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INTRODUCTION: We previously reported that the prevalence of abdominal aortic aneurysms (AAAs) was higher in patients undergoing scheduled transthoracic echocardiography (TTE) than in patients undergoing abdominal ultrasonography (AUS); however, intergroup patient backgrounds differed significantly in that report. PURPOSE: We tested the hypothesis that TTE could detect AAA as effectively as AUS. DESIGN: A propensity score-matching analysis of a cross-sectional study was adopted as the design for this study. METHODS: We enrolled 7,619 and 15,433 patients scheduled to undergo TTE with additional evaluation of abdominal aorta at the end of the routine study and AUS, respectively, from 2009 to 2010 in our hospital, as reported. A propensity score for profiles of patients who underwent TTE or AUS was developed to adjust for potential confounding bias. Consequently, 4,388 patients in each group were matched for analyses. RESULTS: In propensity-matched patients, AAA was detected in 59 patients of the TTE group and in 48 patients of the AUS group; the prevalence of AAA detection did not differ significantly between TTE and AUS groups (P = 0.331). Positive associations were observed between AAA detection and male sex (adjusted odds ratio [OR]: 3.25; 95% confidence interval [CI], 2.05-5.15; P < 0.001), older age (adjusted OR: 1.029; 95% CI: 1.01-1.04; P < 0.001), and the presence of ischemic heart disease (adjusted OR: 1.78; 95% CI: 1.04-3.03; P = 0.033) and hypertension (adjusted OR: 2.16; 95% CI: 1.38-3.37; P = 001). CONCLUSION: TTE detected AAA with comparable efficacy as AUS in propensity-matched groups who underwent scheduled TTE and AUS.
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Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper modulate tumor growth. Chronic exposure to elevated levels of copper in drinking water, corresponding to the maximum allowed in public water supplies, stimulated proliferation of cancer cells and de novo pancreatic tumor growth in mice. Conversely, reducing systemic copper levels with a chelating drug, clinically used to treat copper disorders, impaired both. Under such copper limitation, tumors displayed decreased activity of the copper-binding mitochondrial enzyme cytochrome c oxidase and reduced ATP levels, despite enhanced glycolysis, which was not accompanied by increased invasiveness of tumors. The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis. Interestingly, larger tumors contained less copper than smaller tumors and exhibited comparatively lower activity of cytochrome c oxidase and increased glucose uptake. These results establish copper as a tumor promoter and reveal that varying levels of copper serves to regulate oxidative phosphorylation in rapidly proliferating cancer cells inside solid tumors. Thus, activation of glycolysis in tumors may in part reflect insufficient copper bioavailability in the tumor microenvironment.
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Cobre/toxicidad , Agua Potable/análisis , Neoplasias/fisiopatología , Fosforilación Oxidativa/efectos de los fármacos , Microambiente Tumoral/fisiología , Contaminantes Químicos del Agua/toxicidad , Adenosina Trifosfato/metabolismo , Animales , Disponibilidad Biológica , Western Blotting , Cartilla de ADN/genética , Metabolismo Energético/efectos de los fármacos , Glucólisis/fisiología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Tomografía de Emisión de Positrones , Reacción en Cadena en Tiempo Real de la Polimerasa , RespiraciónRESUMEN
We report 2 cases of reversible ventricular hypertrophy in patients with takotsubo cardiomyopathy (stress-induced cardiomyopathy) during recovery of cardiac function. The first case involved a 72-year-old woman who presented with cerebral infarction. On admission, an elevated troponin I and decreased apical wall motion were observed with normal myocardial perfusion imaging. The second case involved a 79-year-old woman who presented with angina, anxiety resulting from emotional stress, slightly decreased apical wall motion, and normal epicardial arteries. In both cases, apical hypertrophy of the left ventricle was observed at approximately 3 weeks after onset, when the wall motion had improved. The ventricular wall gradually became thinner over time. To our knowledge, this is the first report of reversible ventricular hypertrophy in patients with takotsubo cardiomyopathy. We hypothesize the hypertrophic signaling in the myocardium was stimulated by catecholamines, which are the suggested etiology of takotsubo cardiomyopathy, and the hypertrophied myocardium gradually returned to normal as the syndrome receded.
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Ecocardiografía/métodos , Hipertrofia Ventricular Izquierda/complicaciones , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Cardiomiopatía de Takotsubo/complicaciones , Cardiomiopatía de Takotsubo/diagnóstico por imagen , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Recuperación de la Función , Remisión EspontáneaRESUMEN
Uptake of the anticancer drug cisplatin is mediated by the copper transporter CTR1 in cultured cells. Here we show in human ovarian tumors that low levels of Ctr1 mRNA are associated with poor clinical response to platinum-based therapy. Using a mouse model of human cervical cancer, we demonstrate that combined treatment with a copper chelator and cisplatin increases cisplatin-DNA adduct levels in cancerous but not in normal tissues, impairs angiogenesis, and improves therapeutic efficacy. The copper chelator also enhances the killing of cultured human cervical and ovarian cancer cells with cisplatin. Our results identify the copper transporter as a therapeutic target, which can be manipulated with copper chelating drugs to selectively enhance the benefits of platinum-containing chemotherapeutic agents.
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Adyuvantes Farmacéuticos/farmacología , Quelantes/farmacología , Cisplatino/metabolismo , Cisplatino/uso terapéutico , Cobre/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Adenosina Trifosfatasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Estructuras Animales/efectos de los fármacos , Estructuras Animales/metabolismo , Animales , Carboplatino/uso terapéutico , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quelantes/metabolismo , Cobre/sangre , Transportador de Cobre 1 , ATPasas Transportadoras de Cobre , Aductos de ADN/metabolismo , Modelos Animales de Enfermedad , Supervivencia sin Enfermedad , Femenino , Expresión Génica/genética , Humanos , Ratones , Ratones Endogámicos , Persona de Mediana Edad , Molibdeno/metabolismo , Molibdeno/farmacología , Molibdeno/uso terapéutico , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Resultado del Tratamiento , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
Cisplatin is a chemotherapeutic drug used to treat a variety of cancers. Both intrinsic and acquired resistance to cisplatin, as well as toxicity, limit its effectiveness. Molecular mechanisms that underlie cisplatin resistance are poorly understood. Here we demonstrate that deletion of the yeast CTR1 gene, which encodes a high-affinity copper transporter, results in increased cisplatin resistance and reduced intracellular accumulation of cisplatin. Copper, which causes degradation and internalization of Ctr1 protein (Ctr1p), enhances survival of wild-type yeast cells exposed to cisplatin and reduces cellular accumulation of the drug. Cisplatin also causes degradation and delocalization of Ctr1p and interferes with copper uptake in wild-type yeast cells. Mouse cell lines lacking one or both mouse Ctr1 (mCtr1) alleles exhibit increased cisplatin resistance and decreased cisplatin accumulation in parallel with mCtr1 gene dosage. We propose that cisplatin uptake is mediated by the copper transporter Ctr1p in yeast and mammals. The link between Ctr1p and cisplatin transport may explain some cases of cisplatin resistance in humans and suggests ways of modulating sensitivity and toxicity to this important anticancer drug.