Indeterminant Biliary Strictures: AnWorld journal of gastroenterology, hepatology and endoscopy · 2020
    Article
  13. Review
  14. Article
  15. Article
  16. Use of ModifiedInternational journal of molecular sciences · 2019
    Article
  17. Review
  18. Article
  19. Article
  20. Article
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 1 institution in 1 country.

Emily F RabinskyDepartment of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.
Bishnu P JoshiDepartment of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.
Asha PantDepartment of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.
Juan ZhouDepartment of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.
Xiyu DuanDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
Arlene SmithDepartment of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.
Rork KuickDepartment of Biostatistics, University of Michigan, Ann Arbor, Michigan.
Shuling FanDepartment of Pathology, University of Michigan, Ann Arbor, Michigan.
Asma NusratDepartment of Pathology, University of Michigan, Ann Arbor, Michigan.
Scott R OwensDepartment of Pathology, University of Michigan, Ann Arbor, Michigan.
Henry D AppelmanDepartment of Pathology, University of Michigan, Ann Arbor, Michigan.
Thomas D WangDepartment of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan; Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan.
University of Michigan · US

Funding

Validation & Pathology CoreU54CA163059 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RUBENSTEIN, JOEL H, WANG, THOMAS D · 2011 to 2022
$12.1M
Multiplexed imaging of biliary intra-epithelial neoplasiaR01CA200007 · NCI · UNIVERSITY OF WASHINGTON · PI SEIBEL, ERIC J, WANG, THOMAS D · 2015 to 2019
$2.9M
Targeted Multi-Spectral Dual Axes Confocal Imaging of In Vivo Molecular ExpressioR01CA142750 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KURABAYASHI, KATSUO, LUKER, GARY D · 2010 to 2014
$2.4M
Early Detection of Colorectal Cancer on Near-Infrared Molecular EndoscopyR01CA193377 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WANG, THOMAS D · 2016 to 2020
$2.1M
Multi-Photon endomicroscope for real-time in vivo vertical sectioningR01EB020644 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OLDHAM, KENN R · 2015 to 2018
$1.3M
NCI NIH HHS R01 CA142750NCI NIH HHS R01 CA193377NCI NIH HHS R01 CA200007NCI NIH HHS U54 CA163059NIBIB NIH HHS R01 EB020644
6 · The paper itself

Abstract

BACKGROUND &

aimsConventional white-light colonoscopy aims to reduce the incidence and mortality of colorectal cancer (CRC). CRC has been found to arise from missed polypoid and flat precancerous lesions. We aimed to establish proof-of-concept for real-time endoscopic imaging of colonic adenomas using a near-infrared peptide that is specific for claudin-1.

methodsWe used gene expression profiles to identify claudin-1 as a promising early CRC target, and performed phage display against the extracellular loop of claudin-1 (amino acids 53-80) to identify the peptide RTSPSSR. With a Cy5.5 label, we characterized binding parameters and showed specific binding to human CRC cells. We collected in vivo near-infrared fluorescence images endoscopically in the CPC;Apc mouse, which develops colonic adenomas spontaneously. With immunofluorescence, we validated specific peptide binding to adenomas from the proximal human colon.

resultsWe found a 2.5-fold increase in gene expression for claudin-1 in human colonic adenomas compared with normal. We showed specific binding of RTSPSSR to claudin-1 in knockdown and competition studies, and measured an affinity of 42 nmol/L and a time constant of 1.2 minutes to SW620 cells. In the mouse, we found a significantly higher target-to-background ratio for both polypoid and flat adenomas compared with normal by in vivo images. On immunofluorescence, we found significantly greater intensity for human adenomas (mean ± SD, 25.5 ± 14.0) vs normal (mean ± SD, 9.1 ± 6.0) and hyperplastic polyps (mean ± SD, 3.1 ± 3.7;

conclusionsClaudin-1 is overexpressed in premalignant colonic lesions, and can be detected endoscopically in vivo with a near-infrared, labeled peptide.

Indexed as

APC, adenomatous polyposis coliBSA, bovine serum albuminCLDN1, claudin-1Colon CancerCRC, colorectal cancerDAPI, 4′,6-diamidino-2-phenylindoleEarly DetectionHRP, horseradish peroxidaseIF, immunofluorescenceIHC, immunohistochemistryMolecular ImagingPBS, phosphate-buffered salinePBST, phosphate-buffered saline plus 0.1% Tween-20PFA, paraformaldehydeRT, room temperaturesiCL, control small interfering RNAsiRNA, small interfering RNASSA, sessile serrated adenomaT/B, target-to-backgroundTEER, transepithelial electrical resistanceTFA, trifluoroacetic acidZO-1, zonula occludens-1

Identifiers

PMID27840845
PMCPMC4980721
OpenAlexW2262646853

What OpenQuestion holds

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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.