Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038358 (gastric ulcer)
 5,179 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews cellular and molecular mechanisms of gastrointestinal ulcer healing. Ulcer healing, a genetically programmed repair process, includes inflammation, cell proliferation, re-epithelialization, formation of granulation tissue, angiogenesis, interactions between various cells and the matrix and tissue remodeling, all resulting in scar formation. All these events are controlled by the cytokines and growth factors (EGF, PDGF, KGF, HGF, TGFbeta, VEGF, angiopoietins) and transcription factors activated by tissue injury in spatially and temporally coordinated manner. These growth factors trigger mitogenic, motogenic and survival pathways utilizing Ras, MAPK, PI-3K/Akt, PLC-gamma and Rho/Rac/actin signaling. Hypoxia activates pro-angiogenic genes (e.g., VEGF, angiopoietins) via HIF, while serum response factor (SRF) is critical for VEGF-induced angiogenesis, re-epithelialization and muscle restoration. EGF, its receptor, HGF and Cox2 are important for epithelial cell proliferation, migration re-epithelializaton and reconstruction of gastric glands. VEGF, angiopoietins, nitric oxide, endothelin and metalloproteinases are important for angiogenesis, vascular remodeling and mucosal regeneration within ulcer scar. Circulating progenitor cells are also important for ulcer healing. Local gene therapy with VEGF + Ang1 and/or SRF cDNAs dramatically accelerates esophageal and gastric ulcer healing and improves quality of mucosal restoration within ulcer scar. Future directions to accelerate and improve healing include the use of stem cells and tissue engineering.
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PMID:Cellular and molecular mechanisms of gastrointestinal ulcer healing. 1618 17

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.
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PMID:Gene therapy for gastric diseases. 1853 93