Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Oncotarget ; 8(5): 7740-7752, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-27999190

RESUMO

Pancreatic cancer (PC) shows a high death rate. PC incidence and prognosis are affected by obesity, a pandemic characterized by high levels of leptin. Notch is upregulated by leptin in breast cancer. Thus, leptin and Notch crosstalk could influence PC progression. Here we investigated in PC cell lines (BxPC-3, MiaPaCa-2, Panc-1, AsPC-1), derived tumorspheres and xenografts whether a functional leptin-Notch axis affects PC progression and expansion of pancreatic cancer stem cells (PCSC). PC cells and tumorspheres were treated with leptin and inhibitors of Notch (gamma-secretase inhibitor, DAPT) and leptin (iron oxide nanoparticle-leptin peptide receptor antagonist 2, IONP-LPrA2). Leptin treatment increased cell cycle progression and proliferation, and the expression of Notch receptors, ligands and targeted molecules (Notch1-4, DLL4, JAG1, Survivin and Hey2), PCSC markers (CD24/CD44/ESA, ALDH, CD133, Oct-4), ABCB1 protein, as well as tumorsphere formation. Leptin-induced effects on PC and tumorspheres were decreased by IONP-LPrA2 and DAPT. PC cells secreted leptin and expressed the leptin receptor, OB-R, which indicates a leptin autocrine/paracrine signaling loop could also affect tumor progression. IONP-LPrA2 treatment delayed the onset of MiaPaCa-2 xenografts, and decreased tumor growth and the expression of proliferation and PCSC markers. Present data suggest that leptin-Notch axis is involved in PC. PC has no targeted therapy and is mainly treated with chemotherapy, whose efficiency could be decreased by leptin and Notch activities. Thus, the leptin-Notch axis could be a novel therapeutic target, particularly for obese PC patients.


Assuntos
Leptina/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Pancreáticas/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Comunicação Autócrina/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Humanos , Ligantes , Masculino , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/patologia , Comunicação Parácrina/efeitos dos fármacos , Fatores de Tempo
2.
Dev Neurosci ; 28(4-5): 336-41, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16943656

RESUMO

Mitochondrial dysfunction occurs after traumatic brain injury (TBI) and contributes significantly to subsequent cell death. Heat shock protein 60 (hsp60) is a predominantly mitochondrial protein with important homeostatic functions. Induction of hsp60 has been demonstrated in cerebral ischemia models, possibly reflecting mitochondrial stress. We measured hsp60 concentration in the cerebrospinal fluid (CSF) of 34 infants and children after severe TBI and of 7 control patients by ELISA. Peak CSF hsp60 concentration was increased in TBI patients versus controls (0.84 ng/ml, range 0-44.59, vs. 0.0 ng/ml, range 0-0.48; p<0.05). Induction of hsp60 occurred early after the injury. Peak hsp60 concentration was independently associated with the severity of injury, defined as the admission Glasgow Coma Scale score. These data suggest that increased hsp60 in CSF might reflect the severity of early mitochondrial stress or damage after TBI.


Assuntos
Lesões Encefálicas/líquido cefalorraquidiano , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Chaperonina 60/líquido cefalorraquidiano , Mitocôndrias/metabolismo , Doenças Mitocondriais/líquido cefalorraquidiano , Biomarcadores/análise , Biomarcadores/líquido cefalorraquidiano , Encéfalo/patologia , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/fisiopatologia , Chaperonina 60/análise , Criança , Pré-Escolar , Metabolismo Energético/fisiologia , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Recém-Nascido , Masculino , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Estresse Fisiológico/etiologia , Estresse Fisiológico/metabolismo , Estresse Fisiológico/fisiopatologia , Regulação para Cima/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...