RESUMO
Insulin receptor beta-subunit autophosphorylation, the first event occurring after insulin binding, plays a crucial role in modulation of receptor-associated kinase activity towards exogenous substrates and possibly in the transmission of biological signals of insulin. Receptor autophosphorylation strongly depends on insulin receptor occupancy. Till now the effects of receptor phosphorylation on insulin binding itself have not been clarified. In the present report we demonstrate the absence of any feedback mechanism by which insulin receptor activation by phosphorylation affects binding affinity of insulin receptor itself.
Assuntos
Insulina/metabolismo , Receptor de Insulina/metabolismo , Adenosina/farmacologia , Difosfato de Adenosina/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Membrana Celular/análise , Feminino , Guanosina/farmacologia , Humanos , Masculino , Microssomos Hepáticos/análise , Fosforilação , Placenta/análise , Gravidez , Ratos , Ratos Endogâmicos , Receptor de Insulina/efeitos dos fármacosRESUMO
This is a retrospective study to evaluate the history of hepatocellular carcinoma and find the relationship between clinical, biochemical and ultrasonographic features and survival in Italian patients. In 135 consecutive patients median follow-up was 16 months (range 1-66 months) and median survival from the time of diagnosis was 12 months. Univariate analysis showed that individual variables associated with significantly decreased survival included: absence of therapy, Okuda's Stage III, Child-Pugh's Class C, alpha-fetoprotein greater than 400 ng/ml, presence of symptoms, moderate or severe ascites, tumor involving both lobes, mixed internal echo pattern, and multinodular or massive type. Multiple regression analysis (Cox model) revealed that the mixed internal echo pattern of hepatocellular carcinoma, the presence of moderate or severe ascites and Okuda's Stage III were independent predictors of high risk of death. These data can help in selecting patients whose probability of survival is considered high enough to undergo treatment and may be useful for stratifying patients in randomized controlled trials.