ArticleGene therapy2004
5-Fluorocytosine increases the toxicity of Wnt-targeting replicating adenoviruses that express cytosine deaminase as a late gene.
Article in Gene therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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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.
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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.
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Who cites it
14 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- Comparison of the L3-23K and L5-Fiber Regions for Arming the Oncolytic Adenovirus Ad5-Delta-24-RGD with Reporter and Therapeutic Transgenes.International journal of molecular sciences · 2025Article
- The application of oncolytic viruses in cancer therapy.Biotechnology letters · 2021Review
- Arming Oncolytic Adenoviruses: Effect of Insertion Site and Splice Acceptor on Transgene Expression and Viral Fitness.International journal of molecular sciences · 2020Article
- Effect of Transgene Location, Transcriptional Control Elements and Transgene Features in Armed Oncolytic Adenoviruses.Cancers · 2020Review
- Targeting the Wnt pathway in human cancers: therapeutic targeting with a focus on OMP-54F28.Pharmacology & therapeutics · 2015Review
- Combining virotherapy and angiotherapy for the treatment of breast cancer.Cancer gene therapy · 2013Article
- Bugs and drugs: oncolytic virotherapy in combination with chemotherapy.Current pharmaceutical biotechnology · 2012Review
- Selectivity and efficiency of late transgene expression by transcriptionally targeted oncolytic adenoviruses are dependent on the transgene insertion strategy.Human gene therapy · 2011Article
- A modified E2F-1 promoter improves the efficacy to toxicity ratio of oncolytic adenoviruses.Gene therapy · 2009Article
- Armed replicating adenoviruses for cancer virotherapy.Cancer gene therapy · 2009Review
- Cellular genetic tools to control oncolytic adenoviruses for virotherapy of cancer.Journal of molecular medicine (Berlin, Germany) · 2008Review
- A conditionally replicative adenovirus that codes for a TK-GFP fusion protein (Ad5Delta24TK-GFP) for evaluation of the potency of oncolytic virotherapy combined with molecular chemotherapy.International journal of molecular medicine · 2006Article
- Gene-directed enzyme prodrug therapy with carboxylesterase enhances the anticancer efficacy of the conditionally replicating adenovirus AdDelta24.Gene therapy · 2005Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical studies with oncolytic adenoviruses have shown that existing viruses are safe but lack efficacy. To selectively increase the toxicity of oncolytic adenoviruses targeting colon tumours, we have inserted the yeast cytosine deaminase gene (yCD) after the fibre gene in the major late transcript. yCD was expressed using either an internal ribosome entry site (IRES) or by alternative splicing of a new exon analogous to the Ad41 long fibre exon. The IRES-CD virus gave higher yCD expression on Western blots. Both approaches result in yCD expression restricted to the period after viral DNA replication. Viral burst size was reduced by less than approximately 10-fold by 5-fluorocytosine (5-FC), showing that expression of yCD as a late gene is compatible with virus replication. Cytopathic effect assays in colon cancer cell lines showed that both yCD viruses have approximately 10-fold increased toxicity in the presence of the prodrug 5-FC, which is converted to 5-fluorouracil (5-FU) by yCD. Toxicity was higher following addition of 5-FC immediately after infection. The largest gain in toxicity was seen in HT29 colon cancer cells, which are the least permissive colon cancer cells for the parental virus, indicating that the new 5-FC/yCD viruses may have broader applications for colon cancer therapy than their predecessors.
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Registered trials
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.