RESUMEN
Aedes aegypti and Aedes albopictus are the main vectors of arboviruses such as Dengue, Chikungunya and Zika, causing a major impact on global economic and public health. The main way to prevent these diseases is vector control, which is carried out through physical and biological methods, in addition to environmental management. Although chemical insecticides are the most effective strategy, they present some problems such as vector resistance and ecotoxicity. Recent research highlights the potential of the imidazolium salt "1-methyl-3-octadecylimidazolium chloride" (C18MImCl) as an innovative and environmentally friendly solution against Ae. aegypti. Despite its promising larvicidal activity, the mode of action of C18MImCl in mosquito cells and tissues remains unknown. This study aimed to investigate its impacts on Ae. aegypti larvae and three cell lines of Ae. aegypti and Ae. albopictus, comparing the cellular effects with those on human cells. Cell viability assays and histopathological analyses of treated larvae were conducted. Results revealed the imidazolium salt's high selectivity (> 254) for mosquito cells over human cells. After salt ingestion, the mechanism of larval death involves toxic effects on midgut cells. This research marks the first description of an imidazolium salt's action on mosquito cells and midgut tissues, showcasing its potential for the development of a selective and sustainable strategy for vector control.
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Aedes , Imidazoles , Insecticidas , Larva , Aedes/efectos de los fármacos , Animales , Larva/efectos de los fármacos , Imidazoles/toxicidad , Imidazoles/farmacología , Insecticidas/toxicidad , Insecticidas/farmacología , Humanos , Mosquitos Vectores/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Control de Mosquitos/métodosRESUMEN
Introduction: The tumor microenvironment (TME) of glioblastoma (GB) is characterized by an increased infiltration of immunosuppressive cells that attenuate the antitumor immune response. The participation of neutrophils in tumor progression is still controversial and a dual role in the TME has been proposed. In this study, we show that neutrophils are reprogrammed by the tumor to ultimately promote GB progression. Methods: Using in vitro and in vivo assays, we demonstrate the existence of bidirectional GB and neutrophil communication, directly promoting an immunosuppressive TME. Results and discussion: Neutrophils have shown to play an important role in tumor malignancy especially in advanced 3D tumor model and Balb/c nude mice experiments, implying a time- and neutrophil concentration-dependent modulation. Studying the tumor energetic metabolism indicated a mitochondria mismatch shaping the TME secretome. The given data suggests a cytokine milieu in patients with GB that favors the recruitment of neutrophils, sustaining an anti-inflammatory profile which is associated with poor prognosis. Besides, glioma-neutrophil crosstalk has sustained a tumor prolonged activation via NETs formation, indicating the role of NFκB signaling in tumor progression. Moreover, clinical samples have indicated that neutrophil-lymphocyte ratio (NLR), IL-1ß, and IL-10 are associated with poor outcomes in patients with GB. Conclusion: These results are relevant for understanding how tumor progression occurs and how immune cells can help in this process.
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Glioblastoma , Neutrófilos , Animales , Ratones , Ratones Desnudos , Transducción de Señal , Inmunidad , Microambiente TumoralRESUMEN
OBJECTIVES: To analyze the inflammatory millieu in oral squamous cell carcinoma (OSCC) tumors and the influence of macrophages related-cytokines on the tumor cell migration. MATERIALS AND METHODS: Inflammatory protein profile and macrophage population (M2/M1 ratio) of human OSCC fragments were analyzed by proteomic analysis and flow cytometry assay respectively. To evaluate the effects of inflammation on OSCC behavior, we analyzed the role of polarized macrophages and cytokines (IL-6, IL-1ß and TNF-α) on OSCC cell lines (SCC25 and Cal27) responsiveness by western blotting (cell signaling) and time-lapse (cell migration). Also, it was addressed the crosstalk of IL-6-STAT3 axis with cell migration signaling using a STAT3 inhibitor (Stattic®) and a pull down assay for the RhoGTPase Rac1 activity. RESULTS: It was observed a ~2 fold predominance of M2 over M1 macrophages and a pro-inflammatory state in OSCC fragments. The M2 conditioned media increased migration speed and directionality of highly invasive OSCC cells (SCC25). OSCC cell lines were responsive to cytokine stimuli (IL6, IL-1ß and TNF-α), but only IL-6 increased migration properties of OSCC cells. This effect was dependent on STAT3-phosphorylation levels, which interfered with Rac1 activation levels. CONCLUSION: Our results suggest that the inflammatory milieu might favor invasion and metastasis of OSCC by the direct effect of macrophage-related cytokines on tumor migration.
