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2.
Clin. transl. oncol. (Print) ; 10(4): 219-226, abr. 2008. ilus
Artigo em Inglês | IBECS | ID: ibc-123437

RESUMO

Fatty acid synthase (FASN) is a novel druggable target for metabolically treating and preventing human malignancies. We envisioned that if loss of sensitivity to C75 (a slow-binding FASN inhibitor) occurs in parallel with loss of FASN expression and/or activity, a mathematical assessment of the nature of the interaction between investigational FASN modulators and C75 may predict the ability of experimental compounds to regulate FASN. We statistically compared the arithmetical sums of the anti-proliferative effects obtained when FASN modulators and C75 were used as single agents to those observed experimentally when agents were actually combined in a sequential schedule (i.e., FASN modulator-->C75). A reduced sensitivity to C75 (antagonism) occurred when compounds down-regulated FASN activity/expression, while an enhanced C75 efficacy (synergism) was found following exposure to FASN up-regulators. This "C75-sensitivity test" might offer an easy, rapid and objective method to identify FASN inhibitors with potential anticancer value in human cancer (AU)


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Assuntos
Humanos , Masculino , Feminino , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Ácido Graxo Sintase Tipo I/administração & dosagem , Ácido Graxo Sintase Tipo I , Modelos Teóricos , Neoplasias/tratamento farmacológico , Neoplasias/enzimologia , Interferência de RNA , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , Western Blotting/métodos , Western Blotting , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/farmacologia , Ácido Graxo Sintase Tipo I/química , Imunofluorescência/métodos
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