Evidence map›Paper›PMID 23719066›Full record

ArticleGene therapy2013

MicroRNA-regulated non-viral vectors with improved tumor specificity in an orthotopic rat model of hepatocellular carcinoma.

J A Ronald, R Katzenberg, C H Nielsen, H J Jae, L V Hofmann, S S Gambhir

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 35% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Biomarker-based MicroRNA Therapeutic Strategies for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2014
    Review
  3. 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 at 2 institutions in 2 countries.

J A Ronald1] Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, CA, USA [2] Department of Radiology, Stanford University, Stanford, CA, USA.
R Katzenberg
C H Nielsen
H J Jae
L V Hofmann
S S Gambhir
Stanford University · USRigshospitalet · DK

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Melinda L. Telli · 2007 to 2026
$71.4M
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
UCLA Imaging Resource for Mouse Cancer ModelsR24CA092865 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PHELPS, MICHAEL E · 2001 to 2006
$4.3M
CIHRNCI NIH HHS P30 CA016042NCI NIH HHS P30 CA124435NCI NIH HHS P50 CA114747NCI NIH HHS P50CA114747NCI NIH HHS R01 CA082214NCI NIH HHS R24 CA092865
6 · The paper itself

Abstract

In hepatocellular carcinoma (HCC), tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs (miRNAs) are powerful negative regulators of gene expression and many are downregulated in human HCC. We identified seven miRNAs that are also downregulated in tumors in a rat hepatoma model (P<0.05) and attempted to improve tumor specificity by constructing a panel of luciferase-expressing vectors containing binding sites for these miRNAs. Attenuation of luciferase expression by the corresponding miRNAs was confirmed across various cell lines and in mouse liver. We then tested our vectors in tumor-bearing rats and identified two miRNAs, miR-26a and miR-122, that significantly decreased expression in liver compared with the control vector (6.40 and 0.26%, respectively; P<0.05). In tumor, miR-122 had a nonsignificant trend towards decreased (∼50%) expression, whereas miR-26 had no significant effect on tumor expression. To our knowledge, this is the first work using differentially expressed miRNAs to de-target transgene expression in an orthotopic hepatoma model and to identify miR-26a, in addition to miR-122, for de-targeting liver. Considering the heterogeneity of miRNA expression in human HCC, this information will be important in guiding development of more personalized vectors for the treatment of this devastating disease.

Indexed as

Genetic VectorsAnimalsCarcinoma, HepatocellularCell LineFemaleGene Expression Regulation, NeoplasticGenetic TherapyHEK293 CellsHumansLiver NeoplasmsLiver Neoplasms, ExperimentalMiceMice, Inbred BALB CMicroRNAsOrgan SpecificityRatsMicroRNAs

Identifiers

PMID23719066
PMCPMC3864878
OpenAlexW1998798768

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.