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Movimiento Celular , Citocinas/metabolismo , Neoplasias de la Boca , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral , Macrófagos Asociados a Tumores , Análisis de Varianza , Cadherinas/metabolismo , Comunicación Celular , Línea Celular Tumoral , Forma de la Célula , Medios de Cultivo Condicionados/farmacología , Citometría de Flujo , Humanos , Inflamación , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Invasividad Neoplásica , Fosforilación , Proteómica , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Factor de Necrosis Tumoral alfa/metabolismo , Macrófagos Asociados a Tumores/citología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/fisiología , Proteína de Unión al GTP rac1/metabolismoRESUMEN
Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2 profile, where M1 acts as proinflammatory and antitumor, and M2 is anti-inflammatory and shows protumor activity. Several studies have shown that macrophages are important to the prognosis of patients with different types of cancer. Our aim was to conduct a systematic review to evaluate the role of macrophages in the prognosis of OSCC patients. A search in the Pubmed, Scopus, and ISI Web of Knowledge database was performed, and it was included only studies that evaluated the importance of macrophages in the prognosis of OSCC patients. From initial 286 articles, 14 fully attended the inclusion criteria. In the majority of the articles, it was evaluated only CD68, a panmacrophage marker, or CD163, a M2 marker. Only one article evaluated the M1 marker, CD11c. Besides, 5 articles analyzed the presence of macrophages in different areas of the tumor. Higher concentrations of CD68 and CD163 were associated with worse survival. In conclusion, macrophages are important to OSCC patients' prognosis; however, it is necessary to address in which tumor region the presence of polarized macrophage is more important to the outcome.
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Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/mortalidad , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/mortalidad , Macrófagos/inmunología , Microambiente Tumoral/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores de Tumor/metabolismo , Bases de Datos Bibliográficas , Supervivencia sin Enfermedad , Femenino , Humanos , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Receptores de Superficie Celular/metabolismo , Adulto JovenRESUMEN
Cell invasion and metastasis are involved in clinical failures in cancer treatment, and both events require the acquisition of a migratory behavior by tumor cells. Curcumin is a promising natural product with anti-proliferative activity, but its effects on cell migration are still unclear. We evaluated the effects of curcumin on the proliferation, apoptosis, migration, and cell-cell adhesion of keratinocyte, oral squamous cell carcinoma (OSCC), and fibroblast cell lines, as well as in a xenograft model of OSCC. Curcumin (2 µM) decreased cell proliferation in cell lines with mesenchymal characteristics, while cell death was detected only at 50 µM. We observed that highly migratory cells showed a decrease on migration speed and directionality when treated with 2 or 5 µM of curcumin (50% and 40%, respectively, p < 0.05). Using spheroids, we observed that curcumin dose dependently decreased cell-cell adhesion, especially on tumor-derived spheroids. Also, in a xenograft model with patient-derived OSCC cells, the administration of curcumin decreased tumor growth and aggressiveness when compared with untreated tumors, indicating the potential antitumor effect in oral cancer. These results suggest that lower doses of curcumin can influence several steps involved in tumorigenesis, including migration properties, suggesting a possible use in cancer therapy. Copyright © 2017 John Wiley & Sons, Ltd.
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Carcinoma de Células Escamosas/tratamiento farmacológico , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Curcuma/química , Curcumina/farmacología , Neoplasias de la Boca/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Carcinogénesis , Carcinoma de Células Escamosas/patología , Línea Celular , Proliferación Celular/efectos de los fármacos , Humanos , Queratinocitos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias de la Boca/patología , Células 3T3 NIH , Esferoides Celulares/efectos de los fármacos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A morbimortalidade do traumatismo raquimedular (TRM)numa região da Amazônia é estudada. Em sítios de desmatamento,o TRM pode ocorrer pela queda de árvores derrubadassobre as vítimas, especialmente em locais onde a derrubada deárvores é ilícita e a proteção dos empregados é precária ouinexistente. O trauma decorrente de desmatamento não tem sidoobjeto de pesquisas científicas, é subestimado nas estatísticasoficiais e freqüentemente não é reconhecido nas estatísticas deacidentes de trabalho. Realizou-se um estudo de uma série de16 casos de TRM, atendidos no Serviço de Neurocirurgia daFundação Hospital Estadual do Acre FUNDHACRE, noperíodo de março a dezembro de 2000. As causas dos 16 casosde TRM foram: acidentes em desmatamentos (cinco casos, quecorresponderam a 31,3% do total), acidentes de trânsito (25%),quedas (12,5%), mergulhos em águas rasas (12,5%) e lesãopor projétil de arma de fogo ou arma branca (18,7%). A letalidadehospitalar foi de 6,3% (um caso). Lesões neurológicas residuais (seqüelas de TRM) no momento da alta foram observadasem 14 (93,3%) dentre 15 casos.