Evidence map›Paper›PMID 35962138›Full record

ArticleCancer chemotherapy and pharmacology2022

Effects of a novel toll-like receptor 4 antagonist IAXO-102 in a murine model of chemotherapy-induced gastrointestinal toxicity.

Janine S Y Tam, Elise E Crame, Aurelia S Elz, Janet K Coller, Anthony Wignall, Clive A Prestidge, Joanne M Bowen

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 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
0.8field-weighted citation impact, top 28% 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, 6 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Mucositis and Infection in Hematology Patients.International journal of molecular sciences · 2023
    Article
  5. 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

7 authors at 2 institutions in 2 countries.

Janine S Y TamDiscipline of Physiology, School of Biomedicine, University of Adelaide, Adelaide, SA, 5005, Australia. shuyiejanine.tam@adelaide.edu.au.ORCID 0000-0002-2293-4854
Elise E CrameDiscipline of Physiology, School of Biomedicine, University of Adelaide, Adelaide, SA, 5005, Australia.
Aurelia S ElzClinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.
Janet K CollerDiscipline of Pharmacology, School of Biomedicine, University of Adelaide, Adelaide, SA, Australia.
Anthony WignallClinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.
Clive A PrestidgeClinical and Health Sciences, University of South Australia, Adelaide, SA, Australia.
Joanne M BowenDiscipline of Physiology, School of Biomedicine, University of Adelaide, Adelaide, SA, 5005, Australia.
The University of Adelaide · AUUniversity of South Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionGastrointestinal mucositis (GIM) is a side effect of high-dose irinotecan (CPT-11), causing debilitating symptoms that are often poorly managed. The role of TLR4 in the development of GIM has been clearly demonstrated. We, therefore, aimed to investigate the potential of the TLR4 antagonist, IAXO-102, to attenuate gastrointestinal inflammation as well as supress tumour activity in a colorectal-tumour-bearing mouse model of GIM induced by CPT-11.

methods24 C57BL/6 mice received a vehicle, daily i.p. IAXO-102 (3 mg/kg), i.p. CPT-11 (270 mg/kg) or a combination of CPT-11 and IAXO-102. GIM was assessed using validated toxicity markers. At 72 h, colon and tumour tissue were collected and examined for histopathological changes and RT-PCR for genes of interest; TLR4, MD-2, CD-14, MyD88, IL-6, IL-6R, CXCL2, CXCR1, and CXCR2.

resultsIAXO-102 prevented diarrhoea in mice treated with CPT-11. Tumour volume in IAXO-102-treated mice was lower compared to vehicle at 48 h (P < 0.05). There were no differences observed in colon and tumour weights between the treatment groups. Mice who received the combination treatment had improved tissue injury score (P < 0.05) in the colon but did not show any improvements in cell proliferation or apoptotic rate. Expression of all genes was similar across all treatment groups in the tumour (P > 0.05). In the colon, there was a difference in transcript expression in vehicle vs. IAXO-102 (P < 0.05) and CPT-11 vs. combination (P < 0.01) in MD-2 and IL-6R, respectively.

conclusionIAXO-102 was able to attenuate symptomatic parameters of GIM induced by CPT-11 as well as reduce tissue injury in the colon. However, there was no effect on cell proliferation and apoptosis. As such, TLR4 activation plays a partial role in GIM development but further research is required to understand the specific inflammatory signals underpinning tissue-level changes.

Indexed as

Antineoplastic AgentsMucositisToll-Like Receptor 4Amino SugarsAnimalsDisease Models, AnimalGlycolipidsIrinotecanMiceMice, Inbred C57BLAmino SugarsAntineoplastic AgentsGlycolipidsIAXO-102IrinotecanToll-Like Receptor 4CPT-11Gastrointestinal mucositisMC-38 cellsTLR4 antagonistToll-like receptor 4 (TLR4)Tumour

Identifiers

PMID35962138
PMCPMC9402738
OpenAlexW4290861041

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.