RESUMO
T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-beta, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL.
Assuntos
Diferenciação Celular , Leucemia-Linfoma de Células T do Adulto , Fosfotransferases/fisiologia , Transdução de Sinais/fisiologia , Linfócitos T/citologia , Humanos , Janus Quinases/fisiologia , Leucemia-Linfoma de Células T do Adulto/etiologia , Leucemia-Linfoma de Células T do Adulto/fisiopatologia , Leucemia-Linfoma de Células T do Adulto/terapia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/fisiologia , Receptores Notch/fisiologia , Fator de Crescimento Transformador beta/fisiologiaRESUMO
T-cell acute lymphoblastic leukemia (T-ALL) is a biologically heterogeneous disease with respect to phenotype, gene expression profile and activation of particular intracellular signaling pathways. Despite very significant improvements, current therapeutic regimens still fail to cure a portion of the patients and frequently implicate the use of aggressive protocols with long-term side effects. In this review, we focused on how deregulation of critical signaling pathways, in particular Notch, PI3K/Akt, MAPK, Jak/STAT and TGF-ß, may contribute to T-ALL. Identifying the alterations that affect intracellular pathways that regulate cell cycle and apoptosis is essential to understanding the biology of this malignancy, to define more effective markers for the correct stratification of patients into appropriate therapeutic regimens and to identify novel targets for the development of specific, less detrimental therapies for T-ALL.
Assuntos
Humanos , Diferenciação Celular , Leucemia-Linfoma de Células T do Adulto , Fosfotransferases/fisiologia , Transdução de Sinais/fisiologia , Linfócitos T/citologia , /fisiologia , Janus Quinases/fisiologia , Leucemia-Linfoma de Células T do Adulto/etiologia , Leucemia-Linfoma de Células T do Adulto/fisiopatologia , Leucemia-Linfoma de Células T do Adulto/terapia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/fisiologia , Receptores Notch/fisiologia , Fator de Crescimento Transformador beta/fisiologiaRESUMO
The authors describe a family (mother, son and two daughters) with mitochondrial myopathy. The mother was asymptomatic. Two daughters had lactic acidosis and myoclonic epilepsy, mild dementia, ataxia, weakness and sensory neuropathy. The son suffered one acute hemiplegic episode due to an ischemic infarct in the right temporal region. All the patients studied had hypertension. EEG disclosed photomyoclonic response in the proband patient. Muscle biopsy disclosed ragged-red fibers and abnormal mitochondria by electron microscopy. Biochemical analysis showed a defect of cytochrome C oxidase in mitochondria isolated from skeletal muscle. Several clinical and genetic aspects of the mitochondrial encephalomyopathies are discussed.
Assuntos
Epilepsias Mioclônicas/genética , Mitocôndrias Musculares/ultraestrutura , Doenças Musculares/genética , Acidose Láctica/complicações , Adulto , Eletromiografia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Epilepsias Mioclônicas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitocôndrias Musculares/metabolismo , Músculos/patologia , Doenças Musculares/sangue , Doenças Musculares/complicações , Doenças Musculares/diagnóstico , LinhagemRESUMO
Kinetic studies of T4 and T3 metabolism were performed on 5 healthy volunteers from Rio de Janeiro to obtain normal values for thyroid hormone metabolism. 125I-T4 and 131I-T3 were administered in bolus and blood samples taken during 7 days. Circulating tracers were isolated by Sephadex G-25 chromatography. The kinetic parameters of T4 and T3 metabolism were calculated by noncompartmental methods. Metabolic clearance rates were 1.04 l/day for T4 and 20.7 l/day for T3. The daily production rate was estimated at 94 micrograms/day for T4 and 23 micrograms/day for T3 and their exchangeable pools at 914 micrograms and 25.5 micrograms, respectively. These values are well within the range of those reported by North American or European authors for normal subjects.