Evidence map›Paper›PMID 31707149›Full record

Trial reportEBioMedicine2019

Targeting the COX1/2-Driven thromboxane A2 pathway suppresses Barrett's esophagus and esophageal adenocarcinoma development.

Tianshun Zhang, Qiushi Wang, Wei-Ya Ma, Keke Wang, Xiaoyu Chang, Michele L Johnson, Ruihua Bai, Ann M Bode, Nathan R Foster, Gary W Falk and 3 more

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

Trial report in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Role of Prostaglandin E2 in the Progression of Gastrointestinal Cancer.Cancer prevention research (Philadelphia, Pa.) · 2022
    Review
  4. Article
  5. Review
  6. Article
  7. 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

13 authors at 3 institutions in 2 countries.

Tianshun ZhangThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States.
Qiushi WangThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States.
Wei-Ya MaThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States.
Keke WangThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States.
Xiaoyu ChangThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States.
Michele L JohnsonDivision of Gastroenterology and Hepatology, Mayo Clinic, 200 First Avenue SW, Rochester, MN 55905, United States.
Ruihua BaiThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States; The Affiliated Cancer Hospital of Zhengzhou University, No.127 Dongming Road, Henan 450000 China.
Ann M BodeThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States.
Nathan R FosterDepartment of Health Sciences Research, Mayo Clinic, 200 First Avenue SW, Rochester, MN 55905, United States.
Gary W FalkDepartment of Medicine, University of Pennsylvania, 749 Perelman Center for Advanced Medicine, South Pavilion, Philadelphia, PA 19104, United States.
Paul J LimburgDivision of Gastroenterology and Hepatology, Mayo Clinic, 200 First Avenue SW, Rochester, MN 55905, United States.
Prasad G IyerDivision of Gastroenterology and Hepatology, Mayo Clinic, 200 First Avenue SW, Rochester, MN 55905, United States.
Zigang DongThe Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN 55912, United States. Electronic address: zgdong@hi.umn.edu.
University of Minnesota · USMayo Clinic · USUniversity of Pennsylvania · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBarrett's esophagus (BE), a complication of gastroesophageal reflux disease (GERD), predisposes patients to esophageal adenocarcinoma (EAC). Reliable biomarkers for early detection and discovery of potential drug targets are urgently needed for improved BE and EAC patient outcomes.

methodsPatient biopsy samples were evaluated for COX1/2, and thromboxane A2 synthase (TBXAS) expression. Circulating prostaglandins biosynthesis was determined using enzyme immunoassay kits. Anchorage-independent cell growth assay, crystal violet staining assay, and xenograft experiments were conducted to assess BE and EAC cell growth. A surgical mouse model of reflux (i.e., esophagoduodenostomy) was established and samples were analyzed using an enzyme immunoassay kit, immunohistochemistry, immunoblotting, or RT-PCR. Esophageal biopsy samples (pre- and post-intervention) were obtained from a randomized clinical trial in which participants were administered esomeprazole (40 mg) twice daily in combination with an acetylsalicylic acid (ASA) placebo or 81 or 325 mg ASA for 28 days. Esophageal biopsy specimens before and after the intervention period were analyzed.

findingsCOX2 and TBXAS are highly expressed in BE and EAC patients accompanied by a pronounced elevation of circulating TXA2 levels. ASA suppressed BE and EAC growth by targeting the TXA2 pathway. Additionally, biopsies from 49 patients (with similar baseline characteristics) showed that ASA substantially decreased serum TXA2 levels, resulting in reduced inflammation.

interpretationThis study establishes the importance of the COX1/2-driven TXA2 pathway in BE and EAC pathophysiology and lays the groundwork for introducing a TXA2-targeting strategy for EAC prevention and early detection.

fundingHormel Foundation, Exact Sciences, Pentax Medical, Intromedic and National Cancer.

Indexed as

Molecular Targeted TherapySignal TransductionAdenocarcinomaAnimalsAspirinBarrett EsophagusCarcinogenesisCell Line, TumorCell ProliferationCyclooxygenase 1Cyclooxygenase 2Disease Models, AnimalEsophageal NeoplasmsExtracellular Signal-Regulated MAP KinasesFemaleHumansAspirinCyclooxygenase 1Cyclooxygenase 2Extracellular Signal-Regulated MAP KinasesSTAT3 Transcription FactorThromboxane A2Acetylsalicylic acidBarrett's esophagusEsophageal adenocarcinomaThromboxane A2 pathway

Identifiers

PMID31707149
PMCPMC7113183
OpenAlexW2984356888

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.