Gene Therapy for Gastric Diseases

Abstract

Gene therapy for gastric cancer and gastric ulcer is a rationalized strategy since various genes correlate with these diseases. Since gene expressions in non-target tissues/cells cause side effects, a selective gene delivery system targeted to the stomach and/or cancer must be developed.The route of vector transfer (direct injection, systemic, intraperitoneal, gastric serosal surface and oral administration) is an important issue which can determine efficacy and safety. Strategies for cancer gene therapy can be categorized as suicide gene therapy, growth inhibition and apoptosis induction, immunotherapy, anti-angiogenesis, and others. Combination of the target gene with other genes and/or strategies such as chemotherapy and virotherapy is promising. Candidates for treatment of gastric ulcer are vascular endothelial growth factor, angiopoietin-1, serum response factor, and cationic host defense peptide cathelicidin. In this review, we discuss stomach-and cancer-targeted gene transfer methods and summarize gene therapy trials for gastric cancer and gastric ulcer.

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

“…Thus, stomachtargeted gene transfer is an important method for these refractory gastric diseases. 28) Gene therapy is a rational approach for these severe diseases because a protein defect or deficiency is frequently involved. In most cases, a viral vector has been used as the gene delivery method to the stomach, but selectivity and safety concerns have been raised about viral vectors.…”

“…34) Stomach-selective or -specific gene transfection methods are expected to be safe and effective treatments against refractory gastric ulcer and gastric cancer. 28) Gastric ulcer and gastric cancer are generated in the gastric mucosal side and then invade the gastric serosal side. Gastric serosal surface instillation of pDNA encoding therapeutic genes is thought to help resistance primarily against the invasion of gastric ulcer or gastric cancer to the serosal side.…”

Suppression of gastric cancer growth by baculovirus vectormediated transfer of normal epithelial cell specific-1 gene

“…Although the disease at its early stages is treatable with surgical resection, advanced GC does not generally respond to conventional chemotherapy or radiotherapy. Therefore, gene therapy represents an alternative modality for it [10] . Gene therapy is considered a promising therapeutic modality for cancer and has been successfully applied in animal models using various types of viral vector, gene expression regulation elements, and putative antitumor genes.…”

Combination of Nanoparticles with Physical Stimuli toward Cancer Therapy

“…In contrast, naked pDNA instillation onto the stomach without the physical stimuli resulted in efficient transgene expression. [55][56][57] As mentioned above, physical stimuli such as rubbing the stomach surface could enhance the transgene expression. 43) Thus, appropriate selection of the administration routes would also be an important issue in the physical stimuli-mediated delivery of the nanoparticles.…”