RESUMEN
Cancer-associated fibroblasts (CAFs) are the main component of the tumor stroma and promote tumor progression through several mechanisms. Recent evidence indicates that small noncoding RNAs, microRNAs (miRNAs), play key roles in CAF tumor-promoting properties; however, the role of miRNAs in lung cancer-associated fibroblasts remains poorly defined. We characterized the differential miRNA expression profile of fibroblasts isolated from matched tumor front (F-CAFs), inner tumor (In-CAFs), and normal adjacent (NFs) tissues from four lung adenocarcinoma patients (ADs) using microarray analysis. Proliferation and invasion assays of A549 human lung cancer cells in the presence of conditioned medium from F-CAFs, In-CAFs or NFs were performed to assess tumorigenic properties. Ten identified candidate miRNAs in F-CAFs, In-CAFs and NFs from 12 ADs were then validated by RT-PCR. Both F-CAFs and In-CAFs enhanced the proliferation and invasion of A549 cells compared with NFs; moreover, F-CAFs showed a significantly stronger effect than In-CAFs. RT-PCR validation demonstrated three downregulated miRNAs in F-CAFs compared with NFs (miR-145-3p, miR-299-3p, and miR-505-3p), two in F-CAFs compared with In-CAFs (miR-410-3p and miR-485-5p), but no differentially expressed miRNAs between In-CAFs and NFs. Further target-gene prediction and pathway enrichment analysis indicated that deregulated miRNAs in F-CAFs showed significant associations with "pathways in cancer" (miR-145-3p, miR-299-3p and miR-410-3p), "Wnt signaling pathway" (miR-410-3p and miR-505-3p), and "TGF-beta signaling pathway" (miR-410-3p). Importantly, a tumor-promoting growth factor targeted by those miRNAs, VEGFA, was upregulated in F-CAFs compared with NFs, as judged by RT-PCR. In conclusion, deregulated miRNAs in F-CAFs are potentially associated with CAF tumor-promoting properties.
Asunto(s)
Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Fibroblastos Asociados al Cáncer/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Células A549 , Fibroblastos Asociados al Cáncer/patología , Carcinogénesis/genética , Carcinogénesis/patología , Proliferación Celular , Separación Celular , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Humanos , MicroARNs/metabolismo , Invasividad Neoplásica , Transducción de Señal/genética , Regulación hacia Arriba/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Pleural chronic inflammation (PP) and mesothelial hyperplasia (HP) may be critical to the development of malignant pleural mesothelioma (MPM). Nonetheless, studies searching for mechanistic links involving microRNA (miRNA) regulation among these interrelated processes have not been reported. Using PCR-Array, we identified the miRNAs expressed in pleural tissues diagnosed with MPM (n=5), PP (n=4) and HP (n=5), as well as in non-cancerous/non-inflammatory tissue as the normal control (n=5). We performed bioinformatics and network analysis of differentially expressed miRNAs to identify tumorigenesis-related miRNAs and their biological networks. The targets of four down-regulated miRNAs in MPM (mir-181a-5p, miR-101-3p, miR-145-5p and miR-212-3p), one in PP (mir-101-3p) and one in HP (mir-494) were significantly enriched in "pathways in cancer". Interactome networks revealed that >50% of down-regulated miRNAs in MPM targeted the signaling-activation molecule MAPK1, the transcription factor ETS1 and the mesenchymal transition-associated molecule FZDA, which have been associated with oncogenic function. Comparative analysis revealed that FZD4 was an overlapping gene target of down-regulated miRNAs that were associated with "pathways in cancer" in MPM, PP and HP. Moreover, MAPK1, ETS1 and Cox-2, a pro-inflammatory enzyme associated with over-expression in cancers, were among the 25 overlapping target genes in MPM and PP. This network analysis revealed a potential combinatory effect of deregulated miRNAs in MPM pathogenesis and indicated potential molecular links between pleural inflammation and hyperplasia with tumorigenesis mechanisms in pleura.
Asunto(s)
Carcinogénesis/genética , Neoplasias Pulmonares/genética , Mesotelioma/genética , MicroARNs/análisis , Neoplasias Pleurales/genética , Lesiones Precancerosas/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Hiperplasia/genética , Hiperplasia/patología , Inflamación/genética , Inflamación/patología , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/patología , Mesotelioma Maligno , Persona de Mediana Edad , Neoplasias Pleurales/patología , Transcriptoma , Adulto JovenRESUMEN
Background: The micro-basins of the Chibunga and Guano rivers are located within the sub-basin of the Chambo River, which starts at the thaw of the Chimborazo, crosses the cities of Guano and Riobamba, and ends in the Chambo River. These rivers are considered fluvial hydrological forces and geological limits of the aquifer, located in this sub-basin. For this reason, our investigation addressed the field capacity in the micro-basins of Chibunga and Guano rivers, to determine the maximum retention potential, i.e., the saturation of water in the soil. Methods: We investigated the change of precipitation to runoff through the correlations between the characteristics of the soil and its vegetation. We applied the Curve Number (CN) method introduced by the United States Soil Conservation Service (USSCS); this represents an empirical model, which relates the vegetation cover to the geological and topographic conditions of the soil. Along with the geographic information system, the model allows to represent the variation of runoffs for each micro-basin, according to the different land use categories, over the time frame from 2010 to 2014. Results: We found that the maximum retention potential is directly affected by CN values, representing the runoff potential. Highest values of 100 belong to the wetlands, urban area, snow, and water, as rain is converted directly into runoff, being impervious areas. The Guano river micro-basin possesses clay soil with CN of 78, the soil texture for eucalyptus forest is clay loam, and its CN value, 46, is the lowest of the data set. Knowledge of field capacity allows to properly evaluate the storage capacity of soil and water conservation. Conclusions: Results of this work will be useful in the quantification of the water balance, to determine the water supply and demand.
