Evidence map›Paper›PMID 16437213›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2006

An improved Tet-On regulatable FasL-adenovirus vector system for lung cancer therapy.

Isaac Sipo, Almudena Hurtado Picó, Xiaomin Wang, Jürgen Eberle, Iver Petersen, Stefan Weger, Wolfgang Poller, Henry Fechner

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

9 citing papers in PubMed, 37 citations in OpenAlex.

  1. Immortalization Reversibility in the Context of Cell Therapy Biosafety.International journal of molecular sciences · 2023
    Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. 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

8 authors at 1 institution in 1 country.

Isaac SipoDepartment of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin Germany.
Almudena Hurtado Picó
Xiaomin Wang
Jürgen Eberle
Iver Petersen
Stefan Weger
Wolfgang Poller
Henry Fechner
Charité - Universitätsmedizin Berlin · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gene therapy is a new therapeutic approach for the treatment of human cancers. Gene expression systems that can be regulated by drugs have been developed to improve the safety and efficacy of therapeutic transgene delivery. One of the most promising systems is the tetracycline (Tet)-responsive system in the Tet-On configuration. A major problem of the Tet-On system if used in viral vectors is the high basal activity of the Tet response element (TRE) promoter leading to leaky expression of transgenes under uninduced conditions. We therefore evaluated novel TRE promoters for controlling gene expression in an adenovirus vector (AdV) Tet-On system and further investigated them for expression of the pro-apoptotic CD95/Fas ligand (FasL) in human epithelial carcinoma cell line (HeLa) and lung cancer cells. Plasmid-based reporter gene assays showed that modifications within the tetO (7) and minimal immediate early cytomegalovirus promoter (CMV)(min) sequence of the TRE promoter reduced its leakiness and led to a markedly improved regulatability by doxycycline. Among several TRE promoters tested, a new construct (TRE-Tight1) containing modifications of both the tetO (7) sequence and the CMV(min) showed 11-fold reduced leakiness and 1.5-fold increased absolute transgene expression levels after induction, as compared to the original TRE. Under induced conditions, a TRE-Tight1 promoter-dependent AdV expressing the pro-apoptotic CD95L/FasL induced apoptosis and cell lysis in HeLa cells as efficiently as an AdV containing the original TRE promoter. In contrast to the latter, however, the vector with the modified TRE promoter left cells totally unaffected in the absence of the inducer. Stringently regulated induction of apoptosis and cell death by TRE-Tight1-AdV was also demonstrated in three human lung cancer cell lines. These data show that the novel TRE-Tight1 promoter has a high potential for closely controlled and efficient expression of cytotoxic genes in AdV-based anti-cancer approaches.

Indexed as

AdenoviridaeApoptosisDoxycyclineFas Ligand ProteinGene Expression RegulationGenetic TherapyGenetic VectorsHeLa CellsHumansLung NeoplasmsMembrane GlycoproteinsPromoter Regions, GeneticTetracyclineToxicity TestsTumor Cells, CulturedTumor Necrosis FactorsDoxycyclineFASLG protein, humanFas Ligand ProteinMembrane GlycoproteinsTetracyclineTumor Necrosis Factors

Identifiers

PMID16437213
OpenAlexW2099487269

What OpenQuestion holds

Textmetadata
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.