Expression of genes involved with cell cycle control, cell growth and chromatin modification are altered in hepatoblastomas.

Gray, Steven G.; Hartmann, Wolfgang; Eriksson, Therése; Ekström, Christina; Holm, Stefan; Kytölä, Soili; Schweinitz, Dietrich von; Pietsch, Torsten; Kogner, Per; Sandstedt, Bengt; Ekström, Tomas J.

doi:10.3892/ijmm.6.2.161

Cited by 7 publications

(6 citation statements)

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“…Its role in a proangiogenic signaling pathway through nuclear factor-B and CXC chemokines has been described recently [20]. Deng et al revealed a regulation of the Bcl-2 antiapoptotic activity via interaction with p53, for which altered expression levels have been observed in some HB [21,22]. The down-regulation of Bcl-2 has been proven to be a promising treatment approach in various experimental settings including breast cancer, prostate cancer, and pancreatic cancer, [23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 Gene Silencing in Pediatric Epithelial Liver Tumors

Warmann

Frank

Heitmann

et al. 2008

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 99%

Bcl-2 Gene Silencing in Pediatric Epithelial Liver Tumors

Warmann

Frank

Heitmann

et al. 2008

Journal of Surgical Research

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“…Interestingly, various altered gene expression profiles have been identified in HB offering possible targets for vector-based gene therapy in these tumors [28]. Other studies performed on the HCC also open up new treatment options for a gene therapeutic treatment of the HB: Schmitz et al [29] described effective antitumor activity of adenoviral mediated gene therapy in a HCC cell line, and Armeanu et al [30] reported on adenovirus TRAIL-application to HCC cells.…”

Section: Discussionmentioning

confidence: 98%

Optimizing vector application for gene transfer into human hepatoblastoma cells

et al. 2006

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Gene targeting is currently of distinct interest as an innovative additive treatment option in various malignancies. Its role in pediatric liver tumors has not yet been evaluated thoroughly. For the first time the authors systematically analyzed both lipid-based transfection as well as transduction with adenovirus vectors (Ad) and Sendai virus vectors (SeVV) in order to optimize gene transfer into hepatoblastoma (HB) cells. Two HB cell lines were infected with Ad or SeVV coding for green fluorescent protein (Ad-GFP, SeVV-GFP); transduction efficiencies and apoptosis were assessed using flow cytometry. Furthermore, lipofection of HB cell lines with plasmid-constructs comprising liver-specific promoters was performed using Lipofectamine 2000 and FuGENE 6; lipofection efficiency was monitored by flow cytometry, microscopy, and luciferase activity. The Ad-GFP showed higher transduction rates (61-86%) than the SeVV-GFP (4-24%) depending on the HB cell line used. Infections with first generation SeVV vectors (SeVV-GFP) led to increased target cell apoptosis (7-43%) compared to Ad-GFP (4-16%). The Lipofectamine 2000 revealed a higher transfection efficiency than the FuGENE 6 for both HB cell lines tested. The liver-specific promoters were found to be differently active in the HB cell lines. This study delineates recombinant adenovirus vectors as a promising tool for gene transduction in the HB cells. Furthermore, enhanced activity of the liver-specific promoters in HUH6 cells compared to HepT1 cells supports the observation of varying biological behavior in histologically differing HB tissues.

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“…Treatment efficiency will rely on the successful incorporation of cellular promoters or tumor-specific regulatory sequences into vector systems. Singular reports have described genetic alterations in HB that could possibly serve as target for a related approach [33]. The presented models of gene targeting, promoter analysis, and viral vector application might contribute to establishing modalities leading to the desired requirements.…”

Section: Discussionmentioning

confidence: 99%

In vitro gene targeting in human Hepatoblastoma

et al. 2005

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Poor treatment results in advanced hepatoblastoma (HB) made alternative treatment approaches desirable. Gene-directed tumor therapy is increasingly investigated in different malignancies. The aim of this study was to analyze possible alternatives of gene transfer into HB cells and to study therapeutic applications based on different strategies. Liposomal transfection of HB cells was assessed using liver-specific promoters, and adenovirus and Sendai virus transductions were performed in vitro. Transfer efficiencies were measured via flow cytometry determining expression of vector-encoded marker gene green fluorescent protein. Gene silencing of the anti-apoptotic bcl-2 gene in HUH6 cells was performed using lipofection of small interfering RNA (siRNA). Additionally, suicide gene therapy was carried out through a yeast-derived cytosine deaminase (YCD)-combined yeast uracil phosphoribosyltransferase (YUPRT)-based adenovirus-mediated gene transfer, leading to a potent intracellular prodrug transformation of 5-fluorocytosine into 5-fluorouracil. Treatment efficiencies were monitored via MTT viability assay. Highest gene transfer rates (86%) were observed using adenovirus transduction. We furthermore observed a significant therapeutic effect of adenovirus-mediated YCD::YUPRT suicide gene transfer. Liposomal-mediated anti-bcl-2 siRNA transfer led to a significant improvement of cisplatin treatment in HUH6 cells. Liver-specific promoters were found to be strongly active in HUH6 cells (mixed HB-derived), but less active in HepT1 cells (embryonal HB-derived). Liposomal transfection and viral transduction are effective approaches to genetically manipulate HB cells in vitro. For the first time, we demonstrate a positive effect of siRNA gene silencing in this malignancy. Additionally, we successfully investigated a model of adenovirus-based suicide gene therapy in HB cell cultures. Our data strongly encourage further studies assessing these alternative treatment approaches.

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Expression of genes involved with cell cycle control, cell growth and chromatin modification are altered in hepatoblastomas.

Cited by 7 publications

References 0 publications

Bcl-2 Gene Silencing in Pediatric Epithelial Liver Tumors

Bcl-2 Gene Silencing in Pediatric Epithelial Liver Tumors

Optimizing vector application for gene transfer into human hepatoblastoma cells

In vitro gene targeting in human Hepatoblastoma

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