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[PMID]:29429164
[Au] Autor:Zhang F; Luo DL; Chen Y; Wu HM; Yan JH; Luo XL; He J; Luo LQ; Liu YH
[Ad] Endereço:Department of Pathology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
[Ti] Título:[Expression of ßF1 and T cell receptor γ in T lymphoblastic lymphoma/leukemia].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(2):119-122, 2018 Feb 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To evaluate the expression of ßF1 and T cell receptor (TCR)γ in T lymphoblastic lymphoma/leukemia(T-LBL/ALL), and investigate the clinicopathological features. Fifty-one cases of T-LBL/ALL were collected at Guangdong General Hospital from 2010 to 2016, the expression of ßF1 and TCRγ was assessed by immunohistochemistry. There were 13 cases of children and adolescents, and 38 cases of adults. The expression rates of ßF1 and TCRγ were 27.5%(14/51) and 15.7%(8/51) respectively. The proportion of adults in αß T-LBL/ALL, TCR-silent T-LBL/ALL and γδ T-LBL/ALL was 7/14, 79.3%(23/29)and 8/8 respectively, and the difference was significant ( =0.023). There was no statistical difference in sex, LDH, bone marrow involvement and Ann arbor stage among these three groups( >0.05). γδ T-LBL/ALLs included 6 cases of CD4(-)/CD8(-) phenotype, whereas αß T-LBL/ALL included 7 cases of CD4(+) /CD8(+) phenotype. There was significant difference in CD4/CD8 expression among these three groups( <0.01). γδ T-LBL/ALL occurred only in adults, with predominantly CD4(-)/CD8(-) phenotype. αß T-LBL/ALL occurred more common in children and adolescents, with predominantly CD4(+) /CD8(+) phenotype.
[Mh] Termos MeSH primário: Linfoma de Células T/metabolismo
Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo
Receptores de Antígenos de Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Seres Humanos
Imuno-Histoquímica
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.02.008


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[PMID]:29184402
[Au] Autor:Wu X; Wang L; Qiu Y; Zhang B; Hu Z; Jin R
[Ad] Endereço:Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
[Ti] Título:Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia.
[So] Source:Int J Nanomedicine;12:8025-8034, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores
Nanopartículas/química
Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Compostos de Bifenilo/administração & dosagem
Compostos de Bifenilo/farmacologia
Liberação Controlada de Fármacos
Sinergismo Farmacológico
Feminino
Seres Humanos
Células Jurkat
Ácido Láctico/química
Camundongos
Nanopartículas/administração & dosagem
Nitrofenóis/administração & dosagem
Nitrofenóis/farmacologia
Piperazinas/administração & dosagem
Piperazinas/farmacologia
Ácido Poliglicólico/química
Sulfonamidas/administração & dosagem
Sulfonamidas/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-737); 0 (Biphenyl Compounds); 0 (Nitrophenols); 0 (Piperazines); 0 (Sulfonamides); 0 (polylactic acid-polyglycolic acid copolymer); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid); EC 2.7.11.1 (IRAK1 protein, human); EC 2.7.11.1 (IRAK4 protein, human); EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S146875


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[PMID]:28465412
[Au] Autor:Severson E; Arnett KL; Wang H; Zang C; Taing L; Liu H; Pear WS; Shirley Liu X; Blacklow SC; Aster JC
[Ad] Endereço:Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
[Ti] Título:Genome-wide identification and characterization of Notch transcription complex-binding sequence-paired sites in leukemia cells.
[So] Source:Sci Signal;10(477), 2017 May 02.
