RESUMEN
Associadas a projetos de construção da ideia de nação, no Brasil monárquico foram encaminhadas, pelo governo imperial, algumas iniciativas no sentido de materializar propostas de educação física. O objetivo deste artigo é investigar os sentidos e significados atribuídos ao tema na legislação e nos relatórios anuais do Ministério dos Negócios do Império (1831-1889), com especial interesse pelo que se refere ao Rio de Janeiro. A abordagem do assunto nas fontes pesquisadas evidencia que as visões sobre a educação física se deram a partir de uma matriz que articulava concepções de moral, saúde e civilização, tendo que lidar com as condições concretas de um país recém-independente, periférico e com uma burocracia ainda em formação.
In association with its nation building projects, the imperial government in Brazil under monarchic rule took some concrete actions based on proposals for physical education. The aim of this article is to investigate the meanings and significations attributed to this subject in the legislation and the annual reports issued by the Ministry of Business of the Empire (1831-1889), giving special attention to Rio de Janeiro. The approach to the subject in the sources researched demonstrates that the views of physical education took shape through a web of ideas that associated moral, health and civilization conceptions, in a bid to deal with the concrete circumstances of a newly independent peripheral nation with a bureaucratic structure in the process of formation.
Asunto(s)
Animales , Femenino , Ratones , Carcinoma Pulmonar de Lewis/secundario , Catepsina B/antagonistas & inhibidores , Catepsinas/antagonistas & inhibidores , Endopeptidasas , Leucina/análogos & derivados , Neoplasias Hepáticas Experimentales/prevención & control , Neoplasias Hepáticas Experimentales/secundario , Invasividad Neoplásica/prevención & control , Catepsina L , Colágeno , Cisteína Endopeptidasas , Carcinoma Pulmonar de Lewis/metabolismo , Combinación de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Laminina , Leucina/farmacocinética , Leucina/farmacología , Neoplasias Hepáticas Experimentales/enzimología , Proteoglicanos , Células Tumorales CultivadasRESUMEN
OBJECTIVES: Tumor-associated macrophages that generally exhibit an alternatively activated (M2) phenotype have been linked to tumor progression and metastasis. However, the role of M2-polarized macrophages in the growth and metastasis of lung adenocarcinoma remains enigmatic. The aim of this study was to explore the effect of M2 macrophages on the proliferation and migration of mouse Lewis lung carcinoma cells and tumor-induced lymphangiogenesis. METHODS: Trypan blue staining and the Transwell migration assay were performed to evaluate the effects of activated (M1 or M2) macrophages on the proliferation and migration of Lewis cells. Furthermore, vascular endothelial growth factor-C expression in Lewis cells and nitric oxide secretion from activated macrophages were detected during the co-culture assay. Following treatment with activated macrophages, lymphatic endothelial cells differentiated into capillary-like structures, and the induction of Lewis cell migration was assessed using a twodimensional Matrigel-based assay. RESULTS: In the co-culture Transwell system, the proliferation and migration of Lewis cells were promoted by M2 macrophages. Moreover, the co-culture significantly increased the expression of vascular endothelial growth factor-C by Lewis cells and reduced the secretion of nitric oxide from M2 macrophages, which subsequently led to the capillary morphogenesis of lymphatic endothelial cells. Interestingly, following co-culture with Lewis cells, the function of RAW264.7 cells was polarized toward that of the M2 macrophage phenotype. CONCLUSION: M2-polarized macrophages promoted the metastatic behavior of Lewis cells by inducing vascular endothelial growth factor-C expression. Thus, the interruption of signaling between M2 macrophages and Lewis cells may be considered to be a new therapeutic strategy.
