Evidence map›Paper›PMID 28212575›Full record

ArticleOncotarget2017

Upregulation of mucin glycoprotein MUC1 in the progression to esophageal adenocarcinoma and therapeutic potential with a targeted photoactive antibody-drug conjugate.

Mohammed Adil Butt, Hayley Pye, Rehan J Haidry, Dahmane Oukrif, Saif-U-Rehman Khan, Ignazio Puccio, Michael Gandy, Halla W Reinert, Ellie Bloom, Mohammed Rashid and 6 more

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

13 citing papers in PubMed, 25 citations in OpenAlex.

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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

16 authors at 4 institutions in 1 country.

Mohammed Adil ButtDepartment for Tissue & Energy, University College London, London, UK.
Hayley PyeDepartment for Tissue & Energy, University College London, London, UK.
Rehan J HaidryUpper Gastrointestinal Service, University College London Hospitals NHS Foundation Trust, London, UK.
Dahmane OukrifDepartment of Pathology, University College London, London, UK.
Saif-U-Rehman KhanDepartment for Tissue & Energy, University College London, London, UK.
Ignazio PuccioDepartment for Tissue & Energy, University College London, London, UK.
Michael GandyDepartment for Tissue & Energy, University College London, London, UK.
Halla W ReinertDepartment for Tissue & Energy, University College London, London, UK.
Ellie BloomDepartment for Tissue & Energy, University College London, London, UK.
Mohammed RashidDepartment of Oncology, UCL Cancer Institute, London, UK.
Gokhan YahiogluAntikor BioPharma, Stevenage Bioscience Catalyst, Hertfordshire, UK.
Mahendra P DeonarainDepartment for Tissue & Energy, University College London, London, UK.
Rifat HamoudiDepartment for Tissue & Energy, University College London, London, UK.
Manuel Rodriguez-JustoDepartment of Pathology, University College London, London, UK.
Marco R NovelliDepartment of Pathology, University College London, London, UK.
Laurence B LovatDepartment for Tissue & Energy, University College London, London, UK.
University College London · GBStevenage Bioscience Catalyst · GBUniversity College London Hospitals NHS Foundation Trust · GBCRUK Lung Cancer Centre of Excellence · GB

Funding

Medical Research Council MC_PC_13036
6 · The paper itself

Abstract

backgroundMucin glycoprotein 1 (MUC1) is a glycosylated transmembrane protein on epithelial cells. We investigate MUC1 as a therapeutic target in Barrett's epithelium (BE) and esophageal adenocarcinoma (EA) and provide proof of concept for a light based therapy targeting MUC1.

resultsMUC1 was present in 21% and 30% of significantly enriched pathways comparing BE and EA to squamous epithelium respectively. MUC1 gene expression was x2.3 and x2.2 higher in BE (p=<0.001) and EA (p=0.03). MUC1 immunohistochemical expression increased during progression to EA and followed tumor invasion. HuHMFG1 based photosensitive antibody drug conjugates (ADC) showed cell internalization, MUC1 selective and light-dependent cytotoxicity (p=0.0006) and superior toxicity over photosensitizer alone (p=0.0022).

methodsGene set enrichment analysis (GSEA) evaluated pathways during BE and EA development and quantified MUC1 gene expression. Immunohistochemistry and flow cytometry evaluated the anti-MUC1 antibody HuHMFG1 in esophageal cells of varying pathological grade. Confocal microscopy examined HuHMFG1 internalization and HuHMFG1 ADCs were created to deliver a MUC1 targeted phototoxic payload.

conclusionsMUC1 is a promising target in EA. Molecular and light based targeting of MUC1 with a photosensitive ADC is effective in vitro and after development may enable treatment of locoregional tumors endoscopically.

Indexed as

LightAdenocarcinomaAntineoplastic Agents, ImmunologicalBiomarkersCell Line, TumorCell SurvivalComputational BiologyDisease ProgressionEsophageal NeoplasmsGene Expression ProfilingGene Expression Regulation, NeoplasticGlycoproteinsHumansImmunoconjugatesImmunohistochemistryMucin-1Antineoplastic Agents, ImmunologicalBiomarkersGlycoproteinsImmunoconjugatesMUC1 protein, humanMucin-1antibody-drug conjugateBarrett’s esophagusesophageal adenocarcinomamucinsphotodynamic therapy

Identifiers

PMID28212575
PMCPMC5421911
OpenAlexW2589060258

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.