Asunto(s)
Hidrología , Ríos , Lluvia , Suelo , AguaRESUMEN
To evaluate the acute hemodynamic and acid-base balance effects of hypertonic-hyperoncotic solution (HHS) combined with naloxone in the treatment of hemorrhagic shock in 45 male splenectomized adult mongrel dogs, a severe controlled hemorrhagic shock (20 mmHg mean arterial pressure during 30 min) was established in the groups (n=6) no treatment, shed blood reinfusion, hypertonic-hyperoncotic (saline-dextran) solution alone, naloxone alone (NX), or combination. Interventions included propiopromazine-pentobarbital anesthesia and installation of Swan-Ganz, femoral arterial, and urethral catheters, and exsanguination at 20 mmHg mean arterial pressure during 30 min followed by treatment and observation for 160 min. Fifteen (33%) dogs died before completing the 30-min shock period. Another 33% from the no-treatment group died during the following 90 min. Shed blood improved the cardiac index, arterial pressure, and acid-base balance. NX restored the cardiac index to less than 60% of baseline and reduced vascular resistance. Additionally, NX produced no improvement in acidosis, with 1 dog dead at 95 min posttreatment. HHS restored the cardiac index for 45 min and increased vascular resistance and arterial pressure. Acidosis was not improved. Single-dose HHS combined with naloxone resulted in a high cardiac index, oxygen consumption, and urine output with low peripheral vascular resistance (and no acute mortality) compared with untreated or single-dose groups.
Asunto(s)
Albúminas/uso terapéutico , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Choque/tratamiento farmacológico , Animales , Perros , Soluciones Hipertónicas/uso terapéutico , MasculinoRESUMEN
Se informa un caso de trombocitopenia post-transfusión de sangre de banco; se manifestó por hemorragia intra-abdominal masiva, de múltiples sitios que fue imposible de controlar con los métodos usuales de hemostasis. Se llevó a cabo empacamiento abdominal total con compresas abdominales con lo que se controló satisfactoriamente la hemoragia y 36 horas después se llevó a cabo cirugía para la extracción de las empresas, evolucionando adecuadamente. Se demuestra la utilidad de este procedimiento como medida heroica en este tipo de sangrado transoperatorio
Asunto(s)
Adulto , Humanos , Femenino , Hemorragia Gastrointestinal/terapia , Hemostasis Quirúrgica/métodos , Enfermedades del Colon/cirugía , Fístula Gástrica/cirugía , Fístula Intestinal/cirugía , Complicaciones Intraoperatorias/terapia , Técnicas de SuturaRESUMEN
Se valoraron los expedientes clínicos de 32 enfermos mayores de 65 años sometidos a tratamiento quirúrgico para hipertensión portal hemorrágica. La principal enfermedad asociada fue diabetes mellitus en 10 casos. El electrocardiograma fue normal en 20 casos y alteraciones diversas en los restantes, que no contraindicaban ningún procedimiento. Las pruebas de función respiratoria fueron normales en 12. Diecinueve se encontraban en clase funcional A de Child, cinco en clase B y los restantes en clase C. La cirugía fue realizada electivamente en 23 casos, realizándose 13 cirugías derivativas (12 de ellas selectivas), dos procedimientos completos de Sugiura (abdominal y torácico), cinco procedimientos abdominales de Sugiura y uno torácico; en los dos casos restantes, procedimientos de desvascularización esofagogástrica distintos a los de Sugiura. Los enfermos con clase funcional A-B de Child tuvieron una mortalidad operatoria del 10%. El seguimiento promedio fue de 11.3 meses. De acuerdo a la distribución no paramétrica de Kaplan y Meier la sobrevida calculada a los 12 meses fue de 83%, 77% a los 24 meses, 65% a los 48 meses y 59% a los 72 meses. Se encontró evidencia de resangrado en dos casos y encefalopatía clínica en cuatro. En nueve la cirugía realizada fue urgente. Cinco de los enfermos se encontraban en clase C de Child, tres en clase B y uno en clase A. Se realizaron dos operaciones de Sugiura completas, tres tiempos torácicos, uno abdominal y un procedimiento de desvascularización distinto al de Sugiura y dos procedimientos derivativos. La mortalidad operatoria fue de seis enfermos. Se concluye que los enfermos mayores de 65 años pueden ser manejados quirúrgicamente para control de hipertensión portal hemorrágica siempre que se encuentren en buena clasificación funcional de Child y en forma electiva.