RESUMEN
Activation of inflammasomes has been reported in human pancreatic adenocarcinoma (PAAD); however, the expression pattern and functional role of inflammasome-related proteins in PAAD have yet to be identified. In this study, we systemically examined the expression and role of different inflammasome proteins by retrieving human expression data. Several genes were found to be differentially expressed; however, only interferon-inducible protein 16 (IFI16) expression was found to be adversely correlated with the overall survival of PAAD patients. Overexpression of IFI16 significantly promoted tumor growth, increased tumor size and weight in the experimental PAAD model of mice, and specifically increased the population of tumor-associated macrophages (TAMs) in the tumor microenvironment. Depletion of TAMs by injection of liposome clodronate attenuated the IFI16 overexpression-induced tumor growth in PAAD. In vitro treatment of conditioned medium from IFI16-overexpressing PAAD cells induced maturation, proliferation, and migration of bone marrow-derived monocytes, suggesting that IFI16 overexpression resulted in cytokine secretion that favored the TAM population. Further analysis suggested that IFI16 overexpression activated inflammasomes, thereby increasing the release of IL-1ß. Neutralization of IL-1ß attenuated TAM maturation, proliferation, and migration induced by the conditioned medium from IFI16-overexpressing PAAD cells. Additionally, knockdown of IFI16 could significantly potentiate gemcitabine treatment in PAAD, which may be associated with the reduced infiltration of TAMs in the tumor microenvironment. The findings of our study shed light on the role of IFI16 as a potential therapeutic target for PAAD.
RESUMEN
Brain metastatic triple negative breast cancer (BM-TNBC) is afflicted with unfavorable prognosis. However, the molecular events underlying BM-TNBC remain largely unknown. In the present study, we conducted gene expression microarray analysis using the triple negative breast cancer cell line MDA-MB-231 and its brain metastatic derivative (MDA-MB-231Brm). Results of microarray analysis showed that a total of 4296 genes were differentially expressed, of which 2433 genes were up-regulated and 1863 genes were down-regulated. Gene Ontology (GO), KEGG pathway and protein-protein interaction (PPI) analyses indicated differentially expressed genes functionally categorized as genes of signal transduction, multicellular organismal development, ion transport, nervous system development, plasma membrane, extracellular region, calcium ion binding, GTP binding neuroactive ligand-receptor interaction. The validity of the microarray results was verified by quantitative real-time PCR analysis of twelve representative genes. The present findings revealed molecular basis and events associated with brain metastasis in TNBC, which will potentially contribute to the understanding of underlying mechanism and develop therapeutic targets.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Neoplasias de la Mama Triple Negativas/genética , Neoplasias Encefálicas/secundario , Femenino , Ontología de Genes , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Neoplasias de la Mama Triple Negativas/patología , Células Tumorales CultivadasRESUMEN
BACKGROUND: Studies have reported inconsistent results for the existence of an association between polyunsaturated fatty acid (PUFA) intake and risk of lung cancer. The purpose of this study is to summarize the evidence regarding this relationship using a dose response meta-analytic approach. METHODOLOGY AND PRINCIPAL FINDINGS: We searched the PubMed, EmBase, and Cochrane Library electronic databases for related articles published through July 2013. Only prospective studies that reported effect estimates with 95% confidence intervals (CIs) of lung cancer incidence for greater than 2 categories of PUFA intake were included. We did random-effects meta-analyses of study-specific incremental estimates to determine the risk of lung cancer associated with a 5 g per day increase in PUFA intake. Overall, we included 8 prospective cohort studies reporting data on 1,268,442 individuals. High PUFA intake had little or no effect on lung cancer risk (risk ratio [RR], 0.91; 95% CI, 0.78-1.06; Pâ=â0.230). Furthermore, the dose-response meta-analysis also suggested that a 5 g per day increase in PUFA has no significant effect on the risk of lung cancer (RR, 0.98; 95%CI: 0.96-1.01; Pâ=â0.142). Finally, the findings of dose response curve suggested that PUFA intake of up to 15 g/d seemed to increase the risk of lung cancer. Furthermore, PUFA intake greater than 15 g/d was associated with a small beneficial effect and borderline statistical significance. Subgroup analyses for 5 g per day increment in PUFA indicated that the protective effect of PUFA was more evident in women (RR, 0.94; 95% CI, 0.87-1.01; Pâ=â0.095) than in men (RR, 1.00; 95% CI, 0.98-1.02; Pâ=â0.784). CONCLUSION/SIGNIFICANCE: Our study indicated that PUFA intake had little or no effect on lung cancer risk. PUFA intake might play an important role in lung cancer prevention in women.
