ArticleTheranostics2016
Dihydropyrimidine Dehydrogenase Is a Prognostic Marker for Mesenchymal Stem Cell-Mediated Cytosine Deaminase Gene and 5-Fluorocytosine Prodrug Therapy for the Treatment of Recurrent Gliomas.
Article in Theranostics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- Engineered mesenchymal stem/stromal cells against cancer.Cell death & disease · 2025Review
- Metabolic Reprogramming in Glioblastoma Multiforme: A Review of Pathways and Therapeutic Targets.Cells · 2024Review
- Article
- Gene therapy using genome-edited iPS cells for targeting malignant glioma.Bioengineering & translational medicine · 2023Article
- Aspergillus Niger thermostable Cytosine deaminase-dextran conjugates with enhanced structure stability, proteolytic resistance, and Antiproliferative activity.BMC microbiology · 2023Article
- Cell-Based Therapy for the Treatment of Glioblastoma: An Update from Preclinical to Clinical Studies.Cells · 2021Review
- A novel lncRNA ARST represses glioma progression by inhibiting ALDOA-mediated actin cytoskeleton integrity.Journal of experimental & clinical cancer research : CR · 2021Article
- Stem cells for the treatment of glioblastoma: a 20-year perspective.CNS oncology · 2021Review
- Mesenchymal Stem/Stromal Cell-Based Delivery: A Rapidly Evolving Strategy for Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Epitranscriptomics and epiproteomics in cancer drug resistance: therapeutic implications.Signal transduction and targeted therapy · 2020Review
- Effective control of tumor growth through spatial and temporal control of theranostic sodium iodide symporter (Theranostics · 2020Article
- Antitumor efficacy of cytosine deaminase-armed vaccinia virus plus 5-fluorocytosine in colorectal cancers.Cancer cell international · 2020Article
- Enhancement of the Therapeutic Capacity of Mesenchymal Stem Cells by Genetic Modification: A Systematic Review.Frontiers in cell and developmental biology · 2020Review
- ToxNav germline genetic testing and PROMinet digital mobile application toxicity monitoring: Results of a prospective single-center clinical utility study-PRECISE study.Cancer medicine · 2019Article
- Cytotoxic response of 5-fluorouracil-resistant cells to gene- and cell-directed enzyme/prodrug treatment.Cancer gene therapy · 2018Article
- Mesenchymal Stem Cell Expressing TRAIL as Targeted Therapy against Sensitised Tumour.International journal of molecular sciences · 2018Review
- Immunohistochemical Markers as Predictors of Histopathologic Response and Prognosis in Rectal Cancer Treated with Preoperative Adjuvant Therapy: State of the Art.Gastroenterology research and practice · 2017Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We investigated a therapeutic strategy for recurrent malignant gliomas using mesenchymal stem cells (MSC), expressing cytosine deaminase (CD), and prodrug 5-Fluorocytosine (5-FC) as a more specific and less toxic option. MSCs are emerging as a novel cell therapeutic agent with a cancer-targeting property, and CD is considered a promising enzyme in cancer gene therapy which can convert non-toxic 5-FC to toxic 5-Fluorouracil (5-FU). Therefore, use of prodrug 5-FC can minimize normal cell toxicity. Analyses of microarrays revealed that targeting DNA damage and its repair is a selectable option for gliomas after the standard chemo/radio-therapy. 5-FU is the most frequently used anti-cancer drug, which induces DNA breaks. Because dihydropyrimidine dehydrogenase (DPD) was reported to be involved in 5-FU metabolism to block DNA damage, we compared the survival rate with 5-FU treatment and the level of DPD expression in 15 different glioma cell lines. DPD-deficient cells showed higher sensitivity to 5-FU, and the regulation of DPD level by either siRNA or overexpression was directly related to the 5-FU sensitivity. For MSC/CD with 5-FC therapy, DPD-deficient cells such as U87MG, GBM28, and GBM37 showed higher sensitivity compared to DPD-high U373 cells. Effective inhibition of tumor growth was also observed in an orthotopic mouse model using DPD- deficient U87MG, indicating that DPD gene expression is indeed closely related to the efficacy of MSC/CD-mediated 5-FC therapy. Our results suggested that DPD can be used as a biomarker for selecting glioma patients who may possibly benefit from this therapy.
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