Evidence map›Paper›PMID 33443161›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

A protease-activated, near-infrared fluorescent probe for early endoscopic detection of premalignant gastrointestinal lesions.

Joshua J Yim, Stefan Harmsen, Krzysztof Flisikowski, Tatiana Flisikowska, Hong Namkoong, Megan Garland, Nynke S van den Berg, José G Vilches-Moure, Angelika Schnieke, Dieter Saur and 8 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.2field-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

35 citing papers in PubMed, 67 citations in OpenAlex.

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  15. Pigs: Large Animal Preclinical Cancer Models.World journal of oncology · 2024
    Review
  16. Review
  17. TNF ΔARE Pigs: A Translational Crohn's Disease Model.Journal of Crohn's & colitis · 2023
    Article
  18. A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
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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

18 authors at 7 institutions in 2 countries.

Joshua J YimDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305.
Stefan HarmsenDepartment of Radiology, Bio-X Program and Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0001-5812-7299
Krzysztof FlisikowskiChair of Livestock Biotechnology, Technische Universität München, 85354 Freising, Germany.
Tatiana FlisikowskaChair of Livestock Biotechnology, Technische Universität München, 85354 Freising, Germany.ORCID 0000-0003-0481-117X
Hong NamkoongDepartment of Medicine, Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0002-0816-0426
Megan GarlandDepartment of Cancer Biology, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0002-5622-5095
Nynke S van den BergDepartment of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305.
José G Vilches-MoureDepartment of Comparative Medicine, Stanford School of Medicine, Stanford, CA 94305.
Angelika SchniekeChair of Livestock Biotechnology, Technische Universität München, 85354 Freising, Germany.ORCID 0000-0002-5761-9635
Dieter SaurDivision of Translational Cancer Research, German Cancer Research Center and German Cancer Consortium, 69120 Heidelberg, Germany.
Sarah GlaslHelmholtz Zentrum München, German Research Center for Environmental Health, Institute of Biological and Medical Imaging, 85764 Neuherberg, Germany.
Dimitris GorpasHelmholtz Zentrum München, German Research Center for Environmental Health, Institute of Biological and Medical Imaging, 85764 Neuherberg, Germany.ORCID 0000-0001-9576-8087
Aida HabtezionDepartment of Medicine, Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0002-4473-006X
Vasilis NtziachristosHelmholtz Zentrum München, German Research Center for Environmental Health, Institute of Biological and Medical Imaging, 85764 Neuherberg, Germany.
Christopher H ContagDepartment of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824.ORCID 0000-0002-1011-8278
Sanjiv S GambhirDepartment of Radiology, Bio-X Program and Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA 94305.ORCID 0000-0002-2711-7554
Matthew BogyoDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305; mbogyo@stanford.edu srogalla@stanford.edu.ORCID 0000-0003-3753-4412
Stephan RogallaDepartment of Radiology, Bio-X Program and Molecular Imaging Program, Stanford University School of Medicine, Stanford, CA 94305; mbogyo@stanford.edu srogalla@stanford.edu.ORCID 0000-0002-1311-2672
Stanford University · USHelmholtz Zentrum München · DETechnical University of Munich · DEStanford Medicine · USGerman Cancer Research Center · DEMichigan State University · USUniversity of Pennsylvania · US

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Vittorio Sebastiano · 2007 to 2026
$71.4M
Dual orthogonal fluorescent protease sensors for image guided surgeryR01EB028628 · NIBIB · STANFORD UNIVERSITY · PI BOGYO, MATTHEW · 2019 to 2023
$1.9M
Generation of highly selective activity based probes using chemically modified phageR01EB026285 · NIBIB · STANFORD UNIVERSITY · PI BOGYO, MATTHEW · 2018 to 2021
$1.9M
NIBIB NIH HHS R01 EB026285NIBIB NIH HHS R01 EB028628
6 · The paper itself

Abstract

Fluorescence imaging is currently being actively developed for surgical guidance; however, it remains underutilized for diagnostic and endoscopic surveillance of incipient colorectal cancer in high-risk patients. Here we demonstrate the utility and potential for clinical translation of a fluorescently labeled cathepsin-activated chemical probe to highlight gastrointestinal lesions. This probe stays optically dark until it is activated by proteases produced by tumor-associated macrophages and accumulates within the lesions, enabling their detection using an endoscope outfitted with a fluorescence detector. We evaluated the probe in multiple murine models and a human-scale porcine model of gastrointestinal carcinogenesis. The probe provides fluorescence-guided surveillance of gastrointestinal lesions and augments histopathological analysis by highlighting areas of dysplasia as small as 400 µm, which were visibly discernible with significant tumor-to-background ratios, even in tissues with a background of severe inflammation and ulceration. Given these results, we anticipate that this probe will enable sensitive fluorescence-guided biopsies, even in the presence of highly inflamed colorectal tissue, which will improve early diagnosis to prevent gastrointestinal cancers.

Indexed as

AnimalsColonColonic NeoplasmsColorectal NeoplasmsDisease Models, AnimalEarly Detection of CancerEndoscopyFemaleFluorescenceFluorescent DyesGastrointestinal NeoplasmsGastrointestinal TractMaleMiceMice, Inbred C57BLMolecular ImagingFluorescent Dyesactivity-based probeearly detectionendoscopyfluorescencehigh-risk patients

Identifiers

PMID33443161
PMCPMC7817203
OpenAlexW3116742157

What OpenQuestion holds

Textmetadata
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.