RESUMO
The fibroblast growth factor 8b (FGF8b) oncogene is known to be primarily involved in the tumorigenesis and progression of hormone-related cancers. Its role in other epithelial cancers has not been investigated, except for esophageal cancer, in which FGF8b overexpression was mainly found in tumor biopsies of male patients. These observations were consistent with previous findings in these cancer types that the male sex-hormone androgen is responsible for FGF8b expression. Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer of head and neck commonly found in Asia. It is etiologically associated with Epstein-Barr Virus (EBV) infection, inflammatory tumor microenvironment and relatively higher male predominance. Here, we reported for the first time that FGF8b is overexpressed in this EBV-associated non-hormone-related cancer of the head and neck, NPC. More importantly, overexpression of FGF8b mRNA and protein was detected in a large majority of NPC tumors from both male and female genders, in addition to multiple NPC cell lines. We hypothesized that FGF8b overexpression may contribute to NPC tumorigenesis. Using EBV-associated NPC cell lines, we demonstrated that specific knockdown of FGF8b by small interfering RNA inhibited cell proliferation, migration and invasion, whereas exogenous FGF8b stimulated these multiple phenotypes. Further mechanistic investigation revealed that in addition to NF-κB signaling (a major inflammatory signaling pathway known to be activated in NPC), an important EBV oncoprotein, the latent membrane protein 1 (LMP1), was found to be a direct inducer of FGF8b overexpression in NPC cells, whereas androgen (testosterone) has minimal effect on FGF8b expression in EBV-associated NPC cells. In summary, our study has identified LMP1 as the first viral oncogene capable of directly inducing FGF8b (an important cellular oncogene) expression in human cancer cells. This novel mechanism of viral-mediated FGF8 upregulation may implicate a new role of oncoviruses in human carcinogenesis.
Assuntos
Fator 8 de Crescimento de Fibroblasto/fisiologia , Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 4/patogenicidade , Oncogenes , Carcinoma , Movimento Celular , Proliferação de Células , Feminino , Fator 8 de Crescimento de Fibroblasto/antagonistas & inibidores , Fator 8 de Crescimento de Fibroblasto/genética , Humanos , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/fisiologia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/virologia , Invasividade Neoplásica , RNA Mensageiro/análise , RNA Interferente Pequeno/genética , Proteínas da Matriz Viral/fisiologiaRESUMO
Autogenous tooth transplantation, or autotransplantation, is the surgical movement of a tooth from one location in the mouth to another in the same individual. Once thought to be experimental, autotransplantation has achieved high success rates and is an excellent option for tooth replacement. Although the indications for autotransplantation are narrow, careful patient selection coupled with an appropriate technique can lead to exceptional esthetic and functional results. One advantage of this procedure is that placement of an implant-supported prosthesis or other form of prosthetic tooth replacement is not needed. This article highlights the indications for autogenous tooth transplantation using 3 case reports as examples. A review of the recommended surgical technique as well as success rates are also discussed.