Non-invasive molecular and functional imaging of cytosine deaminase and uracil phosphoribosyltransferase fused with red fluorescence protein

Xing, Ligang; Deng, Xuelong; Kotedia, Khushali; Ackerstaff, Ellen; Ponomarev, Vladimir; Ling, C. Clifton; Koutcher, Jason A.; Li, Gloria C.

doi:10.1080/02841860802256475

Cited by 12 publications

(14 citation statements)

References 24 publications

(45 reference statements)

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“…Recently, Xing et al . 47 developed a CD and CU fusion gene with a monomeric red fluorescent protein. This reporter enabled them to monitor transgene expression and prodrug activation using optical fluorescence imaging of red fluorescent protein and magnetic resonance spectroscopy with fluorine-19.…”

Section: Discussionmentioning

confidence: 99%

Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter

et al. 2010

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The nuclear factor-κB (NF-κB) is known to be activated in many cancer types including lung, ovarian, astrocytomas, melanoma, prostate as well as glioblastoma, and has been shown to correlate with disease progression. We have cloned a novel NF-κB-based reporter system (five tandem repeats of NF-κB responsive genomic element (NF; 14bp each)) to drive the expression cassette for both a fusion between the yeast cytosine deaminase and uracil phosphoribosyltransferase (CU) as a therapeutic gene and the secreted Gaussia luciferase (Gluc) as a blood reporter, separated by an internal ribosomal entry site (NF-CU-IGluc). We showed that malignant tumor cells have high expression of Gluc, which correlates to high activation of NF-κB. When NF-κB was further activated by tumor necrosis factor-α in these cells, we observed up to 10-fold increase in Gluc levels and therefore transgene expression in human glioma cells served to greatly enhance the sensitization of these cells to the prodrug, 5-fluorocytosine both in cultured cells and in vivo subcutaneous tumor xenograft model. This inducible system provides a tool to enhance the expression of imaging and therapeutic genes for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter

et al. 2010

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“…R3327-AT cell lines stably expressing CD/mDsRed and CD/UPRT/mDsRed fusion genes (designated as CD and CDUPRT cells, respectively) were established as previously described (12). Briefly, the expression plasmids were constructed which contain CD or CDUPRT gene fused with DsRed-Monomer (mDsRed) and a Hygromycin B resistance gene.…”

Section: Methodsmentioning

confidence: 99%

Expression of the bifunctional suicide gene CDUPRT increases radiosensitization and bystander effect of 5-FC in prostate cancer cells

Xing

Sun

Deng

et al. 2009

Radiotherapy and Oncology

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Purpose To test a hypothesis that, with 5-fluorocytosine (5-FC) treatment, the co-expression of cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT) can lead to greater radiosensitization and bystander effect than CD-expression alone. Methods and Materials R3327-AT cell lines stably expressing CD or CDUPRT were generated. The 5-FC and 5-FU cytotoxicity, and the radiosensitivity with/without 5-FC treatment, of these cells were evaluated under both aerobic and hypoxic conditions. The bystander effect was assessed by apoptosis staining and clonogenic survival. The pharmacokinetics of 5-FU and 5-FC metabolism was followed in mice bearing CD- or CDUPRT-expressing tumors using 19F MR spectroscopy (MRS). Results CDUPRT-expressing cells were more sensitive to 5-FC and 5-FU than CD-expressing cells. CDUPRT-expression more effectively enhanced the radiosensitizing effect of 5-FC than CD-expression. A 25-fold-lower dose of 5-FC resulted in the same magnitude of radiosensitization in CDUPRT-expressing cells, relative to that in CD-expressing cells. The 5-FC cytotoxicity in co-cultures of parental cells mixed with 10–20% CDUPRT cells was similar as that in 100% CDUPRT cells. 19F MRS measurements showed that expression of CDUPRT leads to enhanced accumulation of fluorine nucleotide (FNuc) in vivo. Conclusion Our study indicates that CDUPRT/5-FC strategy may be more effective than CD/5-FC when used as an adjuvant to radiotherapy.

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“…Jacobs et al showed the use of CD as the therapeutic gene and HSVTK as a PET imaging reporter as well as a therapeutic gene to induce synergistic antitumor activity [55]. In another study, Xing et al monitored noninvasively suicide gene activity by tracking anabolism of 5FU to cytotoxic fluoronucleotides by magnetic resonance spectrometry in a rat prostate model [56]. Phase I clinical trials are underway for high-grade gliomas, and phase II and III clinical trials are underway for replication-competent adenovirus-mediated suicide gene therapy, using double suicide gene therapy modality (yCD/5FC plus HSVTK/GCV) combined with intensity modulated radiation therapy for prostate cancer (http://clinicaltrials.gov, identifier NTC00583492) [57].…”

Section: Cytosine Deaminase/5-fluorocytosine Systemmentioning

confidence: 98%

Gene-Directed Enzyme Prodrug Cancer Therapy

Karjoo

Ganapathy

Hatefi

2014

Gene Therapy of Cancer

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Non-invasive molecular and functional imaging of cytosine deaminase and uracil phosphoribosyltransferase fused with red fluorescence protein

Cited by 12 publications

References 24 publications

Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter

Suicidal gene therapy in an NF-κB-controlled tumor environment as monitored by a secreted blood reporter

Expression of the bifunctional suicide gene CDUPRT increases radiosensitization and bystander effect of 5-FC in prostate cancer cells

Gene-Directed Enzyme Prodrug Cancer Therapy

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