Evidence map›Paper›PMID 30731451›Full record

Trial reportChemotherapy2018

Selective MMP Inhibition, Using AZD3342, to Reduce Gastrointestinal Toxicity and Enhance Chemoefficacy in a Rat Model.

Rachel J Gibson, Ysabella Z A van Sebille, Hannah R Wardill, Anthony Wignall, Joseph Shirren, Imogen A Ball, Nicole Williams, Kiara Wanner, Joanne M Bowen

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.3field-weighted citation impact, top 14% 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

2 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Dual contribution of the gut microbiome to immunotherapy efficacy and toxicity: supportive care implications and recommendations.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022
    Article
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

9 authors at 3 institutions in 2 countries.

Rachel J GibsonDivision of Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
Ysabella Z A van SebilleDivision of Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
Hannah R WardillDiscipline of Physiology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia, hannah.wardill@adelaide.edu.au.
Anthony WignallDiscipline of Physiology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Joseph ShirrenDiscipline of Physiology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Imogen A BallDiscipline of Physiology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Nicole WilliamsDiscipline of Physiology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Kiara WannerDiscipline of Physiology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Joanne M BowenDiscipline of Physiology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
The University of Adelaide · AUUniversity of South Australia · AUUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe common cytotoxic mechanisms that underpin chemoefficacy and toxicity have hampered efforts to deliver effective supportive care interventions, particularly for gastrointestinal (GI) toxicity. Matrix metalloproteinases (MMPs) have been implicated in both tumor growth and GI toxicity, and as such MMP inhibitors present as a novel therapeutic avenue to simultaneously enhance treatment efficacy and reduce toxicity.

objectivesThe aim of this study was to determine the efficacy of an MMP-9/12 inhibitor, AZD3342, on tumor growth and GI toxicity in a rat model.

methodsFemale tumor-bearing Dark Agouti rats (n = 90) were divided into 4 groups: vehicle control; methotrexate (MTX); AZD3342, and MTX + AZD3342. Tumors were measured daily (for 5 days) using digital calipers. GI toxicity was assessed using well-established clinical markers (diarrhea/weight loss), histopathological analysis, and functional assessment of intestinal barrier permeability.

resultsAZD3342 delayed the onset of severe diarrhea by 1 day (vs. MTX) but was unable to improve the overall severity of diarrhea. No changes were detected in tissue morphology or intestinal barrier function. AZD3342 alone suppressed tumor growth (p = 0.003 vs. vehicle) but did not enhance the efficacy of MTX.

conclusionsThis study showed partial efficacy of AZD3342 in reducing tumor growth and delaying the onset of severe diarrhea caused by MTX in rats. We suggest further studies be undertaken targeting appropriate scheduling of AZD3342 as well as investigating different cytotoxic therapies that strongly activate MMP signaling.

Indexed as

AnimalsAntimetabolites, AntineoplasticCell Line, TumorDiarrheaFemaleHumansIntestinal MucosaMatrix Metalloproteinase InhibitorsMatrix MetalloproteinasesMethotrexateNeoplasmsOrganic ChemicalsRandom AllocationRatsTransplantation, HeterologousAntimetabolites, AntineoplasticAZD3342Matrix Metalloproteinase InhibitorsMatrix MetalloproteinasesMethotrexateOrganic ChemicalsAdverse drug reactionsAZD3342Breast cancerDiarrheaGastrointestinal toxicityInterventionMatrix metalloproteinasesMethotrexateMucositisRat model

Identifiers

PMID30731451
PMCPMC6425820
OpenAlexW2911820967

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.