[Is] ISSN:1937-9145
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Notch transcription complexes (NTCs) drive target gene expression by binding to two distinct types of genomic response elements, NTC monomer-binding sites and sequence-paired sites (SPSs) that bind NTC dimers. SPSs are conserved and have been linked to the Notch responsiveness of a few genes. To assess the overall contribution of SPSs to Notch-dependent gene regulation, we determined the DNA sequence requirements for NTC dimerization using a fluorescence resonance energy transfer (FRET) assay and applied insights from these in vitro studies to Notch-"addicted" T cell acute lymphoblastic leukemia (T-ALL) cells. We found that SPSs contributed to the regulation of about a third of direct Notch target genes. Although originally described in promoters, SPSs are present mainly in long-range enhancers, including an enhancer containing a newly described SPS that regulates expression. Our work provides a general method for identifying SPSs in genome-wide data sets and highlights the widespread role of NTC dimerization in Notch-transformed leukemia cells.
[Mh] Termos MeSH primário: Elementos Facilitadores Genéticos
Regulação Leucêmica da Expressão Gênica
Genoma Humano
Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética
Receptores Notch/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Animais
Perfilação da Expressão Gênica
Seres Humanos
Camundongos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo
Regiões Promotoras Genéticas
Ligação Proteica
Receptores Notch/genética
Transdução de Sinais
Fatores de Transcrição/genética
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Notch); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180303
[Lr] Data última revisão:
180303
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE


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[PMID]:29278703
[Au] Autor:Miyashita K; Kitajima K; Goyama S; Kitamura T; Hara T
[Ad] Endereço:Stem Cell Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan; Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
[Ti] Título:Overexpression of Lhx2 suppresses proliferation of human T cell acute lymphoblastic leukemia-derived cells, partly by reducing LMO2 protein levels.
[So] Source:Biochem Biophys Res Commun;495(3):2310-2316, 2018 01 15.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:T cell acute lymphoblastic leukemia (T-ALL) is a malignant cancer with poor prognosis. The transcriptional co-factor LIM domain only 2 (LMO2) and its target gene HHEX are essential for self-renewal of T cell precursors and T-ALL etiology. LMO2 directly associates with LDB1 in a large DNA-containing nuclear complex and controls the transcription of T-ALL-related genes. Recently, we reported that overexpression of the LIM-homeodomain transcription factor, Lhx2, results in liberation of the Lmo2 protein from the Lmo2-Ldb1 complex, followed by ubiquitin proteasome mediated degradation. Here, we found that proliferation of five human T-ALL-derived cell lines, including CCRF-CEM, was significantly suppressed by retroviral overexpression of Lhx2. The majority of Lhx2-transduced CCRF-CEM cells arrested in G phase and subsequently underwent apoptosis. Expression of LMO2 protein as well as HHEX, ERG, HES1 and MYC genes was repressed in CCRF-CEM cells by transduction with Lhx2. Lhx2-mediated growth inhibition was partially rescued by simultaneous overexpression of Lmo2; however, both the C-terminal LIM domain and the homeodomain of Lhx2 were required for its growth-suppressive activity. These data indicate that Lhx2 is capable of blocking proliferation of T-ALL-derived cells by both LMO2-dependent and -independent means. We propose Lhx2 as a new molecular tool for anti-T-ALL drug development.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Proliferação Celular
Proteínas com Domínio LIM/metabolismo
Proteínas com Homeodomínio LIM/metabolismo
Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo
Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia
Proteínas Proto-Oncogênicas/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Regulação para Baixo
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (LHX2 protein, human); 0 (LIM Domain Proteins); 0 (LIM-Homeodomain Proteins); 0 (LMO2 protein, human); 0 (Proto-Oncogene Proteins); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


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[PMID]:29326336
[Au] Autor:Leong WZ; Tan SH; Ngoc PCT; Amanda S; Yam AWY; Liau WS; Gong Z; Lawton LN; Tenen DG; Sanda T
[Ad] Endereço:Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore.
[Ti] Título:ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis.
[So] Source:Genes Dev;31(23-24):2343-2360, 2017 12 01.
