Evidence map›Paper›PMID 28193196›Full record

ArticleBMC cancer2017

Rapid eradication of colon carcinoma by Clostridium perfringens Enterotoxin suicidal gene therapy.

Jessica Pahle, Lutz Menzel, Nicole Niesler, Dennis Kobelt, Jutta Aumann, Maria Rivera, Wolfgang Walther

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
4.4field-weighted citation impact, top 6% 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

41 citing papers in PubMed, 73 citations in OpenAlex.

  1. Review
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  4. Oncology research · 2026
    Review
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  8. Review
  9. Article
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  12. Non-viral Gene Therapy for Melanoma Using Lysenin from Eisenia Foetida.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  13. Review
  14. Review
  15. Review
  16. Gut microbiome: decision-makers in the microenvironment of colorectal cancer.Frontiers in cellular and infection microbiology · 2023
    Review
  17. Claudin and pancreatic cancer.Frontiers in oncology · 2023
    Review
  18. Review
  19. Review
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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

7 authors at 2 institutions in 1 country.

Jessica PahleExperimental and Clinical Research Center, Charité University Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.
Lutz MenzelMax-Delbrück-Center for Molecular Medicine, Rober-Rössle-Str.10, 13125, Berlin, Germany.
Nicole NieslerMax-Delbrück-Center for Molecular Medicine, Rober-Rössle-Str.10, 13125, Berlin, Germany.
Dennis KobeltMax-Delbrück-Center for Molecular Medicine, Rober-Rössle-Str.10, 13125, Berlin, Germany.
Jutta AumannExperimental and Clinical Research Center, Charité University Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.
Maria RiveraExperimental Pharmacology & Oncology (EPO) GmbH Berlin, Rober-Rössle-Str. 10, 13125, Berlin, Germany.
Wolfgang WaltherExperimental and Clinical Research Center, Charité University Medicine, Lindenberger Weg 80, 13125, Berlin, Germany. wowalt@mdc-berlin.de.
Max Delbrück Center · DECharité - Universitätsmedizin Berlin · DE

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
UC Davis Paul Calabresi K12 Clinical Oncology Research Career Development ProgramK12CA138464 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BIRKELAND, ANDREW CHARLES, LARA, PRIMO N. · 2011 to 2025
$11.4M
NCI NIH HHS K12 CA138464NCI NIH HHS P30 CA093373
6 · The paper itself

Abstract

backgroundBacterial toxins have evolved to an effective therapeutic option for cancer therapy. The Clostridium perfringens enterotoxin (CPE) is a pore-forming toxin with selective cytotoxicity. The transmembrane tight junction proteins claudin-3 and -4 are known high affinity CPE receptors. Their expression is highly upregulated in human cancers, including breast, ovarian and colon carcinoma. CPE binding to claudins triggers membrane pore complex formation, which leads to rapid cell death. Previous studies demonstrated the anti-tumoral effect of treatment with recombinant CPE-protein. Our approach aimed at evaluation of a selective and targeted cancer gene therapy of claudin-3- and/or claudin-4- expressing colon carcinoma in vitro and in vivo by using translation optimized CPE expressing vector.

methodsIn this study the recombinant CPE and a translation optimized CPE expressing vector (optCPE) was used for targeted gene therapy of claudin-3 and/or -4 overexpressing colon cancer cell lines. All experiments were performed in the human SW480, SW620, HCT116, CaCo-2 and HT-29 colon cancer and the isogenic Sk-Mel5 and Sk-Mel5 Cldn-3-YFP melanoma cell lines. Claudin expression analysis was done at protein and mRNA level, which was confirmed by immunohistochemistry. The CPE induced cytotoxicity was analyzed by the MTT cytotoxicity assay. In addition patient derived colon carcinoma xenografts (PDX) were characterized and used for the intratumoral in vivo gene transfer of the optCPE expressing vector in PDX bearing nude mice.

resultsClaudin-3 and -4 overexpressing colon carcinoma lines showed high sensitivity towards both recCPE application and optCPE gene transfer. The positive correlation between CPE cytotoxicity and level of claudin expression was demonstrated. Transfection of optCPE led to targeted, rapid cytotoxic effects such as membrane disruption and necrosis in claudin overexpressing cells. The intratumoral optCPE in vivo gene transfer led to tumor growth inhibition in colon carcinoma PDX bearing mice in association with massive necrosis due to the intratumoral optCPE expression.

conclusionsThis novel approach demonstrates that optCPE gene transfer represents a promising and efficient therapeutic option for a targeted suicide gene therapy of claudin-3 and/or claudin-4 overexpressing colon carcinomas, leading to rapid and effective tumor cell killing in vitro and in vivo.

Indexed as

Genes, Transgenic, SuicideGenetic TherapyAnimalsBystander EffectClaudin-3Claudin-4Clostridium perfringensColonic NeoplasmsEnterotoxinsFemaleHumansMiceMice, NudeXenograft Model Antitumor AssaysClaudin-3Claudin-4CLDN3 protein, humanCLDN4 protein, humanenterotoxin, ClostridiumEnterotoxinsClostridium perfringens enterotoxin (CPE)Colon cancerGene therapySuicide gene

Identifiers

PMID28193196
PMCPMC5307849
OpenAlexW2588825125

What OpenQuestion holds

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LicenceCC BY
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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.