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1.
Case Rep Gastroenterol ; 13(1): 85-88, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31043934

RESUMO

Signet-ring cell carcinoma is a rare adenocarcinoma, predominantly affecting the stomach and ovaries. Primary sites elsewhere are rarer. It is recognized that there is an increased cancer risk with the diagnosis of Crohn's disease. We report a patient with Crohn's disease who was diagnosed with signet-ring cell carcinoma in the setting of a Crohn's flare. Diagnosis was made with endoscopy. Treatment included laparoscopic-assisted right hemicolectomy with ileostomy with subsequent chemotherapy as an outpatient.

2.
J Cell Biol ; 214(1): 25-34, 2016 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-27377248

RESUMO

In pancreatic ß-cells, liver hepatocytes, and cardiomyocytes, chronic exposure to high levels of fatty acids (lipotoxicity) inhibits autophagic flux and concomitantly decreases lysosomal acidity. Whether impaired lysosomal acidification is causally inhibiting autophagic flux and cellular functions could not, up to the present, be determined because of the lack of an approach to modify lysosomal acidity. To address this question, lysosome-localizing nanoparticles are described that, upon UV photoactivation, enable controlled acidification of impaired lysosomes. The photoactivatable, acidifying nanoparticles (paNPs) demonstrate lysosomal uptake in INS1 and mouse ß-cells. Photoactivation of paNPs in fatty acid-treated INS1 cells enhances lysosomal acidity and function while decreasing p62 and LC3-II levels, indicating rescue of autophagic flux upon acute lysosomal acidification. Furthermore, paNPs improve glucose-stimulated insulin secretion that is reduced under lipotoxicity in INS1 cells and mouse islets. These results establish a causative role for impaired lysosomal acidification in the deregulation of autophagy and ß-cell function under lipotoxicity.


Assuntos
Ácidos/metabolismo , Autofagia/efeitos dos fármacos , Luz , Lipídeos/toxicidade , Lisossomos/metabolismo , Nanopartículas/efeitos da radiação , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Endocitose/efeitos dos fármacos , Glucose/farmacologia , Concentração de Íons de Hidrogênio , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Lisossomos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Ácido Palmítico/toxicidade , Raios Ultravioleta
3.
Am J Cardiol ; 111(5): 717-22, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23228924

RESUMO

We aimed to determine whether the myocardial extracellular volume (ECV), measured using T1 measurements obtained during cardiac magnetic resonance imaging were increased in patients treated with anthracyclines. We performed cardiac magnetic resonance imaging and echocardiography and measured the ECV in 42 patients treated with anthracyclines. The data from the cardiac magnetic resonance study were compared to those from healthy volunteers. The anthracycline-treated cohort consisted of 21 men and 21 women with a mean age of 55 ± 17 years, who presented a median of 84 months after chemotherapy with a cumulative anthracycline exposure of 282 ± 65 mg/m(2) and a mean left ventricular ejection fraction of 52 ± 12%. The ECV was elevated in the anthracycline-treated patients compared to the age- and gender-matched controls (0.36 ± 0.03 vs 0.28 ± 0.02, p <0.001). A positive association was found between the ECV and left atrial volume (ECV vs indexed left atrial volume, r = 0.65, p <0.001), and negative association was found between the ECV and diastolic function (E' lateral, r = -0.64, p <0.001). In conclusion, the myocardial ECV is elevated in patients with previous anthracycline treatment and is associated with the diastolic function and increased atrial volumes.


Assuntos
Antraciclinas/uso terapêutico , Cardiomiopatias/induzido quimicamente , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Neoplasias/tratamento farmacológico , Antraciclinas/efeitos adversos , Cardiomiopatias/diagnóstico , Cardiomiopatias/fisiopatologia , Espaço Extracelular , Feminino , Humanos , Masculino , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda
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