[Is] ISSN:1549-5477
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The oncogenic transcription factor induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified ( ) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells. The enhancer located 135 kb upstream of the gene locus is activated under a superenhancer in T-ALL cells but not in normal T cells. Notably, ARID5B-bound regions are associated predominantly with active transcription. ARID5B and TAL1 frequently co-occupy target genes and coordinately control their expression. ARID5B positively regulates the expression of TAL1 and its regulatory partners. ARID5B also activates the expression of the oncogene Importantly, ARID5B is required for the survival and growth of T-ALL cells and forced expression of ARID5B in immature thymocytes results in thymus retention, differentiation arrest, radioresistance, and tumor formation in zebrafish. Our results indicate that ARID5B reinforces the oncogenic transcriptional program by positively regulating the TAL1-induced regulatory circuit and in T-ALL, thereby contributing to T-cell leukemogenesis.
[Mh] Termos MeSH primário: Carcinogênese/genética
Proteínas de Ligação a DNA/metabolismo
Regulação Neoplásica da Expressão Gênica
Proteína 1 de Leucemia Linfocítica Aguda de Células T/metabolismo
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Sobrevivência Celular/genética
Proteínas de Ligação a DNA/genética
Elementos Facilitadores Genéticos/genética
Perfilação da Expressão Gênica
Genes myc/genética
Células HEK293
Seres Humanos
Leucemia-Linfoma Linfoblástico de Células T Precursoras
Ligação Proteica
Domínios Proteicos/genética
Timócitos/metabolismo
Timo/crescimento & desenvolvimento
Fatores de Transcrição/genética
Ativação Transcricional/genética
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (ARID5B protein, human); 0 (DNA-Binding Proteins); 0 (T-Cell Acute Lymphocytic Leukemia Protein 1); 0 (Transcription Factors); 135471-20-4 (TAL1 protein, human)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1101/gad.302646.117


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[PMID]:29200162
[Au] Autor:Valliyammai N; Nancy NK; Sagar TG; Rajkumar T
[Ad] Endereço:Departments of Molecular Oncology.
[Ti] Título:Study of NOTCH1 and FBXW7 Mutations and Its Prognostic Significance in South Indian T-Cell Acute Lymphoblastic Leukemia.
[So] Source:J Pediatr Hematol Oncol;40(1):e1-e8, 2018 Jan.
[Is] ISSN:1536-3678
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:NOTCH1/FBXW7 mutations trigger oncogenic NOTCH1 signaling and its downstream target genes play crucial roles in the molecular pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). In the present study, NOTCH1 and FBXW7 mutations were studied in 25 primary T-ALL samples. All 34 exons of NOTCH1 and hotspot exons (exon 9 and exon 10) of FBXW7 were polymerase chain reaction amplified and sequenced for mutations. Our results showed that 13/25 (52%) were NOTCH1-mutated, of which 11 patients (44%) showed mutation in the hotspot exons. Four patients (16%) had mutations in non-hotspot exons of NOTCH1. Notably, 2 T-ALL patients (8%) harbored mutations in both hotspot and non-hotspot exons of NOTCH1, whereas 2 patients (8%) had mutations in the hotspot exons of FBXW7. In all, 7 mutations were identified which were not previously reported. The real-time polymerase chain reaction study in 15 patients revealed that increased expression of activated NOTCH1 was found in NOTCH1/FBXW7 hotspot exon-mutated cases. In addition, NOTCH1/FBXW7-mutated patients had showed upregulated HES1, c-MYC, NOTCH3 gene expression. When survival analysis was performed including samples (n=50) from our previous study, an early treatment response and better survival was observed in NOTCH1/FBXW7 hotspot-mutated patients. Our study suggests that NOTCH1/FBXW7 hotspot-mutated T-ALL cases had better response to ALL BFM-95 protocol.
