RESUMO
BACKGROUND: There is considerable information on the methylation of the promoter regions of different genes involved in gastric carcinogenesis. However, there is a lack of information on how this epigenetic process differs in tumors originating at different sites in the stomach. The aim of this study is to assess the methylation profiles of the MLH1, MGMT, and DAPK-1 genes in cancerous tissues from different stomach sites. METHODS: Samples were acquired from 81 patients suffering stomach adenocarcinoma who underwent surgery for gastric cancer in the Lithuanian University of Health Sciences Hospital Kaunas Clinics in 2009-2012. Gene methylation was investigated with methylation-specific PCR. The study was approved by the Lithuanian Biomedical Research Ethics Committee. RESULTS: The frequencies of methylation in cancerous tissues from the upper, middle, and lower thirds of the stomach were 11.1, 23.1, and 45.4%, respectively, for MLH1; 22.2, 30.8, and 57.6%, respectively, for MGMT; and 44.4, 48.7, and 51.5%, respectively, for DAPK-1. MLH1 and MGMT methylation was observed more often in the lower third of the stomach than in the upper third (p < 0.05). In the middle third, DAPK-1 promoter methylation was related to more-advanced disease in the lymph nodes (N2-3 compared with N0-1 [p = 0.02]) and advanced tumor stage (stage III rather than stages I-II [p = 0.05]). MLH1 and MGMT methylation correlated inversely when the tumor was located in the lower third of the stomach (coefficient, -0.48; p = 0.01). DAPK-1 and MLH1 methylation correlated inversely in tumors in the middle-third of the stomach (coefficient, -0.41; p = 0.01). CONCLUSION: Gene promoter methylation depends on the gastric tumor location.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Metilação de DNA/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Proteínas Quinases Associadas com Morte Celular/genética , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , Estômago/patologia , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND AND OBJECTIVE: In the last decade, the number of publications that report on the use of external beam radiotherapy and high-dose-rate brachytherapy (HDR-BRT) in the treatment of recurrent head and neck cancer has increased, but no studies compare external beam radiotherapy and HDR-BRT. The aim of this study was to evaluate and to compare the efficacy and toxicity of the three-dimensional conformal radiotherapy (3D-CRT) and HDR-BRT in the treatment of recurrent head and neck cancer. MATERIAL AND METHODS: A total of 64 patients with head and neck cancer recurrence were randomly assigned at a 1:1 ratio to receive either 3D-CRT (50Gy/25 fractions) in the control group or HDR-BRT (30Gy/12 fraction) in the experimental group. RESULTS: The overall survival rate of patients treated with HDR-BRT at 1 and 2-years was 74% and 67%, respectively, compare to 3D-CRT group - 51% and 32%, respectively (P=0.002). Local control at 1- and 2-years in patients who received HDR-BRT was 77% and 63% compare with 47% and 25%, respectively, for the patients who received the 3D-CRT (P<0.001). Most patients developed mild to moderate acute mucositis and dermatitis. In the 3D-CRT group, severe late toxicity was determined in 11 patients (35.5%), and in the HDR-BRT group, in 1 patient (3.1%) (P=0.001). There was no grade 5 toxicity. CONCLUSIONS: Following our results, we concluded that HDR-BRT is a more effective and safer treatment approach for head and neck cancer recurrences than 3D-CRT.
