Evidence map›Paper›PMID 39227437›Full record

ArticleJournal of gastroenterology2024

Development of a novel oncolytic adenovirus controlled by CDX2 promoter for esophageal adenocarcinoma therapy.

Naohiko Nakamura, Shuhei Shinoda, Mizuho Sato-Dahlman, Brett Roach, Kari Jacobsen, Masato Yamamoto

Abstract read
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In one paragraph

Article in Journal of gastroenterology, 2024. 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
–field-weighted citation impact
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.

  1. Review
  2. 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

6 authors.

Naohiko NakamuraDepartment of Surgery, University of Minnesota, MMC195, 420 Delaware St. SE, Minneapolis, MN, 55455, USA.
Shuhei ShinodaDepartment of Surgery, University of Minnesota, MMC195, 420 Delaware St. SE, Minneapolis, MN, 55455, USA.
Mizuho Sato-DahlmanDepartment of Surgery, University of Minnesota, MMC195, 420 Delaware St. SE, Minneapolis, MN, 55455, USA.
Brett RoachDepartment of Surgery, University of Minnesota, MMC195, 420 Delaware St. SE, Minneapolis, MN, 55455, USA.
Kari JacobsenDepartment of Surgery, University of Minnesota, MMC195, 420 Delaware St. SE, Minneapolis, MN, 55455, USA.
Masato YamamotoDepartment of Surgery, University of Minnesota, MMC195, 420 Delaware St. SE, Minneapolis, MN, 55455, USA. yamam016@umn.edu.ORCID 0000-0002-2721-6245

Funding

Advanced Oncolytic Adenovirus Enabling Systemic Therapy of PDACR01CA276480 · NCI · UNIVERSITY OF MINNESOTA · PI MASATO YAMAMOTO · 2023 to 2026
$1.4M
NCI NIH HHS R01 CA276480
6 · The paper itself

Abstract

backgroundPrognosis of esophageal adenocarcinoma (EAC) is still poor. Therefore, the development of novel therapeutic modalities is necessary to improve therapeutic outcomes in EAC. Here, we report a novel promoter-controlled oncolytic adenovirus targeting CDX2 (Ad5/3-pCDX2) and its specific anticancer effect for EAC.

methodsWe used OE19, OE33, HT29, MKN28, RH30, and HEL299 cell lines. To establish CDX2 overexpressing OE19 cells, pCMV-GLI1 plasmid was transfected to OE19 (OE19 + GLI1). The virus replication and cytocidal effect of replication competent Ad5/3-pCDX2 were analyzed in vitro. Antitumor effect of Ad5/3-pCDX2 was assessed in xenograft mouse models by intratumoral injection of the viruses. Finally, efficacy of combination therapy with Ad5/3-pCDX2 and 5FU was evaluated.

resultsEAC cells and HT29 showed high mRNA levels of CDX2, but not MKN28, RH30, and HEL299. We confirmed that deoxycholic acid (DCA) exposure enhanced CDX2 expression in EAC cells and OE19 + GLI1 had persistent CDX2 overexpression without DCA. Ad5/3-pCDX2 showed stronger cytocidal effect in OE19 + GLI1 than OE19, whereas Ad5/3-pCDX2 did not kill CDX2-negative cells. Ad5/3-pCDX2 was significantly replicated in EAC cells and the virus replication was higher in OE19 + GLI1 and OE19 with DCA compared to OE19 without DCA exposure. In vivo, Ad5/3-pCDX2 significantly suppressed OE19 tumor growth and the antitumor effect was enhanced in OE19 + GLI1 tumor. In contrast, Ad5/3-pCDX2 did not show significant antitumor effect in MKN28 tumor. Moreover, Ad5/3-pCDX2 significantly increased the efficacy of 5FU in vitro and in vivo.

conclusionsAd5/3-pCDX2 showed specific anticancer effect for EAC, which was enhanced by bile acid exposure. Ad5/3-pCDX2 has promising potential for EAC therapy in the clinical setting.

Indexed as

AdenocarcinomaAdenoviridaeCDX2 Transcription FactorEsophageal NeoplasmsOncolytic VirotherapyOncolytic VirusesPromoter Regions, GeneticXenograft Model Antitumor AssaysAnimalsCell Line, TumorCombined Modality TherapyFluorouracilHumansMiceMice, Inbred BALB CMice, NudeCDX2 protein, humanCDX2 Transcription FactorFluorouracilCDX2Combination therapyEsophageal adenocarcinomaOncolytic adenovirus

Identifiers

PMID39227437
PMCPMC11495994

What Socratic 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 Socratic graph.