[Mh] Termos MeSH primário: Proteína 7 com Repetições F-Box-WD/genética
Mutação
Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética
Prognóstico
Receptor Notch1/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Protocolos de Quimioterapia Combinada Antineoplásica
Asparaginase
Criança
Pré-Escolar
Ciclofosfamida
Citarabina
Análise Mutacional de DNA
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Índia/epidemiologia
Lactente
Recém-Nascido
Masculino
Mercaptopurina
Metotrexato
Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico
Leucemia-Linfoma Linfoblástico de Células T Precursoras/epidemiologia
Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade
Prednisona
Análise de Sobrevida
Vincristina
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (F-Box-WD Repeat-Containing Protein 7); 0 (FBXW7 protein, human); 0 (NOTCH1 protein, human); 0 (Receptor, Notch1); 04079A1RDZ (Cytarabine); 5J49Q6B70F (Vincristine); 8N3DW7272P (Cyclophosphamide); E7WED276I5 (Mercaptopurine); EC 3.5.1.1 (Asparaginase); VB0R961HZT (Prednisone); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180112
[Lr] Data última revisão:
180112
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.1097/MPH.0000000000001006


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[PMID]:27778145
[Au] Autor:Gascho D; Huber B; Bolliger SA; Thali MJ; Schaerli S
[Ad] Endereço:Department of Forensic Medicine and Imaging, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057, Zurich, Switzerland. dominic.gascho@irm.uzh.ch.
[Ti] Título:Splenic rupture and mediastinal mass associated with rare TdT-negative T-LBL/T-ALL lead to sudden death of a juvenile.
[So] Source:Forensic Sci Med Pathol;12(4):523-526, 2016 Dec.
[Is] ISSN:1556-2891
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Morte Súbita/etiologia
Neoplasias do Mediastino/complicações
Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico
Ruptura Esplênica/etiologia
Esplenomegalia/etiologia
[Mh] Termos MeSH secundário: Adolescente
Insuficiência Cardíaca/etiologia
Seres Humanos
Masculino
Neoplasias do Mediastino/diagnóstico por imagem
Doenças Raras
Ruptura Espontânea/etiologia
Ruptura Esplênica/diagnóstico por imagem
Esplenomegalia/complicações
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171208
[Lr] Data última revisão:
171208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:27776559
[Au] Autor:Lonetti A; Cappellini A; Bertaina A; Locatelli F; Pession A; Buontempo F; Evangelisti C; Evangelisti C; Orsini E; Zambonin L; Neri LM; Martelli AM; Chiarini F
[Ad] Endereço:Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
[Ti] Título:Improving nelarabine efficacy in T cell acute lymphoblastic leukemia by targeting aberrant PI3K/AKT/mTOR signaling pathway.
[So] Source:J Hematol Oncol;9(1):114, 2016 10 24.
[Is] ISSN:1756-8722
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Although in recent years, the introduction of novel chemotherapy protocols has improved the outcome of T cell acute lymphoblastic leukemia (T-ALL) patients, refractory and/or relapsing disease remains a foremost concern. In this context, a major contribution was provided by the introduction of the nucleoside analog nelarabine, approved for salvage treatment of T-ALL patients with refractory/relapsed disease. However, nelarabine could induce a life-threatening, dose-dependent neurotoxicity. To improve nelarabine efficacy, we have analyzed its molecular targets, testing selective inhibitors of such targets in combination with nelarabine. METHODS: The effectiveness of nelarabine as single agent or in combination with PI3K, Bcl2, and MEK inhibitors was evaluated on human T-ALL cell lines and primary T-ALL refractory/relapsed lymphoblasts. The efficacy of signal modulators in terms of cytotoxicity, induction of apoptosis, and changes in gene and protein expression was assessed by flow cytometry, western blotting, and quantitative real-time PCR in T-ALL settings. RESULTS: Treatment with nelarabine as a single agent identified two groups of T-ALL cell lines, one sensitive and one resistant to the drug. Whereas sensitive T-ALL cells showed a significant increase of apoptosis and a strong down-modulation of PI3K signaling, resistant T-ALL cells showed a hyperactivation of AKT and MEK/ERK1/2 signaling pathways, not caused by differences in the expression of nelarabine transporters or metabolic activators. We then studied the combination of nelarabine with the PI3K inhibitors (both pan and dual γ/δ inhibitors), with the Bcl2 specific inhibitor ABT199, and with the MEK inhibitor trametinib on both T-ALL