RESUMO
The advancements in epigenetics of oral squamous cell carcinoma (OSCC), are made in regard to DNA hypermethylation of MGMT, DAPK, ECAD (E-cadherin) and p16, as an important component of oral carcinogenesis and new potential biomarkers in molecular diagnostic strategies. The objective of the study was to evaluate the methylation status of the proposed genes and their possible role in the tumor genesis and diagnosis of OSCC. MATERIALS AND METHODS: From sixty surgically treated and molecularly analyzed patients, we obtained three groups of bioptical materials: tumor, normal contralateral and healthy tissues. Comparison of the frequencies of DNA methylation for all transcripts was utilized to validated their potential role in the cancerogenesis and detection of OSCC. RESULTS: The most often methylated genes in the tumor samples were ECAD, MGMT, DAPK followed by p16 genes (90% vs 75% vs 75% vs 52,5%), respectively. We observed frequent methylated genes in contralateral mucosa and consistently unmethylated- 0% in healthy samples. ECAD methylated genes showed the highest sensitivity for diagnosing OSCC in tumor and contralateral tissues (90% and 89,7% respectively, with a specificity of 100%). CONCLUSION: ECAD and MGMT have tumor-specific signatures and can be considered as potential noninvasive diagnostic biomarkers in OSCC.
Assuntos
Carcinogênese/genética , Carcinoma de Células Escamosas/diagnóstico , Metilação de DNA , Neoplasias Bucais/diagnóstico , Regiões Promotoras Genéticas/genética , Biomarcadores Tumorais/genética , Caderinas/genética , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , DNA de Neoplasias/genética , Proteínas Quinases Associadas com Morte Celular/genética , Genes p16 , Humanos , Neoplasias Bucais/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a complication of the bisphosphonate (BP) treatment and its pathopysiology is still not fully understood. The existing preventive and treatment options require updates and more attention. Geranylgeraniol (GGOH) so far demonstrated an increased activity and viability of the cells previously treated with zoledronic acid (ZA). The aim of this study was to evaluate the in vivo effects of GGOH on the development of BRONJ. MATERIALS AND METHODS: A total of 30 male Wistar rats were included in the study, divided into three groups: two experimental groups (EG1 and EG2) and a control group (CG). Rats from EG1 and EG2 were treated with 0,06 mg/kg ZA ip weekly in a duration of five weeks, while CG received saline ip. On the third week all animals underwent extraction of the lower right first molars. The rats from EG2 received a local solution of GGOH in concentration of 5 mM in the socket every day after the tooth extraction. The analyses included clinical evaluation on the wound healing and pathohistological evaluation for presence and level of osteonecrosis. RESULTS: EG2 showed significantly improved wound healing and tissue proliferation, when compared to EG1. EG2 significantly differed from EG1 and CG (p<0,05) for the presence of microscopical osteonecrosis (80% vs 22,2% vs 0%). Regarding to the number of empty lacunes without osteocytes and the level of necrosis, all groups demonstrated significant differences. CONCLUSION: Geranylgeraniol in a form of local solution may be a promising option for prevention and treatment of BRONJ.
