RESUMEN
Esophageal cancer is one of the leading causes of cancer related mortality across the globe. The current treatment options are insufficient and are associated with number of side effects. Therefore there is a pressing need to develop effective and more efficient strategies for the treatment of esophageal cancer. Consistently, natural products are considered potential candidates for develop of cancer chemotherapy. Icariin is a naturally occurring flavonol glucoside and has been reported to possess tremendous pharmacological potential ranging from neuroprotection to anticancer activity. However, the pharmacological role of icariin in esophageal cancer is still largely unclear. Here in the present study, icariin was evaluated for its anticancer activity against KYSE70 esophageal cancer cells and the possible underlying mechanism was determined. Icariin induced cytotoxicity with an IC50 of 40µM in esophageal cancer cells. These inhibitory effects were due to apoptosis through reactive oxygen species (ROS) mediated alterations in mitochondrial membrane potential (MMP). The results indicated that icariin enhanced the accretion of ROS upto 260% and reduced the MMP upto 48% at 100µM. Icariin also induced G2/M cell cycle arrest as evident from the significant increase in the G2 cell populations of KYSE70 esophageal cancer cells. Additionally, icariin inhibited esophageal cancer cell migration, invasion and metastasis by regulating the expression of epithelial to mesenchymal transition (EMT) markers. Results also indicated that icariin reduced cell viability and migration in part through suppression of the PI3K/AKT and STAT3 pathways. Taken together, our results indicate that icariin may prove a potential natural anticancer molecule against esophageal cancer.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Esofágicas/metabolismo , Flavonoides/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Femenino , Flavonoides/uso terapéutico , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Desnudos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Carga Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: Obliterative airway disease (OAD) has been a major obstacle to long-term survival after lung or tracheal transplantations, but the role of airflow has not been examined in the orthotopic or the heterotopic tracheal transplantation models. METHODS: Sixty mice were assigned to two experimental groups. Two C57BL/6 tracheal segments were surgically prepared and then orthotopically transplanted into allogeneic BALB/c recipients. In group A mice, both segments were left patent, whereas in group B mice, one of the donor tracheas was occluded with a silk knot to obstruct airflow. Histology, quantitative OAD measurements, electron microscopy, immunohistochemical staining, and apoptosis measurement of the epithelium were performed. RESULTS: Gross examination at harvest showed patent lumens of all tracheal segments. Group A allografts (ventilating tracheas) showed a markedly higher proportion of ciliated epitheliums and less lymphocyte infiltration in the lamina propria, whereas the epithelium appeared metaplastic in group B, with a higher proportion of flattened attenuated epithelium and loss of the normal ciliate architecture. Quantitative morphometric measurements suggested more prominent OAD manifestations in the nonventilating allografts of group B than were present in group A, although recipient-derived epithelium was observed in all allografts under immunohistochemical staining. The apoptotic indexes of the epithelium were 12.1% in allografts with adequate ventilation (group A) and 66.2% in ventilation-occluded allotracheas (group B). CONCLUSIONS: OAD severity and the epithelial repopulation process are closely related to the physiologic environment of airflow. Further research is warranted to explore the underlying mechanisms of this phenomenon.
Asunto(s)
Bronquiolitis Obliterante/prevención & control , Tráquea/trasplante , Trasplante Homólogo/efectos adversos , Animales , Apoptosis , Bronquiolitis Obliterante/patología , Citocinas/sangre , Trasplante de Pulmón/efectos adversos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Mucosa Respiratoria/patología , Mucosa Respiratoria/ultraestructura , Tráquea/patología , Tráquea/ultraestructura , Trasplante Heterotópico/efectos adversos , Trasplante Homólogo/patologíaRESUMEN
OBJECTIVE: To investigate the role of surgery in the treatment of giant mass lung cancer and to analyze prognostic factors affecting surgical result. METHODS: From August 1992 to August 2005, the clinical data of 137 patients with giant mass lung cancer ( > or =8 cm in diameter) were retrospectively reviewed. 122 cases had radical resection with 63 lobectomies, 48 pneumonectomy and 11 other resection modes, the remaining 15 patients underwent palliative resection. The prognostic factors including sex, tumor size, p-TNM stage, T stage, N stage, histological types and operation extent were analyzed with SPSS 13.0 software. The survival rate was calculated by Kaplan-Meier method and logrank was used for comparing survival difference. Univariate and multivariate prognostic factors for survival were analyzed by Cox proportional hazard regression model. RESULTS: The overall 1-, 3- and 5-year survival rate was 76.0%, 49.2% and 40.1%, respectively. Sex (P = 0.001), p-TNM stage (P = 0.001), N stage (P = 0.042), surgical approach (P = 0.026) and T stage (P = 0.006) were found to be prognostic factors in Cox univariate analysis. p-TNM stage (P = 0.001) were identified as an independent prognostic factor in Cox multivariate analysis. CONCLUSION: p-TNM stage is the crucial prognostic factor in surgical treatment for giant mass lung cancer. Strict selection of candidate for resection and complete resection may be helpful in improving survival in patient with giant mass lung cancer.