cell lines and patient samples at relapse, which displayed constitutive activation of PI3K signaling and resistance to nelarabine alone. The combination with the pan PI3K inhibitor ZSTK-474 was the most effective in inhibiting the growth of T-ALL cells and was synergistic in decreasing cell survival and inducing apoptosis in nelarabine-resistant T-ALL cells. The drug combination caused AKT dephosphorylation and a downregulation of Bcl2, while nelarabine alone induced an increase in p-AKT and Bcl2 signaling in the resistant T-ALL cells and relapsed patient samples. CONCLUSIONS: These findings indicate that nelarabine in combination with PI3K inhibitors may be a promising therapeutic strategy for the treatment of T-ALL relapsed patients.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico
Transdução de Sinais/efeitos dos fármacos
Serina-Treonina Quinases TOR/antagonistas & inibidores
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade
Apoptose/efeitos dos fármacos
Arabinonucleosídeos/uso terapêutico
Arabinonucleosídeos/toxicidade
Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico
Sobrevivência Celular/efeitos dos fármacos
Sinergismo Farmacológico
Seres Humanos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações
Proteínas Proto-Oncogênicas c-akt
Piridonas/uso terapêutico
Pirimidinonas/uso terapêutico
Sulfonamidas/uso terapêutico
Triazinas/uso terapêutico
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Arabinonucleosides); 0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (Pyridones); 0 (Pyrimidinones); 0 (Sulfonamides); 0 (Triazines); 0 (ZSTK474); 33E86K87QN (trametinib); 60158CV180 (nelarabine); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); N54AIC43PW (venetoclax)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171206
[Lr] Data última revisão:
171206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


  9 / 1297 MEDLINE  
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[PMID]:29023469
[Au] Autor:Choi SH; Severson E; Pear WS; Liu XS; Aster JC; Blacklow SC
[Ad] Endereço:Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, United States of America.
[Ti] Título:The common oncogenomic program of NOTCH1 and NOTCH3 signaling in T-cell acute lymphoblastic leukemia.
[So] Source:PLoS One;12(10):e0185762, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL), in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells. ChIP-seq studies show a high concordance of functional NOTCH1 and NOTCH3 genomic binding sites that are enriched in binding motifs for RBPJ, the transcription factor that recruits activated Notch to DNA. The interchangeability of NOTCH1 and NOTCH3 was confirmed by rescue of NOTCH1-dependent T-ALL cells with activated NOTCH3 and vice versa. Despite remarkable overall similarity, there are nuanced differences in chromatin landscapes near critical common Notch target genes, most notably at a Notch-dependent enhancer that regulates MYC, which correlates with responsiveness to Notch pathway inhibitors. Overall, a common oncogenomic program driven by binding of either Notch is sufficient to maintain T-ALL cell growth, whereas cell-context specific differences appear to influence the response of T-ALL cells to Notch inhibition.
[Mh] Termos MeSH primário: Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo
Receptor Notch1/metabolismo
Receptor Notch3/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Regulação Leucêmica da Expressão Gênica
Seres Humanos
Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/biossíntese
Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética
Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética
Proteínas Proto-Oncogênicas c-myc/biossíntese
Proteínas Proto-Oncogênicas c-myc/genética
Receptor Notch1/genética
Receptor Notch3/genética
Elementos de Resposta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunoglobulin J Recombination Signal Sequence-Binding Protein); 0 (MYC protein, human); 0 (NOTCH1 protein, human); 0 (NOTCH3 protein, human); 0 (Proto-Oncogene Proteins c-myc); 0 (RBPJ protein, human); 0 (Receptor, Notch1); 0 (Receptor, Notch3)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171022
[Lr] Data última revisão:
171022
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171013
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185762


  10 / 1297 MEDLINE  
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[PMID]:28973700
[Au] Autor:Alsadi A; Lin D; Alnajar H; Brickman A; Martyn C; Gattuso P
[Ad] Endereço:From the Department of Pathology, Rush University Medical Center, Chicago, Illinois.
