Suppression of gastric cancer cell growth by targeting the β‐catenin/T‐cell factor pathway

Dvory‐Sobol, Hadas; Sagiv, Eyal; Liberman, Eliezer; Kazanov, Diana; Arber, Nadir

doi:10.1002/cncr.22416

Cited by 22 publications

(17 citation statements)

References 41 publications

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“…Although Chen and McCormick [16] demonstrated a similar gene therapy strategy targeting colon cancer by a β-catenin/TCF-response promoter driving the expression of the pro-apoptotic gene Fadd . Beneficial effects have also been observed by inhibition of proliferation of pancreatic and gastric cancer cells using the β-catenin promoter to drive the expression of suicide genes [17,18]. …”

Section: Discussionmentioning

confidence: 99%

Suppression of neointima formation by targeting β-catenin/TCF pathway

2016

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Coronary artery disease is treated by vein grafting and stent implantation. Late vein graft failure and restenosis of stented arteries reduce the success rates of these approaches and are caused by neointima formation. We have previously shown that Wnt proteins are up-regulated during intimal thickening, and have speculated that these lead to activation of downstream genes with β-catenin/T-cell factor (TCF)-responsive promoters. In the present study, we aimed to provide evidence that β-catenin/TCF signalling promotes neointima formation and assess whether targeting this pathway has potential for reducing neointima formation. We utilized a gene therapy approach selectively targeting cells in which the β-catenin/TCF pathway is activated by using a recombinant adenovirus Ad-TOPTK, which carries a herpes simplex virus thymidine kinase (HSV-TK) gene under the control of a β-catenin/TCF-response promoter. Cells with activated β-catenin will therefore be selectively killed. Ad-TOPTK and ganciclovir (GCV) treatment significantly suppressed the growth of the neointima in a murine model of left carotid artery ligation. In summary, we demonstrated that Wnt/β-catenin/TCF signalling promotes neointima formation, by showing that the selective death of cells with activated β-catenin suppressed neointima formation. This highlights the therapeutic potential for reducing late vein graft failure and in-stent restenosis by targeting β-catenin/TCF signalling.

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Section: Discussionmentioning

confidence: 99%

Suppression of neointima formation by targeting β-catenin/TCF pathway

2016

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“…29) However, the immunogenicity of adenoviruses restricts their safety and efficacy for repeated administration. Furthermore, naked pDNA has advantages in terms of ease and productivity.…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with Epidermal Growth Factor Enhances Naked Plasmid DNA Transfer onto Gastric Serosal Surface in Mice

Miyamoto

Baba

Nakajima

et al. 2012

Biological & Pharmaceutical Bulletin

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We have developed a simple administration method, which is gastric serosal surface instillation of naked plasmid DNA (pDNA) in experimental animals. The purpose of this study was to improve gastric gene transfer efficiency by pre-treatment with a macropinocytosis enhancer, such as fetuin or epidermal growth factor (EGF), in mice. A series of concentrations of fetuin were instilled onto gastric serosal surface prior to instillation of naked pDNA in mice; however, fetuin did not improve transgene expression in the stomach 6 h after administration of pDNA. EGF also did not affect transgene expression in the stomach when pDNA was instilled immediately after EGF instillation. On the other hand, when pDNA was instilled onto gastric serosal surface 24 h after EGF treatment, transgene expression in the stomach was significantly improved by 2.6-fold. In addition, transgene-positive cells were increased 5.3-fold by EGF pre-treatment. High transgene expression in the stomach lasted for 48 h in the EGF pre-treatment group in comparison with that in the no pre-treatment group. These findings are valuable to develop an effective method of in vivo gene transfer to the stomach.

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“…To overcome these problems, researchers studied strategy by using an adenoviral vector with a β-catenin/T-cell factor-responsive promoter, which is an activated pathway in gastric cancer cells. 28 However, immunogenicity of adenoviruses restricts safety and efficacy with repeated administration. Plus, naked pDNA has advantages in terms of ease and productivity.…”

Section: Discussionmentioning

confidence: 99%

Highly stomach-selective gene transfer following gastric serosal surface instillation of naked plasmid DNA in rats

et al. 2008

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Short titleStomach-selective gene transfer in rats 2 Background. The purpose of this study was to achieve stomach-selective gene transfer in rats by our simple and novel administration method, which is gastric serosal surface instillation of naked plasmid DNA (pDNA). Methods. Naked pDNA encoding firefly luciferase as a reporter gene was instilled onto the gastric serosal surface in male Wistar rats. As controls, we performed intraperitoneal, intragastric and intravenous administration of naked pDNA. At appropriate time intervals, we measured luciferase activities in the stomach and other tissues. Results. Gene expression in the stomach 6 h after gastric serosal surface instillation of naked pDNA (5 µg) was significantly higher than that using other administration methods. The present study is the first report on stomach-selective gene transfer following instillation of naked pDNA onto the gastric serosal surface in rats. Also, the gene expression level in the stomach 6 h after gastric serosal surface instillation of naked pDNA was markedly higher than that in other tissues. In a dose-dependent study, the gene expression level was saturated over 5 µg. Gene expression in the stomach was detected 3 h after gastric serosal surface instillation of naked pDNA. The gene expression level was peaked 12-24 h after instillation of naked pDNA, then decreased to similar level to 3 h at 48 h. Conclusions.Gastric serosal surface instillation of naked pDNA can be a highly stomach-selective gene transfer method in rats.

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Suppression of gastric cancer cell growth by targeting the β‐catenin/T‐cell factor pathway

Cited by 22 publications

References 41 publications

Suppression of neointima formation by targeting β-catenin/TCF pathway

Suppression of neointima formation by targeting β-catenin/TCF pathway

Pretreatment with Epidermal Growth Factor Enhances Naked Plasmid DNA Transfer onto Gastric Serosal Surface in Mice

Highly stomach-selective gene transfer following gastric serosal surface instillation of naked plasmid DNA in rats

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