5 research outputs found
Estudio de las poblaciones de gotas lipídicas en el insecto vector de la enfermedad de chagas : (Triatoma infestans)
El objetivo del trabajo fue dilucidar las funciones, metabolismo y estructura de las poblaciones de gotas lipídicas en el insecto Triatoma infestans (vinchuca); el insecto es el principal vector del parásito Tripanozoma cruzi, agente causal de la enfermedad de chagas en Argentina y continente americano.Fil: Girotti, Juan R..
Consejo Nacional de Investigaciones Científicas y TécnicasFil: Borús, Delfina L..
Consejo Nacional de Investigaciones Científicas y TécnicasFil: Scelsio, Natalia S..
Consejo Nacional de Investigaciones Científicas y TécnicasFil: Favale, Nicolás O..
Consejo Nacional de Investigaciones Científicas y TécnicasFil: Ves Losada, Ana.
Consejo Nacional de Investigaciones Científicas y Técnica
La coordinación entre esfingolípidos y fosfoinosítidos es esencial para la diferenciación de las células tubulares renales
La diferenciación de las células epiteliales se produce por maduración de la membrana apical y desarrollo de cilio primario. Resultados previos de nuestro laboratorio demostraron que la hipertonicidad extracelular induce la diferenciación de las células MDCK, una línea celular derivada de túbulos colectores renales caninos, y que en este proceso son esenciales los esfingolípidos. Por otro lado, los fosfoinosítidos, otros lípidos bioactivos, son considerados determinantes de la polaridad apico - basal, dada su ubicación en dominios específicos de membrana en células epiteliales polarizadas: con PI(4,5)P2 localizado en el dominio apical y PI(3,4,5)P3 en el basolateral. Esta ubicación específica es la que determina el reclutamiento de complejos importantes de polaridad, como el Par3/Par6/aPKC.Fil: Pescio Lucila G..
Universidad de Buenos AiresFil: Romero, Daniela J..
Universidad de Buenos AiresFil: Santacreu, Bruno J..
Universidad de Buenos AiresFil: Francisco, María N..Fil: Favale, Nicolás O..
Universidad de Buenos AiresFil: Sterin-Speziale, Norma B..
Universidad de Buenos Aire
Venetoclax resistance induced by activated T cells can be counteracted by sphingosine kinase inhibitors in chronic lymphocytic leukemia
The treatment of chronic lymphocytic leukemia (CLL) patients with venetoclax-based regimens has demonstrated efficacy and a safety profile, but the emergence of resistant cells and disease progression is a current complication. Therapeutic target of sphingosine kinases (SPHK) 1 and 2 has opened new opportunities in the treatment combinations of cancer patients. We previously reported that the dual SPHK1/2 inhibitor, SKI-II enhanced the in vitro cell death triggered by fludarabine, bendamustine or ibrutinib and reduced the activation and proliferation of chronic lymphocytic leukemia (CLL) cells. Since we previously showed that autologous activated T cells from CLL patients favor the activation of CLL cells and the generation of venetoclax resistance due to the upregulation of BCL-XL and MCL-1, we here aim to determine whether SPHK inhibitors affect this process. To this aim we employed the dual SPHK1/2 inhibitor SKI-II and opaganib, a SPHK2 inhibitor that is being studied in clinical trials. We found that SPHK inhibitors reduce the activation of CLL cells and the generation of venetoclax resistance induced by activated T cells mainly due to a reduced upregulation of BCL-XL. We also found that SPHK2 expression was enhanced in CLL cells by activated T cells of the same patient and the presence of venetoclax selects resistant cells with high levels of SPHK2. Of note, SPHK inhibitors were able to re-sensitize already resistant CLL cells to a second venetoclax treatment. Our results highlight the therapeutic potential of SPHK inhibitors in combination with venetoclax as a promising treatment option for the patients
Environmental hyperosmolality regulates phospholipid biosynthesis in the renal epithelial cell line MDCK
DataSheet_1_Venetoclax resistance induced by activated T cells can be counteracted by sphingosine kinase inhibitors in chronic lymphocytic leukemia.pdf
The treatment of chronic lymphocytic leukemia (CLL) patients with venetoclax-based regimens has demonstrated efficacy and a safety profile, but the emergence of resistant cells and disease progression is a current complication. Therapeutic target of sphingosine kinases (SPHK) 1 and 2 has opened new opportunities in the treatment combinations of cancer patients. We previously reported that the dual SPHK1/2 inhibitor, SKI-II enhanced the in vitro cell death triggered by fludarabine, bendamustine or ibrutinib and reduced the activation and proliferation of chronic lymphocytic leukemia (CLL) cells. Since we previously showed that autologous activated T cells from CLL patients favor the activation of CLL cells and the generation of venetoclax resistance due to the upregulation of BCL-XL and MCL-1, we here aim to determine whether SPHK inhibitors affect this process. To this aim we employed the dual SPHK1/2 inhibitor SKI-II and opaganib, a SPHK2 inhibitor that is being studied in clinical trials. We found that SPHK inhibitors reduce the activation of CLL cells and the generation of venetoclax resistance induced by activated T cells mainly due to a reduced upregulation of BCL-XL. We also found that SPHK2 expression was enhanced in CLL cells by activated T cells of the same patient and the presence of venetoclax selects resistant cells with high levels of SPHK2. Of note, SPHK inhibitors were able to re-sensitize already resistant CLL cells to a second venetoclax treatment. Our results highlight the therapeutic potential of SPHK inhibitors in combination with venetoclax as a promising treatment option for the patients.</p