Evidence map›Paper›PMID 20635326›Full record

ArticleThe journal of gene medicine2010

Complete regression of human malignant mesothelioma xenografts following local injection of midkine promoter-driven oncolytic adenovirus.

Shuji Kubo, Yoshiko Kawasaki, Norie Yamaoka, Masatoshi Tagawa, Noriyuki Kasahara, Nobuyuki Terada, Haruki Okamura

Abstract read
In one paragraph

Article in The journal of gene medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-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

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. The Oncolytic VirusFrontiers in oncology · 2019
    Article
  6. Impact of Autophagy in Oncolytic Adenoviral Therapy for Cancer.International journal of molecular sciences · 2017
    Review
  7. Review
  8. Oncolytic Viral Therapy for Mesothelioma.Frontiers in oncology · 2017
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. 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 3 institutions in 2 countries.

Shuji KuboLaboratory of Host Defenses, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. s-kubo@hyo-med.ac.jp
Yoshiko Kawasaki
Norie Yamaoka
Masatoshi Tagawa
Noriyuki Kasahara
Nobuyuki Terada
Haruki Okamura
Hyogo Medical University · JPChiba Cancer Center · JPUniversity of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
NCI NIH HHS P30 CA016042NIDDK NIH HHS P30 DK041301
6 · The paper itself

Abstract

backgroundMalignant mesothelioma is a highly aggressive tumor with poor prognosis. We hypothesized that the tumor-specific midkine (Mdk) promoter could confer transcriptional targeting to oncolytic adenoviruses for effective treatment of malignant mesothelioma.

methodsWe analysed Mdk expression by quantitative reverse transcription-polymerase chain reaction in six human mesothelioma cell lines, and tested Mdk promoter activity by luciferase reporter assay. On the basis of these data, we constructed a replication-selective oncolytic adenovirus designated AdMdk-E1-iresTK. This virus contains a Mdk promoter-driven adenoviral E1 gene and herpes simplex virus-thymidine kinase (TK) suicide gene and cytomagalovirus promoter-driven enhanced green fluorescent protein marker gene. Selectivity of viral replication and cytolysis were characterized in normal versus mesothelioma cells in vitro, and intratumoral spread and antitumor efficacy were investigated in vivo.

resultsMdk promoter activity was restricted in normal cells, but highly activated in mesothelioma cell lines. AdMdk-E1-iresTK was seen to efficiently replicate, produce viral progeny and spread in multiple mesothelioma cell lines. Lytic spread of AdMdk-E1-iresTK mediated the efficient killing of these mesothelioma cells, and its in vitro cytocidal effect was significantly enhanced by treatment with the prodrug, ganciclovir. Intratumoral injection of AdMdk-E1-iresTK caused complete regression of MESO4 and MSTO human mesothelioma xenografts in athymic mice. In vivo fluorescence imaging demonstrated intratumoral spread of AdMdk-E1-iresTK-derived signals, which vanished after tumor eradication.

conclusionsThese data indicate that transcriptional targeting of viral replication by the Mdk promoter represents a promising general strategy for oncolytic virotherapy of cancers with up-regulated Mdk expression, including malignant mesothelioma.

Indexed as

Oncolytic VirotherapyPromoter Regions, GeneticAdenoviridaeAnimalsCytokinesGenetic VectorsHumansInjectionsMesotheliomaMiceMice, NudeMidkineSimplexvirusThymidine KinaseXenograft Model Antitumor AssaysCytokinesMidkineThymidine Kinase

Identifiers

PMID20635326
PMCPMC2938764
OpenAlexW2171625824

What OpenQuestion holds

Textmetadata
LicenceTDM
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.