Asunto(s)
Animales , Ratones , Carcinoma Pulmonar de Lewis/secundario , Neoplasias Pulmonares/patología , Macrófagos/fisiología , Factor C de Crecimiento Endotelial Vascular/metabolismo , Línea Celular Tumoral , Ensayos de Migración Celular , Movimiento Celular , Proliferación Celular , Carcinoma Pulmonar de Lewis/metabolismo , Células Endoteliales/patología , Neoplasias Pulmonares/metabolismo , Linfangiogénesis/fisiología , Macrófagos/citología , Factores de Tiempo , Factor C de Crecimiento Endotelial Vascular/fisiologíaRESUMEN
To study the synthesis of [131] iodine [I] labeled histamine-indomethacin [His-IN], its in vivo distribution in Lewis-bearing mice, and its effects on suppression of Lewis lung cancer growth and induction of apoptosis. The present study was carried out in the Experimental Research Center, Sheng Jing Hospital of China Medical University Hospital, Shenyang China between December 2008 and October 2009. Chemical synthesis of His-IN was carried out. Ninety-five C57 mice were allocated into 12 groups, and a series of experiments including the in vivo biological distribution of [131] I-His-IN in C57 mice bearing Lewis lung cancer was explored, and the therapeutic effects of IN and [131] I-His-IN in lung cancer-bearing mice were assessed through tumor suppression experiments, flow cytometry, and detection of tumor necrosis factor. The [131] I-His-IN radionuclide count ratio of the tumor site and surrounding region significantly increased with time, namely, the retention time of [131] I-His-IN radionuclide was longer in the tumor site. A 3.0 mg/kg and 3.5 mg/kg [131] I-His-IN, as well as 3.0 mg/kg and 3.5 mg/kg IN all had tumor suppression and apoptosis induction effects on tumors, among which the 3.5 mg/kg [131] I-His-IN group had significant differences compared with all other groups. The [131] I-His-IN not only retains the tumor-affinity property of IN, the synergistic effect of these 2 also enhances the tumor suppression and pro-apoptotic function
Asunto(s)
Animales de Laboratorio , Masculino , Carcinoma Pulmonar de Lewis/metabolismo , Neoplasias Pulmonares/metabolismo , Factor de Necrosis Tumoral alfa , Histamina/farmacocinética , Cromatografía en Capa Delgada , Sinergismo Farmacológico , Citometría de Flujo , Apoptosis/efectos de los fármacos , Ratas Endogámicas LewRESUMEN
In a search for antitumor agents, we carried out a screening of 4-arylcoumarins isolated from endophytic Streptomyces aureofaciens CMUAc130, by examining their possible inhibitory effect on the growth of s.c. transplanted Lewis lung carcinoma (LLC) in BDF-1 mice by intraperitoneal (i.p.) administration. The 4-arylcoumarins showed antitumor activity with T/C values of 80.8 and 50.0% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-p-methoxylphenylcoumarin treatment, respectively and 81.5 and 44.9% at doses of 1 and 10 mg/kg of 5,7-dimethoxy-4-phenylcoumarin treatment, respectively, compared to adriamycin, which was used a positive control, with T/C value of 55.9% at 2 mg/kg. Furthermore, we investigated the possible effects of these compounds on expression of the bcl-2 and Bax oncoproteins in A427, a human lung cancer cell lines. The cells were cultured in vitro for 24 h in RPMI 1640 with 1.5% (v/v) ethanol, 100 microg/ml 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. Viability was determined by an MTT assay. Total protein was extracted from cell lysates and the bcl-2 and Bax oncoproteins were identified. Western blotting showed a decrease in bcl-2 and an increase in Bax in A427 cell cultured with 5,7-dimethoxy-4-p-methoxylphenylcoumarin or 5,7-dimethoxy-4-phenylcoumarin. We conclude that 5,7-dimethoxy-4-phenylcoumarin is a more potent inhibitor of cell proliferation than 5,7-dimethoxy-4-p-methoxylphenylcoumarin and has more marked effects on oncoprotein expression.
Asunto(s)
Animales , Antineoplásicos/química , Carcinoma Pulmonar de Lewis/metabolismo , Proliferación Celular/efectos de los fármacos , Cumarinas/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Pulmonares/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Streptomyces aureofaciens/química , Proteína X Asociada a bcl-2/análisisRESUMEN
Ceramide generated from sphingomyelin in response to ionizing radiation has been implicated as a second messenger to induce cellular proapoptotic signals. Both ceramide and its metabolic inhibitor, N, N-dimethyl-D-erythro-sphingosine (DMS), might lead to sustained ceramide accumulation in cells more efficiently, thereby sensitizing them to gamma-radiation-induced cell death. To delineate this problem, the clonogenic survival of Lewis lung carcinoma (LLC) cells was evaluated following exposure to radiation together with or without C2-ceramide, DMS, or both. The treatment of ceramide/DMS synergistically decreased the survival of the irradiated cells compared with treatment with ceramide or DMS alone. Ceramide/DMS-treated cells displayed several apoptotic features after gamma-irradiation, including increased sub G1 population, TUNEL-positive fraction, and poly-(ADP-ribose) polymerase (PARP) cleavage. We also observed ceramide/ DMS induced disruption of mitochondrial membrane potential (MMP) and activation of caspase- 9 and -3 in a radiation-dose-dependent manner. Furthermore, pretreatment of LLC cells with ceramide/DMS not only increased the protein expression level of Bax, but also decreased Bcl-2 after gamma-irradiation. Taken together, the present study indicates that the radiosensitizing activity of ceramide/DMS on LLC cells most likely reflects the dominance of pro-apoptotic signals related to the mitochondria-dependent pathway.