Evidence map›Paper›PMID 22388453›Full record

ArticleCancer gene therapy2012

Bystander killing of malignant cells via the delivery of engineered thymidine-active deoxycytidine kinase for suicide gene therapy of cancer.

A Neschadim, J C M Wang, A Lavie, J A Medin

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Cancer gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
4.1field-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

10 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.Journal of controlled release : official journal of the Controlled Release Society · 2013
    Review
  8. Suicide Gene Therapy for Cancer - Current Strategies.Journal of genetic syndromes & gene therapy · 2013
    Article
  9. Article
  10. Frontiers in Suicide Gene Therapy of Cancer.Journal of genetic syndromes & gene therapy · 2012
    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

4 authors at 3 institutions in 2 countries.

A NeschadimDepartment of Medical Biophysics, University Health Network, University of Toronto, Toronto, Ontario, Canada.
J C M Wang
A Lavie
J A Medin
University Health Network · CAUniversity of Illinois Chicago · USUniversity of Toronto · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Activity and specificity of chemotherapeutic agents against solid tumors can be augmented via the targeted or localized delivery of 'suicide' genes. Selective activation of specific prodrugs in cells expressing the 'suicide' gene drives their elimination by apoptosis, while also enabling the killing of adjacent bystander cells. Strong bystander effects can compensate for poor 'suicide' gene delivery, and depend on the prodrugs used and mechanisms for the acquisition of activated drug by the bystander population, such as the presence of gap junctional intercellular communications. Although a number of 'suicide' gene therapies for cancer have been developed and characterized, such as herpes simplex virus-derived thymidine kinase (HSV-tk)-based activation of ganciclovir, their limited success highlights the need for the development of more robust approaches. Limiting activation kinetics and evolution of chemoresistance are major obstacles. Here we describe 'suicide' gene therapy of cancer based on the lentivirus-mediated delivery of a thymidine-active human deoxycytidine kinase variant. This enzyme possesses substrate plasticity that enables it to activate a multitude of prodrugs, some with distinct mechanisms of action. We evaluated the magnitude and mechanisms of bystander effects induced by different prodrugs, and show that when used in combination, they can synergistically enhance the bystander effect while avoiding off-target toxicity.

Indexed as

Genes, Transgenic, SuicideAstrocytomaCell Line, TumorDeoxycytidine KinaseGenetic EngineeringGenetic TherapyGene Transfer TechniquesGlioblastomaHumansThymidineThymidine KinaseTransfectionDeoxycytidine KinaseThymidineThymidine Kinase

Identifiers

PMID22388453
OpenAlexW2067253082

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.