Evidence map›Paper›PMID 21307888›Full record

ArticleGene therapy2011

Potent, tumor-specific gene expression in an orthotopic hepatoma rat model using a Survivin-targeted, amplifiable adenoviral vector.

B-C Ahn, J A Ronald, Y I Kim, R Katzenberg, A Singh, R Paulmurugan, S Ray, L V Hofmann, S S Gambhir

Abstract read
In one paragraph

Article in Gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
4.0field-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

13 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Molecular Imaging with Reporter Genes: Has Its Promise Been Delivered?Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019
    Review
  4. Review
  5. Review
  6. Detecting cancers through tumor-activatable minicircles that lead to a detectable blood biomarker.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  7. Review
  8. Article
  9. Article
  10. Cancer imaging: Gene transcription-based imaging and therapeutic systems.The international journal of biochemistry & cell biology · 2012
    Review
  11. Optical imaging for stem cell differentiation to neuronal lineage.Nuclear medicine and molecular imaging · 2012
    Review
  12. Review
  13. 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

9 authors at 2 institutions in 3 countries.

B-C AhnMolecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
J A Ronald
Y I Kim
R Katzenberg
A Singh
R Paulmurugan
S Ray
L V Hofmann
S S Gambhir
Stanford University · USUniversity of Cambridge · GB

Funding

Stanford Nanocharacterization LaboratoryU54CA119367 · NCI · STANFORD UNIVERSITY · PI GAMBHIR, SANJIV S · 2006 to 2010
$19.8M
Small Animal ImagingP50CA114747 · NCI · STANFORD UNIVERSITY · PI RAO, JIANGHONG · 2005 to 2014
$18.2M
Reporter Imaging of Protein-Protein InteractionsR01CA082214 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GAMBHIR, SANJIV S · 1999 to 2019
$5.9M
CIHRNCI NIH HHS P50 CA114747NCI NIH HHS P50CA114747NCI NIH HHS R01 CA082214NCI NIH HHS U54 CA119367
6 · The paper itself

Abstract

Ideal cancer gene therapies should have high tumor specificity and efficacy, and allow systemic administration to target metastases. We recently developed a bi-directional, two-step transcriptional amplification (TSTA) system driven by the tumor-specific Survivin promoter (pSurv) to amplify the correlated expression of both the reporter gene firefly luciferase (FL) and therapeutic gene tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we compare the specificity and potency of an adenovirus carrying this system (Ad-pSurv-TSTA-TRAIL-FL) to a nonspecific vector (Ad-pCMV-FL) in an orthotopic hepatocellular carcinoma (HCC) rat model after systemic administration. At 24 h after injection of Ad-pCMV-FL, bioluminescence imaging revealed a trend (P=0.30) towards greater FL expression in liver versus tumor. In striking contrast, Ad-pSurv-TSTA-TRAIL-FL showed increased FL activity within the tumor compared with the liver (P<0.01), a strong trend towards reduced liver expression compared with Ad-pCMV-FL (P=0.07), and importantly, similar FL levels within tumor compared with Ad-pCMV-FL (P=0.32). Hence, this vector shows potent, tumor-specific transgene expression even after extensive liver transduction and may be of significant value in avoiding hepatotoxicity in HCC patients. Future studies will explore the benefits of tumor-specific TRAIL expression in this model, the potential to target metastases and the extension of this vector for the treatment of other Survivin-positive tumors is warranted.

Indexed as

AdenoviridaeAnimalsCarcinoma, HepatocellularGene ExpressionGenes, ReporterGene TargetingGenetic VectorsLiver NeoplasmsLuciferases, FireflyMicrotubule-Associated ProteinsPromoter Regions, GeneticRatsSensitivity and SpecificitySurvivinTNF-Related Apoptosis-Inducing LigandTransgenesBirc5 protein, ratLuciferases, FireflyMicrotubule-Associated ProteinsSurvivinTNF-Related Apoptosis-Inducing LigandTnfsf10 protein, rat

Identifiers

PMID21307888
PMCPMC4154811
OpenAlexW1997818839

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.