Evidence map›Paper›PMID 36426854›Full record

ArticleMutagenesis2022

Ex vivo explant model of adenoma and colorectal cancer to explore mechanisms of action and patient response to cancer prevention therapies.

Sam Khan, Gareth J Miles, Constantinos Demetriou, Zahirah Sidat, Nalini Foreman, Kevin West, Ankur Karmokar, Lynne Howells, Catrin Pritchard, Anne L Thomas and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Mutagenesis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.0field-weighted citation impact, top 21% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. A novel preclinical model of the normal human breast.Journal of mammary gland biology and neoplasia · 2024
    Article
  4. Article
  5. Review
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

11 authors at 2 institutions in 1 country.

Sam KhanLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
Gareth J MilesLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
Constantinos DemetriouLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
Zahirah SidatHope Clinical Trials Facility, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom.
Nalini ForemanLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
Kevin WestLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
Ankur KarmokarLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
Lynne HowellsLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
Catrin PritchardLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
Anne L ThomasLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
Karen BrownLeicester Cancer Research Centre, Robert Kilpatrick Clinical Sciences Building, University of Leicester, Leicester LE2 7LX, United Kingdom.
University of Leicester · GBLeicester Royal Infirmary · GB

Funding

Cancer Research UK C10604/A25151Cancer Research UK C325/A13101Department of HealthMedical Research Council MC_PC_16051
6 · The paper itself

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer death in the UK. Novel therapeutic prevention strategies to inhibit the development and progression of CRC would be invaluable. Potential contenders include low toxicity agents such as dietary-derived agents or repurposed drugs. However, in vitro and in vivo models used in drug development often do not take into account the heterogeneity of tumours or the tumour microenvironment. This limits translation to a clinical setting. Our objectives were to develop an ex vivo method utilizing CRC and adenoma patient-derived explants (PDEs) which facilitates screening of drugs, assessment of toxicity, and efficacy. Our aims were to use a multiplexed immunofluorescence approach to demonstrate the viability of colorectal tissue PDEs, and the ability to assess immune cell composition and interactions. Using clinically achievable concentrations of curcumin, we show a correlation between curcumin-induced tumour and stromal apoptosis (P < .001) in adenomas and cancers; higher stromal content is associated with poorer outcomes. B cell (CD20+ve) and T cell (CD3+ve) density of immune cells within tumour regions in control samples correlated with curcumin-induced tumour apoptosis (P < .001 and P < .05, respectively), suggesting curcumin-induced apoptosis is potentially predicted by baseline measures of immune cells. A decrease in distance between T cells (CD3+ve) and cytokeratin+ve cells was observed, indicating movement of T cells (CD3+ve) towards the tumour margin (P < .001); this change is consistent with an immune environment associated with improved outcomes. Concurrently, an increase in distance between T cells (CD3+ve) and B cells (CD20+ve) was detected following curcumin treatment (P < .001), which may result in a less immunosuppressive tumour milieu. The colorectal tissue PDE model offers significant potential for simultaneously assessing multiple biomarkers in response to drug exposure allowing a greater understanding of mechanisms of action and efficacy in relevant target tissues, that maintain both their structural integrity and immune cell compartments.

Indexed as

AdenomaColorectal NeoplasmsHumansTumor Microenvironmentadenomacolorectal cancercurcuminimmune modulationpatient-derived explants (PDEs)

Identifiers

PMID36426854
PMCPMC9730503
OpenAlexW4310054997

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.