[Ti] Título:Hematologic Malignancies Discovered on Investigation of Breast Abnormalities.
[So] Source:South Med J;110(10):614-620, 2017 Oct.
[Is] ISSN:1541-8243
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Hematological malignancies of the breast share a presentation similar to primary breast carcinomas but differ substantially in therapeutic approach and clinical outcomes. In this study, we investigate the frequency of hematological malignancies, their relative primary and secondary occurrences, and further characterize the distinct histopathologies of these malignancies with a special focus on lymphomas. To our knowledge this is one of the largest and most comprehensive studies of breast hematologic malignancies. METHODS: We conducted a retrospective review of our institution's pathology database for hematologic neoplasms diagnosed in breast tissue during a period of 22 years (1992-2014). Clinical characteristics, patient history, histologic subtype, and patient outcomes were analyzed. RESULTS: We identified 52 cases; 46 lymphomas, 4 plasmacytomas, and 2 myeloid sarcomas. The lymphoma cases were 15 diffuse large B-cell lymphomas (DLBCLs), 14 follicular lymphomas (FLs), 8 marginal zone lymphomas (MZLs), 2 anaplastic large T-cell lymphomas, 2 peripheral T-cell lymphomas-not otherwise specified, 1 each of small lymphocytic lymphoma, Burkitt lymphoma, mantle cell lymphoma, B-cell lymphoblastic lymphoma, and T-cell lymphoblastic lymphoma. In total, 30 cases were primary and 22 cases were secondary to the breast. Primary lymphomas accounted for 60% of lymphomas. Most FLs and almost all MZLs were primary. CONCLUSIONS: Primary hematological malignancies of the breast are more common than secondary: 58 % versus 42%. This finding is more evident in lymphomas: 63% versus 37%. The most common hematological malignancy in our study was DLBCL, followed by FL and MZL. Most FLs and almost all MZLs were primary. At the same time, the percentage of primary DLBCLs in our study is lower than the percentage reported in previous studies. We suggest that this could be the result of transformation from low-grade lymphomas. Although rare, hematological malignancies of the breast warrant a higher level of clinical suspicion as they present similarly to breast carcinomas but require a substantially different therapeutic approach.
[Mh] Termos MeSH primário: Neoplasias da Mama/diagnóstico
Carcinoma/diagnóstico
Neoplasias Hematológicas/diagnóstico
Linfoma/diagnóstico
Plasmocitoma/diagnóstico
Sarcoma Mieloide/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Neoplasias da Mama/patologia
Neoplasias da Mama/secundário
Linfoma de Burkitt/diagnóstico
Linfoma de Burkitt/patologia
Diagnóstico Diferencial
Feminino
Neoplasias Hematológicas/patologia
Seres Humanos
Leucemia Linfocítica Crônica de Células B/diagnóstico
Leucemia Linfocítica Crônica de Células B/patologia
Linfoma/patologia
Linfoma de Zona Marginal Tipo Células B/diagnóstico
Linfoma de Zona Marginal Tipo Células B/patologia
Linfoma Folicular/diagnóstico
Linfoma Folicular/patologia
Linfoma Difuso de Grandes Células B/diagnóstico
Linfoma Difuso de Grandes Células B/patologia
Linfoma Anaplásico de Células Grandes/diagnóstico
Linfoma Anaplásico de Células Grandes/patologia
Linfoma de Célula do Manto/diagnóstico
Linfoma de Célula do Manto/patologia
Linfoma de Células T/diagnóstico
Linfoma de Células T/patologia
Meia-Idade
Plasmocitoma/patologia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico
Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico
Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia
Estudos Retrospectivos
Sarcoma Mieloide/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.14423/SMJ.0000000000000710



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