Navegando por Palavras-chave "Clonogenicity"
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- ItemSomente MetadadadosANKHD1 represses p21 (WAF1/CIP1) promoter and promotes multiple myeloma cell growth(Elsevier B.V., 2015-01-01) Dhyani, Anamika; Machado-Neto, Joao A.; Favaro, Patricia [UNIFESP]; Olalla Saad, Sara T.; Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP)ANKHD1 (Ankyrin repeat and KH domain-containing protein 1) is highly expressed and plays an important role in the proliferation and cell cycle progression of multiple myeloma (MM) cells. ANKHD1 downregulation modulates cell cycle gene expression and upregulates p21 irrespective of the TP53 mutational status of MM cell lines. the present study was aimed to investigate the role of ANKHD1 in MM in vitro clonogenicity and in vivo tumourigenicity, as well as the role of ANKHD1 in p21 transcriptional regulation. ANKHD1 silencing in MM cells resulted in significantly low no. of colonies formed and in slow migration as compared to control cells (p < 0.05). Furthermore, in xenograft MM mice models, tumour growth was visibly suppressed in mice injected with ANKHD1 silenced cells compared to the control group. There was a significant decrease in tumour volume (p = 0.006) as well as in weight (p = 0.02) in the group injected with silenced cells compared to those of the control group. Co-immunoprecipitation and chromatin immunoprecipitation (ChIP) assays confirmed the interaction between p21 and ANKHD1. Moreover, overexpression of ANKHD1 downregulated the activity of a p21 promoter in luciferase assays. Decrease in luciferase activity suggests a direct role of ANKHD1 in p21 transcriptional regulation. in addition confocal analysis after U266 cells were treated with Leptomycin B (LMB) for 24 h showed accumulation of ANKHD1 inside the nucleus as compared to untreated cells where ANKHD1 was found to be predominantly in cytoplasm. This suggests ANKHD1 might be shuttling between cytoplasm and nucleus. in conclusion, ANKHD1 promotes MM growth by repressing p21 a potent cell cycle regulator. (C) 2014 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosC-Kit(+) Cells Isolated from Developing Kidneys Are a Novel Population of Stem Cells with Regenerative Potential(Wiley-Blackwell, 2013-08-01) Rangel, Erika Bevilaqua [UNIFESP]; Gomes, Samirah Abreu [UNIFESP]; Dulce, Raul A.; Premer, Courtney; Rodrigues, Claudia O.; Kanashiro-Takeuchi, Rosimeire Miyuki [UNIFESP]; Oskouei, Behzad; Carvalho, Decio A.; Ruiz, Phillip; Reiser, Jochen; Hare, Joshua M.; Univ Miami; Albert Einstein Hosp; Universidade Federal de São Paulo (UNIFESP)The presence of tissue specific precursor cells is an emerging concept in organ formation and tissue homeostasis. Several progenitors are described in the kidneys. However, their identity as a true stem cell remains elusive. Here, we identify a neonatal kidney-derived c-kit(+) cell population that fulfills all of the criteria as a stem cell. These cells were found in the thick ascending limb of Henle's loop and exhibited clonogenicity, self-renewal, and multipotentiality with differentiation capacity into mesoderm and ectoderm progeny. Additionally, c-kit(+) cells formed spheres in nonadherent conditions when plated at clonal density and expressed markers of stem cells, progenitors, and differentiated cells. Ex vivo expanded c-kit(+) cells integrated into several compartments of the kidney, including tubules, vessels, and glomeruli, and contributed to functional and morphological improvement of the kidney following acute ischemia-reperfusion injury in rats. Together, these findings document a novel neonatal rat kidney c-kit(+) stem cell population that can be isolated, expanded, cloned, differentiated, and used for kidney repair following acute kidney injury. These cells have important biological and therapeutic implications. STEM Cells 2013;31:1644-1656
- ItemSomente MetadadadosCafestol, a diterpene molecule found in coffee, induces leukemia cell death(Elsevier France-Editions Scientifiques Medicales Elsevier, 2017) Limaa, Caue S. [UNIFESP]; Spindola, Daniel G. [UNIFESP]; Bechara, Alexandre [UNIFESP]; Garcia, Daniel M. [UNIFESP]; Palmeira-dos-Santos, Caroline [UNIFESP]; Peixoto-da-Silva, Janaina [UNIFESP]; Erustes, Adolfo G. [UNIFESP]; Michelin, Luis F. G. [UNIFESP]; Pereira, Gustavo J. S. [UNIFESP]; Smaili, Soraya S. [UNIFESP]; Paredes-Gamero, Edgar [UNIFESP]; Calgarotto, Andrana K. [UNIFESP]; Oliveira, Carlos R. [UNIFESP]; Bincoletto, Claudia [UNIFESP]To evaluate the antitumor properties of Cafestol four leukemia cell lines were used (NB4, K562, HL60 and KG1). Cafestol exhibited the highest cytotoxicity against HL60 and KG1 cells, as evidenced by the accumulation of cells in the sub-G1 fraction, mitochondrial membrane potential reduction, accumulation of cleaved caspase-3 and phosphatidylserine externalization. An increase in CD11b and CD15 differentiation markers with attenuated ROS generation was also observed in Cafestol-treated HL60 cells. These results were similar to those obtained following exposure of the same cell line to cytarabine (Ara-C), an antileukemic drug. Cafestol and Ara-C reduced the clonogenic potential of HL60 cells by 100%, but Cafestol spared murine colony forming unit-granulocyte/macrophage (CFU-GM), which retained their clonogenicity. The co-treatment of Cafestol and Ara-C reduced HL60 cell viability compared with both drugs administered alone. In conclusion, despite the distinct molecular mechanisms involved in the activity of Cafestol and Ara-C, a similar cytotoxicity towards leukemia cells was observed, which suggests a need for prophylactic-therapeutic pre-clinical studies regarding the anticancer properties of Cafestol. (C) 2017 Elsevier Masson SAS. All rights reserved.
- ItemSomente MetadadadosLithium, a classic drug in psychiatry, improves nilotinib-mediated antileukemic effects(Elsevier France-Editions Scientifiques Medicales Elsevier, 2018) Silva, Janaina Peixoto da [UNIFESP]; Calgarotto, Andrana K. [UNIFESP]; Rocha, Katiucha Karolina [UNIFESP]; Santos, Caroline Palmeira dos [UNIFESP]; Smaili, Soraya Soubhi [UNIFESP]; Pereira, Gustavo Jose da Silva [UNIFESP]; Pericole, Fernando Vieira; Duarte, Adriana da Silva Santos; Saad, Sara Teresinha Olalla [UNIFESP]; Bincoletto, Claudia [UNIFESP]Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating cells, which lead to the emergence of drug resistance. Here we used the lithium, a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to TKIs, were used as a model. Our results demonstrated that the combination of lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when compared to lithium or nilotinib alone, accompanied by GSK-3 beta phosphorylation and Bcr-Abl oncoprotein levels reduction. Interestingly, these events were related to autophagy induction, expressed by increased LC3II protein levels in the group treated with L + N. Furthermore, the clonogenic capacity of progenitor cells from CML patients was drastically reduced by L + N, as well as lithium and nilotinib when used separately. The number of cell aggregates (clusters), were increased by all treatments (L + N, lithium, and nilotinib). This pioneering research has demonstrated that lithium might be of therapeutic value when targeting Bcr-Abl cells with nilotinib because it triggers cell death in addition to exerting classical antiproliferative effects, opening new perspectives for novel target and therapeutic approaches to eradicate CML.