Evidence map›Paper›PMID 24316664›Full record

ArticleCancer biology & therapy2014

Irinotecan disrupts tight junction proteins within the gut : implications for chemotherapy-induced gut toxicity.

Hannah R Wardill, Joanne M Bowen, Noor Al-Dasooqi, Masooma Sultani, Emma Bateman, Romany Stansborough, Joseph Shirren, Rachel J Gibson

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Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

40 citing papers in PubMed, 81 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 2 institutions in 1 country.

Hannah R WardillSchool of Medical Sciences; University of Adelaide; Adelaide, SA Australia.
Joanne M BowenSchool of Medical Sciences; University of Adelaide; Adelaide, SA Australia.
Noor Al-DasooqiSchool of Medicine; University of Adelaide; Adelaide, SA Australia.
Masooma SultaniSchool of Medical Sciences; University of Adelaide; Adelaide, SA Australia.
Emma BatemanSchool of Medicine; University of Adelaide; Adelaide, SA Australia.
Romany StansboroughSchool of Medical Sciences; University of Adelaide; Adelaide, SA Australia.
Joseph ShirrenSchool of Medical Sciences; University of Adelaide; Adelaide, SA Australia.
Rachel J GibsonSchool of Medical Sciences; University of Adelaide; Adelaide, SA Australia.
University of Adelaide · AUIndiana University School of Medicine

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chemotherapy for cancer causes significant gut toxicity, leading to severe clinical manifestations and an increased economic burden. Despite much research, many of the underlying mechanisms remain poorly understood hindering effective treatment options. Recently there has been renewed interest in the role tight junctions play in the pathogenesis of chemotherapy-induced gut toxicity. To delineate the underlying mechanisms of chemotherapy-induced gut toxicity, this study aimed to quantify the molecular changes in key tight junction proteins, ZO-1, claudin-1, and occludin, using a well-established preclinical model of gut toxicity. Female tumor-bearing dark agouti rats received irinotecan or vehicle control and were assessed for validated parameters of gut toxicity including diarrhea and weight loss. Rats were killed at 6, 24, 48, 72, 96, and 120 h post-chemotherapy. Tight junction protein and mRNA expression in the small and large intestines were assessed using semi-quantitative immunohistochemistry and RT-PCR. Significant changes in protein expression of tight junction proteins were seen in both the jejunum and colon, correlating with key histological changes and clinical features. mRNA levels of claudin-1 were significantly decreased early after irinotecan in the small and large intestines. ZO-1 and occludin mRNA levels remained stable across the time-course of gut toxicity. Findings strongly suggest irinotecan causes tight junction defects which lead to mucosal barrier dysfunction and the development of diarrhea. Detailed research is now warranted to investigate posttranslational regulation of tight junction proteins to delineate the underlying pathophysiology of gut toxicity and identify future therapeutic targets.

Indexed as

AnimalsAntineoplastic Agents, PhytogenicCamptothecinClaudin-1DiarrheaFemaleIntestinal MucosaIntestine, LargeIntestine, SmallIrinotecanOccludinRatsTight JunctionsZonula Occludens-1 ProteinAntineoplastic Agents, PhytogenicCamptothecinClaudin-1IrinotecanOccludinZonula Occludens-1 Proteinchemotherapyclaudin-1gut toxicitymucositisoccludinpro-inflammatory cytokinestight junctionszonular-occludens-1

Identifiers

PMID24316664
PMCPMC3928140
OpenAlexW2322536337

What OpenQuestion holds

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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.