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

Base de dados
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Br J Haematol ; 201(4): 718-724, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36786170

RESUMO

Despite the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway being frequently altered in T-ALL/LBL, no specific therapy has been approved for T-ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify pathway members that may be potential therapeutic targets. In the present study, we searched for JAK/STAT pathway members potentially modulated through aberrant methylation and identified SOCS3 hypermethylation as a recurrent event in T-ALL/LBL. Additionally, we explored the implications of SOCS3 deregulation in T-ALL/LBL and demonstrated that SOCS3 counteracts the constitutive activation of the JAK/STAT pathway through different molecular mechanisms. Therefore, SOCS3 emerges as a potential therapeutic target in T-ALL/LBL.


Assuntos
Leucemia-Linfoma de Células T do Adulto , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Janus Quinases/metabolismo , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Fatores de Transcrição STAT/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Linfócitos T/metabolismo
2.
Sci Rep ; 12(1): 3144, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35210498

RESUMO

In the quest for more effective radiation treatment options that can improve both cell killing and healthy tissue recovery, combined radiation therapies are lately in the spotlight. The molecular response to a combined radiation regime where exposure to an initial low dose (priming dose) of ionizing radiation is administered prior to a subsequent higher radiation dose (challenging dose) after a given latency period have not been thoroughly explored. In this study we report on the differential response to either a combined radiation regime or a single challenging dose both in mouse in vivo and in human ex vivo thymocytes. A differential cell cycle response including an increase in the subG1 fraction on cells exposed to the combined regime was found. Together with this, a differential protein expression profiling in several pathways including cell cycle control (ATM, TP53, p21CDKN1A), damage response (γH2AX) and cell death pathways such as apoptosis (Cleaved Caspase-3, PARP1, PKCδ and H3T45ph) and ferroptosis (xCT/GPX4) was demonstrated. This study also shows the epigenetic regulation following a combined regime that alters the expression of chromatin modifiers such as DNMTs (DNMT1, DNMT2, DNMT3A, DNMT3B, DNMT3L) and glycosylases (MBD4 and TDG). Furthermore, a study of the underlying cellular status six hours after the priming dose alone showed evidence of retained modifications on the molecular and epigenetic pathways suggesting that the priming dose infers a "radiation awareness phenotype" to the thymocytes, a sensitization key to the differential response seen after the second hit with the challenging dose. These data suggest that combined-dose radiation regimes could be more efficient at making cells respond to radiation and it would be interesting to further investigate how can these schemes be of use to potential new radiation therapies.


Assuntos
Ciclo Celular/efeitos da radiação , Dano ao DNA , Regulação da Expressão Gênica/efeitos da radiação , Timócitos/metabolismo , Raios X/efeitos adversos , Animais , Relação Dose-Resposta à Radiação , Feminino , Humanos , Camundongos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA