ArticleJournal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract2009
Effectiveness of HSV-tk suicide gene therapy driven by the Grp78 stress-inducible promoter in esophagogastric junction and gastric adenocarcinomas.
Article in Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Universal strategy to generate lentiviral vectors encoding lethal proteins.Molecular therapy. Advances · 2026Article
- TK1 in gastric cancer: Helicobacter pylori-driven oncogenesis biomarker, utility, and emerging targeted therapies.Frontiers in oncology · 2026Review
- Article
- Strategies for Targeting Gene Therapy in Cancer Cells With Tumor-Specific Promoters.Frontiers in oncology · 2020Review
- Endoplasmic reticulum chaperone glucose-regulated protein 78 in gastric cancer: An emerging biomarker.Oncology letters · 2018Review
- A Universal Tumor-Specific Promoter for Cancer Gene Therapy.Doklady. Biochemistry and biophysics · 2018Article
- Combination of MPPa-PDT and HSV1-TK/GCV gene therapy on prostate cancer.Lasers in medical science · 2018Article
- Review
- Should peri-gastrectomy gastric acidity be our focus among gastric cancer patients?World journal of gastroenterology · 2014Article
- Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential.Nature reviews. Cancer · 2014Review
- Dual systemic tumor targeting with ligand-directed phage and Grp78 promoter induces tumor regression.Molecular cancer therapeutics · 2012Article
- Bicistronic vector for combined expression of the HSVtk killer gene and cytokine GM-CSF gene in cancer cells.Doklady. Biochemistry and biophysicsArticle
- Targeted Inhibitory Effect of Nasopharyngeal Carcinoma Cells by HreTechnology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe thymidine kinase gene of the herpes simplex virus (HSV-tk) is a suicide gene when administrated with the prodrug ganciclovir (GCV). This study investigated the effectiveness of HSV-tk activation as gene therapy for gastroesophageal junction and gastric adenocarcinomas using either the stress-inducible Grp78 promoter or the murine leukemia virus long-terminal repeat (LTR) promoter.
methodsThe HSV-tk gene, controlled by either the Grp78 promoter or the LTR promoter, was transduced into the gastroesophageal junction adenocarcinoma cell line SK-GT-5 and the gastric adenocarcinoma cell line MKN-74. Cell viability after exposure to varying concentrations of GCV was compared. The same cell lines were used to develop a nude mouse model for studies of the HSV-tk/GCV effect in vivo. The effect of intraperitoneal GCV injection on growth of the subcutaneous tumors was measured. HSV-TK expression was measured by Western blot and reverse transcription polymerase chain reaction.
resultsCell viability in vitro was significantly lower in the HSV-tk expressing (HSV-tk+) cells compared to control (no HSV-tk) cells after exposure to GCV. MKN-74tk+ cells were more sensitive to GCV killing than SK-GT-5tk+ cells. After culture with 1 microg/ml GCV for 10 days, MKN-74/tk cells were totally killed, whereas most SK-GT-5/tk cells survived. Cell viability was significantly lower under glucose starvation conditions when HSV-tk expression was regulated by the Grp78 promoter compared with the LTR promoter. MKN-74 tumors formed with HSV-tk+ cells in nude mice were eliminated after administration of GCV for 3 weeks, but GCV had no effect on tumors formed from HSV-tk- cells. Eradication of tumor formed with Grp78-tk cells was faster than that with LTR-tk cells. HSV-TK protein and mRNA were expressed in the transduced, but not the non-transduced tumors.
conclusionHSV-tk xwith ganciclovir suicide gene therapy results in significant cell killing in gastroesophageal junction and gastric adenocarcinoma cells both in vitro and in vivo, but complete tumor elimination only occurred with the gastric adenocarcinoma cell tumors. The most effective approach in this study used the Grp78 promoter in glucose-starvation stress conditions.
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