Transduction of cytosine deaminase gene makes rat glioma cells highly sensitive to 5-fluorocytosine

Ge, Kai; Lu, Xu; Zheng, Zhiming; Xu, Dehua; Sun, Liguang; Liu, Xinyuan

doi:10.1002/(sici)1097-0215(19970516)71:4<675::aid-ijc26>3.0.co;2-9

Cited by 38 publications

(12 citation statements)

References 23 publications

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“…The CD gene used for GDEPT has been cloned from Escherichia coli (E. coli; Austin and Huber, 1993) and has been shown in a number of in vitro studies to enhance mammalian cell sensitivity to 5-FC by up to 2000-fold (Ge et al, 1997). In vivo anti-tumour activity of the CD/5-FC combination has been demonstrated in several animal models, including ®brosarcomas (Mullen et al, 1994), carcinomas (Huber et al, 1993(Huber et al, , 1994Ohwada et al, 1996;Kanai et al, 1997;Bentires-Alj et al, 2000), gliomas (Ge et al, 1997;Ichikawa et al, 2000) and metastatic formations of different origin (Consalvo et al, 1995;Topf et al, 1998).…”

Section: Cytosine Deaminase/5-fluorocytosinementioning

confidence: 99%

Gene directed enzyme/prodrug therapy of cancer: Historical appraisal and future prospectives

2001

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Gene therapy of cancer is a novel approach with the potential to selectively eradicate tumour cells, whilst sparing normal tissue from damage. In particular, gene-directed enzyme prodrug therapy (GDEPT) is based on the delivery of a gene that encodes an enzyme which is non-toxic per se, but is able to convert a prodrug into a potent cytotoxin. Several GDEPT systems have been investigated so far, demonstrating effectiveness in both tissue culture and animal models. Based on these encouraging results, phase I/II clinical trials have been performed and are still ongoing. The aim of this review is to summarise the progress made in the design and application of GDEPT strategies. The most widely used enzyme/prodrug combinations already in clinical trials (e.g., herpes simplex 1 virus thymidine kinase/ganciclovir and cytosine deaminase/5-¯uorocytosine), as well as novel approaches (carboxypeptidase G2/CMDA, horseradish peroxidase/indole-3-acetic acid) are described, with a particular attention to translational research and early clinical results.

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Section: Cytosine Deaminase/5-fluorocytosinementioning

confidence: 99%

Gene directed enzyme/prodrug therapy of cancer: Historical appraisal and future prospectives

2001

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“…C6 cell lines exhibit an aggressive growth pattern, which could recapitulate the hallmarks of clinical glioma. [14e,27] After the treatment with naked Lv‐CD (or SS‐HPT/Lv‐CD) and 5‐FC by intraperitoneal (i.p.) administration (Figure b), the tumor volume curve showed an decelerated tumor growth in the naked Lv‐CD and SS‐HPT/Lv‐CD groups.…”

Section: Resultsmentioning

confidence: 99%

A Hybrid Nanovector of Suicide Gene Engineered Lentivirus Coated with Bioreducible Polyaminoglycosides for Enhancing Therapeutic Efficacy against Glioma

Fan

Shao

Zhang

et al. 2019

Adv Funct Materials

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An emerging hybrid nanovector integrating the merits of both viral and nonviral vectors has attracted much attention as the next generation of promising gene vectors to overcome the primary challenge of cancer gene therapy. Due to its inherent advantages, lentivirus (Lv) has been increasingly applied and investigated in medical fields. Herein, a new hybrid nanovector (SS‐HPT/Lv) composed of the Lv core and reduction‐responsive hyperbranched polyaminoglycoside (SS‐HPT) shell is designed via electrostatic interaction. In comparison with polybrene (commercial enhanced transfection reagent), SS‐HPT endows the hybrid nanovector with better biosafety. Furthermore, both the appropriate nanoparticle sizes and positive surface potentials contribute to the endocytosis and rescue of SS‐HPT/Lv from endocytic vesicles. Regarding therapeutic application, lentiviral vector acquires permanent transgene expression with the capability of integrating to the host chromosome, and SS‐HPT/Lv exhibits an improved transduction efficacy. The cytosine deaminase/5‐fluorocytosine suicide gene therapy system mediated by SS‐HPT/Lv performs an enhanced antitumor efficiency and extends the survival time of glioma‐bearing rats. Such a hybrid nanovector strategy would open a new avenue to the development of gene vectors for treating malignant cancers.

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“…Delivery of CD either by replication-deficient adenovirus, oncolytic adenovirus or retrovirus caused tumor regression of both C6 and 9L rat models of glioma [Ge et al, 1997;Ichikawa et al, 2000;Wang et al, 2003;Conrad et al, 2005]. Areas of necrosis surrounded by apoptotic cells were observed [Ichikawa et al, 2000] as was demylenation and gliosis within areas of normal brain tissue.…”

Section: B Cytosine Deaminase/5-fluorocytosinementioning

confidence: 99%

Gene Therapy and Targeted Toxins for Glioma

Castro

Candolfi

Kroeger

et al. 2005

CGT

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The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted, this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors.

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Transduction of cytosine deaminase gene makes rat glioma cells highly sensitive to 5-fluorocytosine

Cited by 38 publications

References 23 publications

Gene directed enzyme/prodrug therapy of cancer: Historical appraisal and future prospectives

Gene directed enzyme/prodrug therapy of cancer: Historical appraisal and future prospectives

A Hybrid Nanovector of Suicide Gene Engineered Lentivirus Coated with Bioreducible Polyaminoglycosides for Enhancing Therapeutic Efficacy against Glioma

Gene Therapy and Targeted Toxins for Glioma

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