RESUMO
BACKGROUND: ONO-4817 is a novel matrix metalloproteinase (MMP) inhibitor which has a broad inhibitory spectrum for MMPs. We investigated the inhibitory effect of ONO-4817 on cervical lymph node metastasis of tongue carcinoma. MATERIALS AND METHODS: HSC-3-M3, a cell line derived from human tongue carcinoma with high metastatic potential for lymph node, was used. The direct cytotoxicity of ONO-4817 was assessed by MTT assay and the gelatinolytic activity by gelatin zymography and film in situ zymography (FIZ). The inhibitory effect on lymph node metastasis was examined by orthotopic implantation model with nude mice. RESULTS: ONO-4817 had no direct cyototoxicity on HSC-3-M3 cells. Gelatin zymography and FIZ demonstrated a suppression of MMP-9 activation and a marked inhibition of gelatinolysis. Additionally, a suppression of cervical lymph node metastasis was shown by therapeutic experiment. CONCLUSION: The MMP inhibitor, ONO-4817, is a candidate for adjunctive therapy of cervical lymph node metastasis in tongue carcinoma.
Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Éteres Fenílicos/farmacologia , Neoplasias da Língua/tratamento farmacológico , Animais , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/secundário , Divisão Celular/efeitos dos fármacos , Colagenases/metabolismo , Precursores Enzimáticos/antagonistas & inibidores , Precursores Enzimáticos/metabolismo , Humanos , Metástase Linfática , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Língua/enzimologia , Neoplasias da Língua/patologia , Células Tumorais Cultivadas , Redução de Peso/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Cases of squamous cell carcinoma of the maxillary sinus initially treated at Keio University Hospital between January 1981 and December 1998 studied retrospectively involved 60 untreated cases--46 men and 14 women aged 36 to 86 years (mean: 59.8 years). Of these, 7 had T2, 41 T3 and 12 T4 tumors based on 1997 AJCC TNM classification. Seven (11.7%) had nodal involvement but none had distant metastasis at diagnosis. Of the 60, 53 (88.3%) were stage III or IV. Prognostic factors and survival were statistically analyzed for 59 cases, excluding the 60th who died of another cause. Follow-up was 4 to 227 months, with a median of 59 months and a mean of 38 months. Of the 59, 48 (81.4%) underwent neoadjuvant chemotherapy (NAC). Survival was estimated using the Kaplan-Meier method as univariate analysis. Cause-specific 5-year survival was 56.8% for all stages, 68.2% for T2, 60.0% for T3, and 41.7% for T4. T stage classification was thus a significant independent prognostic factor in multivariate analysis using Cox's proportional hazards model (p = 0.0240). It also identified T stage classification (p = 0.0486) and NAC (p = 0.0419) as significant independent factors affecting survival with organ preservation. We also statistically analyzed 48 cases treated with NAC, which showed complete response (CR) for 11, partial response (PR) for 25, no change (NC) for 11, and progressive disease (PD) for 1. Responders (CR + PR) showed significantly better survival and organ preservation than nonresponders (NC + PD). The NAC response enables us to predict prognosis. T4 cases without NAC response should be treated intensively.
