Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros

Base de dados
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Int J Surg Pathol ; 31(5): 612-615, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35898185

RESUMO

A 76-year-old gentleman presented with persistent lower urinary tract symptoms. Multiple biopsies, radiological correlation and ancillary studies were required to achieve a diagnosis. The main differential diagnoses lies between urothelial carcinoma and anaplastic large cell lymphoma (ALCL), both of which are known to be positive for p63 and GATA3. An accurate diagnosis is crucial as the management is significantly different. To avoid misdiagnosis a comprehensive immunohistochemistry panel is necessary. Primary bladder lymphomas are rare. Our case represents the first case of primary ALK-negative TP63-rearranged ALCL. We reviewed the literature and discussed the potential pitfalls for misdiagnosis.


Assuntos
Carcinoma de Células de Transição , Linfoma Anaplásico de Células Grandes , Neoplasias da Bexiga Urinária , Masculino , Humanos , Idoso , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Receptores Proteína Tirosina Quinases/genética , Erros de Diagnóstico , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor
2.
Nat Commun ; 11(1): 6211, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277497

RESUMO

Intensive chemotherapy for acute leukemia can usually induce complete remission, but fails in many patients to eradicate the leukemia stem cells responsible for relapse. There is accumulating evidence that these relapse-inducing cells are maintained and protected by signals provided by the microenvironment. Thus, inhibition of niche signals is a proposed strategy to target leukemia stem cells but this requires knowledge of the critical signals and may be subject to compensatory mechanisms. Signals from the niche require receptor-mediated endocytosis, a generic process dependent on the Dynamin family of large GTPases. Here, we show that Dynole 34-2, a potent inhibitor of Dynamin GTPase activity, can block transduction of key signalling pathways and overcome chemoresistance of leukemia stem cells. Our results provide a significant conceptual advance in therapeutic strategies for acute leukemia that may be applicable to other malignancies in which signals from the niche are involved in disease progression and chemoresistance.


Assuntos
Cianoacrilatos/farmacologia , Dinaminas/antagonistas & inibidores , Endocitose/efeitos dos fármacos , Indóis/farmacologia , Leucemia Mieloide/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Doença Aguda , Animais , Linhagem Celular Tumoral , Dinaminas/metabolismo , Humanos , Leucemia Mieloide/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Camundongos Transgênicos , Células-Tronco Neoplásicas/efeitos dos fármacos , Nicho de Células-Tronco/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
4.
Nat Commun ; 9(1): 3535, 2018 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-30166543

RESUMO

Pre-leukemic stem cells (pre-LSCs) give rise to leukemic stem cells through acquisition of additional gene mutations and are an important source of relapse following chemotherapy. We postulated that cell-cycle kinetics of pre-LSCs may be an important determinant of clonal evolution and therapeutic resistance. Using a doxycycline-inducible H2B-GFP transgene in a mouse model of T-cell acute lymphoblastic leukemia to study cell cycle in vivo, we show that self-renewal, clonal evolution and therapeutic resistance are limited to a rare population of pre-LSCs with restricted cell cycle. We show that proliferative pre-LSCs are unable to return to a cell cycle-restricted state. Cell cycle-restricted pre-LSCs have activation of p53 and its downstream cell-cycle inhibitor p21. Furthermore, absence of p21 leads to proliferation of pre-LSCs, with clonal extinction through loss of asymmetric cell division and terminal differentiation. Thus, inducing proliferation of pre-LSCs represents a promising strategy to increase cure rates for acute leukemia.


Assuntos
Ciclo Celular/genética , Evolução Clonal/genética , Leucemia Mieloide Aguda/genética , Animais , Ciclo Celular/fisiologia , Evolução Clonal/fisiologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Masculino , Camundongos , Células-Tronco Neoplásicas/metabolismo , Sequenciamento do Exoma/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA