Adenovirus-mediated transduction of Escherichia coli uracil phosphoribosyl-transferase gene sensitizes cancer cells to low concentration of 5-fluorouracil: A new way to overcome the resistance of chemotherapeutic agent

Kanai, Fumihiko; Kawakami, Takayuki; Ohashi, Makoto; Shiratori, Yasushi; Omata, Masao

doi:10.1016/s0016-5085(98)82520-1

Cited by 57 publications

(83 citation statements)

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“…Although the true mechanisms for the downregulation of OPRT expression in human cancers are still unclear, an experimental study has suggested the loss of 3q to be a genetic change responsible for the decreased OPRT activity and acquired resistance to 5-FU (Hidaka et al, 2003). Furthermore, the adenoviral-mediated transduction of OPRT gene was reported to result in a marked sensitisation of tumour cells to 5-FU cytotoxicity (Kanai et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

et al. 2006

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The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eightytwo carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r ¼ 0.203), between the TS and DPD expression (r ¼ 0.098), or between the OPRT and DPD expression (r ¼ 0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P ¼ 0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P ¼ 0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P ¼ 0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P ¼ 0.0003), OPRT status (hazard ratio 2.543; P ¼ 0.0005), and DPD status (hazard ratio 2.840; Po0.0001) to all be significant prognostic factors for the survival of resected NSCLC patients postoperatively treated with UFT.

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Section: Discussionmentioning

confidence: 99%

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

et al. 2006

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“…This enzyme, expressed naturally in E. coli, converts the chemotherapeutic drug 5-fluorouracil (5-FU) into 5-fluorouridine monophosphate, a highly toxic compound. Adenoviral delivery of the upp gene has been shown to increase the sensitivity of human cancer cell lines to 5-FU 23,24 . To assess whether bacterial invasion can lead to sensitization to 5-FU, HeLa cells were incubated for 2 h with E. coli BM2710 pGB2Oinv-hly at an MOI of 50 (an MOI compatible with survival; Figure 1b).…”

Section: Effect Of Bacterial Invasion On the Sensitivity Of Mammalianmentioning

confidence: 99%

“…The E. coli enzymes deoD and upp have been used in gene therapy studies, and adenovirus-mediated expression of these genes has been shown to sensitize mammalian cells to 6-MPDR 20-22 and 5-FU, 23,24 respectively. Invasion with E. coli sensitized Caco-2 cells to 6-MPDR ( Figure 4) and HeLa cells to the action of 5-FU (Figure 5a).…”

Section: Invasive E Coli As a Therapeutic Delivery Vector Rj Critchlmentioning

confidence: 99%

Potential therapeutic applications of recombinant, invasive E. coli

et al. 2004

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“…13 We had previously reported the efficacy of a new suicide gene derived from a fusion of the S. cerevisiae CDase (FCY1) and UPRTase genes (FUR1). 14 This suicide gene, designated FCU1 (GenBank Accession Number AF312392), encodes a bifunctional chimeric protein that combines the enzymatic activities of FCY1 and FUR1 and efficiently catalyzes the direct conversion of 5-FC into the toxic metabolites 5-FU and 5-FUMP.…”

Section: Introductionmentioning

confidence: 99%

Modified vaccinia virus Ankara as a vector for suicide gene therapy

et al. 2007

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Modified vaccinia virus Ankara (MVA) has been used successfully to express various antigens for the development of vaccines. Here we show that MVA can also be used as an efficient vector for the transfer of suicide genes to cancer cells. We have generated a new and highly potent suicide gene, FCU1, which encodes a fusion protein derived from the yeast cytosine deaminase and uracil phosphoribosyltransferase genes. We now describe the therapeutic benefit of using MVA to deliver and express the FCU1 gene in cancer cells. MVA-mediated transfer of the FCU1 gene to various human tumor cells results in the production of a bifunctional intracellular enzyme, such that exposure to the prodrug 5-FC suppresses the growth of the tumor cells both in vitro and in vivo. Moreover, we report a more potent tumor growth delay at lower doses of 5-FC using MVA-FCU1 in comparison to adenovirus encoding FCU1. Prolonged therapeutic levels of cytotoxic 5-FU were detected in tumors in mice treated with both MVA-FCU1 and 5-FC while no detectable 5-FU was found in the circulation. This original combination between MVA and FCU1 represents a potentially safe and attractive therapeutic option to test in man.

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Adenovirus-mediated transduction of Escherichia coli uracil phosphoribosyl-transferase gene sensitizes cancer cells to low concentration of 5-fluorouracil: A new way to overcome the resistance of chemotherapeutic agent

Cited by 57 publications

References 0 publications

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT

Potential therapeutic applications of recombinant, invasive E. coli

Modified vaccinia virus Ankara as a vector for suicide gene therapy

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