Recepteur d'origine nantais (RON) is a receptor tyrosine kinase belonging to the subfamily of which c-MET is the prototype. Large epidemiologic studies have confirmed the strong association between RON and gastric cancer development. Constitutive activation of RON signaling directly correlates with tumorigenic phenotypes of gastric cancer and a poor survival rate in advanced gastric cancer patients. In this review, we focus on recent evidence of the aberrant expression and activation of RON in gastric cancer tumors and provide insights into the mechanism of RON signaling associated with gastric cancer progression and metastasis. Current therapeutics against RON in gastric cancer are summarized.
Epidemiologic Studies ; Humans ; Neoplasm Metastasis ; Phenotype ; Protein-Tyrosine Kinases ; Proto-Oncogene Proteins c-met ; Stomach Neoplasms ; Survival Rate

PURPOSE: Human papillomavirus (HPV) is a significant cause of cervical cancer-related deaths worldwide. Because HPV is a sexually transmitted mucosal pathogen, enhancement of antigen-specific mucosal immune response likely serves good strategy for vaccination. However, mucosal vaccines generally do not induce strong enough immune responses. Previously we proved that a bacterial flagellin, Vibrio vulnificus FlaB, induce strong antigen-specific immune responses by stimulating the Toll-like receptor 5. In this study, we tested whether FlaB could serve as an effective mucosal adjuvant for a peptide-based HPV preventive cancer vaccine. MATERIALS AND METHODS: Mice were intranasally administered with a mixture of FlaB and E6/E7 protective peptides in 5-day interval for a total of two times. Five-days after the last vaccination, cellular immune responses of the vaccinated mice were analyzed. Tumor growth was also observed after a subcutaneous implantation of TC-1 cells bearing E6/E7 antigens. RESULTS: Intranasal administration of the E6/E7 peptide mixture with FlaB elicited a strong antigen-specific cytotoxic T lymphocyte activity and antigen-specific interferon-gamma production from splenocytes and cervical lymph node cells. Furthermore, FlaB, as a mucosal adjuvant, conferred an excellent protection against TC-1 tumor challenge with high survival rates in E6/E7 immunized animals. CONCLUSION: These results indicate that FlaB can be a promising mucosal adjuvant for nasal HPV vaccine development.
Administration, Intranasal ; Animals ; Flagellin ; Humans ; Immunity, Cellular ; Immunity, Mucosal ; Immunization ; Interferon-gamma ; Lymph Nodes ; Lymphocytes ; Mice ; Peptides ; Survival Rate ; Toll-Like Receptor 5 ; Ursidae ; Vaccination ; Vaccines ; Vibrio vulnificus