RESUMEN
Lung cancer treatment using cisplatin (DDP) in combination with other drugs are effective for the treatment of non-small cell lung cancer (NSCLC). The aim of this study was to prepare a layer-by-layer nanoparticles (NPs) for the co-loading of DDP and oridonin (ORI) and to evaluate the antitumor activity of the system in vitro and in vivo. Novel DDP and ORI co-loaded layer-by-layer NPs (D/O-NPs) were constructed. The mean diameter, surface change stability and drug release behavior of NPs were evaluated. In vitro cytotoxicity of D/O-NPs was investigated against DDP resistant human lung cancer cell line (A549/DDP cells), and in vivo anti-tumor efficiency of D/O-NPs was tested on mice bearing A549/DDP cells xenografts. D/O-NPs have a diameter of 139.6 ± 4.4 nm, a zeta potential value of +13.8 ± 1.6 mV. D/O-NPs could significantly enhance in vitro cell toxicity and in vivo antitumor effect against A549/DDP cells and lung cancer animal model compared to the single drug loaded NPs and free drugs. The results demonstrated that the D/O-NPs could be used as a promising lung cancer treatment system.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Células A549 , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Cápsulas , Línea Celular Tumoral , Cisplatino/administración & dosificación , Diterpenos de Tipo Kaurano/administración & dosificación , Liberación de Fármacos , Sinergismo Farmacológico , Humanos , Lípidos , Ratones , Ratones Endogámicos BALB C , Nanopartículas , Tamaño de la Partícula , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The globular heads of the human C1q receptor (gC1qR) are multi-compartmental and multi-functional cellular proteins. The list of biological responses mediated by the gC1qR includes growth perturbation and morphological abnormalities, along with the initiation of apoptosis. However, the effects of the gC1qR on the apoptosis of cervical squamous carcinoma cells (C33a and SiHa) have not been demonstrated. METHODS: Here, human cervical tissues were examined for the expression of the gC1qR using real-time PCR and Western blot analysis. Apoptotic death of C33a and SiHa cells was assessed by flow cytometric analysis to detect the subG1 population. Viability, migration and proliferation of C33a and SiHa cells were detected via the water-soluble tetrazolium salt (WST-1) assay, the Transwell assay and the (3)H-thymidine incorporation into DNA assay ((3)H-TdR), respectively. RESULTS: These data showed that expression of the gC1qR protein was significantly decreased in human cervical squamous cell carcinoma tissues relative to normal cervix tissues. C33a and SiHa cells transfected with a GFP-gC1qR vector resulted in the up-regulation of cellular apoptosis and an apparent increase in the expression of the p38 mitogen-activated protein kinase (p38 MAPK). Further, the changes in C33a and SiHa cells viability, migration and proliferation observed upon overexpression of gC1qR could be abrogated using the p38 MAPK inhibitor SB202190. CONCLUSION: These data indicate that gC1qR inhibits viability, migration and proliferation of cervical squamous cells carcinoma via the p38 MAPK signalling pathway.
Asunto(s)
Apoptosis , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Glicoproteínas de Membrana/metabolismo , Receptores de Complemento/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Movimiento Celular , Proliferación Celular , Supervivencia Celular , Femenino , Humanos , Glicoproteínas de Membrana/genética , Receptores de Complemento/genética , Células Tumorales CultivadasRESUMEN
PURPOSE: To explore the appropriate method of mediastinal lymph node dissection for selected clinical stage IA (cIA) non-small cell lung cancer (NSCLC). METHODS: From 1998 through 2002, the curative-intent surgery was performed to 105 patients with cIA NSCLC who had been postoperatively identified as pathologic-stage T1. According to the method of intraoperative medistinal lymph node dissection, they were divided into radical systematic mediastinal lymphadenectomy (LA) group (n = 42) and mediastinal lymph-node sampling (LS) group (n = 63). The effects of LS and LA on morbidity, N staging, overall survival (OS) and disease-free survival (DFS) were investigated. Also, associations between clinicopathological parameters and survival were analyzed. RESULTS: The mean numbers of dissected lymph nodes per patient in the LA group was significantly greater than that in the LS group (15.59 +/- 3.08 vs. 6.46 +/- 2.21, P < 0.001), and the postoperative overall morbidity rate was higher in the LA group than that in the LS group (26.2 vs. 11.1%, P = 0.045). There were no significant difference in migration of N staging, OS and DFS between two groups. However, for patients with lesions between 2 and 3 cm, the 5-year OS in LA group was significantly higher than that in LS group (81.6 vs. 55.8%, P = 0.041), and the 5-year DFS was also higher (77.9 vs. 52.5%, P = 0.038). For patients with lesions of 2 cm or less, 5-year OS and DFS were similar in both groups. Multivariate analysis showed that lymph node metastasis was the unique unfavorable prognostic factor (P < 0.001). CONCLUSIONS: After being intraoperatively identified as stage T1, patients with lesions between 2 and 3 cm in cIA NSCLC should be performed with LA to get a potentially better survival, and patients with lesions of 2 cm or less should be performed with LS to decrease invasion.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/secundario , Neoplasias Pulmonares/patología , Escisión del Ganglio Linfático , Mediastino/patología , Mediastino/cirugía , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/cirugía , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To elucidate that recompression is the most efficient measure in removing the pathogenic factors. METHOD: When rabbits were suffering from severe DCS, their pressure were immediately compressed to 0.5 Mpa. Precordial region was monitored continuously with a Doppler flow meter, micrography of the bulbar conjunctiva was done intermittently and the behaviors of the animals were recorded. RESULT: Effects of therapeutic recompression and elimination of circulating bubbles were correlated to rate and extent of recovery of microvascular function. The animals' DCS with severe dysfunction or failure of blood vessels, DCS became worse owing to progressive impairment of microvascular function during recompression and decompression. CONCLUSION: The pressure could only cancel the tension provoked by supersaturated gas in the blood so as to relieve the spasm of the compensatory blood vessels, which can restore the blood circulation and reverse the developing course of the DCS. The pressure, however, couldn't recover the function of the blood vessels with severe dysfunction or failure, or repair the injured tissues, or eliminate the circulating bubbles directly.
Asunto(s)
Enfermedad de Descompresión/terapia , Embolia Aérea/fisiopatología , Microcirculación/fisiopatología , Presión del Aire , Animales , Cámaras de Exposición Atmosférica , Conjuntiva/fisiopatología , Modelos Animales de Enfermedad , ConejosRESUMEN
OBJECTIVE: To explain the etiology of decompression sickness (DCS) and to elucidate its pathogenic mechanism. METHOD: Tunica conjunctiva was examined by microscopy and blood pressure was measured at the exposed femoral arteries in inadequately decompressed animals after hyperbaric exposure. Then pathological examinations were done. RESULT: Animals with vascular spasm and dysfunction after decompression showed DCS symptoms. Severe DCS was found in the period of increasing of blood pressure swelling. Appeared in endothelial cells, fracted, hemorrhages were also formed in the body of DCS animals. CONCLUSION: DCS is a disease with vascular spasm and dysfunction caused by decompression. It's resulted from anoxia or pathological change caused by vascular spasm, dysfunction or even failure of blood vessels due to the gas tension (etiology) provoked by supersaturated gas in the blood during descending of ambient pressure. Vascular spasm and dysfunction impede the elimination of gas from the blood, and once the gas amount is sufficient to cause severe ischemia of the circulation system, the state of disease would be severe.