Evidence map›Paper›PMID 36940215›Full record

ArticlePloS one2023

11β-HSD1 inhibition does not affect murine tumour angiogenesis but may exert a selective effect on tumour growth by modulating inflammation and fibrosis.

Callam T Davidson, Eileen Miller, Morwenna Muir, John C Dawson, Martin Lee, Stuart Aitken, Alan Serrels, Scott P Webster, Natalie Z M Homer, Ruth Andrew and 3 more

Open access · goldFull text read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.4field-weighted citation impact, top 36% 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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

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

13 authors at 3 institutions in 1 country.

Callam T DavidsonBHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Eileen MillerBHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Morwenna MuirCancer Research UK Edinburgh Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0001-5835-3886
John C DawsonCancer Research UK Edinburgh Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Martin LeeCancer Research UK Edinburgh Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Stuart AitkenMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0003-4867-4568
Alan SerrelsCancer Research UK Edinburgh Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Scott P WebsterBHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Natalie Z M HomerBHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Ruth AndrewBHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Valerie G BruntonCancer Research UK Edinburgh Centre, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Patrick W F HadokeBHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Brian R WalkerBHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0002-2416-1648
The Queen's Medical Research Institute · GBEdinburgh Cancer Research · GBInstitute of Genetics and Cancer · GB

Funding

British Heart Foundation FS/13/52/30637British Heart Foundation PG/15/10/31277British Heart Foundation RG/11/4/28734Cancer Research UK 24837Cancer Research UK 25919Cancer Research UK C157/A24837Cancer Research UK C157/A25140Wellcome TrustWellcome Trust 107049/Z/15/Z
6 · The paper itself

Abstract

Glucocorticoids inhibit angiogenesis by activating the glucocorticoid receptor. Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces tissue-specific glucocorticoid action and promotes angiogenesis in murine models of myocardial infarction. Angiogenesis is important in the growth of some solid tumours. This study used murine models of squamous cell carcinoma (SCC) and pancreatic ductal adenocarcinoma (PDAC) to test the hypothesis that 11β-HSD1 inhibition promotes angiogenesis and subsequent tumour growth. SCC or PDAC cells were injected into female FVB/N or C57BL6/J mice fed either standard diet, or diet containing the 11β-HSD1 inhibitor UE2316. SCC tumours grew more rapidly in UE2316-treated mice, reaching a larger (P<0.01) final volume (0.158 ± 0.037 cm3) than in control mice (0.051 ± 0.007 cm3). However, PDAC tumour growth was unaffected. Immunofluorescent analysis of SCC tumours did not show differences in vessel density (CD31/alpha-smooth muscle actin) or cell proliferation (Ki67) after 11β-HSD1 inhibition, and immunohistochemistry of SCC tumours did not show changes in inflammatory cell (CD3- or F4/80-positive) infiltration. In culture, the growth/viability (assessed by live cell imaging) of SCC cells was not affected by UE2316 or corticosterone. Second Harmonic Generation microscopy showed that UE2316 reduced Type I collagen (P<0.001), whilst RNA-sequencing revealed that multiple factors involved in the innate immune/inflammatory response were reduced in UE2316-treated SCC tumours. 11β-HSD1 inhibition increases SCC tumour growth, likely via suppression of inflammatory/immune cell signalling and extracellular matrix deposition, but does not promote tumour angiogenesis or growth of all solid tumours.

Indexed as

GlucocorticoidsNeoplasms11-beta-Hydroxysteroid Dehydrogenase Type 1AnimalsFemaleFibrosisInflammationMiceNeovascularization, PathologicPyrazolesThiophenes11-beta-Hydroxysteroid Dehydrogenase Type 1(4-(2-chlorophenyl-4-fluoro-1-piperidinyl)(5-(1H-pyrazol-4-yl)-3-thienyl)methanoneGlucocorticoidsPyrazolesThiophenes

Identifiers

PMID36940215
PMCPMC10027213
OpenAlexW4327896555

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read37
identifiers read8
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.