Evidence map›Paper›PMID 32060615›Full record

ArticleCancer chemotherapy and pharmacology2020

The GLP-2 analogue elsiglutide reduces diarrhoea caused by the tyrosine kinase inhibitor lapatinib in rats.

Bronwen J Mayo, Kate R Secombe, Anthony D Wignall, Emma Bateman, Daniel Thorpe, Claudio Pietra, Dorothy M Keefe, Joanne M Bowen

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Article in Cancer chemotherapy and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 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

8 authors at 3 institutions in 2 countries.

Bronwen J MayoDivision of Health Sciences, School of Pharmacy and Medical Sciences, University of South Australia, Level 4, Playford Building, Adelaide, South Australia, 5005, Australia. Bronwen.mayo@unisa.edu.au.ORCID http://orcid.org/0000-0002-6799-7226
Kate R SecombeAdelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Anthony D WignallDivision of Health Sciences, School of Pharmacy and Medical Sciences, University of South Australia, Level 4, Playford Building, Adelaide, South Australia, 5005, Australia.
Emma BatemanAdelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Daniel ThorpeDivision of Health Sciences, School of Pharmacy and Medical Sciences, University of South Australia, Level 4, Playford Building, Adelaide, South Australia, 5005, Australia.
Claudio PietraHelsinn Healthcare, Lugano, Switzerland.
Dorothy M KeefeAdelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Joanne M BowenAdelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
The University of Adelaide · AUUniversity of South Australia · AUHelsinn (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeLapatinib is a small molecule tyrosine kinase inhibitor used to treat breast cancer, often in combination with chemotherapy. Diarrhoea commonly occurs in up to 78% of patients undertaking lapatinib treatment. The mechanism of this diarrhoea is currently unknown. Elsiglutide is a GLP-2 analogue known to increase cell proliferation and reduce apoptosis in the intestine.

methodsWe used a previously developed rat model of lapatinib-induced diarrhoea to determine if co-treatment with elsiglutide was able to reduce diarrhoea caused by lapatinib. Additionally, we analysed the caecal microbiome of these rats to assess changes in the microbiome due to lapatinib.

resultsRats treated with lapatinib and elsiglutide had less severe diarrhoea than rats treated with lapatinib alone. Serum lapatinib levels, blood biochemistry, myeloperoxidase levels and serum limulus amebocyte lysate levels were not significantly different between groups. Rats treated with lapatinib alone had significantly higher histopathological damage in the ileum than vehicle controls. This increase was not seen in rats also receiving elsiglutide. Rats receiving lapatinib alone had lower microbial diversity than rats who also received elsiglutide.

conclusionsElsiglutide was able to reduce diarrhoea from lapatinib treatment. This does not appear to be via reduction in inflammation or barrier permeability, and may be due to thickening of mucosa, leading to increased surface area for fluid absorption in the distal small intestine. Microbial changes seen in this study require further research to fully elucidate their role in the development of diarrhoea.

Indexed as

AnimalsAntidiarrhealsDiarrheaGlucagon-Like Peptide 2Intestinal MucosaLapatinibMaleProtein Kinase InhibitorsRatsRats, WistarAntidiarrhealsGlucagon-Like Peptide 2LapatinibProtein Kinase InhibitorsBreast cancerDiarrhoeaElsiglutideLapatinibTyrosine kinase inhibitor

Identifiers

PMID32060615
OpenAlexW3005888810

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.