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1.
Pediatr Transplant ; 22(8): e13291, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30220110

RESUMEN

AML with the RAM immunophenotype is associated with extremely poor prognosis. We report a rare case of monozygotic twins presenting simultaneously at the age of 2 years with RAM AML. Each twin underwent a myeloablative 7/10 unrelated umbilical cord blood transplant. Pretransplant Twin A's bone marrow was negative for MRD by flow cytometry (<0.01%) unlike Twin B's bone marrow (0.07%). Twin A is alive in remission 3 years from transplant. Twin B developed primary graft failure, but subsequently rescued with a haploidentical stem cell transplant. However, she relapsed and died 13 months from diagnosis. The twins' clinical courses demonstrate that upfront intensive chemotherapy to achieve negative MRD, followed by allogeneic hematopoietic stem cell transplant as postremission intensification strategy, should be considered in this high-risk AML.


Asunto(s)
Inmunofenotipificación , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/inmunología , Médula Ósea/patología , Preescolar , Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedades en Gemelos , Resultado Fatal , Femenino , Sangre Fetal/metabolismo , Citometría de Flujo , Humanos , Leucemia Mieloide Aguda/genética , Neoplasia Residual , Pronóstico , Inducción de Remisión , Trasplante Homólogo , Gemelos Monocigóticos
2.
Antiviral Res ; 95(1): 49-56, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22609829

RESUMEN

Epstein-Barr virus (EBV) infection and latency has been associated with malignant diseases including nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and immune deficiency associated lymphoproliferative diseases. EBV-encoded latent membrane protein 2A (LMP2A) recruits Lyn and Syk kinases via its SH2-domain binding motifs, and modifies their signaling pathways. LMP2A transgenic mice develop hyperproliferative bone marrow B cells and immature peripheral B cells through modulation of Lyn kinase signaling. LMP2A/λ-MYC double transgenic mice develop splenomegaly and cervical lymphomas starting at 8 weeks of age. We reasoned that targeting Lyn in LMP2A-expressing B cells with dasatinib would provide a therapeutic option for EBV-associated malignancies. Here, we show that dasatinib inhibits B cell colony formation by LMP2A transgenic bone marrow cells, and reverses splenomegaly and tumor growth in both a pre-tumor and a syngeneic tumor transfer model of EBV-associated Burkitt lymphoma. Our data support the idea that dasatinib may prove to be an effective therapeutic molecule for the treatment of EBV-associated malignancies.


Asunto(s)
Antineoplásicos/administración & dosificación , Linfocitos B/efectos de los fármacos , Linfoma de Burkitt/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Proteína Oncogénica p55(v-myc)/biosíntesis , Pirimidinas/administración & dosificación , Tiazoles/administración & dosificación , Proteínas de la Matriz Viral/biosíntesis , Animales , Linfoma de Burkitt/patología , Dasatinib , Modelos Animales de Enfermedad , Expresión Génica , Herpesvirus Humano 4/patogenicidad , Ratones , Ratones Transgénicos , Esplenomegalia/tratamiento farmacológico , Esplenomegalia/patología
3.
J Androl ; 24(1): 120-30, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12514093

RESUMEN

Sertoli cells isolated from 6-day postpartum mouse testes were conditionally immortalized with the simian virus 40 large tumor antigen gene (SV40-LTAg) under the control of a promoter inducible with ponasterone A, an analog of ecdysone. This strategy produced 2 cell lines, which exhibited mixed phenotypes. We first tested the conditional expression of the LTAg gene in the presence or absence of ponasterone A. The results showed that both cell lines expressed LTAg when the inducer was present in the culture media. When ponasterone A was removed, the majority of the cells died. After 60 generations, however, the continued expression of LTAg in the absence of the hormone indicated that unknown changes may have occurred in the genome of the cells. One of the cell lines was further subcloned, resulting in 7 new lines exhibiting a morphology resembling that of Sertoli cells in tissue culture. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed on RNA collected from each cell line in order to determine which cells were phenotypically similar to Sertoli cells in vivo. All cell lines expressed the products of the Sertoli cell-specific genes stem cell factor (SCF) and sulfated glycoprotein-2 (SGP-2), in addition to alpha-inhibin, GATA-1, and steroidogenic factor-1. Further, the lines express growth and differentiation factors known to act upon germ cells in vivo and in vitro such as leukemia inhibitory factor (LIF), transforming growth factor beta (TGF-beta), and basic fibroblast growth factor (bFGF). Moreover, when used as feeder layers in cocultures, at least 2 of these lines are able to maintain the viability of type A spermatogonia for at least 7 days and to support the first steps of spermatogonial differentiation.


Asunto(s)
Sustancias de Crecimiento/metabolismo , Células de Sertoli/metabolismo , Fosfatasa Alcalina/metabolismo , Animales , Animales Recién Nacidos , Antígenos Transformadores de Poliomavirus/genética , Antígenos Virales de Tumores/genética , Línea Celular Transformada , Supervivencia Celular , Células Cultivadas , Técnicas de Cocultivo , Expresión Génica , Inmunohistoquímica , Masculino , Ratones , Microscopía Electrónica , Microscopía de Contraste de Fase , Oncogenes , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células de Sertoli/citología , Células de Sertoli/fisiología , Células de Sertoli/ultraestructura , Espermatogonias/fisiología
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