Selection of tumour specific promoters for adenoviral gene therapy of cholangiocarcinoma

Lie-A-Ling, Michael; Bakker, C. M.; Deurholt, Tanja; Hoekstra, Ruurdtje; Wesseling, John G.; Afford, Simon C.; Bosma, Piter J.

doi:10.1016/j.jhep.2005.06.007

Cited by 10 publications

(7 citation statements)

References 35 publications

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“…The mRNA expression of MK was high in both cholangiocarcinoma cells and cholangiocytes; therefore, it was not suitable as a candidate TSP for cholangiocarcinoma. It should be noted that our results are partially inconsistent with those from a previous study, which reported that the mRNA expression of both hTERT and CK19 genes in cholangiocarcinoma cells was significantly higher compared with that in normal primary human hepatocytes (13). This inconsistency may be explained by the fact that the previous study used a different cholangiocarcinoma cell line, CC-LP-1.…”

Section: Genescontrasting

confidence: 99%

“…In this case, the promoters of the genes of cholangiocarcinoma-specific biomarkers serve as potential TSPs to be used for cholangiocarcinoma gene therapy. In this regard, certain established biomarkers, such as COX-2, MK, MUC1, hTERT and the bile duct marker CK19 appear to be promising candidates, as there were tumor-specifically upregulated (13). However, the results on cholangiocarcinoma-specific promoters have been inconsistent.…”

Section: Genesmentioning

confidence: 99%

“…In addition, the expression of transduced genes does not occur in non-proliferating primary liver cells when adenoviral vector is implicated in gene therapy (12). Other studies have demonstrated the effectiveness of potential TSPs constructed in adenoviral vectors used in gene therapy in cholangiocarcinoma; however, the selection of different TSPs may yield inconsistent results (13,14). The aim of the present study was to investigate cholangiocarcinoma-specific biomarker genes and their promoters, which are functional in cholangiocarcinoma cells but remain silent in non-tumorous primary human liver cells, in order to determine the value of the potential application of cholangiocarcinoma-specific TSP in gene therapy.…”

Section: Introductionmentioning

confidence: 99%

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High promoter activity of cytokeratin‑19 gene in cholangiocarcinoma

et al. 2018

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Conditionally replicating adenoviral vectors constructed with tumor-specific promoters (TSPs) offers a viable tool for the treatment of cholangiocarcinoma. The aim of the present study was to investigate cholangiocarcinoma-specific TSPs that remain active in adenoviral constructs in gene therapy. The mRNA expressions of cyclooxygenase-2, cytokeratin-19 (CK19), mucin-1, midkine and telomerase reverse transcriptase were determined in human cholangiocarcinoma cell lines, primary human hepatocytes and cholangiocytes using reverse transcription-quantitative polymerase chain reaction. The candidate promoters constructed in adenoviral vectors were analyzed for their activities in cholangiocarcinoma cell lines, primary human hepatocytes and cholangiocytes using dual-luciferase reporter assays. The mRNA expression of CK19 was markedly higher in the QBC939 cell line, indicating specificity to cholangiocarcinoma. Moreover, the promoter activity of CK19 in the adenoviral vector in infected cholangiocarcinoma cells was found to be significantly stronger compared with that in infected primary human hepatocytes and cholangiocytes. CK19 may be implicated in the pathogenesis of cholangiocarcinoma, as demonstrated by the stronger activity of its promoter, as well as the higher expression of mRNA in tumor cells. Therefore, the use of the promoter sequence of the CK19 gene may represent a potential tool in cholangiocarcinoma-specific adenoviral gene therapy.

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Section: Genescontrasting

confidence: 99%

Section: Genesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High promoter activity of cytokeratin‑19 gene in cholangiocarcinoma

et al. 2018

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“…Clinically, adenovectors could be administered into the bile by a duodenal fiberscope, such as during endoscopic retrograde cholangiography (ERC), or through a drainage tube, such as via percutaneous transhepatic cholangio-drainage (PTCD). Recently, the telomerase reverse transcriptase and cytokeratin-19 promoters have been reported to be highly expressed in cholangiocarcinoma, and may be suitable for adenoviral gene therapy [16]. Improvement in the tumor specificity of our method may result from using these promoters instead of the CAG promoter.…”

Section: Discussionmentioning

confidence: 99%

Oncolytic Gene Therapy Combined with Double Suicide Genes for Human Bile Duct Cancer in Nude Mouse Models

Kojima¹,

Honda²,

Hamada³

et al. 2009

Journal of Surgical Research

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“…Gene therapy has also been proposed as a strategy to overcome drug resistance; for instance, using vectors to induce the expression of a drug transporter or a tumour suppressor protein under the control of cancer-specific promoters upregulated in CCA cells, such as Baculoviral IAP Repeat Containing 5 (BIRC5), Telomerase Reverse Transcriptase (TERT), Cytokeratin 19 (CK19) or Cyclooxygenase-2 (COX-2). 46,47…”

Section: Multiple Mechanisms Of Pharmacoresistance (Mprs) Permit Cca ...mentioning

confidence: 99%