RESUMO
PURPOSE: Vocal fold leukoplakia is a premalignant precursor of squamous cell carcinoma. Although many efforts have been contributed to therapy of this disease, none exhibits a satisfactory result. The aims of this study were to investigate the effectiveness and feasibility of andrographolide therapy in vocal fold leukoplakia and to explore the preliminary mechanism underlying. MATERIALS AND METHODS: Forty-one eligible patients were enrolled in the study. The patients were treated for 10-minute exposures of 5 ml (25mg/ml) andrographolide injection aerosols twice a day, and 2 weeks was considered as one treatment course. Electronic laryngoscope was used to observe the condition of vocal fold leukoplakia during the treatment. Every patient received one or two treatment courses, and the follow-up was carried out for 12 months. Toxic reactions of treatments were evaluated on the basis of the standards of the United States MD Anderson Cancer Center. Moreover, laryngeal carcinoma cell line Hep2 was applied to explore the mechanism of effect of andrographolide. Anti-proliferative effect on Hep2, cell nuclear morphology, express of mitogen-activated protein kinases (MAPK) and pro-apoptotic protein were detected after andrographolide treatment. RESULTS: We found that andrographolide exhibited significant curative effects on treatments, which were accompanied by thinning of the lesion of leukoplakia, reduction in the whitish surface area, and return of pink or red epithelium. A complete response up to 85% was observed, and no toxic side effect events occurred during the study. No patient with a complete response had a recurrence in the follow-up. Moreover, cellular experiments in Hep2 indicated that andrographolide activated MAPK pathway and caspase cascade, and finally induced apoptosis in laryngeal carcinoma cell. CONCLUSIONS: The advantages of andrographolide are connected with minimally invasive and localized character of the treatment and no damage of collagenous tissue structures, which are more convenient and less painful for patients. These results suggest that andrographolide treatment is a viable strategy for curing vocal fold leukoplakia.
Assuntos
Diterpenos/administração & dosagem , Neoplasias Laríngeas/tratamento farmacológico , Leucoplasia/tratamento farmacológico , Prega Vocal , Administração por Inalação , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Biópsia , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/fisiopatologia , Laringoscopia , Leucoplasia/diagnóstico , Leucoplasia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estereoisomerismo , Fatores de Tempo , Resultado do Tratamento , Qualidade da VozRESUMO
Obstructive sleep apnoea (OSA) is a very common sleep and breathing disorder that occurs in worldwide. It is important to develop a more effective treatment for OSA to overcome lung cell apoptosis during intermittent hypoxia (IH). A mitochondrial separation protein inhibitor (Mdivi-1) has been demonstrated to be a powerful tool for inhibiting apoptosis. In the present study, the protective effect and possible mechanism of apoptosis in lung cells during IH was investigated using in vivo and in vitro experiments. Following IH exposure for 4 weeks, the lung tissues of Sprague Dawley rats exhibited interstitial lesions, while Mdivi-1 reduced these pulmonary interstitial lesions. B-cell lymphoma (Bcl)-2 mRNA and protein expression levels were decreased however caspase-3, caspase-9 and dynamin-related protein 1 (Drp-1) mRNA and protein expression levels were increased. Following Mdivi-1 intervention, Bcl-2 mRNA and protein expression levels were increased while caspase-3, caspase-9 and Drp-1 mRNA and protein expression levels were decreased (P<0.05). After exposure to IH for 12 h, the apoptosis rate of WTRL1 cells in rats increased gradually with the IH time (P<0.05). Bcl-2 mRNA and protein expression levels were decreased, whereas caspase-3, caspase-9, cytochrome C (Cyt-C) and Drp-1 mRNA levels were increased, and caspase-3, caspase-9 and Drp-1 protein expression levels were increased. After Mdivi-1 intervention, Bcl-2 mRNA and protein expression levels were increased but caspase-3, caspase-9, Cyt-C and Drp-1 mRNA levels were decreased along with caspase-9, Cyt-C and Drp-1 protein expression levels which were decreased (P<0.05). The results of the present study suggest that Mdivi-1 may be a potential agent for treating OSA because it inhibits the mitochondrial pathway and reduces apoptosis.
RESUMO
Previous studies have demonstrated that oncogenes, tumor suppressor genes, and hypoxic factors are involved in the pathogenesis, development, and progression of head and neck cancer. In this study, we investigated the expression of HIF-1α, GLUT-1, and beclin-1 in head and neck cancers and analyzed the relationship between these markers and clinicopathologic factors. 44 paraffin-embedded samples of head and neck cancer specimens were collected. The expression of HIF-1α, GLUT-1, Ki 67, and beclin-1 was detected by immunohistochemical technique. The expression of HIF-1α, GLUT-1, Ki 67, and beclin-1 in head and neck cancers were higher than those for the corresponding paracancerous tissues. Stratification analysis revealed a significant difference between GLUT-1 expression in older patients with laryngeal/hypopharyngeal SCC and younger patients with laryngeal/hypopharyngeal SCC. No significant differences in GLUT-1 or beclin-1 or HIF-1α or Ki 67 expression were found between clinicopathologic characteristics, including lymph node metastasis, T stage, clinical stage, and location, for any of the cancer types studied. Pearson analysis revealed that there was a negative correlation between beclin-1 and HIF-1α (r=0.482, P=0.001), and between beclin-1 and Ki-67 (r=-0.366, P=0.0151). Whether beclin-1 plays a role in carcinogenesis in head and neck cancers should be further studied.