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1.
Blood ; 114(15): 3265-75, 2009 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-19641183

RESUMO

The gene(s) responsible for natural killer (NK)-cell lymphoma/leukemia have not been identified. In the present study, we found that in NK-cell lymphoma lines (n = 10) and specimens of primary lymphoma (n = 10), levels of miR-21 and miR-155 expression were inversely related and were significantly greater than those found in normal natural killer (CD3(-)CD56(+)) cells (n = 8). To determine the functions of these microRNAs in lymphomagenesis, we examined the effects of antisense oligonucleotides (ASOs) targeting miR-21 (ASO-21) and/or miR-155 (ASO-155) in NK-cell lymphoma lines overexpressing one or both of these miRNAs. Conversely, cells showing little endogenous expression of miR-21 or miR-155 were transduced by the use of lentiviral vectors, leading to their overexpression. Reducing expression of miR-21 or miR-155 led to up-regulation of phosphatase and tensin homologue (PTEN), programmed cell death 4 (PDCD4), or Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1). ASO-21- and ASO-155-treated cell lines all showed down-regulation of phosphorylated AKT(ser473). Moreover, transduction with either miR-21 or miR-155 led to down-regulation of PTEN and PDCD4 or SHIP1 with up-regulation of phosphorylated AKT(ser473). Collectively, these results provide important new insight into the pathogenesis of NK-cell lymphoma/leukemia and suggest targeting miR-21 and/or miR-155 may represent a useful approach to treating NK-cell lymphoma/leukemia.


Assuntos
Regulação Neoplásica da Expressão Gênica , Células Matadoras Naturais , Linfoma/metabolismo , MicroRNAs/biossíntese , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Neoplásico/biossíntese , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Feminino , Humanos , Inositol Polifosfato 5-Fosfatases , Lentivirus , Linfoma/genética , Linfoma/patologia , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Oligodesoxirribonucleotídeos Antissenso , PTEN Fosfo-Hidrolase/biossíntese , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Monoéster Fosfórico Hidrolases/biossíntese , Monoéster Fosfórico Hidrolases/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Neoplásico/antagonistas & inibidores , RNA Neoplásico/genética , Proteínas de Ligação a RNA/biossíntese , Proteínas de Ligação a RNA/genética , Transdução Genética
2.
Intern Med ; 47(7): 651-3, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18379154

RESUMO

To prevent fungal infections in patients undergoing treatment for hematological malignancies, we investigated the use of oral itraconazole solution as opposed to itraconazole or fluconazole capsules. Herein, we report five lymphoma patients with severe vincristine neurotoxicity in strong association with oral itraconazole solution. Four patients suffered from severe myalgia with or without arthralgia which clinically resembled polymyalgia rheumatica. Two patients suffered from constipation due to subileus and one patient had a severe paralytic ileus. Appropriate management of the above symptoms, which included discontinuation of oral itraconazole solution, resulted in rapid recovery from neurotoxicity. Given the more consistent plasma concentrations of oral itraconazole solution when compared to itraconazole capsules and the ability of itraconazole to interfere with hepatic vincristine metabolism, we strongly recommend avoiding the combined administration of oral itraconazole solution and vincristine.


Assuntos
Itraconazol/efeitos adversos , Linfoma/tratamento farmacológico , Síndromes Neurotóxicas/diagnóstico , Vincristina/efeitos adversos , Administração Oral , Idoso , Sinergismo Farmacológico , Feminino , Humanos , Itraconazol/administração & dosagem , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/prevenção & controle , Soluções Farmacêuticas/administração & dosagem , Soluções Farmacêuticas/efeitos adversos , Vincristina/administração & dosagem
3.
Rinsho Ketsueki ; 48(4): 326-31, 2007 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-17515125

RESUMO

A 43-year-old female was admitted with therapy-resistant pancreatitis and an abdominal tumor around the pancreatic head. Laboratory data revealed leukocytosis with a white blood cell count of 18200/microl, 25% atypical cells and an LDH of 13410 IU/l. The bone marrow was comprised of 78.4 percent lymphoblastoid cells which were positive for CD10, CD19 and CD20, and the cytogenetic study of which demonstrated the presence of t(8;14) (q24;q32) and t(14;18) (q32;q21) in the same clone. The patient was diagnosed as having Burkitt's lymphoma (BL) with t(8;14) and t(14;18). Although CODOX-M and IVAC therapy combined with rituximab achieved complete remission, she died of rapid progressive disease during whole brain irradiation before autologous peripheral blood stem cell transplantation. Even if the intensive chemotherapy with rituximab is given adequately, durable remission may not be achieved in BL with translocation of t(8;14) and t(14;18). A more effective therapy remains to be established for the treatment of this disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/genética , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 8/genética , Translocação Genética/genética , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Progressão da Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Evolução Fatal , Feminino , Humanos , Ifosfamida/administração & dosagem , Metotrexato/administração & dosagem , Recidiva , Indução de Remissão , Rituximab , Vincristina/administração & dosagem
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