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Ingestión de Alimentos/fisiología , Ácidos Grasos Insaturados/administración & dosificación , Neoplasias Pulmonares/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Ácidos Grasos Omega-3/administración & dosificación , Conducta Alimentaria , Femenino , Humanos , Neoplasias Pulmonares/etiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Previous observational studies regarding the existence of an association between folate intake and the risk of breast cancer have been inconsistent. This study aimed to summarize the evidence regarding this relationship using a dose-response meta-analytic approach. METHODOLOGY AND PRINCIPAL FINDINGS: We performed electronic searches of the PubMed, EmBase, and Cochrane Library databases to identify studies published through June 2013. Only prospective observational studies that reported breast cancer effect estimates with 95% confidence intervals (CIs) for more than 2 folate intake categories were included. We excluded traditional case-control studies because of possible bias from various confounding factors. Overall, we included 14 prospective studies that reported data on 677,858 individuals. Folate intake had little effect on the breast cancer risk (relative risk (RR) for highest versus lowest categoryâ=â0.97; 95% CI, 0.90-1.05; Pâ=â0.451). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of breast cancer (RRâ=â0.99; 95% CI, 0.98-1.01; Pâ=â0.361). Furthermore, we used restricted cubic splines to evaluate the nonlinear relationship between folate intake and the risk of breast cancer, and discovered a potential J-shaped correlation between folate intake and breast cancer risk (Pâ=â0.007) and revealed that a daily folate intake of 200-320 µg was associated with a lower breast cancer risk; however, the breast cancer risk increased significantly with a daily folate intake >400 µg. CONCLUSION/SIGNIFICANCE: Our study revealed that folate intake had little or no effect on the risk of breast cancer; moreover, a dose-response meta-analysis suggested a J-shaped association between folate intake and breast cancer.
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Neoplasias de la Mama/etiología , Ácido Fólico/administración & dosificación , Complejo Vitamínico B/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Ácido Fólico/efectos adversos , Humanos , Estudios Observacionales como Asunto , Estudios Prospectivos , Factores de Riesgo , Complejo Vitamínico B/efectos adversosRESUMEN
BACKGROUND: Studies have reported inconsistent results regarding the existence of an association between folate intake and the risk of lung cancer. The purpose of this study was to summarize the evidence from prospective cohort studies regarding this relationship by using a dose-response meta-analytic approach. METHODOLOGY AND PRINCIPAL FINDINGS: In September 2013, we performed electronic searches in PubMed, Embase, and the Cochrane Library to identify studies examining the effect of folate intake on the incidence of lung cancer. Only prospective cohort studies that reported the effect estimates about the incidence of lung cancer with 95% confidence intervals (CIs) for more than 2 categories of folate intake were included. Overall, we examined 9 cohort studies reporting the data of 566,921 individuals. High folate intake had little effect on the risk of lung cancer (risk ratio [RR], 0.92; 95% CI, 0.84-1.01; Pâ=â0.076). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of lung cancer (RR, 0.99; 95% CI, 0.97-1.01; Pâ=â0.318). Subgroup analysis suggested that the potential protective effect of low folate intake (100-299 µg/day) was more evident in women than men, while the opposite was true of high folate intake (>400 µg/day). Finally, subgroup analyses of a 100 µg/day increment in folate intake indicated that its potential protective effect was more evident in men than in women. CONCLUSION/SIGNIFICANCE: Our study revealed that folate intake had little or no effect on the risk of lung cancer. Subgroup analyses indicated that an increased folate intake was associated with a reduced risk of lung cancer in men. Furthermore, low folate intake may be a protective factor for women, and high folate intake for men.
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Anticarcinógenos/uso terapéutico , Ácido Fólico/uso terapéutico , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/prevención & control , Complejo Vitamínico B/uso terapéutico , Anticarcinógenos/administración & dosificación , Anticarcinógenos/efectos adversos , Estudios de Cohortes , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/efectos adversos , Humanos , Incidencia , Pulmón/efectos de los fármacos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico , Masculino , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Complejo Vitamínico B/administración & dosificación , Complejo Vitamínico B/efectos adversosRESUMEN
BACKGROUND: Omega-3 fatty acids are known to prevent cardiac death. However, previous observational studies have suggested that omega-3 fatty acids are associated with cancer risk in adults. We conducted a meta-analysis based on randomized controlled trials to evaluate the effect of omega-3 fatty acids on the risk of cancer incidence, nonvascular death, and total mortality. METHODS: In February 2013, we performed electronic searches in PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials on cancer incidence, nonvascular death, and total mortality. Relative risk (RR) was used to measure the effect of omega-3 fatty acid supplementation on the risk of cancer incidence, nonvascular death, and total mortality using a random-effect model. The analysis was further stratified by factors that could affect the treatment effects. RESULTS: Of the 8,746 identified articles, we included 19 trials reporting data on 68,954 individuals. These studies reported 1,039 events of cancer, 2,439 events of nonvascular death, and 7,025 events of total mortality. Omega-3 fatty acid supplementation had no effect on cancer incidence (RR, 1.10; 95% CI: 0.97-1.24; P = 0.12), nonvascular death (RR, 1.00; 95% CI: 0.93-1.08; P = 1.00), or total mortality (RR, 0.95; 95% CI: 0.88-1.03; P = 0.24) when compared to a placebo. Subgroup analysis indicated that omega-3 fatty acid supplementation was associated with a reduction in total mortality risk if the proportion of men in the study population was more than 80%, or participants received alpha-linolenic acid. CONCLUSIONS: Omega-3 fatty acid supplementation does not have an effect on cancer incidence, nonvascular death, or total mortality.
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Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Neoplasias/epidemiología , Humanos , Incidencia , Neoplasias/mortalidad , Neoplasias/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de RiesgoRESUMEN
A digital micromirror device (DMD) modulates laser intensity through computer control of the device. We experimentally investigate the performance of the modulation property of a DMD and optimize the modulation procedure through image correction. Furthermore, Laguerre-Gaussian (LG) beams with different topological charges are generated by projecting a series of forklike gratings onto the DMD. We measure the field distribution with and without correction, the energy of LG beams with different topological charges, and the polarization property in sequence. Experimental results demonstrate that it is possible to generate LG beams with a DMD that allows the use of a high-intensity laser with proper correction to the input images, and that the polarization state of the LG beam differs from that of the input beam.